ISSN 1155-5645

Pediatric
Anesthesia
Volume 28 Number 1 2018

@medicinejournal
An international journal published by

Affiliated with the Association of Paediatric Anaesthetists of Great

Britain and Ireland, the European Society of Paediatric Anaesthesia,
Association des Anesthésistes Réanimateurs Pédiatriques
d’Expression Française (the French-Language Society of Paediatric
Anaesthesia), the Canadian Pediatric Anesthesia Society, the
Chinese Society of Pediatric Anesthesiology, the Italian Society of
Paediatric Anaesthesia, the Japanese Society of Pediatric
Anesthesiology, the Paediatric Anaesthesia Community of South
Africa, the Scientific Working Group of Pediatric Anesthesia of the
German Society of Anaesthesiology, the Society of Pediatric
Anesthesia and the Society for Paediatric Anaesthesia in New
Zealand and Australia

PAN_28_1_Issueinformation-online.indd i 05-12-2017 16:17:31

 Pediatric Anesthesia
E D I TO R - I N - C H I E F
A. Davidson (Melbourne, Australia)

A S S O C I AT E E D I TO R - I N - C H I E F E D U CAT I O N E D I TO R
Brian Anderson (Auckland, New Zealand) Mark Thomas (London, UK)

C O R R E S P O N D E N C E E D I TO R
David Polaner (Denver, USA)

SECTION EDITORS Britta Regli-von Ungern-Sternberg STATISTICS EDITOR

Adrian Bosenberg (Seattle, USA) (Perth, Australia) Katherine Lee (Melbourne, Australia)
Joe Cravero (Boston, USA) Francis Veyckemans (Lille, France) SOCIAL MEDIA EDITOR
Susan Goobie (Boston, USA) Laszlo Vutskits (Geneva, Switzerland) Hannah Gill (Bristol, UK)
Dean Kurth (Philadelphia, USA) Suellen Walker (London, UK)
Chandra Ramamoorthy (Stanford, USA)

EDITORIAL BOARD
Dean Andropoulos (Houston, USA)
Mark Ansermino (Vancouver, Canada)
Victor Baum (Charlottesvile, USA)
Thomas Engelhardt (Aberdeen, UK)
Tom Hansen (Odense, Denmark) Steven Shafer (Stanford, USA)
Pablo Ingelmo (Montreal, Canada)
Qingquan Lian (Wenzhou, China)
Andreas Loepke (Cincinnati, USA)
Allison Ross (Durham, USA)

ASSOCIATE EDITORS
Nicole Almenrader (Rome, Italy)
Karin Becke (Nurnberg, Germany)
Patrick Birmingham (Chicago, USA)
Robin Cox (Calgary, Canada)
Jurgen de Graaff (Rotterdam, The Netherlands)
Geoff Frawley (Melbourne, Australia)
Narasimhan Jagannathan (Chicago, USA)
Peter Larsson (Stockholm, Sweden)
Christine Mai (Boston, USA)
Shobha Malviya (Michigan, USA)
Steven Roberts (Liverpool, UK)
Nada Sabourdin (Paris, France)
Justin Skowno (Sydney, Australia)
Santhanam Suresh (Chicago, USA)
Shoichi Uezono (Tokyo, Japan)
Isabeau Walker (London, UK)
Gina Whitney (Denver, USA)
Ma-Zhong Zhang (Shanghai, China)
Yunxia Zuo (Chengdu, China)

PA S T E D I TO R S - I N - C H I E F
Gordon Bush
Ted Sumner
Neil Morton

Devoted to the publication of information of interest and importance to
practising anesthetists everywhere, Pediatric Anesthesia aims to be truly
international in policy and flavour. The scientific and clinical content of the
journal covers a wide selection of medical disciplines in all areas relevant to
anesthesia and intensive care in newborns, infants and children. Pediatric
Anesthesia has an intercontinental Editorial Board, which is supported by
Associate Editors from around the world, to ensure that the journal is pub-
lishing the best work from the front line of research in the field. In addition
to top quality scientific research papers and thorough and up to date reviews,
there are thought provoking editorials and sections covering case presenta-
tions; and correspondence.
This journal is affiliated with the following societies: The European Society for
Paediatric Anaesthesia, the Association of Paediatric Anaesthetists of Great
Britain and Ireland, Association des Anesthésistes Réanimateurs Pédiatriques
d’Expression Françfaise (the French-Language Society of Paediatric
Anaesthesia), the Italian Society of Paediatric Anaesthesia, the Japanese Society
of Pediatric Anesthesiology, the Society for Pediatric Anesthesia, the Society for
Paediatric Anaesthesia in New Zealand and Australia, Paediatric Anaesthesia
Community of South Africa, and Chinese Society of Pediatric Anesthesiology.
Pediatric Anesthesia is indexed by: Index Medicus, MEDLINE, Current
Contents/Clinical Medicine, EMBASE, SciSearch, Research Alert, Ad
Referendum Anaesthesiology, SUBIS, Current Opinion in Anaesthesiology
Editorial correspondence should be directed to: A. Davidson, care of Louise
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PAN_28_1_Issueinformation-online.indd ii 05-12-2017 16:17:32

 Instructions to authors
GENERAL
Pediatric Anesthesia’s mission is to advance the science and clinical practice of paediatric anaesthe-
sia, pain management and peri-operative medicine through dissemination of research, education
and quality improvement.
Priority is given to high-quality original research that advances knowledge, safety, organisation or
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Accepted article types
Research reports – Research reports should follow the Minimal standards for reporting in Pediatric An-
esthesia” http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1460-9592/homepage/Minimal_stan-
PAN_28_1_Issueinformation-online.indd iii
dards_for_reporting_in_Pediatric_Anesthesia.pdf. Clinical Implications, please add 1-2 sentences an-
swering the following questions: a. What is already known about the topic b. What new information this
study adds. A structured abstract of no more than 300 words should include the following: Background;
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mum references – 25. Word counts include all text from the introduction to the end of the text after the
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strategy. If the review is a meta-analysis it should be submitted and structured as a research report
with an abstract, background methods, results discussion, and a clearly articulated aim, search
strategy etc. Summary of no more than 300 words giving information on methods of selecting
the publications cited. Maximum words – 4000; maximum figures and tables – 6; maximum refer-
ences – no limit. Word counts include all text from the introduction to the end of the text after the
disclosures.
Focused reviews – Concise reviews are encouraged and should cover a topic which is of relevance
to pediatric anesthesia, conveying a small number of key points that must be based on solid
evidence. Summary of no more than 200 words. Maximum words – 1500; maximum figures and
tables – 2; maximum references – 10 Word counts include all text from the introduction to the end
of the text after the disclosures.
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mum words – 1000; maximum figures or tables – 1; maximum references – 5 Word counts include all
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and references.
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Randomised clinical trials (RCTs) must conform to the CONSORT statement (http://www.consort-
statement.org) on the reporting of RCTs. A flow diagram of subjects, the trial protocol, and the registra-
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05-12-2017 16:17:32
 Pediatric Anesthesia
N U M B E R 2 8 , I S S U E 1 , J A N U A RY 2 0 1 8

CONTENTS
In this issue
3 In this issue: January 2018 A. Davidson

Editorials
4 What can we learn (or not) from in vitro airway studies for clinical applications in children? N. Jagannathan and
B.S. von Ungern-Sternberg
6 We need personalized assessments for implicit bias in higher risk situations D.B. Waisel

Educational Review
8 New solutions to reduce wrong route medication errors R.S. Litman, V.I. Smith and P. Mainland

Systematic Reviews
13 The anatomy of the pediatric airway: Has our knowledge changed in 120 years? A review of historic and recent
investigations of the anatomy of the pediatric larynx J. Holzki, K.A. Brown, R.G. Carroll and C.J. Coté
23 Donohue syndrome: A review of literature, case series, and anesthetic considerations A. Kirkwood, G. Stuart and
L. Harding
28 Assessment of sedation level prior to neonatal intubation: A systematic review E.H.M. de Kort, N.M. Halbmeijer,
I.K.M. Reiss and S.H.P. Simons

Research Reports
37 Pressure-flow characteristics of breathing systems and their components for pediatric and adult patients C. Wenzel,
S. Schumann and J. Spaeth
46 Introducing the 6-4-0 fasting regimen and the incidence of prolonged preoperative fasting in children H. Andersson,
P.M. Hellström and P. Frykholm
53 Ultrasound-guided pudendal nerve block in children: A new technique of ultrasound-guided transperineal
approach I. Gaudet-Ferrand, P. De La Arena, S. Bringuier, O. Raux, L. Hertz, N. Kalfa, C. Sola and C. Dadure
59 Clinical implications of de Barsy syndrome L.L. Warner, D.A. Olsen and H.M. Smith
63 Incidence and predictors of 30-day postoperative readmission in children D. Vo, D. Zurakowski and D. Faraoni

Case Report
71 Nitroglycerin: An unusual solution to intraoperative hypothermia in a 4-year-old burn patient E.J. Goenaga Díaz,
J.E. Carter and T.W. Templeton

Correspondence
73 In response to “Interventions designed using quality improvement methods reduce the incidence of serious airway
events and airway cardiac arrests during pediatric anesthesia” B.H. Cloyd
74 Continuous Erector Spinae Plane block for thoracic surgery in a pediatric patient J.C. De la Cuadra-Fontaine, M. Concha,
F. Vuletin and H. Arancibia
75 Mispositioning the end of a cuff inflating line in long-axis ultrasound imaging of the pediatric larynx and
trachea K. Kayashima and K. Imai

Pediatric Anesthesia is indexed in Index Medicus, MEDLINE, Current Contents/Clinical Medicine, EMBASE/
Excerpta Medica, Sci Search, Research Alert, Ad Referendum Anaesthesiology,
SUBIS and Current Opinion in Anaesthesiology

PAN_28_1_Issueinformation-online.indd 1 05-12-2017 16:17:32

DOI: 10.1111/pan.13299

In this issue: January 2018

NEW SOLUTIONS TO REDUCE WRONG ROUTE MEDICATION ERRORS

New connectors will be coming your way soon. This fascinating review covers the history and new developments of the tubing connectors.

INCIDENCE AND PREDICTORS OF 30-DAY POSTOPERATIVE READMISSION IN CHILDREN

Developing quality outcome measures is important. For better or worse, hospital readmission is one that is frequently used. This large study
identifies children at risk of readmission.

INTRODUCING THE 6-4-0 FASTING REGIMEN AND THE INCIDENCE OF PROLONGED PREOPERATIVE FASTING IN
CHILDREN

Another study that will hopefully help children being less grumpy and thirsty.

THE ANATOMY OF THE PEDIATRIC AIRWAY: HAS OUR KNOWLEDGE CHANGED IN 120 YEARS? A REVIEW OF
HISTORIC AND RECENT INVESTIGATIONS OF THE ANATOMY OF THE PEDIATRIC LARYNX

There is still argument over the basic shape of a child’s larynx. This paper presents a strong case for the funnel.

ASSESSMENT OF SEDATION LEVEL PRIOR TO NEONATAL INTUBATION: A SYSTEMATIC REVIEW

In the neonatal intensive care, endotracheal intubation is a not infrequent and a stressful event for the infant. Proving adequate sedation
beforehand is important but evidence to guide best practice is scarce. This paper reviews how adequate sedation is assessed.

Andrew Davidson
Editor-in-Chief

Pediatric Anesthesia. 2018;28:3. wileyonlinelibrary.com/journal/pan © 2017 John Wiley & Sons Ltd | 3
DOI: 10.1111/pan.13280
EDITORIAL
What can we learn (or not) from in vitro airway studies for
clinical applications in children?
Albert Einstein once said, “if you can’t explain it simply, you don’t
understand it well enough”, implying that thorough knowledge and
comprehension of a topic is a prerequisite for its useful application.
Baseline knowledge of many topics in pediatric anesthesia, however,
are so limited that they even preclude safe research in human sub-
jects, let alone provide simple explanation and clinical application. In
vitro research studies aim to bridge this knowledge gap by integrat-
ing laboratory findings to clinical trials, in an attempt to bring novel
concepts from “bench-to-bedside”. The main advantages of an
in vitro study are the ability to identify potential suitability for
human subjects testing, or to assess the underlying human physiol-
ogy or material properties of certain equipment. Alternatively, the
results of an in vitro study may be convincing enough to pursue
human subjects testing. However, their inability to fully emulate
real-life clinical conditions remains a major limitation.
Einstein also gave us further advice: “A theory can be proved by
experiment; but no path leads from experiment to the birth of a the-
ory.” Within the context of pediatric anesthesia research, this quote
reminds us that just because a model is available, it should not mean
that one should proceed to perform in vitro trial. Similarly, the 19th
century French physiologist, Claude Bernard remarked, “The experi-
menter who does not know what he is looking for will never under-
stand what he finds.” The design of an in vitro study should
foremost have a translational application in mind. Herein this edito-
rial, we discuss the potential advantages and limitations associated
with recent in vitro research in pediatric anesthesia.
When embarking on a new in vitro airway study, a few questions
should be considered as a litmus test for whether to proceed with a
particular design. Failure to resoundingly answer “yes” to one of the
following questions, should be a flag for revisiting the study question
its merits, and/or its methodological aspects:
• Is an in vitro study the only way we can study this topic because
human subjects study is impossible or harmful?
• Will the results of this in vitro study have potential to help design
better in vivo studies?
• Will the results of this study have potential to alter current prac-
tices or improve patient care?
1 | EQUIPMENT RESEARCH
Two recent interesting in vitro studies with potential clinical implica-
tions involve the use of infant lung models. The first, conducted by
4 | © 2017 John Wiley & Sons Ltd wileyonlinelibrary.com/journal/pan
Mohr et al., aimed to assess the impact of tracheal tube (TT) short-
ening in infants, a not uncommon clinical practice to reduce the
work of breathing in neonates and infants.1 The authors used an
infant lung model to test this hypothesis for the existing practice.
However, the study showed that shortening the TT did not reduce
work of breathing in this infant lung model. Although this in vitro
study environment was not identical to in vivo settings, these results
may discourage clinicians from shortening the TT, and potentially
help design future clinical studies to further explore the impact of
shortening TTs when caring for infants.
The second study is a quality improvement project assessing
breathing circuit compliance in infants.2 Glenski et al. performed an
in vitro study on infant test lungs by performing preuse self-tests on
nonexpanded, and then subsequently expanded breathing circuits.
The authors found that this led to falsely elevated tidal volumes in
infants less than 10 kg during pressure-controlled ventilation. The
results obtained from their study were then applied clinically in real
infants and led to a practice change in the authors’ institution after
department-wide education and implementation.
Both of these studies are fine examples of the use of laboratory
testing to explore common clinical practices and challenge the valid-
ity of existing clinical paradigms to better define patient care without
risking patient morbidity.
2 | MANIKIN STUDIES
As the Chemistry Nobel Laureate put it, “A theory has only the alter-
native of being right or wrong. A model has a third possibility: it
may be right, but irrelevant.” The latter is unfortunately true for
many medical manikin models—as there are few high-quality pedi-
atric manikins that can truly emulate the anatomic/physiologic condi-
tions of a real-life patient, thereby limiting their relevance and
generalizability. While manikin studies may be suitable to teach,
train, acquire, and assess skills by emulating rarely encountered clini-
cal situations, manikins may be useful in evidence-based training in
the simulated management of the difficult airway. For example, how
to assess various airway device performance in a Pierre Robin mani-
kin.3 Although this type of manikin may be useful for teaching and
training purposes, the results observed from such a manikin study
may not be translated to real-life clinical conditions. Certain vari-
ables, such as secretions, dynamic changes (reflex activation of the
airway, light anesthesia, oxygen desaturations), are difficult to emu-
late. Even high fidelity simulation with better features cannot
Pediatric Anesthesia. 2018;28:4–5.
EDITORIAL
completely remove the sense of an artificial environment and may
not be reflective of real clinical practice/behavior. The time pressure
and stress experienced in actual clinical practice cannot be replicated
and experienced during performances on a manikin. Although these
limitations exist, manikins have been a valuable tool to train on, and
enhances clinical education. Situations exist where it may be unethi-
cal to perform a clinical trial, or test experimental equipment on
human subjects. In these situations, the use of manikins and/or ani-
mal models (see below) become a more suitable study model, how-
ever the translational value of a manikin is highly questionable.
3 | ANIMAL STUDIES
Animal models often serve as a reasonable alternative to human sub-
jects for rarely encountered clinical situations. The Cannot Intubate,
Cannot Oxygenate (CICO) scenario in children is rarely encountered
in real practice, with limited data regarding best practices, and
anatomical differences in infants make extrapolation of adult evi-
dence problematic.4 Moreover, the assessment of various
approaches and/or techniques cannot be ethically and feasibly stud-
ied in human subjects. Therefore, animal models have served as
alternative in vitro study models for these purposes. The use of rab-
bit and/or piglet models may provide helpful information on efficacy
of certain oxygenation and percutaneous techniques and maybe a
more realistic approach compared to manikin models.5 Similar to
manikin studies, animal models may not exactly duplicate real-life
clinical conditions, or necessarily translate to a transfer of skills into
clinical practice, they may provide the only alternative environment/
condition to emulate rare clinical conditions, and therefore help
guide practice.
In conclusion, in vitro models can be useful (or not) to help clini-
cians guide clinical practice by possibly emulating extremely rare clin-
ical situations, act as a preliminary model prior to human subjects
testing, or offer information that would preclude progression to
human trials. Investigators should carefully consider which models
and study designs may fulfill these criteria in order to ‘separate the
wheat from the chaff’ to help us guide better practice choices for
clinicians.
FUNDING
Britta S von Ungern-Sternberg holds the Callahan Chair in Paediatric
Anaesthesia and is partly funded by the Late Frank Callahan, the
| 5
Princess Margaret Hospital Foundation and the Stan Perron Charita-
ble Trust.
DISCLOSURES
Britta S von Ungern-Sternberg is a Section Editor of Pediatric Anes-
thesia. Narasimhan Jagannathan is an Associate Editor of Pediatric
Anesthesia.
ORCID
Britta S. von Ungern-Sternberg http://orcid.org/0000-0002-8043-
8541
Narasimhan Jagannathan1,2
Britta S. von Ungern-Sternberg3,4
1
Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, USA
2
Department of Pediatric Anesthesia, Northwestern University Feinberg
School of Medicine, Chicago, IL, USA
3
Department of Anesthesia and Pain Management, Princess Margaret
Hospital for Children, Perth, WA, Australia
4
Medical School, Division of Anaesthesiology and Pain Medicine, The
University of Western Australia, Perth, WA, Australia
Email: britta.regli-vonungern@health.wa.gov.au
REFERENCES
1. Mohr R, Thomas J, Cannizzaro V, et al. Impact of endotracheal tube
shortening on work of breathing in neonatal and pediatric in vitro
lung models. Pediatr Anesth. 2017;27:942-948.
2. Glenski TA, Diehl C, Clopton RG, Friesen R. Breathing circuit compli-
ance and accuracy of displayed tidal volume during pressure-con-
trolled ventilation of infants: a quality improvement project. Pediatr
Anesth. 2017;27:935-941.
3. Hippard HK, Kalyani G, Olutoye OA, Mann DG, Watcha MF. A com-
parison of the Truview PCD and the GlideScope Cobalt AVL video-
laryngoscopes to the Miller blade for successfully intubating manikins
simulating normal and difficult pediatric airways. Pediatr Anesth.
2016;26:613-620.
4. Sabato SC, Long E. An institutional approach to the management of
the ‘Can’t Intubate, Can’t Oxygenate’ emergency in children. Pediatr
Anesth. 2016;26:784-793.
5. Prunty SL, Aranda-Palacios A, Heard AM, et al. The ‘Can’t intubate
can’t oxygenate’ scenario in pediatric anesthesia: a comparison of the
Melker cricothyroidotomy kit with a scalpel bougie technique. Pediatr
Anesth. 2015;25:400-404.
DOI: 10.1111/pan.13289
EDITORIAL
We need personalized assessments for implicit bias in higher
risk situations
In a previous issue of Pediatric Anesthesia, Rosenbloom et al1 and
2
Maher et al present studies looking at different approaches to
assessing health and healthcare disparities.
Healthcare disparities affect racial, ethnic, gender, socioeconomic,
geographic, and other cohorts in areas such as insurance coverage,
access to care, quality of care, and clinician actions. In a “Limited
Evaluation of the Association of Race and Anesthetic Medication
Administrations”, Rosenbloom et al1 examined whether there were
healthcare disparities between patient race and administration of
medication. In their study, race was self-reported as either Black or
White. They found no racial disparities in the use of preoperative or
intraoperative medications.
Health (as compared to healthcare) disparities are variations in mor-
bidity and mortality among groups. Maher et al2 found that African-
American children undergoing spinal fusion bled more and had an
increased rate and volume of blood transfusion. Limited data availability
in their retrospective study makes it difficult to determine etiologies for
this disparity. Studies that indicate increased bleeding in African-Ameri-
can patients in other procedures suggests a physiologic component.
Physiologic causes may be due to genetics or may arise from inadequate
living conditions, prior healthcare, and optimization for surgery. In this
study, race was self-identified at registration from a prepopulated list
that included: 2 or more races; American Indian or Alaska Native; Black
or African-American; Caucasian/White; Native Hawaiian or Other Paci-
fic Islander; Not reported/declined; or Other (free text).
Studying disparities in populations who have a history of unequal
access, inadequate care and poorer outcomes increases awareness
of the general and specific issues. That said, we need to approach
these studies with some caution.
1 | BLACK IS NOT BLACK, WHITE IS NOT
WHITE
Darker-skinned Black people are more discriminated against than
lighter-skinned Black people in both Black and White communities,
although there is some evidence of recent improvement in that area.3
Colorism, which is bias attached to skin shade, is present across soci-
eties and races. In studies assessing conscious or unconscious bias of
clinicians, it would be nice to categorize the patients not only by race
but also by prejudices within that race, such as categorizing patients
as either lighter skinned or darker skinned. And because the outcome
is a function of an interpersonal relationship, the race and skin shade
of anesthesiologists should also be categorized.
6 | © 2017 John Wiley & Sons Ltd wileyonlinelibrary.com/journal/pan
Genomes differ within the same socially constructed race category
(eg, Black, White, Native American, and Pacific Islander).4 Self-assess-
ment of race does not indicate genetic structure.5 Biological differ-
ences are better off determined at the genetic level, unless it is well
shown that the relevant genes are consistent with self-assessed race.
2 | RISKS WITH RACE OR GENETIC-BASED
ASSESSMENTS OF PATIENTS
In the medical system in the United States, costly health insurance
for “high-risk” patients often makes good insurance unaffordable,
and inexpensive insurance may limit the care options offered, creat-
ing additional disparities. Genetic data already affect the costs and
availability of life insurance and long-term care insurance.6 There are
loopholes in the Genetic Information Nondiscrimination Act, which
was designed to limit the harms of genetic testing. For example, a
client that knows but does not share a genetic predisposition to a
disease may lose the benefits of insurance later because of “guilt by
omission.” Considering Maher et al’s study, it is disquieting to add
genetic discrimination to a cohort associated with health and health-
care disparities.
To a cynic like me, the harms of the potential consequences of
genetic data will only increase; while you may think me “crying
wolf”, who would have thought 20 years ago that body mass index
and tobacco use would either limit getting insurance or require pay-
ing higher premiums.
Despite these risks, these studies need to be done.
3 | CONCLUSION
Clinicians scorn interpersonal healthcare disparity data: “It is not rel-
evant to me, because I am not prejudice.” But implicit bias is ubiqui-
tous. A systematic review7 of papers found that implicit bias—
unconscious and automatic—was negatively correlated with indica-
tors of quality care. Implicit bias occurs by race, ethnicity, socioeco-
nomic status, gender, age, body habitus, disease, disability, and
whether the patient contributed to their disease. We need to recog-
nize higher risk situations where unconscious bias may affect patient
care, have the wherewithal to acknowledge the possibility of implic-
itly biased behavior, and take overt actions to minimize it.
Studies like these help us recognize higher risk situations, such
as variation in preoperative drug administration when anesthetizing
Pediatric Anesthesia. 2018;28:6–7.
EDITORIAL
children of color. In addition to the previously described cohorts at
risk of harm from implicit bias, disparity research is needed in other
populations of patients receiving anesthesia, including patients who
require interpreters, are having surgical treatment for gender dys-
phoria, have a nonbinary gender or are agender, are obese, or with
whom we have a subpar relationship (the pejoratively termed “diffi-
cult” patient). Situations in which disparities may occur include the
quality of preoperative discussions, the extent of trainee supervision,
and the performance of postoperative visits.
Future studies should incorporate technically more complex fac-
tors that affect performance, such as numbers of rooms covered,
complexity of cases, times of day, extent of trainee supervision, and
other sources of production pressure. Studying additional factors
may identify opportunities for system-level improvements, or at least
identify higher risk situations for disparate management.
To improve care, we need personalized assessments of our
behaviors to identify individual higher risk situations. Unfortunately,
a congenital and justified distrust of organizational responses to
personalized data makes these assessments unwelcome in our
community, highlighting another (discounted) systemic barrier to
serving our patients.
CONFLICT OF INTEREST
No conflict of interest.
ORCID
David B. Waisel http://orcid.org/0000-0002-5307-4092
| 7
David B. Waisel
Department of Anesthesiology, Perioperative and Pain Medicine, Boston
Children’s Hospital, Harvard Medical School, Boston, MA, USA
Email: david.waisel@childrens.harvard.edu
REFERENCES
1. Rosenbloom J, Senthil K, Long A, et al. A limited evaluation of the
association of race and anesthetic medication administration: a single-
center experience with appendectomies. Pediatr Anesth. 2017;27:
1142-1147.
2. Maher K, Owusu-Akyaw K, Zhou J, et al. African-American race is
associated with increased blood transfusion in pediatric scoliosis sur-
gery. 2016. http://www.asaabstracts.com/strands/asaabstracts/abstract.
htm?year=2016&index=16&absnum=4342. Accessed December 5,
2017.
3. Hunter M. The consequences of colorism. In: Hall R, ed. Melanin Mil-
lenn. Skin Color as 21st Century International Discourse. Dordrecht,
Netherlands: Springer; 2013:247-256.
4. Solberg OD, Mack SJ, Lancaster AK, Single RM, Sanchez-mazas A,
Thomson G. Balancing selection and heterogeneity across the classical
human leukocyte antigen loci: a meta-analytic review of 497 popula-
tion studies. Hum Immunol. 2008;69:443-464.
5. Boquett J, Schu€ler-faccini L, Jobim LF, et al. Self-assessment of color
categories and its relationship with HLA profiling in Brazilian bone
marrow donors. Biol Blood Marrow Transplant. 2015;21:1140-1144.
6. Peikoff K. Fearing punishment for bad genes. New York Times [Inter-
net]. New York City; April 8, 2014; D1. https://www.nytimes.com/
2014/04/08/science/fearing-punishment-for-bad-genes.html. Accessed
September 8, 2017.
7. FitzGerald C, Hurst S. Implicit bias in healthcare professionals: a sys-
tematic review. BMC Med Ethics. BMC Med Ethics. 2017;18:19.
Accepted: 28 September 2017

DOI: 10.1111/pan.13279

EDUCATIONAL REVIEW

New solutions to reduce wrong route medication errors

Ronald S. Litman1,2 | Victoria I. Smith3 | Phoebe Mainland4

1
Department of Anesthesiology & Critical
Care, The Children’s Hospital of Summary
Philadelphia, Philadelphia, PA, USA Wrong route medication errors due to tubing misconnections are potentially life-
2
Institute for Safe Medication Practices,
threatening complications that have been made possible by the universal use of the
Horsham, PA, USA
3
Drexel University, Philadelphia, PA, USA Luer connector. The new International Organization of Standardization standards for
4
Department of Anaesthesia and small bore connectors, ISO 80369 series, have been developed to reduce the risk of
Perioperative Medicine, AlfredHealth,
these types of erroneous connections. Tubing connectors for different routes of
Melbourne, VIC, Australia
clinical application will contain differently designed connectors that are physically
Correspondence
incompatible. However, design and manufacturing standards have progressed slowly,
Dr Ronald S. Litman, Department of
Anesthesiology & Critical Care, The and clinical roll-outs have been delayed, despite the implementation of California
Children’s Hospital of Philadelphia,
laws to promote their use. We are currently in a state of transition where new con-
Philadelphia, PA, USA.
Email: Litmanr@email.chop.edu nectors for enteral and neuraxial use will be entering the clinical market in the next
few years, and increasing use will identify additional patient safety concerns.
Funding information
The preparation of this review was funded
by departmental resources. KEYWORDS
Medication errors, small bore connectors, tubing misconnections
Section Editor: Mark Thomas

1 | INTRODUCTION
Much of the practice of hospital-based medicine can be traced to
the use of a universal tubing connector that allows connection
between medical devices from different manufacturers throughout
the world. This connector was originally created in 1896 by Karl
€er Company of
Schneider, an instrument maker for the H. Wulfing Lu
Paris. It consisted of a glass cylinder and plunger with a “male” inser-
tion tip that was constructed with a 6% taper to snugly fit into the
corresponding “female” ports of various types of medical instillation
devices, such as intravenous, urethral, or intrauterine catheters.1
€ er traveled to the United States, where he sold the patent of his
Lu
universal syringe to Maxwell W. Becton and Fairleigh S. Dickinson,
who used it to start their fledgling company they called Becton Dick-
2
inson. And as they say, the rest is history. In the 1930s, Becton
Dickinson added an external cuff locking mechanism to prevent acci-
TM
dental disconnections, the eponymous Luer-Lok we all still use
today.3 Over the ensuing century throughout the 1900s, the Luer-
tipped syringe became the USA industry standard for nearly all types
of medical tubing connections. Until the 1980s, many syringe manu-
facturers in Europe continued to use the similar but incompatible
Rekord type syringe tip. But, in 1988, 3 pilots and 67 spectators lost
their lives, and many hundreds were injured from the spread of
flames in the Ramstein Air Base air show disaster.4 Some authors
have speculated that during the rescue effort, the incompatibility of
intravascular tubing between the USA army hospital and the German
paramedics contributed to the inability to resuscitate many of the
injured spectators.1 In 1995, the International Organization of Stan-
dardization (ISO) published an international standard specifying the
consistent use of the Luer-tipped syringe.5 This standard has since
been used throughout the world.
There are always unintended consequences when standardization
processes occur. Because of the universal nature of Luer connectors,
delivery systems for intravascular (IV), enteral, respiratory, and neu-
raxial* medical devices have been accidentally interconnected to
each other, either directly, or indirectly using adaptors that were not
intended for that specific use.6-8 These accidental misconnections
result in wrong route medication errors, and have resulted in patient
harm. As not all substances are safe when administered via different
routes, wrong route administrations can have severe consequences,
such as when an enteral feed is administered by the IV route, or a
drug that is ordinarily safe to administer by vein becomes toxic when
administered into one of the neuraxial spaces, such as intrathecal,
*The term “neuraxial” describes the route of administration into the intrathecal, epidural,
and perineural spaces, as well as other areas of regional infiltration of local anesthetic to
achieve pain control.

8 | © 2017 John Wiley & Sons Ltd wileyonlinelibrary.com/journal/pan Pediatric Anesthesia. 2018;28:8–12.
LITMAN ET AL.
epidural, or perineural. Although published cases of wrong route
medication errors are likely widely underreported, published reports
describe such accidental connections that resulted in patient harm.
A 2011 systematic review of enteral-to-IV misconnections
described 116 cases in 34 publications, which resulted in the death
9
of 21 patients. Despite widespread recognition of the severity of
this type of medication error,10 new reports continue to appear,
such as a 6-week-old infant who was accidently administered breast
milk intravenously.11
The accidental administration of intravascular medications into
the neuraxial spaces has been amply reported.12-17 Some of these
reports describe devastating consequences. For example, a 59-year-
old male was left permanently disabled after he was accidentally
administered high-dose gadolinium into his external ventricular drain
during an imaging study.18 The continued occurrence of similar cases
prompted an impassioned editorial pleading for the urgent imple-
mentation of preventative measures.19,20
Although administration of toxic substances into the intravascular
and neuraxial spaces are the most commonly reported wrong route
medication errors, additional types of calamities involving tubing
with the universal Luer connection have occurred with disastrous
outcomes. These include the accidental administration of enteral
feed into the suction port of a tracheostomy, and fatal air emboli,
one after the connection of high-flow oxygen into an intravascular
port, another after the connection of the tubing of an automated
noninvasive blood pressure cuff that was accidently connected to an
intravenous port.21
1.1 | The new small bore connector standards
Over the past several decades, there has been a concerted effort
across the globe to devise ways to reduce the wrong route errors
22-24
that resulted from the use of universal Luer connectors. Organi-
zations in the USA including the Food and Drug Administration,6
Emergency Care Research Institute,7 and the Joint Commission on
Healthcare8 have issued warnings and sentinel events regarding the
danger of universal Luer connectors and the need for caution. Similar
statements and warnings have been issued in other countries, such
as Patient Alerts from the National Patient Safety Agency in Eng-
land.25 In response to increasing awareness of this problem, a pro-
ject to develop unique connectors for medical devices used in
different applications started initially in 1997 by a Forum Task Group
of the European Committee for Standardization (CEN). Later this
was handed over to the ISO to create new standards for tubing con-
nectors that would prevent interconnectivity. After extensive collab-
oration between biomedical engineers, computer design experts,
manufacturers, consultants, and clinicians, it resulted in the ISO
80369 series of standards for Small Bore Connectors. The first stan-
dard of the series, General Principles, was published in 2010. These
new standards consist of design specifications of male and female
connectors that are unique for different routes of application into
which medications or other substances may be administered. The
goal of these new specifications is to reduce the possibility of wrong
| 9
route connections by preventing physical compatibility between
delivery routes. The Luer connector dimensions will remain for
intravascular and hypodermic applications only (Table 1 and Fig-
ure 1). The new standards were subsequently endorsed by the Asso-
ciation for the Advancement of Medical Instrumentation (AAMI),26
and The Joint Commission released a follow up Sentinel Event in
2014 urging healthcare providers to begin preparing for the new
connectors and to continue to vigilantly avoid misconnections until
the new connectors debut.27
The only regulatory or legislative solution to wrong route errors
occurred in 2015 when the California legislature passed Assembly
Bill 444,28 which contains 3 main provisions:
1. Beginning January 1, 2016, a health facility is prohibited from
using an intravenous connector that would fit into a connector
other than the type it was intended for.
2. Beginning July 1, 2016, a health facility is prohibited from using
an enteral feeding connector that would fit into a connector
other than the type it was intended for.
3. Beginning January 1, 2017, a health facility is California from
using an epidural connector that would fit into a connector other
than the type it was intended for.
All of the above prohibitions stipulate that an exception can be
made when an emergency or urgent situation exists or if the prohibi-
tion would impair the ability to provide appropriate health care.
The successful implementation of the changes will not be possi-
ble without the participation of medical device manufacturers, who
will now be required to produce and distribute devices with connec-
tors that comply with the new design specifications. The design for
the connector for enteral use was the first to be confirmed, in
response to the California legislation deadline. A consortium of man-
ufacturers of enteral devices and enteral feed manufacturers was
formed, known as the Global Enteral Device Supplier Association
(GEDSA, www.gedsa.org), a nonprofit trade association to promote
adoption of devices compliant with ISO 80369-3, enteral and other
standards in the series, and to address operational and safety issues
in implementing products. GEDSA launched the Stay Connected initia-
tive (stayconnected.org), a communications program with the goal to
facilitate transition to devices compliant with the ISO 80369 series
of Small Bore Connectors and begin implementation of these
changes throughout the world.
T A B L E 1 New International Organization of Standardization (ISO)
80369 connector series
ISO standard Delivery route
80369-2 Respiratory
80369-3 Enteral
80369-5 Limb cuff inflation
80369-6 Neuraxial
80369-7 Intravascular (6% tapered Luer)
10 | LITMAN
In collaboration with the ISO Committee Working Group respon-
sible for the ISO 80369 series of standards and GEDSA, specific
‘clinical advisory groups’ of international experts (from the United
States and Europe, and for neuraxial, Australia) have been formed to
give input to clinical requirements for implementation of enteral and
neuraxial devices.
The first new ISO small bore connectors to be introduced into
clinical use will be the enteral (ISO 80369-3) connectors and the
neuraxial (ISO 80369-6) connectors. Each will have a unique size
and shape and will be physically incompatible with Luer connectors
and the other new small bore connectors. Many manufacturers have
informally agreed upon (ie, it is not standardized) a name and color
allocation for these new connections. The enteral (eg, nasogastric, or
percutaneous gastric or jejunal feeding tubes) connectors may be
known as ENFitâ, and devices may have purple coloring of the syr-
inges and tubing (Figure 2). These have been introduced throughout
the USA and Europe beginning in 2016.29 The neuraxial connectors
(eg, perineural infiltration, epidural, and intrathecal administration)
may be known as NRFitTM, may have yellow coloring of syringes and
tubing, and are expected to be introduced into clinical practice in
2017. As the use of colors purple and yellow is not standardized,
there are on the market devices using these colors that are not nec-
essarily compliant with ISO 80369 series, and may be used for other
clinical applications.
Because some patients have an indwelling enteral device such as
a percutaneous feeding tube, manufacturers have also made avail-
able adaptors for enteral devices that facilitate connection between
old and new systems during the transitional phase. The use of transi-
tion sets or adaptors is not planned for neuraxial devices.
F I G U R E 2 New ENFitâ connector to be used for connecting
enteral feeds (Courtesy of, and used with permission from GEDSA)
ET AL.
F I G U R E 1 The new small bore
connectors International Organization of
Standardization (ISO) 80369 series
(Courtesy of, and used with permission
from Phoebe Mainland, MBBS, FANZCA
and Kyle Steele)
With the introduction of these new connector systems into clini-
cal practice, previously unidentified problems have arisen.30 For
example, use of the new EnFitâ connectors resulted in dosing inac-
curacies with the lowest volume (1 mL, 3 mL, and 5 mL) ENFitâ syr-
inges. After considerable effort and study, a new low-dose ENFitâ
tip syringe has been designed, with the intention of limiting the dose
inaccuracy to less than 10% (NeoMedâ Inc. “Low Dose Tip”).31 How-
ever, one major syringe manufacturer, Becton Dickinson, made the
decision to abandon the ENFitâ design, and launch a new type of
enteral syringe design in its place (http://www.bd.com/hypodermic/
products/enteral/). At the time of this writing, all other enteral syr-
inge manufacturers produce devices with the ENFitâ connector,
although proprietary non-Luer devices are also on the market. It will
remain to be seen whether the Becton Dickinson enteral syringe will
retain compatibility with other manufacturers’ products.
Similar problems are expected to arise with clinical introduction
of the NRFitTM connector for neuraxial devices. For example, as
the NRFitTM has a smaller internal diameter lumen than its Luer
counterpart, flow rates of cerebrospinal fluid during diagnostic or
therapeutic (eg, intrathecal chemotherapy) lumbar punctures will
decrease, thus possibly affecting clinical practice.32,33 These proce-
dures may take longer to perform and could result in patient
safety concerns if clinicians do not wait long enough to collect
adequate amounts of fluid, or falsely abandon the procedure think-
ing the correctly placed needle has been misplaced into another
space.
The ISO 80369 standard for the connector for limb cuff inflation
in adult blood pressure measurement has been published, and is
based on a currently available design with devices. Compliant cuffs
and tubing are already on the market. There are plans for additional
designs in ISO 80369-5 for inflation tourniquets for limbs and for
neonatal/pediatric blood pressure cuffs. In the coming years, addi-
tional connectors in the ISO 80369 series will also be introduced for
respiratory equipment, such as oxygen tubing with different connec-
tors for high pressures (eg, oxygen to facemask) and low pressures
(eg, gas sampling in anesthesia systems).
Despite the legislation in California mandating use of different
connectors for enteral and neuraxial tubing by the beginning of
2017, to date rollout has been inconsistent between centers, yet
slow and steady transitions are occurring. The most consistent road-
block to implementation is finding consistent supply of devices with
LITMAN ET AL.
the new connectors from manufacturers, especially in larger hospital
systems that may have constraints on equipment suppliers (Personal
communication, Rory Jaffe MD, MBA, Executive Director, California
Hospital Patient Safety Organization).
2 | SUMMARY
Wrong route medication errors due to tubing misconnections are
potentially life-threatening complications that have been made pos-
sible by the universal use of the Luer connector. The new ISO
80369 series of standards for small bore connectors have been
developed to reduce the risk of these types of erroneous connec-
tions. Tubing connectors for different routes of clinical application
will contain differently designed connectors that are physically
incompatible. However, design and manufacturing standards have
progressed slowly, and clinical roll-outs have been slow, despite
the implementation of California laws to promote their use. We
are currently in a state of transition where new connectors for
enteral and neuraxial use will be entering the clinical market in
the next few years, and increasing use will identify additional
patient safety concerns. A supplementary podcast that provides an
overview of this article as well as discussion of the below reflec-
tive questions is available here: [https://youtu.be/5PIF9JYqZOE].
REFLECTIVE QUESTIONS
1. Does use of the universal Luer connector predispose to wrong
route medication errors?
2. What are the new ISO 80369 small bore connector standards?
3. How will you monitor patient safety concerns when new small
bore connectors are used clinically?
ETHICAL APPROVAL
No ethical board approval was required for this review article.
CONFLICT OF INTEREST
The authors claim no conflicts of interest pertaining to the material
discussed within this review.
ORCID
Ronald S. Litman http://orcid.org/0000-0001-8626-8267
REFERENCES
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ny/about-bd. Accessed October 23, 2017.
| 11
3. Milamed DR, Brown K, Murphy E. Luer’s lure: from an international
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7. ECRI. Top 10 health technology hazards for 2011. Health Dev.
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8. The Joint Commission. Tubing misconctions—A persistent and
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10. Harris G.U.S. Inaction Lets Look-Alike Tubes Kill Patients. The New
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11. Do€ ring M, Brenner B, Handgretinger R, Hofbeck M, Kerst G. Inad-
vertent intravenous administration of maternal breast milk in a six-
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12. Ajmal M. Accidental intrathecal injection of aminophylline in spinal
anesthesia. Anesthesiology. 2011;114:998-1000.
13. Mohseni K, Jafari A, Nobahar MR, Arami A. Polymyoclonus seizure
resulting from accidental injection of tranexamic acid in spinal anes-
thesia. Anesth Analg. 2009;108:1984-1986.
14. Reddy GK, Brown B, Nanda A. Fatal consequences of a simple mis-
take: how can a patient be saved from inadvertent intrathecal vin-
cristine? Clin Neurol Neurosurg. 2011;113:68-71.
15. D’Addario A, Galuppo J, Navari C, et al. Accidental intrathecal admin-
istration of vincristine. Am J Forensic Med Pathol. 2010;31:83-84.
16. Townley KR, Lane J, Packer R, Gupta RK. Unintentional infusion of
phenylephrine into the epidural space. A&A Case Rep. 2016;6:124-
126.
17. Beckers A, Verelst P, van Zundert A. Inadvertent epidural injection
of drugs for intravenous use. A review. Acta Anaesthesiol Belg.
2012;63:75-79.
18. Singh S, Rejai S, Antongiorgi Z, Gonzalez N, Stelzner M. Misconnec-
tions in the critically Ill: injection of high-dose gadolinium into an
external ventricular drain. A&A Case Rep. 2016;6:121-123.
19. Birnbach DJ, Brull SJ, Prielipp RC. J’Accuse! failure to prevent epidural
and spinal catheter misconnections. A&A Case Rep. 2016;6:107-110.
20. Gelb AW, Mainland P, Phillips P, et al. J’agis! Anesth Analg.
2016;123:798-799.
21. U.S. Food and Drug Administration. Medical Device Safety: Examples
of Tubing and Luer Misconnections. https://www.fda.gov/medicalde
vices/productsandmedicalprocedures/generalhospitaldevicesandsupplie
s/tubingandluermisconnections/ucm313275.htm. Accessed October
23, 2017.
22. NHS. Safer spinal (intrathecal), epidural and regional devices. 2011.
http://www.nrls.npsa.nhs.uk/resources/?entryid45=94529. Accessed
October 23, 2017
23. Update on ISO 80369 series of Small Bore Connectors in medical
devices. The Association of Anaesthetists of Great Britain and Ire-
land (AAGBI). https://www.aagbi.org/sites/default/files/Neuraxial-
FAQ-Version-2017-03-23.pdf. Accessed October 23, 2017.
24. AAMI/FDA. Infusion Device Summit. 2010. http://s3.amazonaws.c
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I_FDA_Summit_Report.pdf. Accessed October 23, 2017
12 | LITMAN
25. Sentinel Event Alert. 2014. http://www.jointcommission.org/assets/
1/6/SEA_53_Connectors_8_19_14_final.pdf. Accessed October 23,
2017.
26. California So. Assembly Bill No. 444, Chapter 198. An act to amend
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27. ISMP. Update on Implementation of the New ENFit Enteral Connec-
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ismp.org/newsletters/acutecare/showarticle.aspx?id=114. Accessed
October 23, 2017.
28. ISMP. Another twist in the ENFit implementation process. Acute
Care ISMP Medication Safety Alert. 2016;21:4.
29. Bledsoe S, Oschman A, Hampson K, Hoebing W, Pabst D. Transition
to ENFit enteral devices: special challenges for pediatric institutions.
Am J Health Syst Pharm. 2016;73:1781-1783.
30. Monteiro RS, Pillai A, Choi SW, Bogod D, Yentis SM. Flow charac-
teristics of Luer and non-Luer spinal needles. Anaesthesia.
2017;72:749-754.
ET AL.
31. Kinsella SM. The shock of the ‘Nuer’: the UK experience with new
non-Luer neuraxial equipment and implications for obstetric anaes-
thesia. Int J Obstet Anesth. 2013;22:1-5.
32. Kinsella SM, Goswami A, Laxton C, Kirkham L, Wharton N, Bowen
M. A clinical evaluation of four non-Luer spinal needle and syringe
systems. Anaesthesia. 2012;67:1217-1224.
33. Sharpe P, Scott S, Gross JM. An evaluation of non-Luer safety
connectors for neuraxial procedures. Anaesthesia. 2013;68:562-
570.
How to cite this article: Litman RS, Smith VI, Mainland P. New
solutions to reduce wrong route medication errors. Pediatr
Anesth. 2018;28:8–12. https://doi.org/10.1111/pan.13279
Accepted: 11 October 2017

DOI: 10.1111/pan.13281

SYSTEMATIC REVIEW

The anatomy of the pediatric airway: Has our knowledge

changed in 120 years? A review of historic and recent
investigations of the anatomy of the pediatric larynx

Josef Holzki1 | Karen A. Brown2 | Robert G. Carroll3† | Charles J. Cote

4

1
Department of Pediatrics, Centre
ge, Che
Hospitaliere de Lie ^ ne

e, Belgium Summary
2
Department of Anesthesia, McGill Background: There is disagreement regarding the anatomy of the pediatric airway,
University Health Center, The Montreal
particularly regarding the shape of the cricoid cartilage and the location of the nar-
Children0 s Hospital, Queen Elizabeth
Hospital Foundation of Montreal Chair in rowest portion of the larynx.
Pediatric Anesthesia, Montreal, QC, Canada
Aims: The aim of this review is to clarify the origin and the science behind these
3
Radiology & Diagnostics, Quantitative
Imaging Inc., Largo, FL, USA differing views.
4
Harvard Medical School, MassGeneral Methods: We undertook a review of published literature, University Libraries, and
Hospital for Children, The Massachusetts
authoritative textbooks with key search words and phrases.
General Hospital, Boston, MA, USA
Results: In vivo observations suggest that the narrowest portion of the airway is
Correspondence
more proximal than the cricoid cartilage. However, in vitro studies of autopsy speci-
Josef Holzki, Department of Pediatrics,
ge,
Centre Hospitaliere Universitaire de Lie mens measured with rods or calipers, confirm that the nondistensible and circular or
Che^ ne

e, Belgium.
near circular cricoid outlet is the narrowest level. These anatomic studies confirmed
Email: josef.holzki@arcor.de
the classic “funnel” shape of the pediatric larynx. In vivo studies are potentially mis-
Section Editor: Mark Thomas
leading as the aryepiglottic, vestibular, and true vocal folds are in constant motion
with respiration. These studies also do not consider the effects of normal sleep,
inhalation agents, and comorbidities such as adenoid or tonsil hypertrophy that
cause some degree of pharyngeal collapse and alter the normal movement of the
laryngeal tissues. Thus, the radiologic studies suggesting that the narrowest portion
of the airway is not the cricoid cartilage may be the result of an artifact depending
upon which phase of respiration was imaged.
Conclusion: In vivo studies do not take into account the motion of the highly pliable
laryngeal upper airway structures (aryepiglottic, vestibular, and vocal folds). Maximal
abduction of these structures with tracheal tubes or bronchoscopes always demonstrates
a larger opening of the glottis compared to the outlet of the cricoid ring. Injury to the lar-
ynx depends upon ease of tracheal tube or endoscope passage past the cricoid cartilage
and not passage through the readily distensible more proximal structures. The infant
larynx is funnel shaped with the narrowest portion the circular or near circular cricoid car-
tilage confirmed by multiple in vitro autopsy specimens carried out over the past century.

KEYWORDS
age, airway, child, infant, neonate, otolaryngology, techniques

†
Robert Carroll MD passed away unexpectedly on August 13, 2016.

Pediatric Anesthesia. 2018;28:13–22. wileyonlinelibrary.com/journal/pan © 2017 John Wiley & Sons Ltd | 13
14 | HOLZKI
1 | INTRODUCTION
The lumen of the infant larynx is described as oval, cylindrical, spher-
ical, conical, and funnel shaped with the narrowest portion being the
nondistensible cricoid cartilage. Following publication of Eckenhoff’s
classic paper, the descriptor “funnel shaped” was widely adopted.1
However, recent in vivo investigations and reviews have questioned
the shape and location of the narrowest portion of the infant
larynx,2-8 however, one in vivo study documented a circular outlet
of the cricoid ring.9 We were intrigued by these assertions that con-
tradict traditional anatomic concepts.1,10-15 As a correct understand-
ing of airway anatomy is fundamental to the safe use of tracheal
tubes in infants and children, these contradictory observations
prompted our review.
2 | MATERIALS AND METHODS
Using the key words and phrases: “pediatric/infant anatomy of the
airway, larynx, dimensions, narrowest part of, pediatric laryngoscopy—
bronchoscopy, difference from adults”, we searched PubMed, the
ge, 4000 Lie
University Library Lie
ge, Belgium, for Historical French
language articles not found on the Internet, Springer Book archives,
the University Library Cologne, Kerpenerstrasse 62, 50937, Ger-
€ r Medizin, Gleuelerstrasse
many, and Deutsche Zentralbibliothek fu
€ln, Germany (Table 1), original research and textbooks.
60, 50931 Ko
We investigated in vitro anatomical descriptions dating back to 1897
and in vivo endoscopic and radiologic airway assessments. We con-
centrated on dimensions of the laryngeal lumen, the narrowest part
of the larynx, and the shape of the cricoid outlet. Only anatomy
reports presenting at least 2 methods of investigation (measure-
ments, calibrations, and photographs) were selected.
3 | RESULTS
Our search revealed autopsy data from hundreds of pediatric laryn-
ges10-14,16-18 and one textbook.15 In vivo studies also reported data
from hundreds of children.2,3,6-9 All investigations examined children
from preterm to 15 years (Table 1).
3.1 | Chronological in vitro autopsy reports
In 1897, Bayeux10 reported autopsy data from 28 infants and chil-
dren. After abandoning plaster casts which distorted the anatomy,
he used wax castings and calibration rods which proved to be more
accurate; as wax liquefies at 40°C it molds to surfaces without dis-
tortion or dilatation. In all specimens, the A-P dimension of the glot-
tis was larger than the cricoid ring (Figure 1A). Calibration rods
demonstrated that the nondistensible cricoid outlet was the narrow-
est part of the larynx and that it was nearly circular. To further
assess the caliber of the glottis, he divided the arch of the cricoid
ring (Figure 1B), confirming that the transverse dimension of the
ET AL.
vocal cords is larger than the cricoid ring. This observation supported
the notion of a funnel shape. He concluded that “the cricoid cartilage
is unquestionably the narrowest part of the pediatric larynx”, noting
that this configuration could persist into adolescence. Peter11
reported additional anatomical details: (i) The cricothyroid membrane
(conus elasticus) slants posteriorly impinging on the laryngeal lumen
narrowing the anterior aspect of the subglottic space Figure 2A). (ii)
In infancy, the laminae of the cricoid tilt posteriorly. As the length of
the cricoid cartilage in infants is 8.4  1.4 mm, this posterior angula-
tion should confer an ellipsoid shape to the subglottic space.9
Indeed, Peter reported that the A-P dimension of the glottis is larger
than the near circular cricoid outlet (funnel shape). During develop-
ment, the posterior laminae gradually assume an upright position
(Figure 2B).
In his classic paper, Eckenhoff compared the investigations of
Bayeux and Peter with his clinical observations during direct laryn-
goscopy.1 With the vocal cords widely abducted, the outlet of the
cricoid ring appeared smaller than the glottis. He concluded that “in
the infant, the lamina is inclined posteriorly at its superior aspect, so
that the larynx is funnel shaped with the narrowest point of the funnel
at the laryngeal exit” (Figures 2B, 3A-D). This report brought scien-
tific descriptions of the pediatric larynx to the attention of anesthesi-
ologists and introduced the descriptor “funnel shaped” and the
concept of a round cricoid.
Butz12 examined 24 fresh unpreserved laryngeal autopsy speci-
mens (premature infants to adolescents). Using dilators in 7 speci-
mens, he found that the glottis accepted sizes 4 Fr larger than the
tracheal origin; the larynx became consistently narrower from the
glottis to the cricoid outlet (funnel shape). The cricoid ring in all
specimens tended to be circular in cross-sections.* Too-Chung and
Green16 investigated the rate of growth of the cricoid cartilages.
They examined larynges (only 5/68 preserved) from 15 newborns
(1 day-1 week), 44 infants (>1 week-1 year), and 9 children (2-
15 years). They measured the interior dimension of the cricoid ring
at its lower border with a Vernier caliper. They observed a slightly
larger transverse cricoid diameter in neonates and a gradual cross-
over to a larger A-P diameter in children until 2 years. At 5 months,
they reported a circular outlet and at 15 years, they observed aver-
age A-P/transverse diameters of 1:0.97. The ratio of all groups was
between 1:0.91 and 1:1.1, near circular. Tucker et al17 published
serial cross-sections of larynges from 21 children (3 months-4 years)
and demonstrated the “V”-shape of the backward tilted cricoid lami-
nae (Figure 4A). This observation explains both the funnel shape of
the cricoid lumen and the posterolateral endocricoid ulcerations
commonly associated with prolonged tracheal intubation.15,19 Holin-
ger et al15 expanded upon these observations based upon combined
endoscopic experiences from GF Tucker and B. Benjamin.17,19 They
concluded that: “The lumen of the glottis is somewhat pentagonal in
shape, as the vocal folds taper inferiorly into the subglottic larynx,
where the lumen is elliptical with the greater diameter in the A-P
*In anatomy, there never exist geometrical structures like rings, funnels, or ellipses, only
similarities to these geometrical forms.
HOLZKI ET AL. | 15

T A B L E 1 Summary of in vitro and in vivo studies with comments and conclusions

Cricoid-A-P/transverse diameter
Author (y) N Age ratio (r) and conclusions Comments
In vitro studies
Bayeux (1897)10 28 4 mo-14 y Calibration, splitting of cricoid arch, “The cricoid cartilage is
caliper measurements. unquestionably the narrowest
part of the pediatric larynx.”
Peter (1936)11 15 1 d-17 y r = 1/1.1 The cricoid outlet has a near circular shape
(moderately larger in the transverse dimension).
He confirmed that the A-P dimension of the
glottis is larger than the cricoid outlet (funnel shape).
Butz (1968)12 18 1 d-1 y “In all cases the glottis accepted
a dilator at least 4 Fr larger that
the tracheal origin” “the larynx
seems to consistently funnel
down to the opening diameter
of the trachea.” (7 infant larynges)
Too-Chung & 15 1 d-1 wk r = 1/1.08 The cricoid is near circular, described “It was noticeable immediately
Green (1974)16 with a slightly larger transverse cricoid diameter that the child’s cricoid is elliptical
in neonates with crossover at 2 y to near circular at 15 y in shape, the coronal diameter
being greater.”
52 2 wk-1 y r = 1/0.91 Slightly larger A-P diameter
9 2-15 y r = 1/1.02 (circular diameter)
Tucker et al (1977) 17
21 3 mo-4 y “V” shape of backward tilted lamina
Eckel et al (1999)20 43 1-60 mo They measured glottic length in mm; subglottic
cartilaginous cross-section, subglottic airway
and tracheal airway in mm2. All cross-sections
were shorter than glottic length, tracheal diameters
always larger than the subglottic airway, showing the
subglottic airway as the narrowest part of the
pediatric larynx
Sellars & Keen 21 1 d-2 wk r = 1:1.13 in 16/21 r = 1:0.87 in 5/21 This large contrast
(1990)18 between A-P/transverse diameters has never been
reported in the literature
Holinger (1997)15 Large experience over more than 20 y of airway “When viewed from the side, the
endoscopy and teaching together with Tucker laryngeal lumen is slightly larger
an Benjamin superiorly at the glottic level and
narrower at the inferior aspect
of the cricoid cartilage” “The
cricoid ring is a smooth round circle”
Fayoux et al (2006)13 150 Preterm-3 mo “The narrowest part of the airway was
the cricoid area. . .in each age group.”
Fayoux et al (2008)14 274a 15-41 wk There was no significant difference between “The diameter of the cricoid lumen
gestation the A-P and lateral diameter of the cricoid (circular) was significantly less than that of
the trachea and glottic lumen.”
26a 1 d-1 m Same ratios as in the premature group
Total examinations 672
In vivo studies
Litman et al (2003)2 99 2 mo-13 y “The narrowest portion of the larynx
was the transverse dimension at the
level of the vocal cords.” “Transverse
dimensions were narrower than A-P
dimensions at all levels of the larynx
above the cricoid ring and in most
children at the cricoid ring.” “The
cricoid ring is functionally the
narrowest portion of the larynx.”

(Continues)
16 | HOLZKI ET AL.

TABLE 1 (Continued)
Cricoid-A-P/transverse diameter
Author (y) N Age ratio (r) and conclusions Comments
Dalal et al (2009) 3
128 6 mo-13 y Videos at the glottis and superior aspect of cricoid “Our study reveals the Cricoid-A-P
ring were obtained. Pictures were plotted on graph dimension is larger than its
paper. Mean cross-sectional areas of cricoid and Cricoid-transverse dimension
paralyzed glottis were compared (cricoid ellipsoid). suggesting that the cricoid is ellipsoid
rather than round.” “in anesthetized
paralyzed children, the glottis is
narrower than the cricoid from
infancy to adolescence.”
Wani et al (2016)6 130 1 mo-9 y r = 1/1.02 (practically circular) “The cone shaped airway characteristic,
which has been historically proposed,
was not observed. Given that the
subglottic transverse diameter is the
smallest area dimension, one must
assume this is the most likely area of
resistance for the passage of an
endotracheal tube rather than only
the cricoid.” “The subglottic area and
the cricoid change from an elliptical
to a round (circular) shape.”
Wani et al (2017)7 40 1 d-12 moc r = 1/1.36 at subglottic region. r = 1/1.098 “Increase in transverse dimensions
at cricoid level (near circular) observed from subglottis to
cricoid. . . A-P dimensions showed a
decrease from subglottis to the
cricoid.” “The mean cross-sectional
area at the 2 levels were similar.”
“The cricoid is not round as has been
observed in older children” “The ratio
between the transverse and A-P
diameters at the cricoid was 0.89.”
Wani et al (2017)b,8 54 2 mo-8 y Air volumes in the subglottic, cricoid to the tracheal “An increase in airway volumes was
regions were examined. The coaxial view of the observed from the subglottis
airway from the caudad end shows a funnel shape (0.17 mm3) to the cricoid (0.19 mm3).”
Wani (2016)b,21 102 1 mo-10 y r = 1:1.0 overall but ranged from 0.91 to 1.06.
(9 age Age groups 2-3, 6-8 y had a moderately larger
groups) transverse than A-P diameter of the cricoid
(near circular)
Total 553
a
Note that 150/300 larynges were also reported in their 2008 publication (personal communication).
b
It is not known if some of these patients were included in prior publications.
c
Note that 11 patients were reported in a prior study.

dimension. At the inferior aspect of the cricoid cartilage the lumen and
the cartilage are a smooth round shape (Figure 3B,C,D)”. The authors
illustrated the 2-dimensional inverted funnel shape in coronal sec-
tions as typical for adducted vocal cords in autopsy specimens. They
further described the glottic level as pliable and larger than the rigid
cricoid outlet. To have a holistic view of the lumen of the larynx, A-
P and coronal sections of the larynx should be combined with the
cross-sections of the larynx at different levels (Figure 3); the authors
confirmed the common site of injury from tracheal tubes and the
autopsy work of previous investigators.10-12,16,17
Sellars and Keen18 reported A-P/transverse diameters of 21
autopsy specimens (newborn-2 weeks) at the inner aspect of the cri-
coid ring (measurements higher in the larynx were not made). In 16/
21 specimens, the A-P diameter exceeded the transverse, however,
in 5 specimen transverse diameters were considerably larger than
the A-P diameters (different from Too-Chung). Thus, the A-P/trans-
verse ratios in this age group may vary. Eckel et al20 examined 43
larynges (<5 years) by the method of plastination which preserves
the larynx as it appears in situ and found that cricoids tended to be
circular. Mid-larynx cross-sections proximal to the cricoid arch
demonstrated the transverse diameter to be wider than the glottis
(Figure 4B). They also found that the transverse diameter of the
cadaveric glottis was narrower than the A-P dimension, resulting in
an almost triangular shape (Figure 4B). This is consistent with what
is expected as in death, the soft tissues of the upper airway revert
to their neutral position (Figure 3B) similar to several in vivo reports
(see further).6,7 More recently, Fayoux et al13 examined serial sec-
tions from 150 nonpreserved infant larynges (preterm-3 months)
HOLZKI ET AL.
(A) (B)
F I G U R E 1 A, Soot print from a wax casting (Bayeux) showing a
lateral view of pediatric larynx from a 5-year-old child. The A-P
diameter at the level of the cricoid outlet is about 44% smaller than
at the level of the vocal cords. B, Depiction of the anterior view of
pediatric larynx from another 5-year-old child by Bayeux. A
measuring rod could not exit the outlet of the cricoid ring until the
arch of the cricoid ring was divided, demonstrating that the outlet of
the cricoid ring is the narrowest part of the pediatric larynx
within 6 hours after death (near physiologic conditions). They used 3
methods to evaluate the laryngeal lumen: (i) tracheal tubes (analo-
0 ynx at the glottis and superior aspect of cricoid ring in 128 children
gous to Bayeux s calibration rods); (ii) nondilatable, cylindrical bal-
loons, recording the change in pressure as the balloon was moved
along the length of the larynx; and (iii) determination of the A-P/
transverse diameters with calipers of the cricoid ring and the inter-
arytenoid distance (IAD) at the vocal processes at the posterior glot-
tis. The narrowest diameters in anteroposterior and transverse
laryngeal plane (28 weeks gestational age (GA) until the 3rd month
of life) was the cricoid ring (Fig. S1) (funnel shape). Building upon
other investigations,12,15 these measurements provide important
insights regarding the mechanism of injuries during airway instru-
mentation: (i) the risk for glottic injury increases if tracheal tubes
with an OD larger than the IAD are introduced in the larynx; and (ii)
the risk for injury at the level of the posterior cricoid cartilage
increases if a tracheal tube with an OD smaller than the IAD, but lar-
ger than the outlet of the cricoid ring is introduced.19 In a second
series, they examined cricoid and tracheal diameters from 274 non-
fixed larynges (15-41 weeks GA) and 26 infants (0-1 month) within
6 hours after death.14 They concluded that “Cricoid diameters were
always significantly less than tracheal diameters and IAD” and “there
was no significant difference between the A-P and lateral diameter of
the cricoid.” This study confirmed that throughout intrauterine life
until the first month of life that the cricoid ring is narrower than the
glottis (funnel shape). They further documented the triangular-
shaped lumen of the glottis in all specimens.
‡
Unpublished observations from 2 authors (JH and MHR) of 16
autopsy specimens (0-7 months), demonstrated a ratio of 1/1.02 at
‡
MA Rothschild, Institution of Legal Medicine, University of Cologne, Germany.
| 17
the cricoid outlet and that the cricoid arch and posterior lamina have
a 4-fold height discrepancy which creates an oblique entrance to the
cricoid ring (Figure 4C). Therefore, methods which identify the cri-
coid cartilage by the tip of the lamina vs the superior aspect of the
anterior cricoid arch are likely to demonstrate different measure-
ments (Figure 3). All outlets of the investigated larynges were round
with A-P/transverse ratios between 1/0.99 and 1/1.05.
3.2 | In vivo clinical reports
Litman et al2 reviewed laryngeal MRIs in 99 anesthetized, sponta-
neously breathing children (2 months-13 years). The A-P/transverse
diameters of the larynx were measured at the vocal cords and cri-
coid level. Transverse diameters increased linearly in a caudad direc-
tion through the larynx, while A-P diameters did not change much
relative to the different laryngeal levels. The larynx was described as
conical in the transverse (coronal) section with the apex at the vocal
cords and as cylindrical in the A-P dimension. The narrowest por-
tions of the larynx were at the glottic opening and the immediate
sub-vocal cord level but functionally, the cricoid ring was described
as the narrowest portion of the larynx. In the horizontal view, they
described the subglottic superior aspect of the cricoid ring as ellip-
soid. They also commented that contraction of the laryngeal muscles
influenced the dimension of the larynx above the cricoid ring. Dalal
et al3 photographically estimated the cross-sectional areas of the lar-
under anesthesia and neuromuscular blockade. They reported that
the relaxed glottis was narrower than the cricoid ring. They also
found that the infant larynx was cylindrical in the A-P dimension but
conical in the transverse dimension. Interestingly, the authors stated:
“Further studies are needed to determine whether these static airway
measurements in anesthetized and paralyzed children reflect the
dynamic characteristics of the glottis and cricoid in children”, acknowl-
edging differences between in vivo and in vitro studies.
Wani et al6 have reported several studies. They initially reported
observations from 130 laryngeal CT scans in children (1 month-
9 years); a description of the glottis was not part of that study. All
children were under natural sleep, sedation, or sevoflurane anesthe-
sia. They estimated the A-P/transverse dimensions from immediately
below the vocal cords and at the level of the cricoid ring; the lumen
of the larynx was ellipsoid immediately below the vocal cords (A-P
9.2 mm vs transverse 7.5 mm) changing to a circular shape at the
level of the cricoid outlet (A-P 8.5 mm vs transverse 8.3 mm, a cir-
cle). Thus, the A-P dimension at the subglottic level was greater than
that of the cricoid but the transverse diameter of the cricoid was lar-
ger than at the subglottic level; the cross-sectional areas at the 2
levels were not different. They concluded: “The cone shaped airway
characteristic, which has been historically proposed, was not observed.
Given that the subglottic transverse diameter is the smallest area
dimension, one must assume this is the most likely area of resistance
for the passage of an endotracheal tube rather than only the cricoid.”
These authors published a similar study examining the ratio of the
cricoid cartilage to the left mainstem bronchus from 102 CT scans
18 | HOLZKI ET AL.

(A) (B)

F I G U R E 2 A, Endoscopic picture (2.2 mm Hopkins lens, JH) of the glottis of a 1-year-old child, spontaneously breathing under inhalation
anesthesia. Note that the vocal cords are in an almost parallel (adducted) position. The anterior subglottic narrowing is caused by the
posteriorly slanting thyroid cartilage and the cricothyroid membrane, narrowing the subglottic space anteriorly. B, Drawing showing the lateral
view of an A-P section through a neonatal larynx (autopsy specimen by Peter).11 The backward tilted lamina results in a cricoid lumen which
has a large, slanting entrance and an approximately 46% smaller circular outlet. The height ratio between arch and lamina is 1:4 (see also
Figure 4C)

(B)

(A)

(C)

(D)

F I G U R E 3 Influence of the level of cross-sections on the configuration of the laryngeal lumen, regardless of the method of investigation. A,
A-P section of the larynx of an 8-month-old infant specimen (JH). B, Cross-sections at the vocal cord level from autopsy specimens (Holinger
et al, 8-month-old infant, and Eckel et al, 3-month-old infant, with permission by Wolters Kluwer and Springer).15,20 “Tear-drop”-like entrance
to the glottic opening (CT-scan by Sirisopana et al,9 child <3 y, with permission of Wolters Kluwer) showing a clear tissue-air interface but no
cartilaginous structures. C, Cross-sections at mid-level of the larynx show an oval shape. The posterior V-shape of the lamina is visible in these
anatomical cross-sections (Holinger,15 Eckel, courtesy of the author).20 The hyperdense lining of the lumen in the MRI (not depicting
cartilages!) represents the intensely perfused laryngeal mucosa (Litman et al2 with permission by Wolters Kluwer). D, Cross-sections through
the outlet of larynx showing a circular configuration (Holinger et al15 Eckel, courtesy of the author.20 CT-scan (Sirisopana et al9 with
permission by Wolters Kluwer)

from children 1 month to 10 years of age.21 This report did not transverse diameter 1.02/1) similar to their previous study.6 Another
assess subglottic dimensions but confirmed the near circular cricoid study7 reported observations of 40 laryngeal CT scans of infants (0-
with the A-P diameter slightly greater than the transverse (A-P/ 12 months) during similar conditions as the studies above (11 had
HOLZKI ET AL. | 19

(a) (b) (c)

F I G U R E 4 Influence of the level of cross-section on the configuration of the laryngeal lumen, regardless of the method of investigation. A,
Cross-section above the arch of the cricoid ring of an infant larynx at the level of the anterior ligamentous cricothyroid membrane (Tucker
et al17 with permission from Rights Link). The V-shaped lamina of the cricoid, bounding the oval lumen of the mid-larynx by two-thirds from
posterior, demonstrates an “elliptical” mucosal lumen at this level, obscuring the underlying surface” of the cricoid. B, Cross-section at the level
of the vocal cords (2-month-old infant, plastination technique, Eckel et al20 with permission of Springer). The cranial part of lamina and vocal
processes of the arytenoid cartilages are clearly visible, demonstrating the tight connection between the vocal cords, the vocal process, and
the superior lamina. C, Photo of a freshly trimmed cricoid ring of a neonate (autopsy specimen, courtesy MA Rothschild, Institution of Legal
Medicine, University Cologne, Germany, from unpublished data). The high lamina, the short arch, the oblique entrance of the cricoid ring, and
of the plane level of the circular cricoid outlet (see Figures 2B and 3A) demonstrate the difficulty of precisely defining the anatomy of the
pediatric cricoid ring by cross-sections only

been previously reported to have a circular outlet5). They found that
the cricoid had a larger A-P than transverse diameter (6.7 vs
6.1 mm) but at the subglottic level, they again found that the trans-
verse diameter was less than the cricoid and the A-P diameter was
greater (7.2 A-P vs 5.3 mm transverse). They concluded that the air-
way in neonates and infants between the subglottic area and the cri-
coid remains ellipsoid, “that the airway is wider anteroposteriorly and
narrows in the transverse dimension from the subglottis to the cricoid in
infants.” However, the mean cross-sectional area at the 2 levels was
similar (29.9 vs 32.1 mm3). It is possible that this ellipsoid shape is
secondary to the slices not being exactly perpendicular to the axis of
the cricoid. They also acknowledged that they did not standardize
the phase of respirations which might also have impacted their mea-
surements by the variable position of the vocal cords. A fourth study
reported 3D CT scan reconstructions of the upper airway at 3 mm
intervals from 54 children 2 months to 8 years8 but only 4 were
infants. The airway volumes in subglottic and cricoid levels were
0.17  0.06 vs 0.19  0.07 mm3, respectively. The authors com-
mented that the narrowest portion of the airway was subglottic but
“we cannot comment whether this region or others such as the cricoid
represent the most rigid aspect of the airway.”
4 | DISCUSSION
Our literature review revealed 2 views of the infant larynx: the tradi-
tional “funnelists” and the “nonfunnelists”. The in vivo studies2,3,6-8
all suggest that the narrowest portion of the pediatric larynx in spon-
taneously breathing sleeping or anesthetized infants and children is
at the laryngeal inlet (nonfunnelists), whereas the in vitro studies
describe the narrowest portion of the pediatric larynx as the
nondistensible cricoid cartilage (funnelists).10-14,16-18 How can we
reconcile these apparent contradictory observations? Is the larynx
funnel-shaped or cylindrical? Is the narrowest portion at the level of
the glottis or the cricoid ring? We believe that these divergent views
reflect the methods of evaluation used (in vivo vs in vitro). Autopsy
data confirm the nondistensible cricoid ring10-15,20 as the narrowest
portion, however, the laryngeal lumen varies in form and size at dif-
ferent levels (predominantly cylindrical in transverse but conical in
A-P dimensions). As the pediatric larynx consists of pliable (supra-
glottis, glottis, and proximal subglottis) and rigid parts (the cricoid
ring) (Figures 3, 4C), describing laryngeal anatomy depends upon the
methodology used for assessment. Studies which employ horizontal
cross-sections to identify the level of the cricoid outlet by CT scans
or MRI are less precise than autopsy specimens for several reasons:
a slice thickness of 2.5-3.0 mm, the angulation of the cricoid, and
inability to precisely show the cartilaginous structures.10-12,15,16
More importantly, these measurements may vary greatly in vivo
compared with in vitro because the laryngeal tissue folds (vocal,
vestibular, and aryepiglottic folds) are dynamic, pliable structures13
that change position and shape with the phase of respirations
(change in transverse but minimal in the A-P dimension).7,8,22 With
inspiration, the laryngeal muscles contract, stretching open the
aryepiglottic, vestibular (false cords), and vocal folds, so that the dis-
tance between these structures increases (Figure 5A). With expira-
tion or neuromuscular blockade (Figure 5B), these soft tissue folds
return to a neutral position by the stability of the cuneiform and cor-
niculate cartilages.23 With voluntary glottic closure (lifting heavy
weights), or involuntary glottic closure (laryngospasm), contraction of
the intrinsic laryngeal muscles closes the larynx at 3 levels
(aryepiglottic, vestibular, and vocal folds). Thus, the various tissue
folds of the larynx are in constant motion and the distance between
20 | HOLZKI
them depends upon the phase of respiration during which the exami-
23
nation was made (or death). Although the paralyzed vocal cords are
always in a near cadaveric position (Figure 5B), they never impede the
advancement of tracheal tubes. A further consideration is what hap-
pens to these structures during sleep or anesthesia compared to the
awake state. It is well known that there is collapse of pharyngeal tis-
sues during natural sleep and during anesthesia. Such narrowing of the
upper airway facilitates apposition of the laryngeal tissue folds further
narrowing the upper airway above the cricoid cartilage, particularly if
there is accompanying tonsillar or arytenoid hypertrophy.24,25 The
effects of sleep, anesthetic medications, or arytenoid/tonsillar hyper-
trophy were not considered in the in vivo studies.
The maximum interarytenoid diameter (IAD) can be measured
in vivo, but in vitro measurements may be more accurate with mea-
13
suring rods or calipers as these tissue folds are easily distended.
After neuromuscular blockade, the vocal cords relax and assume a
parallel position (Figure 5B). Transverse interarytenoid diameters
(IAD) vary from zero (laryngospasm) to a maximum diameter when
13
fully abducted. In autopsy specimens, the vocal cords adopt a
cadaveric position; in vivo they are adducted to different degrees
depending upon the phase of respiration but rarely maximally
abducted as seen in Figure 5A.
Litman et al,2 Dalal et al,3 and Wani et al6-8 presented age related
but seemingly constant A-P diameters of glottis and proximal subglot-
tis. Litman specifically stated that “active contraction of the laryngeal
muscles influenced the dimension of the larynx”. Wani et al commented
that they did not control for the phase of respirations; the patients in
the Dalal et al study were paralyzed. These investigators reported
upper transverse laryngeal diameters narrower than those from
autopsy specimens. We assume that this is because their methodolo-
gies did not consider the conditions at the time of evaluation, ie, the
pliability of the tissues in vivo and respiratory related motion of glottis
and proximal subglottic structures. In contradistinction, autopsy stud-
ies measured A-P diameters of the glottis and cricoid outlet in hun-
dreds of specimens with calipers or rods providing the most accurate
means for determining the narrowest level of the larynx (similar to
(A)
F I G U R E 5 A, Fully abducted vocal cords during inspiration under inhalation anesthesia for functional checkup. Note the pronounced
cricothyroid membrane and the tapering down to the narrower outlet of the cricoid ring (JH). B, Adducted vocal cords after neuromuscular
blockade (JH), ie, return to neutral position from the stabilizing effect of cuneiform and corniculate cartilages
ET AL.
tracheal tubes)10,13,14; the maximum IADs were always larger than the
rigid cricoid outlet (Figure 6A,B). When studying the laryngeal anat-
omy from the viewpoint of intubation, the only meaningful way to
compare the lumen at various levels of the larynx, is by gently intro-
ducing measuring rods (or tracheal tubes)10,12,13 which maximally dis-
tend the soft tissues of the laryngeal folds without injury.
Wani et al6-8 have presented several studies with possible overlap-
ping patient populations. Given that several hundred CT scans were
retrospectively reviewed and only 40 selected for one study (11 previ-
ously reported) and 56 for another, it is possible that observer bias
could have influenced their conclusions regarding the shape of the cri-
coid and the subglottic region. It is also unclear if the CT cuts were
obtained at sufficiently thin intervals to allow accurate assessment the
cricoid outlet. Wani et al8 did not cite the 300 investigations by Fay-
oux et al who documented the opposite of their assertions (Fig. S1).
Furthermore, in their most recent study of 3D CT-imaging, they found
a mean airway volume difference between the subglottic area and the
cricoid outlet of only 0.02 mm3 which is of uncertain clinical rele-
vance. Furthermore, two of their other studies found no difference in
cross-sectional areas of these same 2 levels.6,7 These differences in
the transverse measures between the subglottis and the cricoid are
likely clinically unimportant in contrast to the A-P dimensions (Fig-
ure 6B). It is unclear to us why the resistance to tracheal tube passage
would differ with similar cross-sectional areas. Wani et al’s8 observa-
tions of the cricoid cartilage are similar to Peter0 s; there appear to be
minute differences of cricoid dimensions from study to study that
overall indicate that the cricoid outlet is nearly circular.
5 | CONCLUSION
We reviewed 9 autopsy studies published over the last century
that documented the narrowest portion of the infant larynx as the
nondistensible cricoid cartilage, supporting the concept that the
infant larynx is in fact funnel-shaped.10-16,18,20 Six in vitro studies
described the cricoid cartilage as circular or nearly circular10-15; two
(B)
HOLZKI ET AL. | 21

(A) (B)

F I G U R E 6 A, Reconstruction of an infant larynx based on fresh autopsy specimen (see Figure 4C) and investigations by Bayeux, Peter, and
Eckel. An oval-shaped lumen of the cricoid can be described only above the cricoid arch (=oblique, oval entrance to the cricoid ring) which
tapers down to the narrower, circular outlet, being narrower than the glottic and cricoid inlet. Thus, a tracheal tube which is passed through
the cricoid is always located posteriorly within the pediatric larynx because of the funnel shape (always a smaller outlet at the cricoid
compared with the more proximal, larger, and distensible structures) which forces the tracheal tube posteriorly and limits the amount of leak
behind the tube (see Fig. S2). B, Lateral neck xerogram of a 2-day-old term infant (CJC). The image demonstrates clearly the more posteriorly
located position of the cricoid outlet and the overall funnel shape

in vitro studies reported an ellipsoid cricoid outlet.16,18 Thus, there
is some disagreement about the actual shape of the cricoid ring.
Two studies described the cricoid ring as V-shaped in the posterior
part and a near circular cricoid outlet without comparing it with
the glottic level15,17 but providing important information about the
cricoid structure. Two in vivo studies described the cricoid as ellip-
3,21
soid in shape but 4 in vivo studies reported it as circular or
nearly circular2,8,9,21; most in vivo studies describe the cricoid as
either circular or near circular which permits safe intubation with
round tracheal tubes which contrary to one review, permit a mini-
mal leak during mechanical ventilation (Fig. S2).4 Five in vivo stud-
ies reported that the narrowest portion of the larynx was proximal
to the cricoid cartilage2,3,6-8 but there was no difference in cross-
6-8
sectional area or volume when the 2 levels were compared.
It is clear that the nonfunnelists believe that the cricoid outlet is
larger than the subglottic region; however, they did not fully con-
sider in vivo laryngeal dynamics or the known effects of sedatives
and sleep upon upper airway tone and secondary mild obstruction.
As there is enormous pliability of the laryngeal tissue folds, the resis-
tance to passing a tracheal tube through the vocal cords and struc-
tures above the cricoid arch is very low. Thus, these structures can
be actively opened (Figure 5A), whereas the cricoid ring is rigid and
nondistensible. The real issue is not what appears to narrow the lar-
ynx by continuous motion of soft tissues above the cricoid but
rather the actual narrowest nondistensible portion of the larynx
where intubation injuries are most likely if too large tracheal tubes
are placed. Overall, all studies that we reviewed are in agreement
despite differing conditions at the time of evaluation (natural sleep,
anesthesia, and autopsy).
We therefore submit that the original conclusions of Bayeux in
1897 supporting the “funnelist viewpoint” remain valid today10:
“If the intubating hand feels a small resistance against the passing
of a tube, it is not caused by the vocal cords but the cricoid ring. If one
wanted to grant the active vocal cords within a surrounding of pliable
muscles a greater importance for tube selections than the non-dilatable
cricoid ring, it would mean to support a theory that the resistance of
the perineum is larger (for the passing newborn head) than that of the
entrance of the pelvis)”.10
ACKNOWLEDGMENTS
Hans Hoeve MD, pediatric otorhinolaryngologist (Sophia Children0 s
Hospital Rotterdam) contributed with his knowledge of the anatomy,
physiology, and pathology of the pediatric airway to this article.
ETHICAL APPROVAL
The photos of the endoscopic pictures and the autopsy specimen
were anonymously archived according to the ethical standards of
the respective institutions.
CONFLICT OF INTEREST
The authors report no conflict of interest.
ORCID
Josef Holzki http://orcid.org/0000-0002-3415-859X
22 | HOLZKI ET AL.

17. Tucker GF, Tucker JA, Vidic B. Anatomy and development of the cri-
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Accepted: 28 September 2017
DOI: 10.1111/pan.13273
SYSTEMATIC REVIEW
Donohue syndrome: A review of literature, case series, and
anesthetic considerations
Alana Kirkwood | Grant Stuart | Louise Harding
Department of Anaesthesia, Great Ormond
Street Hospital, London, UK
Correspondence
Dr Alana Kirkwood, Department of
Anaesthesia, Great Ormond Street Hospital,
London, UK.
Email: alanakirkwood@hotmail.com
Section Editor: Francis Veyckemans
Pediatric Anesthesia. 2018;28:23–27.
Summary
Background: Donohue syndrome is a rare autosomal recessive disorder of insulin
resistance, causing a functional defect in insulin receptor function, and affecting the
ability of the insulin to bind the receptor. Features include severe hyperinsulinism
and fasting hypoglycemia, along with severe failure to thrive despite feeding. An
accelerated fasting state results in muscle wasting, decreased subcutaneous fat, and
an excess of thick skin. A reduced thoracic diameter is accentuated by increased
abdominal distension, which impacts on respiratory reserve.
Cardiac disease develops early in life, with progressive hypertrophic cardiomyopathy
as a result of hyperinsulinism. Prognosis is poor with the majority of patients dying
in infancy of sepsis. The aim of this review is to report our experience of providing
anesthesia for patients with Donohue syndrome, and inform guidance for safe
management of these children, based on a comprehensive literature review.
Methods: A literature search was carried out using PubMed, Medline, and the
Cochrane Library, and using the MESH search terms detailed below. Patients were
identified by formal request to the department of pediatric endocrinology at Great
Ormond Street Hospital. Each patient’s notes were searched manually and electroni-
cally for both clinical presentation and outcome, and anesthesia records.
Discussion: There is currently no published literature relating to anesthetic manage-
ment of Donohue syndrome. We report a case series of 5 patients with Donohue
syndrome who have presented to our institution. This small series of children with
this complex disorder demonstrates a clearly increased risk of general anesthesia.
Many of the risks relate to restrictive lung disease and abdominal distension which
worsens with bag valve mask ventilation and limited respiratory reserve which leads
to precipitous desaturation. During induction, a spontaneously breathing technique
is recommended. If required, bag valve mask ventilation should be accompanied by
constant gastric aspiration. Intubation is challenging, and a difficult airway plan,
including a second experienced anesthetist and ENT support, should be in place.
These children are predisposed to developing cardiomyopathy and therefore at risk
of cardiovascular collapse under anesthesia.
KEYWORDS
Donohue syndrome, insulin, insulin resistance, leprechaunism, Mendenhall syndrome, receptor
wileyonlinelibrary.com/journal/pan © 2017 John Wiley & Sons Ltd | 23
24 | KIRKWOOD ET AL.

1 | INTRODUCTION

Donohue first described a condition he termed dysendocrinism in a What is already known

white female infant born to first cousins in 1948.1 She was born
with intrauterine growth retardation (IUGR), weighing only 1.75 kg
• There is as yet no published literature regarding anes-
thetic risk and management of children with Donohue
and presented with further weight loss on day 28 of life. She was
syndrome.
underdeveloped and poorly nourished with abundant hair, loose skin,
and obvious muscle wasting. A systolic murmur was noted. She had
What this article adds
marked abdominal distension and multiple subcutaneous abscesses
across the scalp, back, and forehead. She deteriorated rapidly and • This case series, alongside a comprehensive literature
died aged 8 weeks. review, details our institutions experience and suggests
2
Donohue and Uchida noted the same clinical features and phe- guidance for management of these children who pose
notype in the second child of the same family in 1954. The term significant anesthetic risk.
3
Leprechaunism was coined to describe this syndrome as those
affected had the appearance of these caricatures. To avoid this pejo-
rative term, it is now more widely referred to as Donohue syn- in these children is due to an accelerated fasting state, and they
drome. have a blunted response to exogenous insulin.7 These biochemical
findings are associated with hypertrophy of the pancreatic islets of
Langerhans. In addition, there is hypertrophy of other organs, includ-
2 | EPIDEMIOLOGY/INCIDENCE ing splenomegaly and hepatomegaly. Excess glycogen and iron depo-
sition with bile duct cholestasis have all been described in these
Donohue syndrome is a rare disorder with an incidence of 1 in 4 patients. They often have enlarged kidneys and nephrocalcinosis,
million live births,4,5 although this may be underreported. There is a with atrophic adrenal glands.9 There are frequent lymphoid hypopla-
strong association with parental consanguinity. It is an autosomal sia and cystic gonadal appearances.
recessive disorder caused by a functional defect in the Insulin Cardiac disease may be a feature of Donohue syndrome,
Receptor gene on chromosome 19p13. This causes insulin resistance manifesting after 1-2 months of life with significant hypertrophic
by a variety of mechanisms, and there are currently 50 described cardiomyopathy.10,11 The cardiomyopathy is attributed to supraphys-
6
mutations of the insulin receptor gene. Having been studied exten- iological hyperinsulinism and is mediated via IGF1. This can also be
7,8
sively, it is now thought the disorder results from a defect in insu-
lin receptor function, affecting the ability of the receptor to bind
insulin. There are 2 milder forms of insulin resistance with the same
mechanism: Rabson Mendenhall Syndrome and Type A Insulin Resis- BOX 1 Characteristic Features of Donohue Syndrome

tance syndrome. The prognosis is dependent on the degree of insu- Facial features Elfin like pointed chin
lin resistance; children with classic Donohue syndrome die in
Microcephaly
infancy, the majority from bronchopneumonia. In other milder forms
Low set prominent ears
of insulin resistance, patients can live into adulthood. In all syn-
Orbital hypertelorism
dromes of insulin resistance, survival may be improved by Insulin-like
Broad nose
growth factor 1 (IGF1) therapy, although its efficacy in Donohue
Thick lips
syndrome is still unclear.
Facial hair
Skin features Hypertrichosis

3 | CLINICAL AND PATHOLOGICAL Acanthosis nigricans

FEATURES Excessive thick, hyperelastic skin
Decreased subcutaneous fat
Children with Donohue syndrome present with severe intra- and Muscle wasting
extrauterine growth retardation. Intrauterine growth retardation is Other features Large hands and feet (relative to body)
typically seen acutely from 7 months gestation. Birth weights are Low body weight for age
typically <0.4th percentile. Postnatally there is severe failure to Hypotonia
thrive with marasmus and malnutrition despite feeding.
Abdominal distension
Severe hyperinsulinism combined with fasting hypoglycemia and
Reduced lateral thoracic dimensions
postprandial hyperglycemia are the hallmarks of Donohue syndrome
Hyperplasia of nipples, genitals, other organs
(Box 1). A combination of this biochemical triad and the presence of
clinical features are sufficient to make the diagnosis. Hypoglycemia
KIRKWOOD ET AL.
seen transiently in other forms of hyperinsulinism such as infants of
diabetic mothers where the in utero exposure to elevated insulin
levels causes fetal cardiomyopathy which resolves spontaneously
after birth.
Bone age is severely delayed and abnormalities of the meta-
physics and epiphysis are evident on pathological examination.12
4 | CLINICAL COURSE AND TREATMENT
Due to their accelerated fasting state and disordered homeostatic
response to hypoglycemia, these children fail to gain weight or
length despite adequate feeding. They lose muscle mass and are at
risk of sepsis due to immunodeficiency.
The only current treatment option in Donohue syndrome is IGF-
1 therapy. The aim of therapy is to prevent compensatory hyperin-
sulinemia, which is the cause of many of the features of the syn-
drome, including the cardiomyopathy. Clinically, the aim is to
support linear growth and development and improve life expectancy.
IGF has approximately 6% of the hypoglycemic effect of insulin.13 It
is known to be structurally similar to insulin and can bind in vivo to
cause increased peripheral glucose uptake, increased glycogen syn-
thesis, and inhibition of protein catabolism. It is hypothesized that
recombinant IGF-1 therapy may have these advantageous anabolic
effects in insulin resistance. There is scant evidence for its use in
insulin resistance syndromes14 with the majority of literature being
in the form of case studies.15,16 In the small number of case studies
available, some found IGF-1 therapy ineffective in these patients,
while others found modest reductions in levels of hyperinsulinemia,
along with improved glucose utilization. Although combined numbers
in these studies are small,15-18 IGF-1 therapy appears to be both bio-
chemically and clinically effective. As well as having long-term
improvements in glucose control and secondary effects of hyperinsu-
linemia, there also appears to be an acute reduction in both glucose
and insulin levels following a bolus dose of IGF-1. Long-term IGF-1
therapy necessitates regular fundoscopy14,17 to assess for the devel-
opment of retinopathy.
5 | MATERIALS AND METHODS
A literature search was carried out using PubMed, Medline, and
Cochrane library, and using the following (MESH) search terms:
Donohue syndrome, Leprechaunism, Mendenhall syndrome, insulin
resistance, receptor, insulin.
Patients were identified by a formal request made to the
department of pediatric endocrinology at Great Ormond Street
Hospital. Each patient’s notes were searched both electronically
and manually, looking for initial presentation and antenatal/birth
history, clinical diagnosis and progress, and outcomes. The anes-
thesia records were examined for documentation of procedure,
induction technique, grade of laryngoscopy, and any adverse
events.
| 25
6 | CASE SERIES
The above literature search yielded no results with relevance to
anesthetic management.
We, therefore, report our experience of 5 children with Donohue
syndrome undergoing 12 general anesthetics and suggest anesthetic
considerations in this rare population.
Of the 5 children, all presented in infancy with intrauterine
growth retardation (IUGR) and low birth weights, 2 being less than
the 0.4th percentile. Four of the five were born to consanguineous
parents. Three presented in the first week of life with episodes of
hyperglycemia and hypoglycemia and were found to be hyperinsu-
linemic.
Four of these children have undergone 12 general anesthetics
for indications including insertion of percutaneous gastrostomy,
insertion of central venous access, endoscopy, MRI, and laparotomy.
A 5th child was assessed as having too high a risk for general anes-
thesia.
For 7 of the 12 anesthetics (3 patients), there was documented
difficulty with bag mask ventilation. These usually required a 2 per-
son technique and manual decompression of abdominal distension
by placement of a nasogastric tube into the stomach. A laryn-
goscopy grade of IIb or above was noted on 5 occasions (2
patients) with ENT assistance and rigid bronchoscopy being
required on one occasion. A previous intubation in this patient had
been uneventful (Grade II laryngoscopy). One induction associated
with intermittent desaturations was marked by postoperative cere-
bral edema and seizures requiring prolonged care on the pediatric
intensive care unit.
Two anesthetics (in 2 patients) were marked by cardiac arrests
secondary to difficult manual ventilation, intubation, and hypoxia. On
both occasions, circulation was restored with CPR and both were
extubated postoperatively on PICU. Other adverse events included
accidental perioperative extubation with subsequent difficult mask
ventilation and significant desaturation, and multiple failed intuba-
tions requiring ENT support (described above).
None of the children were noted to have particularly difficult
venous access.
Of the 5 children, 2 have subsequently died, one is being palli-
ated and 2 are being managed on IGF-1 therapy. Where significant
cardiac disease became a feature, the risk vs benefit ratio was re-
evaluated and on occasion surgery was declined.
Table 1 represents airway difficulties and adverse events noted
in the above case series.
7 | DISCUSSION
There is currently no published literature or guidelines on the anes-
thetic management of this complex condition. This small case series
shows clearly that these children have a high anesthetic risk. It is
important to weigh the risks of anesthesia against the benefits of
the surgery. Where surgery is necessary, difficulty can be reasonably
26 | KIRKWOOD ET AL.

T A B L E 1 Tabular summary of 5 patient case series—anesthesia experience, airway management, and adverse events
Mask
Anesthetic ventilation Adverse Cardiac
Pt episode Weight difficulty Laryngoscopy events arrest Details
1 1 <0.4th N 1 N N
percentile
2 N 1 N N
3 N Laryngeal N N
mask airway
2 1 3 kg Y 1 (periarrest) Y Y Failed intubation, difficult mask ventilation
leading to cardiac arrest. Grade 1 periarrest intubation
2 Y 1 N N
3 Y 2B Y N Accidental perioperative extubation. Difficult mask
ventilation. Prolonged desaturation.
4 Y 2B N N
5 Y 3 N N
6 Y Laryngeal N N
mask airway
3 1 1.09 kg N 2 Y Y Cardiac arrest postextubation, followed by difficult mask
ventilation and prolonged desaturation
4 1 2.7 kg N 2 N N
2 Y 3 Y N Difficult mask ventilation requiring 2 person technique,
multiple failed intubations, ENT rigid bronchoscope
required. Prolonged hypoxic period

predicted and a difficult intubation/ventilation plan must be in place
with senior support available.
Because of their low birth weight and failure to thrive they are
prone to many of the usual risks of neonatal anesthesia including diffi-
cult intravenous access, hypothermia, and hypoglycemia. Patients with
Donohue syndrome can develop hypoglycemia with minimal fasting
and should, therefore, receive intravenous maintenance with dextrose
preoperatively. They require close glycemic control in the periopera-
tive period. Studies show an intact hypothalamo-pituitary axis in these
children, and it can, therefore, be assumed that children with Donohue
syndrome will mount a normal stress response to surgery.
Cardiomyopathy and biventricular hypertrophy are not present at
birth, but are almost universal within 1-2 months of age. This may
not be clinically evident, and therefore, a preoperative echocardio-
graph should be carried out. Anesthesia in a patient with Donohue
syndrome and hypertrophic obstructive cardiomyopathy carries con-
siderably more risk and should be avoided whenever possible.
The small thoracic diameter and significant abdominal distension
in these patients leads to a reduction in chest compliance and makes
bag valve mask ventilation problematic. They have minimal func-
tional reserve and even brief periods of apnea cause profound desat-
urations that can lead to hypoxic cardiac arrest. Manual ventilation
and consequent gastric insufflation with preexisting abdominal dis-
tension exacerbate this situation, and therefore, we would suggest
insertion of a large bore nasogastric tube prior to induction or as
soon after induction as possible. Airway adjuncts (including a laryn-
geal mask airway) for difficult mask ventilation should be readily
available, and we would suggest an experienced second anesthetist
where possible. Intubation in Donohue syndrome can be challenging.
Laryngoscopy is hindered by reduced mouth size and rapid desatura-
tion. An uncomplicated anesthetic does not preclude difficulties in
future cases. We would recommend a spontaneously breathing gas
induction technique in these patients, to minimize both bag valve
mask ventilation and apnea time. Intravenous access should be
placed prior to induction or as soon as possible thereafter. A difficult
airway plan should also be in place including senior help, indirect
laryngoscopy, and if possible, the involvement of the ENT team.
Children with Donohue syndrome are at risk of cardiovascular col-
lapse either due to hypoxia or to an associated cardiomyopathy, and
therefore, we would suggest that all resuscitation equipment and
drugs are readily available throughout general anesthesia.
We note that this review is significantly weakened by its retro-
spective nature. In many cases, information was not available and
therefore not able to be included. Despite attempts to contact all fami-
lies involved, no consent was obtained meaning that our case descrip-
tions have necessarily been vague in order for individuals to remain
unidentifiable. Nonetheless we feel that the high-risk nature of this
condition and the significant anesthetic challenges involved make this
message a valuable addition to the literature on the subject.
ETHICAL APPROVAL
Discussed with Great Ormond Street Ethics Committee Chair.
Despite attempts to contact parents, we were unable to gain paren-
tal consent. As discussed with the journal editor, the article has been
significantly modified to ensure individuals are unidentifiable.
KIRKWOOD ET AL.
CONFLICT OF INTEREST
The authors report no conflict of interest.
ORCID
Alana Kirkwood http://orcid.org/0000-0003-1867-7186
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disorder. J Pediatr. 1954;45:505-519.
3. Fernhoff PM. 50 years ago in the journal of pediatrics. J Pediatr.
2004;145:697.
4. Mohamed S. An infant with Leprechaunism, ambiguous genitalia and
poor glycemic control: a management challenge. Acta Endocrinologica
(Buc). 2014;10:134-139.
5. Martınez-Frıas M, Bermejo E, Rodrıguez-Pinilla E, Martınez-Fernan-
dez ML. Sındrome de Donohue (Leprechaunismo). ECEMC. 2010;24:
1-2.
6. Kosztolanyi G. Leprechaunsism/Donohue syndrome/insulin receptor
gene mutations: a syndrome delineation story from clinicopathologi-
cal description to molecular understanding. Eur J Pediatr. 1997;156:
253-255.
7. Kobayashi M, Olefsky JM, Elders J, et al. Insulin resistance due to a
defect distal to the insulin receptor: demonstration in a patient with
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8. Taylor SI, Roth J, Blizzard RM, Elder MJ. Qualitative abnormalities in
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1981;78:7157-7161.
9. Tinka Hovnik T, Bratanic N, Podkrajsek KT. Severe progressive
obstructive cardiomyopathy and renal tubular dysfunction in Donohue
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drome de Donohue ou leprechaunisme: a propos d’un cas. Arch Pedi-
atr. 2014;21:206-210.
11. Baykan A, Cansever M, Konuskan B. Hypertrophic cardiomyopathy with
leprechaunism. J Pediatr Endocrinol Metab. 2008;21:317-318.
12. Patterson J, Watkins WL. Leprechaunism in a male infant. J Pediatr.
1962;60:731.
13. Quin JD, Fisher BM, Paterson KR, Inoue A, Beastall GH, MacCuish
AC. Acute response to recombinant insulin-like growth factor I in a
patient with Mendenhall’s syndrome. N Engl J Med. 1990;323:1425-
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14. McDonald A, Williams RM, Regan FM, Semple RK. IGF-I treatment
of insulin resistance. Eur J Endocrinol. 2007;157:51-56.
15. de Kerdanet M, Caron-Debarle M, Nivot S, et al. Ten-year improve-
ment of insulin resistance and growth with recombinant human insu-
lin-like growth factor 1 in a patient with insulin receptor mutations
resulting in leprechaunism. Diabetes Metab. 2014;41:331-337.
16. Nakae J, Kato M, Kato M, Murashita M, et al. Long term effects of
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17. Semple RK, Williams RM, Dunger DB. What is the best management
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How to cite this article: Kirkwood A, Stuart G, Harding L.
Donohue syndrome: A review of literature, case series, and
anesthetic considerations. Pediatr Anesth. 2018;28:23–27.
https://doi.org/10.1111/pan.13273
Accepted: 17 October 2017
DOI: 10.1111/pan.13285
SYSTEMATIC REVIEW
Assessment of sedation level prior to neonatal intubation:
A systematic review
Ellen H. M. de Kort1,2
Sinno H. P. Simons2
1
Department of Pediatrics and
Neonatology, Maxima Medical Center,
Veldhoven, The Netherlands
2
Division of Neonatology, Department of
Pediatrics, Erasmus MC Sophia Children’s
Hospital, Rotterdam, The Netherlands
Correspondence
Ms. Ellen H. M. de Kort, Department of
Neonatology, Maxima Medical Center,
Veldhoven, The Netherlands.
Email: e.dekort@mmc.nl
Funding information
Fonds NutsOhra; Netherlands Organisation
for Health Research and Development,
Grant/Award Number: 90713494
Section Editor: Francis Veyckemans
1 | INTRODUCTION
A significant proportion of preterm and critically ill newborn infants
needs endotracheal intubation at some point during their admission
to the Neonatal Intensive Care Unit (NICU) or because of anesthesia.
Indications range from respiratory insufficiency in case of pulmonary
28 | © 2017 John Wiley & Sons Ltd
| Nienke M. Halbmeijer2 | Irwin K. M. Reiss2 |
Summary
Background: Adequate premedication before neonatal endotracheal intubation
reduces pain, stress, and adverse physiological responses, diminishes duration and
number of attempts at intubation, and prevents traumatic airway injury. Therefore,
intubation should not be started until an adequate level of sedation is reached. It is
not clear how this should be measured in the clinical situation.
Objectives: The aim of this study is to provide a systematic review of the usability
and validity of scoring systems or other objective parameters to evaluate the level
of sedation before intubation in neonates. Secondary aims were to describe parame-
ters that are used to determine the level of sedation and criteria on which the deci-
sion to proceed with intubation is based.
Methods: Literature was searched (January 2017) in the following electronic data-
bases: Embase, Medline, Web of Science, Cochrane Central Registrar of Controlled
Trials, Pubmed Publisher, and Google Scholar.
Results: From 1653 hits, 20 studies were finally included in the systematic review.
In 7 studies, intubation was started after a predefined time period; in 1 study, pre-
oxygenation was the criterion to start with intubation; and in 12 studies, intubation
was started in case of adequate sedation and/or relaxation. Only 4 studies
described the use of 3 different objective scoring system, all in the neonatal inten-
sive care unit, which are not validated.
Conclusion: No validated scoring systems to assess the level of sedation prior to
intubation in newborns are available in the literature. Three objective sedation
assessment tools seem promising but need further validation before they can be
implemented in research and clinical settings.
KEYWORDS
intubation, newborn infant, premature, premedication, sedation
morbidity, sepsis, or necrotizing enterocolitis, and the administration
of surfactant, to surgical procedures such as bowel surgery, surgical
closure of a patent ductus arteriosus, laser coagulopathy in case of
retinopathy of prematurity, or placement of a surgical central venous
catheter. Endotracheal intubation is a painful and stressful procedure
and often is associated with adverse physiological responses such as
wileyonlinelibrary.com/journal/pan Pediatric Anesthesia. 2018;28:28–36.
DE KORT ET AL.
bradycardia, hypoxemia, systemic hypertension, and intracranial
hypertension.1-7 The use of premedication before intubation reduces
the risk of these adverse events, and also reduces the duration and
number of attempts needed for successful intubation and prevents
traumatic injury to face, eyes, gums, tongue, and glottic structures.6-11
Neonatal intubation should therefore be preceded by sedative
premedication.
The goal of administering premedication is to achieve a proper
level of sedation before intubation is started or muscle relaxants
are administered. Still the question is how this level of sedation
should be defined and how this should be measured in the clinical
situation.
2 | OBJECTIVES
Our primary objective was to provide a systematic review of studies
assessing the usability and validity of objective scoring systems or
parameters to evaluate the level of sedation before intubation in
newborn infants. Because we presumed that very few studies have
addressed this issue, our secondary objective was to describe com-
mon practice, addressing the following 2 questions:
1. On what parameter(s) and/or criteria is the decision to proceed
with intubation after the administration of premedication based?
2. Which (objective) scores or other parameters are used to deter-
mine the level of sedation after administration of premedication?
3 | MATERIALS AND METHODS
3.1 | Study design
This systematic review was conducted according to the guidelines of
the Preferred Reporting Items for Systematic Reviews and Meta-
Analyses (PRISMA).12
3.2 | Criteria for considering studies for this review
3.2.1 | Types of studies
For our primary objective, eligible for inclusion were randomized
controlled trials (RCTs), quasi-RCTs, controlled clinical trials, and
observational studies evaluating the use of objective scoring systems
or parameters to assess level of sedation. For our secondary objec-
tives, also single-case studies, poster presentations, editorials, and
reviews were eligible for inclusion, provided these extensively
reported the complete procedure from administration of premedica-
tion to start of the intubation. Availability of full text was imperative.
3.2.2 | Types of study population
The target population consisted of preterm and term neonates who
needed endotracheal intubation.
| 29
3.2.3 | Types of interventions
For the primary objective, studies evaluating an objective score or
parameter to assess the level of sedation after administration of
premedication were included. For the secondary objectives, studies
addressing any type of intervention were included.
3.2.4 | Types of outcome measures
For the primary objective, studies with degree of sedation during
intubation as outcome measure were included. For the secondary
objective, studies addressing any type of outcome measure were
included.
3.3 | Data collection and analysis
3.3.1 | Electronic searches
The following electronic databases were searched: Embase, Medline,
Web of Science, Cochrane Central Registrar of Controlled Trials,
Pubmed Publisher, and Google Scholar. The search strategies are
outlined in Table 1. There were no restrictions on the basis of publi-
cation date or publication status. The search strategy also had no
restriction in language. The search was performed on January 27,
2017.
3.3.2 | Selection of studies
Two authors (EdK and NH) independently assessed titles and
abstracts of the search results. Full copies of all potentially relevant
studies were obtained. Both authors made a decision on final inclu-
sion after retrieval of full copies independently. Disagreements were
resolved by consensus; if necessary a third author was consulted
(SS). Only articles written in English, Dutch, German, and French
were selected.
3.3.3 | Data extraction
Two authors (EdK and NH) extracted details of the included studies
independently. The following data were extracted: use of premedica-
tion, used drugs or combination of drugs, scores or parameters
determining the decision to proceed with intubation, sedation as
parameter to proceed with intubation, actions undertaken in case of
insufficient sedation.
3.3.4 | Quality appraisal individual studies
Because no studies were found reporting on the usability and
validity of scoring systems or other parameters to assess the
level of sedation, and we thus only report on common practice
as described in the methods sections of the reports, evaluation
of the methodological quality and the risk of bias was not
relevant.
30 | DE KORT ET AL.

T A B L E 1 Search strategies
Electronic database Search strategy
Embase (intubation/de OR “respiratory tract intubation”/exp OR (intubat*):ab,ti) AND (newborn/de OR “newborn intensive care”/exp
OR prematurity/de OR “low birth weight”/exp OR “newborn care”/de OR (newborn* OR (new* NEXT/1 born*) OR neonat*
OR nicu OR nicus OR prematur* OR preterm* OR “low birth weight” OR lbw OR vlbw OR elbw):ab,ti) AND (premedication/
exp OR “hypnotic sedative agent”/exp OR “sedative agent”/exp OR “conscious sedation”/de OR “deep sedation”/de OR
“anesthetic agent”/exp OR “muscle relaxation”/de OR “muscle relaxant agent”/exp OR “neuromuscular blocking agent”/exp
OR (premedicat* OR sedat* OR anesthetic* OR anaesthetic* OR ((musc* OR neuromusc*) NEAR/3 (relax* OR block*))):ab,
ti) NOT ([animals]/lim NOT [humans]/lim) NOT (“cesarean section”/de OR pregnancy/exp OR “pregnant woman”/de OR
(cesarean* OR caesarean* OR pregnan*):ab,ti)
Medline (intubation/OR “Intubation, Intratracheal”/OR (intubat*).ab,ti.) AND (exp infant, newborn/OR “Intensive Care Units,
Neonatal”/OR “Intensive Care, Neonatal”/OR (newborn* OR (new* ADJ born*) OR neonat* OR nicu OR nicus OR
prematur* OR preterm* OR “low birth weight” OR lbw OR vlbw OR elbw).ab,ti.) AND (premedication/OR exp “Hypnotics
and Sedatives”/OR “conscious sedation”/OR “deep sedation”/OR exp “anesthetics”/OR “muscle relaxation”/OR exp
“Neuromuscular Agents”/OR (premedicat* OR sedat* OR anesthetic* OR anaesthetic* OR ((musc* OR neuromusc*) ADJ3
(relax* OR block*))).ab,ti.) NOT (exp animals/NOT humans/) NOT (“cesarean section”/OR exp pregnancy/OR “pregnant
women”/OR (cesarean* OR caesarean* OR pregnan*).ab,ti.)
Cochrane ((intubat*):ab,ti) AND ((newborn* OR (new* NEXT/1 born*) OR neonat* OR nicu OR nicus OR prematur* OR preterm* OR
“low birth weight” OR lbw OR vlbw OR elbw):ab,ti) AND ((premedicat* OR sedat* OR anesthetic* OR anaesthetic* OR
((musc* OR neuromusc*) NEAR/3 (relax* OR block*))):ab,ti) NOT ((cesarean* OR caesarean* OR pregnan*):ab,ti)
Web of Science TS=(((intubat*)) AND ((newborn* OR (new* NEAR/1 born*) OR neonat* OR nicu OR nicus OR prematur* OR preterm* OR
“low birth weight” OR lbw OR vlbw OR elbw)) AND ((premedicat* OR sedat* OR anesthetic* OR anaesthetic* OR ((musc*
OR neuromusc*) NEAR/2 (relax* OR block*)))) NOT ((cesarean* OR caesarean* OR pregnan*)) NOT ((animal* OR rat OR
rats OR mouse OR mice OR murine) NOT (human* OR child* OR patient*)))
Google Scolar Intubation|intubated newborn|newborns|neonates|neonatal|nicu|nicus|premature|preterm|”low birth weight”|lbw|vlbw|elbw
premedication|sedation|anesthetic|anaesthetic|”muscular|neuromuscular relaxation|blockers” -cesarean -caesarean -pregnancy
-pregnant

relaxation.7,13-23 Nevertheless, no more than 4 of these 12 studies

4 | RESULTS
4.1 | Study selection
A flowchart of study selection is provided in Figure 1. The initial
electronic database search yielded 2597 records, which number was
reduced to 1652 after duplicates were removed. One additional
record found in reference lists was added. Thus, the titles and
abstracts of in total 1653 records were screened on relevance to the
primary and secondary objectives. None of the studies appeared rel-
evant to the primary objective. Regarding the secondary objective,
full text was obtained from 75 records and 1578 records were
excluded. Of these 75 records, 5 were excluded because of language
restriction (1 record) or unavailability (4 records). Of the remaining
70 records, full text was read. The studies’ methods sections were
screened for information about parameters on which the decision to
start with intubation was based. Twenty studies provided this
information and these were included in the final analysis of our
secondary objective.
4.2 | Study characteristics and results of individual
studies
Table 2 shows the characteristics of the 20 included studies. In 12
studies, the decision to proceed with intubation after the administra-
tion of premedication was based on the degree of sedation or
used an objective scoring system.13-16 In one other of the 12 stud-
ies, disappearance of the eyelash reflex was considered an indicator
of hypnosis and therefore as the criterion to start with intubation.21
In the control group, loss of muscle tone was the criterion to start
with intubation.21 The methods section did not describe, however,
how muscle relaxation was rated. In the remaining 7 studies that
based the start of the intubation on the degree of sedation and/or
relaxation, it was not clear if sedation and/or relaxation were rated
either in an objective or a rather subjective way.7,17-20,22,23
In 8 of the 12 studies, the intubating clinician’s observation of
insufficient sedation led to the administration of more premedication
to achieve an adequate level of sedation and/or relaxation.7,13,14,17-
19,21,22
In the remaining 4 studies, this was not mentioned at
all.15,16,20,23
In 7 of all 20 included studies, intubation was started after a cer-
tain period of time had elapsed after the administration of premedi-
cation.5,6,24-28 The methods section of these studies neither made
clear if level of sedation also played a role, nor if all patients were
adequately sedated upon start of the intubation procedure. In one
study, preoxygenation was the leading parameter to start with intu-
bation.29
Only 4 of the 20 studies used an objective scoring system to
assess the level of sedation before proceeding with intubation.
These objective scoring systems are outlined in Table 3. The first
scoring system is a sedation score used in 2 different reports.
DE KORT ET AL.
F I G U R E 1 Flowchart of included and
excluded studies
Smits et al used this score in their dose-finding study for propofol
in newborns and de Kort et al used the score in a study on the
use of remifentanil in preterm infants undergoing the INSURE pro-
13,14
cedure. The score is adopted from the study of Naulaers et al
into the effectiveness of methohexital as premedication for elec-
15
tive intubation. The level of sedation is assessed from the motor
response to a firm stimulus by rubbing of the feet (1 = sponta-
neous movement, 2 = moves on touch, 3 = moves on stimulus,
4 = no movement). In both studies, sedation was presumed to be
effective with scores 3 and 4, upon which intubation was started.
Another scoring system is the relaxation score also used in the
report of Smits et al, combining this score with the above-mentioned
sedation score. After the administration of propofol, level of sedation
and muscle relaxation were determined. For relaxation, the muscle
tone of the extremities was assessed (1 = hypertonic, 2 = normal
tone, 3 = mildly hypotonic, and 4 = hypotonic). Also, scores 3 and 4
reflect effective relaxation. Both relaxation and sedation were
assessed by the intubating neonatologist. Additional propofol was
| 31
administered if sedation and relaxation were found unsatisfactory,
until a satisfactory condition was achieved with no predefined maxi-
mum dose of propofol.13 In the report of de Kort et al,14 in case of
ineffective sedation, additional remifentanil was administered up to a
predefined maximum, with a conversion to propofol in case of
persisting inadequate sedation.
The third score is from Thall et al, in their report describing how
to perform dose-finding studies for premedication in neonatal intu-
bation. For this purpose they used the Neonatal Pain, Agitation and
Sedation Scale (N-PASS) first described by Hummel et al.30 The
score consists of 5 variables that should all be scored within 5 min-
utes of the first sedative administration: crying/irritability, behavior
state, facial expression, extremity tone, and vital parameters. Each
item is scored on a 5-point scale from 2 to +2, with 2 corre-
sponding to highest sedation and +2 corresponding to highest infant
discomfort. For the purpose of endotracheal intubation, Thall et al16
considered a score between 7 and 3 to reflect a good sedative
state.

T A B L E 2 Characteristics of included studies
First author, year, country
Smits A, 2016, Belgium
De Kort, 2016,
The Netherlands
Avino D, 2014, Belgium
Baleine J, 2014, France
Durrmeyer X, 2014, France
Thall PF, 2014, USA
Simons S, 2013,
The Netherlands
Penido MG, 2011, Brazil
Choong K, 2010, Canada
Welzing L, 2010, Germany
Lemyre B, 2009, Canada
Van Looy, 2008, USA
Ghanta S, 2007, Australia
Dempsey E, 2006, Ireland
Milesi C, 2006, France
Study design
Prospective observational
Prospective observational
Noninferiority randomized trial
Prospective observational
Prospective observational
Not applicable
Prospective observational
Double-blinded randomized trial
Double-blinded randomized
controlled trial
Prospective observational
Prospective observational
Prospective observational
Randomized, open-label
controlled trial
Prospective observational
Prospective observational
32
|
Parameter for Consequences insufficient seda-
Premedication start intubation Start intubation tion/relaxation
Propofol Sedation and relaxation Good sedation and relaxation Additional propofol in case of
scores unsatisfactory relaxation and
sedation according to physician
Remifentanil Sedation Good sedation score Additional remifentanil until good
sedation score
SG: remifentanil Time SG: after complete remifentanil
CG: morphine, atropine infusion; CG: 3 min after
and midazolam midazolam infusion
Nasal midazolam Sedation At hypnosis, muscle relaxation or Second dose in case of arousal at
apnea introduction of tube or
excessively awake at 5 min
Atropine, sufentanil Relaxation At onset of paralysis Extra atracurium (up to a
and atracurium predefined maximum)
Not applicable Sedation Good sedation score Not applicable
Propofol Sedation When sedation was scored yes by Extra propofol (up to a maximum
treating physician of 3 doses)
SG: propofol, remifentanil Time 2 min after remifentanil infusion
CG: midazolam, remifentanil
SG: remifentanil, atropine Time 30 s after last drug administration
and placebo
CG: fentanyl, atropine and
succinyl-choline
Propofol Time 75 s after propofol administration
Atropine, fentanyl and Relaxation Cessation of spontaneous None mentioned
Succinyl-choline movements (succinyl-choline
(the latter only in GA ≥ 34 wks) group) or sufficient relaxation
Midazolam and fentanyl Time 1-2 min after medication Another dose of fentanyl in case
administration of 3 failed attempts
SG: propofol Hypnosis and relaxation SG: disappearance of eyelash reflex SG: 1 extra dose of propofol, after
CG: morphine, atropine and CG: muscle relaxation that conversion to
suxamethonium CG: repeating doses of
suxamethonium
Mivacurium and fentanyl Preoxygenation Saturation > 95%, typically 2 min
after fentanyl infusion
Nitrous oxide Relaxation At suppression of muscle tone
(cessation of movements and
DE
hypotonia limbs and jaw)
KORT
(Continues)
ET AL.
 DE KORT ET AL. | 33

5 | DISCUSSION
Consequences insufficient seda-

This systematic review was performed to provide insight into the

availability of validated objective scoring systems to assess newborn

Up to 4 extra doses of
infants’ level of sedation prior to intubation. The literature as per

suxamethonium

None mentioned
None mentioned

January 27, 2017 does not provide such a validated scoring system.
tion/relaxation

The decision to proceed with the intubation procedure after

administering premedication should be based on the preintubation
sedation level. However, studies reporting on this issue show that
level of sedation is not always the key factor to proceed with intu-
bation. In several studies intubation proceeded when a certain per-
fasciculations and begin of muscle
SG: once spontaneous movements

iod of time had elapsed after the administration of premedication,

1-2 min after preoxygenation

assuming this amount of time being sufficient for drug effect. How-
No reaction to heel rubbing
CG: after fentanyl infusion

At disappearance of muscle

ever, as drug pharmacokinetics and pharmacodynamics can differ

considerably depending on gestational age and postnatal age, suffi-
1 min after infusion

cient drug effect may need a different period of time in individual

Start intubation

patients. Using the same time frame in all neonates may very well
had ceased

flaccidity

lead to a proportion of patients not being adequately sedated

for the procedure. To guide individualized dosing, we strongly
recommend basing the start of the intubation on the actual level of
sedation and administering extra doses if necessary.
SG: relaxation CG: time

In the majority of studies included in this review, quality of seda-

tion is indeed the key factor to guide intubation. However, this is
start intubation
Parameter for

assessed in very diverse ways, often rather subjective or not further

Relaxation

Sedation

specified. Validated scoring systems are lacking, especially prior to

Time

Time

elective intubation in the operating room. However, the literature

describes 3 objective assessment tools used in the NICU: the easy-
to-perform sedation score first described by Naulaers et al, the also
easy-to-perform relaxation score first used by Smits et al, and the
SG: morphine, atropine and
SG: atropine, fentanyl, and

more extensive scoring system suggested by Thall et al which is

CG: atropine, fentanyl

based on the N-PASS described by Hummel et al.13,14,16,30

The purpose of validated objective scoring systems is to be able
suxamethonium
Premedication

SG: thiopental
SG: morphine

to predict effective sedation during the intubation procedure before

CG: placebo

CG: placebo
Methohexital
mivacurium

CG: none

actually starting the procedure, thereby preventing neonates from

intubation without effective sedation. Validation of such scoring sys-
tems can be done by comparing the scoring system with the actual
level of sedation during the intubation procedure in a larger group of
Randomized placebo controlled

patients. In neonatal intubation studies, the actual level of sedation

Randomized controlled trial

Prospective observational

during an intubation procedure is frequently assessed with the vali-

Randomized controlled

dated intubation score adopted from Viby-Mogensen et al.31 In this

Randomized study

non blinded trial

intubation score, the items ease of laryngoscopy, position of the

nonblinded trial

vocal cords, coughing, jaw relaxation, and movement of the extremi-

Study design

ties are all judged on a 4-point scale. A score of 2 or less on each

item reflects effective sedation.13,14,24,25
CG, control group; SG, study group.

Although both using the Viby-Mogenson intubation score to

qualify level of sedation during the intubation procedure, the reports
Naulaers G, 1997, Belgium
First author, year, country
(Continued)

Lemyre B, 2004, Canada

of Smits et al and De Kort et al do not provide enough information

Buthada A, 2000, USA
Roberts K, 2006, USA

Oei J, 2002, Australia

to draw any conclusions about the accurateness of the sedation and

relaxation scores. In the sedation score, the absence of a motor reac-
tion or only a slight motor reaction to a firm stimulus is presumed to
TABLE 2

indicate the neonate will tolerate the insertion of the endotracheal

tube into the supraglottic airway. However, in this assumption, the
used stimulus should be stronger than the act of inserting an
 34
|

T A B L E 3 Objective scoring systems

Highest sedation Lowest sedation

Level of sedation
Sedation Score 4 3 2 1
Motor response No movements Movement on firm stimulus Movement on slight touch Spontaneous movements
to firm stimulus
Definition Effective sedation = score 3 or 4
Relaxation score 4 3 2 1
Extremities tone Hypotonic Mildly hypotonic Normal tone Hypertonic
Definition Effective relaxation = score 3 or 4
Good sedative state 2 1 0 1 2
Crying/irritability No cry with painful stimuli Moans or cries minimally No sedation/no pain signs Irritable or crying at High-pitched or silent
with painful stimuli intervals, consolable continuous cry, inconsolable
Behavior state No arousal to any stimuli, Arouses minimally to stimuli, little No sedation/no pain signs Restless, squirming, Arching, kicking, constantly awake of
no spontaneous movements spontaneous movement awakens frequently arouses minimally/no movement
Facial expression Mouth is lax, no expression Minimal expression with stimuli No sedation/no pain signs Any pain expression intermittent Any pain expression continual
Extremities tone No grasp reflex, flaccid tone Weak grasp reflex, ↓ muscle tone No sedation/no pain signs Intermittent clenched toes, fists, Continual clenched fists, toes, finger
finger splay, body is not tense splay, body is tense
Vital signs No variability with stimuli, <1% variability from No sedation/no pain signs ↑ 10%-20% from baseline, ↑ 20% from baseline, SaO2 < 75%
hypoventilation or apnea baseline with stimuli SaO2 76%-85% with with stimulation—slow recovery
stimulation—quick recovery
Definition Good sedative state = total
score on all 5 items 7 to 3
DE
KORT
ET AL.
DE KORT ET AL.
endotracheal tube. The question rises if the act of inserting an endo-
tracheal tube, mainly via the nasal route, requires a stronger stimulus
than heel rubbing. For example, by anesthesiologists, the much fir-
mer stimulus of pinching the trapezius muscle is frequently used
before inserting a supraglottic airway. Validation of that stimulus in a
clinical study has not been reported. In summary, although both
sedation and relaxation scores seem potentially useful scores in the
neonatal population, validation of these scores is mandatory before
further use.
The scoring system suggested by Thall et al concerns a compre-
hensive and precise scoring system, which is likely to adequately
reflect the level of sedation. Also, different definitions can be used
in case of different needs of sedation level according to its purpose.
However, to the best of our knowledge, clinical trials using this scor-
ing system are lacking. Therefore, any conclusion about its accuracy
and usability is not possible and validation is needed before future
use. Even if validated, the scoring system must prove its suitability in
daily practice. In neonatal intubation, fast performance of the proce-
dure is mandatory, especially when fast acting agents are used. The
extensiveness of the score could possibly make it time consuming
and therefore less suitable.
Despite the lack of validated objective scoring systems, several
reports do have shown that premedication before neonatal intuba-
tion has become standard practice in the majority of neonatal
10,11,32-38
units. There is however much debate about which
premedication or premedication regimen is best. Studies evaluating
certain premedication strategies are mainly focused on using 1 dos-
ing strategy for the entire neonatal population. However, pharma-
codynamics and pharmacokinetics are influenced by factors such as
gestational age, postnatal age and morbidity. For example, Smits
et al13 found that neonates of different gestational ages needed
different doses of propofol for adequate sedation. Most important
in our opinion is that the used premedication achieves effective
sedation. It should also have a quick recovery to allow for fast
extubation, and no significant side effects. The search for the most
suitable premedication strategy should be directed toward personal-
ized medicine and focus on administering just enough premedica-
tion to achieve adequate sedation in the individual patient. In this
point of view, a scoring system that adequately indicates the level
of sedation is mandatory.
The work of field and the techniques used differ between pedi-
atric anesthesiologists and neonatologists. For example, they have
different drug choices, pursue different levels of anesthesia (deep vs
superficial) and require different duration of sedation (hours vs min-
utes). However, the goals of administering premedication during
induction in the operating room and before intubation in the NICU
are comparable and in both situations the level of sedation should
be objectively assessed before continuing the procedure. With this
in mind, neonatologists and anesthesiologists can possibly share
valuable knowledge in this area of the field. With the availability of
a validated scoring system that can make a distinction between dif-
ferent levels of sedation, it should even be possible to use a single
scoring system for both settings.
| 35
Limitation of this review is that we used the description of the
intubation procedure in the methods section to answer the ques-
tions of our secondary objective. Because describing the entire pro-
cedure from administration of premedication to intubation was not
the primary goal of the included studies, it is possible that these
descriptions were not complete and that more scoring systems or
other parameters were used in practice.
6 | CONCLUSION
Validated scoring systems to assess the level of sedation prior to
intubation in newborns are not available in the literature. Three
objective sedation assessment tools seem promising but need further
validation before they can be implemented in research and clinical
settings. Future research is necessary to find a physical stimulus that
enables clinicians to better anticipate the response to insertion of an
endotracheal tube and laryngoscopy and to find the best premedica-
tion regimen to achieve the preset goals.
ACKNOWLEDGMENTS
We greatly thank Wichor M. Bramer of the Erasmus Medical Center
library for performing the electronic database search for this system-
atic review and Ko Hagoort for editing the manuscript. This research
was supported by a grant from Fonds NutsOhra. S. Simons was
financially supported by a personal grant of the Netherlands Organi-
sation for Health Research and Development (ZonMw nr
90713494).
DISCLOSURES
The authors report no conflict of interest.
ORCID
Ellen H. M. de Kort http://orcid.org/0000-0003-0469-0128
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How to cite this article: de Kort EHM, Halbmeijer NM, Reiss
IKM, Simons SHP. Assessment of sedation level prior to
neonatal intubation: A systematic review. Pediatr Anesth.
2018;28:28–36. https://doi.org/10.1111/pan.13285
Accepted: 17 October 2017

DOI: 10.1111/pan.13284

RESEARCH REPORT

Pressure-flow characteristics of breathing systems and their

components for pediatric and adult patients

Christin Wenzel | Stefan Schumann | Johannes Spaeth

Department of Anesthesiology and Critical

Care, Faculty of Medicine, Medical Center,
University of Freiburg, Freiburg, Germany
Correspondence
Johannes Spaeth, Department of
Anesthesiology and Critical Care, University
Medical Center Freiburg, Freiburg, Germany.
Email: johannes.spaeth@uniklinik-freiburg.de
Funding information
This work was supported by institutional
funding.
Section Editor: Prof Britta von Ungern-
Sternberg
Summary
Background: Breathing circuits connect the ventilator to the patients’ respiratory
system. Breathing tubes, connectors, and sensors contribute to artificial airway resis-
tance to a varying extent. We hypothesized that the flow-dependent resistance is
higher in pediatric breathing systems and their components compared to respective
types for adults.
Aims: We aimed to characterize the resistance of representative breathing systems
and their components used in pediatric patients (including devices for adults) by
their nonlinear pressure-flow relationship.
Methods: We used a physical model to measure the flow-dependent pressure gradi-
ent (ΔP) across breathing tubes, breathing tube extensions, 90°- and Y-connectors,
flow- and carbon dioxide sensors, water traps and reusable, disposable and coaxial
breathing systems for pediatric and for adult patients. ΔP was analyzed for usual flow
ranges and statistically compared at a representative flow rate of 300 mL∙s
1 (ΔP300).
Results: ΔP across pediatric devices always exceeded ΔP across the corresponding
devices for adult patients (all P < .001 [no 95% CI includes 0]). ΔP300 across breath-
ing system components for adults was always below 0.2 cmH2O but reached up to
4.6 cmH2O in a flow sensor for pediatric patients. ΔP300 was considerably higher
across the reusable compared to the disposable pediatric breathing systems (1.9 vs
0.3 cmH2O, P < .001, [95% CI
1.59 to
1.56]).
Conclusion: The resistances of pediatric breathing systems and their components
result in pressure gradients exceeding those for adults several fold. Considering the
resistance of individual components is crucial for composing a breathing system
matching the patient’s needs. Compensation of the additional resistance should be
considered if a large composed resistance is unavoidable.

KEYWORDS
airway—resistance, anesthesia—pediatric, device—equipment, respiratory—mechanics,
ventilation—mechanical

1 | BACKGROUND airway resistance may lead to increased work of breathing1 or emer-

gence of intrinsic positive end-expiratory pressure.2 At any rate, the
During mechanical ventilation, the breathing circuit connects the pressure gradient across artificial airways causes the monitored air-
ventilator to the patient’s respiratory system. Each component of way pressure to differ from the pressure that is actually applied to
the breathing circuit contributes to total airway resistance. A large the patient’s lungs.3 It has been demonstrated that the endotracheal

Pediatric Anesthesia. 2018;28:37–45. wileyonlinelibrary.com/journal/pan © 2017 John Wiley & Sons Ltd | 37
38 | WENZEL
tube is the individual component with the highest contribution to
airway resistance.4 Also, breathing circuit filters were shown to con-
tribute—to a lesser extent—to the artificial resistance.5 However,
research on other components of the breathing circuit is lacking or
outdated6 considering the continuously growing product range.
Pediatric anesthesiologists have to deal with devices for both
pediatric and adult patients—due to the large variability of their
patients’ individual needs. We hypothesized that breathing systems
and components for pediatric patients in particular are associated
with high resistance. We therefore investigated the pressure-flow
characteristics of representative breathing systems and their compo-
nents for pediatric and adult patients. In this regard, the flow-depen-
dent pressure gradients (ΔP) across the investigated devices were
determined in a laboratory environment. In order to enable calcula-
tion of ΔP for an arbitrary flow rate, we additionally determined
resistance coefficients for each component.
2 | MATERIALS AND METHODS
Breathing systems, silicone breathing tubes of different lengths, tube
extensions, water traps, connectors (Y-piece, 90°-connector and
combined), and sensors (flow sensor, flow sensor combined with
Y-piece and 90°-connector and cuvette for CO2 sensor) were inves-
tigated. Table 1 lists specifications of all investigated devices. Fig-
ure 1 illustrates the designs of the investigated connectors and
sensors (not including breathing systems and breathing tubes). Con-
ventional reusable breathing systems, conventional disposable
breathing systems, and coaxial breathing systems were investigated.
Conventional breathing systems were investigated with and without
a water trap.
2.1 | Setup for measurements
In order to measure the pressure-flow characteristics of the individu-
ally investigated devices, they were streamed with a sinusoidal gas
flow generated by a piston pump. For including maximal flow rates
that may typically occur in adult and pediatric patients during
mechanical ventilation,7 we chose flow rate amplitudes

1
500 mL∙s (devices for pediatrics) or 700 mL∙s
1 (devices for
adults). Flow rate was measured using a pneumotachograph (Fleisch
Type 1, Dr. Fenyves & Gut, Hechingen, Germany). Pressures were
measured at a distance of 1.5 cm from both ends of the respectively
investigated device via piezoresistive pressure sensors (Type 4, SI-
€ rdlingen, Germany). Pressure measure-
Special Instruments GmbH, No
ment sites at both ends were of identical inner diameters to avoid
the Bernoulli effect.
For measurements across breathing tubes and breathing systems,
these were arranged with a defined sagging of 33% of their total
length, in order to simulate clinical conditions. Flow rate and pres-
sure signals were sampled at 200 Hz. Twelve sinusoidal cycles were
recorded for each condition. All measurements were repeated 6
times after dismantling and reassembly of the setup.
ET AL.
What is already known
• The endotracheal tube is the pivotal individual compo-
nent determining the total airway resistance in mechani-
cally ventilated pediatric patients.
• Rohrer’s coefficients characterize sufficiently the nonlin-
ear pressure-flow relationships of endotracheal tubes.
They can be used to calculate tracheal pressure from the
pressure measured at the airway opening and moreover
to compensate for the endotracheal tube’s resistance.
What this article adds
• Specific breathing system components (connectors, sen-
sors, breathing tubes) for pediatric patients contribute to
total airway resistance by a considerable amount. This
should be considered when composing a breathing circuit
which matches the patient’s needs best.
• The flow-dependent pressure gradients for a wide range
of breathing system components used in pediatric venti-
lation therapy (including components for adult patients)
were quantified. Rohrer’s coefficients for the breathing
system components, enabling calculation of the pressure
gradient across the components, are provided.
2.2 | Calculation of flow-dependent pressure
gradient
In order to characterize the devices’ nonlinear resistances, the coeffi-
cients describing the pressure-flow relationship of the respective
device, ie, Rohrer coefficients (K1 and K2) and inertance (I), were
_ and
determined from the continuously measured ΔP, flow rate (V),
€ via multiple linear regression analysis
derived volume acceleration (V)
of Equation 18:
DP ¼ K1  V_ þ K2  V_ 2 þ I  V
€ (1)
of In order to facilitate the comparison between components, ΔP
was calculated from K1 and K2, following Equation 1, at a represen-
tative flow rate of 300 mL∙s
1 (ΔP300). As volume acceleration in
such calculation would be arbitrary, we assumed a constant flow
€ = 0) implying that the inertance term of Equation 1 is negligible.
(V
2.3 | Statistical analyses
Data are presented as mean  SD if not indicated otherwise. For
ΔP300, Rohrer’s coefficients and inertance, no SD is given if below
0.02. Pressure and flow measurements were recorded using self-
written acquisition software, developed in LabView (ver. 7.1,
National Instruments, Austin, TX, USA) and analyzed using MATLAB
(ver. 2014 R1, The MathWorks, Natick, MA, USA). For comparison
of ΔP300, ANOVA were calculated followed by post hoc t-tests if
WENZEL ET AL. | 39

T A B L E 1 Names, reference numbers

Pediatric Adult
(REF), and dimensions of breathing
systems and components Length ID Length ID
REF [cm] [mm] REF [cm] [mm]
Breathing tubes
Silicon 2165848 60 10 2165627 60 19
Silicon 66-10-110a 110 10 2166038 110 19
Silicon 66-10-150a 150 10 2166046 150 19
Tube extensions MP01860 10 10 MP01845 15 12
Water trap 8404760 n.a. 5 8404985 n.a. 15
Connectors
Y straight M27077 n.a. 15-5 M25650 n.a. 15
a
90° angled 60-65-002 n.a. 15 8412235 n.a. 15
Combined Y and 8403077 n.a. 15-5 M25682 n.a. 15
90°
Sensors
Straight flow 8411130 n.a. 10-5 n.a. n.a. n.a.
sensor
Angled flow 8410185 n.a. 15-5 n.a. n.a. n.a.
sensor
Cuvette CO2 6870280 n.a. 15-5 6870279 n.a. 15-12
sensor
Breathing systems
Reusable Assembledb 150 10 Assembledb 150 19
Disposable MP00331 150 15 MP00300 150 22
Assembled + WT 66-10- 180 10 66-12- 180 22
085a + WT 085a + WT
Readymade + WT MP00362 180 15 MP00337 180 22
Coaxial inspiratory MP00379 150 11 MP00315 150 16
Coaxial expiratory 170 12c 190 15c

ID, inner diameter; WT, water trap.

Reference numbers refer to Dr€ager Medical (Lu €beck, Germany) or if marked (a) to VBM Medizintech-
nik GmbH (Sulz am Neckar, Germany).
b
Breathings system manually assembled from: silicon breathing tube 150 cm, Y straight connector,
and 90° angled connector.
c
Listed is the actual diameter of the expiratory hose of the coaxial tube.

appropriate (GraphPad PRISM, ver. 6.02, GraphPad Software Inc., La
Jolla, CA, USA). A P-value < .05 was considered significant. For each
statistical comparison, the 95% confidence interval of the difference
[95% CI] is given.
3 | RESULTS
In all investigated breathing system components ΔP increased dispro-
portionately with increasing flow and their pressure-flow characteris-
tics could be reliably described by Rohrer’s coefficients and inertance
(Table 2). K1 and K2 were higher in pediatric devices compared to
respective values found in devices used in adults. This difference
was more pronounced for K2. Inertance reached highest values in
devices with low inner diameter but large volume, such as breathing
tubes and breathing systems. ΔP across pediatric components was
always higher compared to ΔP across the corresponding components
for adults (Figure 2; all P < .001, [no 95% CI includes 0]).
ΔP300 was ≤ 0.2 cmH2O in all breathing system components for
adults. In pediatric components ΔP300 was larger compared to the
components for adults and ranged up to 4.6 cmH2O in a combined
flow sensor for pediatric patients (Table 3). In breathing tubes for
adults, ΔP300 did not depend significantly on tube length but
increased in pediatric breathing tubes with increasing length. ΔP300
varied depending on the direction of flow in pediatric components
with asymmetric geometry.
In conventional breathing systems for adults, ΔP300 was < 0.2 cmH2O.
In pediatric breathing systems, ΔP300 was considerably higher
40 | WENZEL
F I G U R E 1 Technical schemes of connectors and sensors
included in the study. Schemes refer to types and dimensions given
in Table 1. Left: components used in pediatric patients; right:
components used in adult patients. TE = tube extension,
WT = water trap, C1 = connector Y straight, C2 = connector 90°
angled, C3 = combined Y and 90°, S1 = straight flow sensor,
S2 = combined flow sensor, S3 = CO2 sensor. Please note that the
components S1 and S2 for adult patients are not applicable (n.a.)
ET AL.
(Figure 3). In the reusable breathing system, ΔP300 amounted up to
1.9 cmH2O, whereas ΔP300 was only 0.3 cmH2O in the disposable
breathing system. Inclusion of a water trap into a conventional pedi-
atric breathing system led to an increase of ΔP300 in both the reusable
(1.9 to 2.1 cmH2O; P < .001, [95% CI 0.23 to 0.27]) and the dispos-
able type (0.3 to 0.4 cmH2O; P < .001, [95% CI 0.13 to 0.14];
Figure 3). In coaxial breathing systems, ΔP300 differed between
inspiratory and expiratory flow in both systems for pediatric patients
(0.8 vs 0.6 cmH2O; P < .001, [95% CI
0.30 to
0.22]) and systems
for adults (0.3 vs 0.5 cmH2O; P < .001, [95% CI 0.20 to 0.21]).
4 | DISCUSSION
The main findings of the present study can be summarized as follows:
(i) the pressure gradient across breathing system components
depends nonlinearly on flow and can be described by Rohrer’s
approach; (ii) at flow rates relevant for the ventilation of pediatric
patients, the pressure gradient across pediatric breathing systems and
their components can be considerable, whereas it is consistently low
across devices for adults; and (iii) reusable pediatric breathing systems
exhibit a higher resistance compared to disposable and coaxial ones.
The higher resistance of breathing system components for pedi-
atric patients can be explained by the generally smaller physical
dimensions of the pediatric components (Table 1). It is well known
that a streamed tube’s inner diameter is the pivotal determinant for
resistance to gas flow.9 Moreover, decreasing the inner diameter
promotes higher gas velocities and thus turbulent flow. This leads to
a nonlinear resistance that increases with the flow rate. This nonlin-
earity also becomes apparent in the quadratic coefficient (K2) of the
pressure-flow relationship we determined in the present study.
Breathing systems’ components for pediatric patients are gener-
ally designed to fit small dimensions in order to decrease additional
dead space. However, small dimensions impose a greater artificial
airway resistance. The tolerable dead space volume of a breathing
circuit depends on the required tidal volume. Limiting dead space to
the smallest volume possible is particularly relevant in neonatal and
infant patients but may be less important in adolescent pediatric
patients. While total airway resistance may be less important during
controlled mechanical ventilation, it is quite relevant during sponta-
neous breathing support where it contributes to the patient’s work
of breathing. In that case, adult patients may easily compensate for
the comparatively low additional airway resistance of their breathing
systems. By contrast, pediatric patients, particularly when critically ill,
may fail to overcome the high resistance imposed by pediatric
breathing systems. Composing a breathing circuit is therefore a
trade-off between dead space volume and airway resistance.
Differences between resistances of adult and pediatric breathing
system components may be of particular relevance for the pediatric
anesthesiologist, who deals with both depending on the patient’s
individual needs. Knowledge of the respective resistances may be
crucial to avoid ventilation problems related to increased additional
airway resistance. The present study aims at providing these facts.
 WENZEL
ET AL.

T A B L E 2 Rohrer’s coefficients (K1, K2) and inertance (I) for breathing systems and components
Pediatric Adult

Inspiration Expiration Inspiration Expiration

K1 [cmH2O/ K2 [cmH2O/ K1 [cmH2O/ K2 [cmH2O/ I [cmH2O/ K1 [cmH2O/ K2 [cmH2O/ K1 [cmH2O/ K2 [cmH2O/ I [cmH2O/
s/L] L2/s2] s/L] L2/s2] L*s2] s/L] L2/s2] s/L] L2/s2] L*s2]
Breathing tubes
Silicon (60 cm) 0.90 2.26 0.93
2.36 0.11 0.05 0.06 0.01
0.19 0.03
Silicon (110 cm) 1.30 3.41 1.26
3.24 0.19 0.11 0.11 0.07
0.24 0.06
Silicon (150 cm) 1.76 4.34 1.80
3.88 0.28 0.12 0.08 0.06
0.02 0.07
Tube extensions 0.23 4.33 0.17
5.22 0.05 0.00 1.92 0.19
1.62 0.03
Water trap 0.13 4.13 0.14
4.25 0.02 0.01 0.13 0.03
0.16 0.01
Connectors
Y straight 0.10 2.27 0.11
2.88 0.02 0.01 0.52 0.03
0.62 0.01
90° angle 0.07 1.07 0.00
1.88 0.02 0.02 0.47 0.06
0.76 0.01
Combined Y and 90° 0.22 5.34 0.20
8.31 0.02 0.04 0.71 0.18
0.66 0.01
Sensors
Straight flow sensor 1.53 30.18 1.18
35.05 0.07 n.a. n.a. n.a. n.a. n.a.
Angled flow sensor 0.23 50.29 0.53
37.73 0.08 n.a. n.a. n.a. n.a. n.a.
Cuvette CO2 sensor 1.78 7.79 0.90
14.52 0.05 0.15 0.26 0.03
0.68 0.01
Systems
Reusable 1.24 16.15 1.21
16.66 0.35 0.10 1.02 0.14
0.76 0.08
Disposable 0.26 2.33 0.19
2.56 0.11 0.01 1.45 0.02
1.44 0.07
Reusable + WT 1.78 17.10 1.82
17.45 0.39 0.12 1.40 0.20
1.02 0.10
Disposable + WT 0.34 3.59 0.26
3.77 0.17 0.01 1.71 0.01
1.68 0.07
Coaxial inspiratory 0.12 8.85 n.a. n.a. 0.14 0.08 2.46 n.a. n.a. 0.11
Coaxial expiratory n.a. n.a. 0.41
5.01 0.11 n.a. n.a. 0.33
3.91 0.10

n.a., not applicable; WT, water trap.

SD was < 0.02 cmH2O for all measurements and is therefore not given.
|
41
42 | WENZEL ET AL.

F I G U R E 2 Inspiratory flow-dependent pressure gradient (ΔP) across breathing tubes (upper left panel), tube extensions and water traps
(middle left panel), connectors (lower left panel), and sensors (upper right panel) used for pediatric (solid lines) and adult patients (dashed lines).
Please note the reference line at a flow rate of 300 mL s
1, referring to ΔP300 (see also Table 3). The lower right panel shows the pressure
gradients at a flow rate of 300 mL s
1 (ΔP300) depending on the devices’ lowest inner diameters (open symbols = devices used in pediatric
patients; filled symbols = devices used in adult patients)

Typically, a breathing system includes tubes, a Y-piece, and a 90°
connector. We investigated such basic combined systems (below
referred to as reusable) and found that ΔP300 reached almost
2 cmH2O in the pediatric model. Referring to Lowe et al10 such
basic systems account for about two-third of specific airway
resistance found in 3-year-old children.
Adding components for specific purposes, such as a carbon diox-
ide sensor or a tube extension, would further increase ΔP to a rele-
vant extent. In this regard, the routine use of breathing circuit filters
might be questioned. The filter intended for use in pediatric patients
would additionally provide approximately 0.5 cmH2O at a flow rate
of 300 mL∙s
1.5 Furthermore, our results demonstrate that straight
WENZEL ET AL. | 43

T A B L E 3 Pressure gradients at a flow rate of 300 ml∙s
1 (ΔP300)

across breathing systems and components for inspiration (insp.) and
expiration (exp.)
Pediatric Adult

ΔP300 ΔP300

Insp. Exp. Insp. Exp.

[cmH2O] [cmH2O] [cmH2O] [cmH2O]
Breathing tubes
Silicon (60 cm) 0.48 0.49 0.02 0.02
Silicon (110 cm) 0.70 0.67 0.04 0.04
Silicon (150 cm) 0.92 0.89 0.04 0.04
Tube extension 0.46 0.52 0.17 0.21
Water trap 0.41 0.43 0.00 0.02
Connectors
Y straight 0.24 0.29 0.05 0.06
90° angle 0.12 0.17 0.05 0.09
Combined Y and 0.55 0.81 0.08 0.11
90°
Sensors
Straight flow 3.17 3.51 n.a. n.a.
sensor
Angled flow 4.60 3.55 n.a. n.a.
sensor
Cuvette CO2 1.24 1.58 0.07 0.07
sensor
Breathing systems
Reusable 1.83 1.86 0.10 0.11
Disposable 0.29 0.29 0.13 0.14
F I G U R E 3 Flow-dependent pressure gradient (ΔP) across
Reusable + WT 2.07 2.12 0.16 0.15
different breathing systems used for pediatric patients for inspiration
Disposable + WT 0.42 0.42 0.14 0.15 and expiration. Please note the reference line at a flow rate of
Coaxial 0.84 n.a. 0.25 n.a. 300 mL s
1, referring to ΔP300. WT = water trap
inspiratory
Coaxial n.a. 0.57 n.a. 0.45
increased disproportionally with increasing flow rate and decreased
expiratory
disproportionally with decreasing flow rate. As already discussed,
WT, water trap; n.a., not applicable. ΔP300 reached almost 2 cmH2O in the pediatric reusable breathing
SD was < 0.02 cmH2O for all measurements and is therefore not given.
systems. By contrast, it was comparably low in the disposable
and the coaxial types. Again, this is attributable to the different
connectors generally provided a lower resistance compared to inner diameters, being lower in the reusable system. It is notewor-
angled ones; with regard to DP the use of straight connectors thy that ΔP across the reusable breathing system overestimated
appears preferable. the sum of ΔP across the respective isolated components. This
The pediatric flow sensors represent significant sources of resis- may be caused by flow phenomena at the connection sites
tance. These sensors measure the flow rate by hot-wire anemome- promoting additional turbulences.12 Such flow phenomena also
try, a technique which usually comes with a minimal resistance. 11
account for the differences of ΔP between inspiration and
However, the hour-glass shape of the investigated sensor’s case in expiration that became evident in some devices with asymmetric
question caused an additional resistance comparable to that of an geometry.
endotracheal tube with 4.5 mm inner diameter.3 Compared to these Including a water trap in the breathing systems increased ΔP to a
sensors the resistance of the other pediatric components was rather minor extent (≤0.2 cmH2O) which we consider to be of subordinate
low. However, it is the sum of resistances that accounts for total air- clinical relevance. Without a water trap, liquid may accumulate in
way resistance. the tubing system. The narrowing of the tube at the accumulation
The flow-dependent pressure gradient differed considerably site would increase resistance in a nonpredictable manner and more-
among breathing systems for pediatric patients, whereas it was over lead to self-triggering of the ventilator.13 Therefore, we would
consistently low in breathing systems for adults. In all systems, ΔP not suggest omitting the use of water traps.
44 | WENZEL
Coaxial breathing systems incorporate the inspiratory tube within
the expiratory one, thus facilitating clinical handling at the expense
of the lumen’s cross-sectional area. In a recent study, we compared
14
coaxial and conventional breathing systems for adults. The coaxial
breathing systems exhibited particularly high resistances compared
to conventional ones. Interestingly, in the present study, the pedi-
atric coaxial breathing system showed a comparably low resistance.
In contrast to the coaxial breathing systems for adults, the effective
cross-sectional areas of the pediatric coaxial tubing system were
even larger than those of the respective conventional ones. In both
types of coaxial tubing systems, resistance differed between inspira-
tion and expiration, which can be attributed to differences in the
effective cross-sectional areas of the inspiratory and the expiratory
tube.
By addressing the flow-dependent pressure gradient we aim to
facilitate the transfer of our results into clinical routine. From a clini-
cal point of view, artificial airway resistance implies a diagnostic and
a therapeutic problem. The diagnostic problem is that airway pres-
sure but not pulmonary pressure is the standard measure of routine
clinical monitoring. However, airway pressure differs from pulmonary
pressure by the extent of ΔP across all artificial airway components.
Knowledge of ΔP would allow for estimating pulmonary pressure
from airway pressure measurement and thus give a better estimation
of the pressure actually loading the lung. The therapeutic problem
concerns especially spontaneous breathing during which breathing
system resistance adds to the patient’s work of breathing. In order
to compensate for the additional work of breathing caused by the
breathing circuit, one may increase the inspiratory pressure support
by the amount of ΔP estimated for the peak flow rate. However, this
would lead to overcompensation at the beginning of the inspiration
and would not apply to expiration.15 An adequate compensation
needs to dynamically adapt airway pressure to ΔP resulting from the
current flow rate. Some ventilators do compensate for the resistance
16
of the endotracheal tube (automatic tube compensation). This can
effectively reduce the additional work of breathing and particularly
relieve patients with high ventilatory demand from the effort
required to overcome the artificial airways.17 Compensating ΔP of
the other components of the breathing circuit would allow further
relief for the patient. The present study provides resistive coeffi-
cients for these additional components, being essential for such an
approach.
5 | LIMITATIONS
The investigated artificial airway components represent a limited
sample of the available commercial products. Our aim was to include
a representative collection of components. Furthermore, it has to be
conceded that other types of the same categories may show differ-
ing characteristics and that the investigated devices are subject to
technical advancement.
In order to allow for easier comparison of the resistances of the
investigated airway components we arbitrarily chose an exemplary
ET AL.
flow rate of 300 mL s
1. This flow rate may appear disproportionally
high for small infants.18 However, we consider this flow rate repre-
sentative for a wide range of spontaneously breathing pediatric
patients.
6 | CONCLUSION
The resistances of breathing systems and breathing system compo-
nents for pediatric patients result in considerable pressure gradients
exceeding those of corresponding devices for adults several fold.
Taking into consideration the resistance of individual components is
crucial for composing a breathing system matching the patient’s
needs. Compensation for the additional work of breathing should be
considered if a large composed resistance is unavoidable. Resistance
coefficients for several breathing system components for pediatric
and adult patients are provided.
CONFLICT OF INTEREST
None declared.
ACKNOWLEDGMENTS
The authors gratefully acknowledge the technical support of Mat-
thias Schneider, an outstanding mechanical engineer.
ORCID
Johannes Spaeth http://orcid.org/0000-0003-3931-6400
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the endotracheal tube in mechanically ventilated pediatric patients.
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ciples and Applications. Philadelphia: Elsevier-Saunders; 2013:233-234.
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in respiratory resistance measurements. Lung. 1979;156:33-42.
13. Sansome AJ. Inappropriate triggering. Anaesthesia. 1988;43:1065-
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17. Guttmann J, Haberthur C, Mols G, et al. Automatic tube compensa-
tion (ATC). Minerva Anestesiol. 2002;68:369-377.
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How to cite this article: Wenzel C, Schumann S, Spaeth J.
Pressure-flow characteristics of breathing systems and their
components for pediatric and adult patients. Pediatr Anesth.
2018;28:37–45. https://doi.org/10.1111/pan.13284
Accepted: 11 October 2017

DOI: 10.1111/pan.13282

RESEARCH REPORT

Introducing the 6-4-0 fasting regimen and the incidence of

prolonged preoperative fasting in children

Hanna Andersson1 | Per M. Hellstrӧm2 | Peter Frykholm1

1
Department of Surgical Sciences,
Section of Anaesthesia and Intensive Care,
Uppsala University Hospital, Uppsala,
Sweden
2 erative fasting guidelines.
Department of Medical Sciences,
Gastroenterology, Uppsala University
Hospital, Uppsala, Sweden
Correspondence
Hanna Andersson, Department of Surgical
Sciences, Section of Anesthesiology and
Intensive Care Medicine, Uppsala Universitet
Medicinska och farmaceutiska
vetenskapsomradet – Uppsala University
Hospital ing 70, Uppsala, Sweden.
Email: hanna.andersson@surgsci.uu.se
Section Editor: Francis Veyckemans
Summary
Background: Children often starve for longer than recommended by current preop-
Aims: We studied the effects of implementing a more lenient fasting regimen on
the duration of clear fluid fasting, as well as the incidence of extended fasting in
children.
Methods: Preoperative duration of clear fluid fasting was recorded for patients
scheduled for procedures in a unit applying the standard 6-4-2 fasting regimen. This
group was compared with a cohort in the same unit 1 year after transitioning to a
6-4-0 fasting regimen. The latter includes no limitations on clear fluid intake until
the child is called to theater. A third cohort from a unit in which the 6-4-0 fasting
regimen has been implemented for over a decade was also studied for comparison.
Results: Patients fasting according to the 6-4-2 fasting regimen (n = 66) had a med-
ian fasting time for clear fluids of 4.0 h and a 33.3% incidence of fasting more than
6 h. After transitioning to the 6-4-0 fasting regimen (n = 64), median duration of
fasting for clear fluids decreased to 1.0 h, and the incidence of fasting more than
6 h decreased to 6.3%. In the second unit (n = 73), median fasting time was 2.2 h
and the proportion of patients fasting more than 6 h was 21.9%.
Conclusion: The introduction and implementation of the 6-4-0 fasting regimen
reduces median fluid fasting duration and the number of children subjected to
extended fasting.

KEYWORDS
anesthesia, children, fasting, fluids, preoperative

1 | INTRODUCTION At our center, we were troubled by the logistic problems of

In most countries, similar fasting guidelines are applied to chil-
1,2
dren and adults; 6 h for solids, and 2 h for clear fluids.
Despite clear recommendations of 2-h fasting for clear liquids,
children are still being subjected to unnecessarily long preopera-
3-5
tive starvation intervals in routine practice. The most common
reasons for prolonged fasting are incorrect preoperative instruc-
tions, changes in the surgical schedule and parents not following
instructions.4,5
ensuring reasonable fasting times while following the Scandina-
vian guidelines.6 We questioned the rationale for clear fluid fast-
ing and thus implemented a regimen in which the latter was
omitted from the year 2000 and onwards. When another unit in
our hospital planned to adopt the 6-4-0 regimen, we decided to
study the effects of the transition on actual fasting times. We
hypothesized that this more liberal regimen would be easier to
follow and hence would reduce the incidence of prolonged
fasting in daily clinical practice.

46 | © 2017 John Wiley & Sons Ltd wileyonlinelibrary.com/journal/pan Pediatric Anesthesia. 2018;28:46–52.
ANDERSSON ET AL.
The aim of the study was to compare the duration of fluid fast-
ing as well as the incidence of extended fasting in daily clinical prac-
tice, with the standard 6-4-2 regimen vs the 6-4-0 regimen in
children scheduled for elective surgery.
2 | MATERIALS AND METHODS
Following local ethics committee approval (Ethics Committee of
Uppsala, Sweden Dnr. 2014/487/1) children and parents received
information about the study at the preoperative assessment and oral
consent was obtained from all parents or legal guardians. The
requirement for written informed consent was waived by the ethics
committee. The study was not preregistered as a clinical trial as
there was no randomized intervention and it may thus be regarded
as an audit of a change in practice.
All patients under 17 years of age, scheduled for elective pro-
cedures, were asked to participate in the study. Emergency cases
and patients that were already intubated on arrival at the operation
theater were excluded. On arrival at the operation theater, the
accompanying nurse and parents were asked when the child last
had had anything to eat or drink and the reported respective times
were documented using a standardized case report form. A few
sips of water with the premedication did not count as if the
patient had had a drink. In total, 203 children were included in the
study.
Three different groups were analyzed. Group 1 consisted of chil-
dren undergoing surgery at the departments of ear-nose-throat
(ENT), oral surgery, or plastic surgery when applying the 6-4-2 fast-
ing regimen (ENT_2 h, n = 66). These parents were informed to fast
their child 6 h for solids, 4 h for breast milk and formula, and 2 h
for clear fluids. Group 2 consisted of children in that same depart-
ment, 1 year after introducing the 6-4-0 fasting regimen (ENT_0 h,
n = 64). The latter includes fasting for solids for 6 h, milk-containing
fluids for 4 h, but no definite limitation on clear fluid intake until the
child is called to theater (Table 1). Group 3 consisted of children in
the main pediatric operation unit where the 6-4-0 fasting regimen
has been implemented since the year 2000 (MP_0 h, n = 73). The
shift of fasting regimen at the ENT unit was made during the sum-
mer season and registration was paused during the first year after
the shift. Before changing fasting regimen, ward nurses received oral
information and local standard preoperative procedures were chan-
ged. No changes were made in how information was given to
patients and caregivers. The 6-4-0 fasting regimen allows almost all
elective pediatric patients to drink up until called to theater. How-
ever, individual assessments are made for each patient and proce-
dure by both anesthetist and surgeon. These individual assessments
were not registered in this study.
Measured outcomes were actual total fluid fasting times, ie, time
from last drink to induction. For post hoc analysis, cut-offs for pro-
longed fasting were set at 4, 6, and 12 hours. Children under
36 months of age were defined as toddlers and analyzed as a sub-
group. We also studied the difference between children scheduled
| 47
What is already known
• Children are fasted for longer than recommended by
international preoperative fasting guidelines.
What new information does this study add
• Removing the time limit for clear fluids reduces median
fasting times as well as the incidence of extended preop-
erative fasting.
T A B L E 1 The 6-4-0 fasting regimen
• For pediatric patients, 0- to 16-year old
• Allows for clear fluids up until the patient is called to surgery (rou-
tinely 30 min before induction)
• Clear fluids are defined as: water, fruit punch, fruit juice without
pulp, coffee or tea without milk, and ice lollies/popsicles. We do
not allow carbonated drinks, milk, or yoghurt
• Four-hour fasting for breast milk, infant formula, and milk-based
products like yoghurt. Parents are encouraged to wake up and feed
babies under 12 months at 4 AM if they are scheduled as first proce-
dure in the morning
• Patients instructed to fast for solids from midnight, but 6-h fasting
accepted when appropriate
• Most patients are individually assessed by a pediatric anesthetist
and the prescribed fasting interval may thus be customized if
increased risk of aspiration is suspected
as first case, in the morning and in the afternoon, and between inpa-
tients and ambulatory surgery patients.
2.1 | Anesthesia methods
Individual anesthesia methods were not registered in this study. In
the ENT department, the routine anesthesia induction in children is
intravenous with propofol or mask induction with sevoflurane.
Remifentanil is given to facilitate intubation without muscle relax-
ants. Sevoflurane is used for maintenance. In the pediatric unit, most
children receive a laryngeal mask airway after i.v. induction with
propofol, and continue with sevoflurane and spontaneous breathing.
For intubation, the routine i.v. induction is with thiopenthone, fen-
tanyl, and atracurium. Intubated children receive an oro-gastric tube,
but the stomach is not routinely suctioned in elective cases. Classic
deep extubation is not practiced, but LMAs (and occasionally ETTs,)
are often removed when the child is still asleep after a bolus of
propofol.
2.2 | Information about fasting times
Most children and caregivers are informed about fasting times by a
nurse at the preoperative assessment visit. Inpatients admitted for
elective surgery are usually seen by a pediatric anesthetist the day
48 | ANDERSSON ET AL.

before surgery. Some patients are only assessed through their medi- T A B L E 2 Patient characteristics
cal records. In those cases, outpatients receive a telephone call from ENT 6-4-2 ENT 6-4-0 MP 6-4-0
the outpatient nurse, in which information about fasting is included. (n = 66) (n = 64) (n = 73)
The final operation list is set in the afternoon the day before sur- Age (mean, 5 (0-15) 6 (0-15) 6 (0-15)
gery, after which ward and outpatient nurses give the final informa- range)
tion about when to stop (or not to stop) eating and drinking, <3 years, n (p) 18 (27.3%) 16 (25.0%) 26 (35.6%)
respectively. Some of the children included in this study may have 3-5 years, n (p) 22 (33.3%) 17 (26.6%) 14 (19.2%)
been recommended longer fasting intervals than 0 or 2 h due to an >6 years, n (p) 26 (39.4%) 31 (48.4%) 33 (45.2%)
increased assessed risk for aspiration at the preoperative assessment ASA
or by the surgeon due to the planned procedure. However, we did 1, n (p) 41 (62.1%) 43 (67.2%) 32 (43.8%)
not register what information the patients and caregivers were given
2, n (p) 23 (34.8%) 20 (31.3%) 34 (46.6%)
about fasting times, and hence these children will also have been
3, n (p) 2 (3%) 1 (1.6%) 7 (9.6%)
included in this study.
Time of surgery
First case, n 24 (36.4%) 16 (25.0%) 32 (43.8%)
2.2.1 | Statistics and sample size calculation (p)
Morning, n 28 (42.4%) 33 (51.6%) 25 (34.2%)
Power analysis concluded that 36 patients per group were needed to (p)
detect a difference in mean fasting time of 4.5 h, with a significance Afternoon, n 14 (21.2%) 15 (23.4%) 16 (21.9%)
level of 0.05 and a power of 80%. To ensure sufficient size for the sub- (p)
group analysis, recruitment of at least 60 patients was planned for each In/outpatient status
study group. All reported data were analyzed using Microsoft Excel Inpatients, n 24 (36.4%) 13 (20.3%) 38 (52.1%)
2016MSO (Redmond, WA, USA), Statistica Statistical Software (Tulsa, (p)
OK, USA) and the R package “rcmdr” (Rcmdr: R Commander. R package Outpatients, 42 (63.6%) 51 (79.7%) 35 (47.9%)
version 2.3-2.). Total fasting times were not normally distributed and n (p)
hence presented as median values with 95% confidence intervals. The
95% confidence interval for medians was calculated using boot-strap-
ping. Due to unequal variance, comparison of total fasting times 34.8% to 6.2% (OR = 0.13, 95% CI: 0.03-0.35, P < .001), and
between groups was performed using Kruskal-Wallis ANOVA. Fre- patients fasting 12 h or more decreased from 15.2% to 3.1%
quencies of patients fasting for extended times were reported as per- (OR = 0.18, 95% CI: 0.03-0.72, P = .032).
centages. The effect of the predictors “group”, “age”, “time of day for
surgery”, and “in/outpatient status” on the outcome “fasting 6 hours or
3.2 | Duration of fasting in the main pediatric
more” were quantified by binary logistic regression analyses. In crude
anesthesia unit
analyses, the effect of each predictor was separately evaluated against
the outcome. Adjusted analyses were not performed, due to the small Median fasting duration for clear fluids in the main pediatric anes-
sample size. Odd ratios (OR) and their 95% confidence intervals (CI) are thesia unit (n = 73) was 2.3 h (95% CI 1.7-3.0 h). This was signifi-
presented. The level of significance was set to a = 0.05. cantly shorter than group 1 (P < .001), and also significantly longer
than group 2 (P < .01). The distribution of fluid fasting duration at
the main pediatric anesthesia unit is shown in Figure 1.
3 | RESULTS The incidence of prolonged fasting was lower in the main pedi-
atric anesthesia unit, compared to the ENT unit before the transition,
Patients characteristics are shown in Table 2. Fasting times for solids with 34.2% of children fasting 4 h or more (OR = 0.41, 95% CI:
did not differ between the groups. The results presented below only 0.20-0.80, P = .01), 23.3% fasting 6 h or more (OR = 0.57, 95% CI:
describe the differences in clear fluid fasting. 0.27-1.19, P = .135), and 8.2% of children fasting 12 h or more
(OR = 0.5, 95% CI: 0.16-1.44, P = .207).

3.1 | Fasting duration decreased when shifting

fasting regimen in the ENT unit
In group 1 (n = 66), the median fasting time for clear fluids of 4.0 h
(95% CI 3.1-4.5 h) was higher than median fasting time in group 2
(n = 64) of 1.0 h (95% CI 0.9-1.5 h) (P < .0001), see Figure 1.
After shifting fasting regimen in the ENT unit, patients fasting
4 h or more decreased from 56.1% to 18.8% (OR=0.18, 95% CI:
0.08-0.39, P < .001), patients fasting 6 h or more decreased from
3.3 | Other variables affecting the outcome of
fasting 6 h or more
Older children had lower odds of fasting 6 h or more, compared to
children under 3 years of age (children aged 3-5 years: OR = 0.52,
95% CI: 0.23-1.15, P = .135; children over 6 years: OR = 0.39, 95%
CI 0.17-0.91, P = .031). The proportions of children fasting for more
than 6 h stratified by age and group are displayed in Figure 2.
ANDERSSON ET AL.
F I G U R E 1 Distribution of fasting duration before and after the
shift to 0-h fasting for clear liquids in the ENT unit, and in the main
pediatric anesthesia unit
Children scheduled in the morning or afternoon had lower odds
of fasting 6 h or more, compared to children scheduled as first case
(morning patients OR = 0.50, 95% CI 0.30-0.81, P = .014; afternoon
patients OR = 0.31, 95% CI 0.11-0.79, P = .020). The proportions of
children fasting for more than 6 h stratified by the time of day for
surgery and group are displayed in Figure 3.
| 49
4 | DISCUSSION
After shifting from 2- to 0-hour fasting for clear fluids, the median fast-
ing duration was reduced from 4 to 1 hour and the proportion of
patients fasting for more than 6 h was reduced from 33.3% to 6.3%.
The main benefit of the 6-4-0 fasting regimen is that it simplifies the
logistics of planning for minimized preoperative fasting. Fasting times
in the main pediatric unit was longer than in the ENT unit when apply-
ing the same fasting regimen. This may in part be described by the
slightly different clientele. The proportion of outpatients in the ENT
and the main pediatric unit was 80% and 50%, respectively. We have
seen in earlier pilot studies that our outpatients have a better compli-
ance to the fasting regimen and that inpatients are more frequently
recommended longer fasting intervals, due to co-morbidity and perhaps
more complex surgery. Furthermore, compliance to the fasting regimen
by medical personnel could be higher 1 year after a big transition.
Regardless of fasting regimen, there is a need for continuing education
of medical personnel on current fasting routines and for clarifying infor-
mation to patients and parents, to avoid prolonged fasting.
Although increasingly liberal guidelines have been published over
the last 2 decades, old routines and habits are deeply set. Previous
studies report mean fluid fasting duration to be 6-9 hour when
applying a 6-4-2 fasting regimen, even with an actively managed
list.3,4,7 In clinical practice, guidelines cannot be expected to be fol-
lowed to the letter. Rearrangements of the surgery schedule often
occur due to emergency cases or other unforeseen events. It is
nearly impossible to set an exact time for induction in children not
scheduled as first case in the morning. The recently published study
by Newton et al showed that an ambitious quality improvement pro-
ject with education of staff, more frequent communication by both
anesthetists and nurses and updated documents could reduce the
fasting time in pediatric outpatients. The single biggest improvement
came from implementation of 1-hour fasting for clear fluids.7
The 6-4-0 regimen allows for water, fruit punch, or ice lollies up
until the child is called to the operation theater, which makes life easier
for both parents and the anesthesiologist running the operating room
schedule. In the present study, shifting from 2- to 0-hour fasting for
clear liquids reduced fasting time in all patient categories, but had the
greatest effect among afternoon patients in whom the proportion of
children fasting more than 6 hour decreased from 36% to 0%.
In our institution, all infants and toddlers that breastfeed or drink
infant formula from the bottle are actively encouraged to feed at
4 hour before their planned procedure, to avoid prolonged fasting in
our youngest patients. Older children often sleep through the night,
sometimes resulting in extended fasting times. Allowing a light
breakfast for children scheduled later in the day might be safe, but
further research on this matter is necessary.
Young age seemed to entail longer mean duration of fasting. The
duration of fasting was reduced with the shift of fasting regimen,
but we could still observe a trend for toddlers and infants to be
fasted for longer intervals than older children. Small children under
1 year of age sometimes only drink breast milk or formula and hence
are fasted for 4 hour. This could perhaps explain the longer mean
50 | ANDERSSON ET AL.

FIGURE 2 Proportion of patients fasting more than 6 h in different age groups

FIGURE 3 Proportion of patients fasting more than 6 h dependent on time of day for procedure

fasting duration in this subgroup. Introducing the 6-4-0 fasting regi- T A B L E 3 Group, age, time of surgery, and in/outpatient status in
men reduced the incidence of prolonged fasting for the youngest relation to the outcome fasting 6 h or more. Results from crude
children under 36 months of age. Reducing preoperative starvation regression analysisa

has greatest significance in these youngest children, as initially sug- ORb 95% CIc P
8
gested by the seminal study of Thomas. Group
Pediatric patients are more sensitive to fasting than adults due to ENT_2h (1) Reference
their significantly smaller glycogen stores in liver and skeletal muscles, ENT_0h (2) 0.13 0.03-0.35 <.001
and the younger the child, the faster they will develop hypoglycemia MP_0h (3) 0.57 0.27-1.19 .135
and ketogenesis.9 Shortened preoperative fasting times reduce the
Age
concentration of ketone bodies, osmolality, and anion gap, diminish
<3 y Reference
postoperative insulin resistance, and improve hemodynamic condi-
3-6 y 0.52 0.23-1.15 .109
tions.10-12 Another potential problem with fasting among pediatric
>6 y 0.39 0.17-0.91 .031
patients is preoperative discomfort. Children allowed to drink close to
Time of surgery
surgery experience less thirst, hunger, and anxiety, show better behav-
3,13,14 First case Reference
ior, and are more comfortable. Some children may fast for many
hours without experiencing symptoms of hypoglycemia, while others Morning 0.50 0.30-0.81 .014

are more vulnerable. Moreover, 0-hour fasting for clear liquids is no Afternoon 0.31 0.11-0.79 .020

guarantee against hypoglycemia or dehydration in every patient, but it In/outpatient status

provides the opportunity for parents to intervene and ameliorate symp- Inpatients Reference
toms when their children are thirsty or grumpy, possibly because of Outpatients 0.79 0.40-1.57 .488
developing hypoglycemia (Table 3). a
Logistic regression analyses with each predictor at a time against the
outcome.
b
Odds ratio.
4.1 | Is this really safe? c
95% confidence interval for odds ratio.

The goal of preoperative fasting is to reduce the risk of perioperative

pulmonary acid aspiration. The fear of perioperative pulmonary aspi- emptying of clear fluids follows an exponential curve with a half-
ration is the biggest holdback for the implementation of more liberal time of 10-27 min.6,17,18 An empty stomach can be expected, but
fasting regimens. However, clear fluids ingested 1 or 2 h prior to not guaranteed, regardless of fasting regimen. The incidence of peri-
anesthesia do not seem to affect gastric volume or pH.13-16 Gastric operative pulmonary aspiration in children ranges from 1 to 10 in
ANDERSSON ET AL.
10 000,19-25 and was not increased when applying 0-h fasting for
clear liquids.25 In the current study, there was no case of pulmonary
aspiration in any of the groups, but the study was not powered to
detect a difference in pulmonary aspiration.
Several conditions are associated with a higher risk of pulmonary
aspiration, the majority due to delayed gastric emptying.20,21,23,24 Safe
anesthesia technique is the most important factor for minimizing the
risk of pulmonary aspiration. At our center, children with American
Society of Anesthesiologists (ASA) physical classification class III or IV,
and those with anatomical deviations or disorders leading to increased
risk for regurgitation and/or gastric motility disorders, as well as chil-
dren reporting problems with regurgitation, may sometimes be pre-
scribed longer fasting intervals. We emphasize that it is always up to
the attending anesthetist to judge if there is an increased risk of
regurgitation and thence adapt the prescribed preoperative fasting.
4.2 | Limitations
As the 6-4-0 regimen had only been implemented in the ENT unit
for a year, we could expect high compliance to the regimen by ward
nurses. If our follow-up survey had been conducted after more than
1 year, it is possible that the effect would have been less obvious,
as suggested by the longer median fasting duration in the patients
anesthetized in the main pediatric unit, where the 6-4-0 fasting regi-
men has been implemented for much longer. Furthermore, this study
was not powered for analysis of confounding factors such as age,
out/inpatient status, and type of surgery, even though these factors
affect fasting intervals.
The information about the study at the preoperative assessment
might also have influenced how the parents and patients complied
with the fasting regimen. In addition, we cannot assume that all par-
ents reported fasting times correctly. Children may eat or drink with-
out parents reporting it, or even knowing about it. However, this
effect should have been similar for all groups.
Finally, the study was neither randomized nor blinded, thus
observer bias was possible.
ACKNOWLEDGMENTS
The authors thank Albin Wiklund for his help with patient recruit-
ment and data collection and statistician Katarina Selling for assis-
€ 14. Brady M, Kinn S, Ness V, et al. Preoperative fasting for preventing
tance with statistical analysis. All medical personnel at the OPO
anesthesia unit and main pediatric anesthesia unit are acknowledged
for their assistance with data collection.
ETHICAL APPROVAL
This study was approved by the Ethics Committee of Uppsala, Swe-
den, Dnr. 2014/487/1.
CONFLICT OF INTEREST
The authors have no conflicts of interest.
| 51
ORCID
Hanna Andersson http://orcid.org/0000-0002-1462-0513
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11. Dennhardt N, Beck C, Huber D, et al. Optimized preoperative fast-
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15. Splinter WM, Schaefer JD. Unlimited clear fluid ingestion two hours
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16. Schmidt AR, Buehler P, Seglias L, et al. Gastric pH and residual vol-
ume after 1 and 2 h fasting time for clear fluids in children†. Br J
Anaesth. 2015;114:477-482.
17. Schmitz A, Kellenberger CJ, Liamlahi R, et al. Gastric emptying after
overnight fasting and clear fluid intake: a prospective investigation
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Anaesth. 2011;107:425-429.
18. Schmitz A, Kellenberger CJ, Lochbuehler N, et al. Effect of different
quantities of a sugared clear fluid on gastric emptying and residual
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imaging. Br J Anaesth. 2012;108:644-647.
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How to cite this article: Andersson H, Hellstrӧm PM,
Frykholm P. Introducing the 6-4-0 fasting regimen
and the incidence of prolonged preoperative
fasting in children. Pediatr Anesth. 2018;28:46-52.
https://doi.org/10.1111/pan.13282
Accepted: 17 October 2017
DOI: 10.1111/pan.13286
RESEARCH REPORT
Ultrasound-guided pudendal nerve block in children: A new
technique of ultrasound-guided transperineal approach
Isabelle Gaudet-Ferrand1
Laurent Hertz1 | Nicolas Kalfa3 | Chrystelle Sola1
1
Department of Pediatric Anesthesia,
Lapeyronie University Hospital, Montpellier
University, Montpellier, France
2
Department of Anesthesiology and Critical
Care Medicine, Lapeyronie University
Hospital, Montpellier, France
3
Department of Pediatric Surgery,
Lapeyronie University Hospital, Montpellier,
France
4
Department of Pediatric Anesthesia,
Lapeyronie University Hospital, Montpellier,
France
5
Inserm Unit 1051 INM, Montpellier,
France
Correspondence
Isabelle Gaudet-Ferrand, Department of
Pediatric Anesthesia, Lapeyronie University
Hospital, Montpellier, France.
Email: i-gaudetferrand@chu-montpellier.fr
Funding information
Fundings were obtained from Montpellier
University Hospital.
Section Editor: Adrian Bosenberg
Pediatric Anesthesia. 2018;28:53–58.
| Pablo De La Arena1 | Sophie Bringuier2 | Olivier Raux1 |
| Christophe Dadure4,5
Summary
Background: Transperineal pudendal nerve block guided by nerve stimulator is used
in pediatric anesthesia as an alternative to caudal analgesia in perineal surgery. The
risk of rectal puncture or intravascular injection is inherent to this blinded technique.
We described a new technique of transperineal pudendal nerve block, with ultra-
sound guidance, to improve safety of the technique.
Aims: The first goal of this study was to describe this new technique and to test its
feasibility. The second objective was to evaluate intra operative effectiveness and
postoperative pain control.
Methods: After parental and children consent, this prospective descriptive study
included children aged 1-15 years, ASA status I-III, scheduled for general anesthesia
associated with bilateral pudendal nerve block for an elective perineal surgery. After
standardized general anesthesia, the anesthesiologist performed pudendal nerve
block under ultrasound guidance with “out of plane” approach and evaluated the
visualization of anatomical structures (ischial tuberosity, rectum, and pudendal
artery), of the needle and of the local anesthetic spread. Pudendal nerve block
failure was defined as an increase in mean arterial blood pressure or heart rate more
than 20% compared to baseline values after surgical incision. In the postoperative
period, the need for rescue analgesia was noted.
Results: During the study period, 120 blocks were performed in 60 patients, includ-
ing 59 boys. Quality of the ultrasonographic image was good in 81% of blocks, with
easy visualization of ischium and rectum in more than 95% of cases. Localization of
the tip of the needle was possible for all pudendal nerve blocks, directly or indi-
rectly. The spread of local anesthetic was seen in 79% of cases. The block was
effective in 88% of cases.
Conclusion: The new technique of ultrasound-guided pudendal nerve block, described
in this study, seems to be easy to perform with a good success rate, and probably
improves safety of the puncture and of the injection by real-time visualization of
anatomical structures and local anesthetic spread.
KEYWORDS
anesthesia, child, pain, pudendal nerve, regional, ultrasound
wileyonlinelibrary.com/journal/pan © 2017 John Wiley & Sons Ltd | 53
54 | GAUDET-FERRAND
1 | INTRODUCTION
The pudendal nerve is a mixed nerve, formed from the anterior rami
of the second, third, and fourth nerves of the sacral plexus (S2-S4).
Its terminal branches, that leave the Alcock’s canal and travel
through the ischiorectal fossa, ensure the innervation of a big part
of the perineum (forming a triangle with base located behind the
anus and tip in front of the penis or clitoris). The efficacy of puden-
dal nerve block is well known in clinical practice. In adults, this tech-
nique is widely used, but only few studies are referenced in pediatric
anesthesia. In children, it is considered as an efficient alternative of
caudal analgesia in hypospadias surgery with better postoperative
pain management.1,2 The transperineal approach guided by nerve
stimulator is considered as the reference in efficacy studies despite
lack of data comparing the technique with or without use of nerve
1-6
stimulator. Different types of motor responses are possible with
nerve stimulation: rectal (anal sphincter contraction) or perineal (con-
traction of the transversalis perineum superficial muscle and move-
ment of the penis/clitoris). Usually, the local anesthetic is injected
when at least one of these responses is present.3 A variant of this
technique requires 2 injection points (anterior and posterior).4-6 Even
if no complication related to these transperineal “blinded” approach
was described in the literature, the risk of rectal or vascular puncture
is inherent to the technique. In children, ultrasound (US) guidance
has revolutionized the practice of regional anesthesia, with increas-
ing use regularly this last decade.7 Advantages of US guidance in
pediatric regional anesthesia are the real-time visualization of
patient’s anatomy, the precise positioning of the needle, and the
direct visualization of local anesthetic spread. New techniques based
on US guidance have also appeared. The aim of this study was to
evaluate the feasibility and efficacy of a new transperineal technique
of US-guided pudendal nerve block in children, in order to improve
safety of the puncture by visualizing ischiorectal fossa and the adja-
cent anatomical structures.
2 | MATERIALS AND METHODS
2.1 | Study design and participants
This prospective descriptive study was conducted in the Pediatric
Anaesthesia Unit in Lapeyronie University hospital (Montpellier,
France). Institutional Review Board approval was received from the
South Mediterranean IV Ethical Board. Written informed parental
consent was obtained from all participants and assent of children
was checked after explanations appropriate to their age. All chil-
dren aged 1-15 years, ASA status class I-III, scheduled for general
anesthesia associated with bilateral pudendal nerve block for an
elective perineal surgery, were candidate to participate. Exclusion
criteria were any contraindication to regional anesthesia, ASA
physical status IV-V, and refusal by the parents or the child. Data
were collected from induction of anesthesia to H24 postopera-
tively after admission in recovery room. The primary objective of
this descriptive study was to evaluate the feasibility and ease of
ET AL.
What is already known
• Transperineal pudendal nerve block guided by nerve
stimulator is an efficient analgesia technique for perineal
surgery in children.
What new information this study adds
• Using a similar transperineal approach, the pudendal
nerve block can be easily performed under real-time
ultrasound guidance, avoiding occult rectal puncture and
intravascular injection.
this new technique, and the occurrence of complication during
its performance. Evaluation of efficiency on pain relief (morphi-
nomimetic consumption in the intraoperative period, and rescue
analgesia requirement in the postoperative period) was the second
objective.
2.2 | Study protocol
Perioperative anesthetic management was standardized. Propofol
and/or sevoflurane were used for induction, in association with a
continuous infusion of remifentanil at 1 lg/kg/min for 2 minutes.
Airway control was assured through insertion of a tracheal tube or a
laryngeal mask. The maintenance of anesthesia was provided by
sevoflurane (1.2 MAC) in a equal mix of oxygen and nitrous oxide,
and remifentanil 0.05 lg/kg/min. Mechanical ventilation was
adapted to obtain a normal range of EtCO2 (30-40 mm Hg). Then,
US-guided PNB was performed bilaterally in standard aseptic condi-
tion following local protocol, by a senior anesthesiologist or a resi-
dent trained in the technique. If an inguinal incision was required for
surgery, an US-guided ilio-inguinal or transversus abdominis plane
block was added to pudendal nerve block. Baseline values of blood
pressure and heart rate were defined under general anesthesia with-
out nociceptive stimulation and after regional anesthesia procedure.
In all patients, perineal skin incision was allowed at least 15 minutes
after performing the PNB. The return to baseline infusion rate of
remifentanil (0.05 lg/kg/min) was required before perineal incision.
An increase in mean arterial blood pressure or heart rate more than
20% compared to baseline values was considered as an unsuccessful
PNB. In case of block failure, incremental remifentanil titration was
started. Fifteen minutes before the end of surgery, all patients
received systemic analgesia, using paracetamol (Perfalganâ; Bristol-
Myers Squibb, Rueil-Malmaison, France) 15 mg/kg and ketoprofen
(Profenidâ; Sanofi-Aventis, Paris, France) 1 mg/kg if there was no
contraindication. Remifentanil was stopped after closure of the skin.
Rescue analgesia by IV nalbuphine (Nubainâ; Dupont Pharma, Paris,
France) 0.2 mg/kg was administered in the postanesthetics care unit
(PACU) if necessary. Postoperative analgesia was also standardized
such as systematic oral paracetamol (15 mg/kg) every 6 hours asso-
ciated with oral ibuprofen (10 mg/kg) every 8 hours. Oral tramadol
(1 mg/kg) was prescribed as rescue analgesia.
GAUDET-FERRAND ET AL.
2.3 | Ultrasound-guided pudendal nerve block
procedure
After general anesthesia induction and airway control, children were
positioned supine, hips in abduction, flexed legs, and soles of the
feet joined (“Frog position”). Ultrasound images were obtained using
a portable US unit (LOGIQe ; GE Healthcare, Wauwatosa, WI, USA)
and an 8-13 MHz linear array probe. The long axis of the US probe
was positioned on a horizontal line connecting the ischial tuberosity,
previously palpated, to the anus (Figure 1). Ischial tuberosity is read-
ily identified such as a hypoechoic area, bounded superiorly by a
hyperechoic line. The probe was then moved medially on the same
axis, until the rectum appeared as another hypoechoic area. The
ischiorectal fossa is located between the ischium, laterally and the
rectum, medially. Pudendal artery can be searched using color Dop-
pler (Figure 2). After careful skin preparation with alcohol povidone-
iodine according to our local hygiene protocol, a 22 Gauge 50 mm
insulated needle (Sonoplex stimâ, Pajunk, Geisingen, Germany) was
then introduced at the middle of the superior edge of the probe, in
an out-of-plane approach, with an inclination of 15° in the sagittal
plane, in an anterior-posterior direction (Figure 3). Position of the tip
of the needle was identified by direct vision, through movement of
adjacent anatomical structures or with saline injection. Nerve stimu-
lation (0.5-1 mA) was started only after the operator considered the
tip of needle in correct placement in the ischiorectal fossa, and the
potential motor response was noted. After a negative aspiration test,
0.2 mL/kg of a solution of 0.2% Ropivacaine (Naropeineâ, Astra
Zeneca, Rueil Malmaison, France) added to 1 lg/mL of clonidine
(Catapressanâ, Bohringer Ingelheim, Reims, France), was injected in
the ischiorectal fossa under real-time US scanning (Figure 4).
F I G U R E 1 Anatomical landmarks of ultrasound-guided pudendal
nerve block: the ischiorectal fossa
| 55
FIGURE 2 Pudendal artery with color Doppler, in the ischiorectal
fossa
2.4 | Measurement and data collected
For each block, feasibility and ease of technique were as assessed
by the following data: sonographic identification of anatomical
structures and visualization of needle and local anesthetic spread.
The sonographic identification of ischium and rectum was evaluated
as easy, hard, or impossible. Artery identification, with and without
Doppler, was noted. The occurrence of response to nerve stimula-
tion (2 Hz, 0.5-1 mA) and its specificity (rectal, perineal), puncture
complications, and duration of the procedure were also collected.
Intraoperative pain was assessed by hemodynamic parameters and
the maximum rate of remifentanil infusion required during surgery.
The efficacy of postoperative analgesia was assessed using a
FLACC scale8 in children up to 6 years, and VAS (visual analog
scale) in older children. This assessment was repeated every
15 minutes in the PACU and every 4 hours until discharge. If the
FLACC or VAS score was >3, the child received nalbuphine in
PACU or tramadol in hospitalization unit as rescue analgesia. Post-
operative analgesia was evaluated during 24 hours through the
need of rescue analgesia.
2.5 | Statistical analysis
Patients’ characteristics were presented using mean and SD for con-
tinuous variables and frequencies and proportions for categorical
variables. Comparisons between successful and unsuccessful puden-
dal nerve block were done using Student or Wilcoxon rank test for
continuous variables and chi-square or Fisher test for categorical
ones. Correlations between continuous variables were performed
using Pearson correlation coefficient. Statistical bilateral significance
threshold was set at 5%. Statistical analyses were performed using
SAS version 9.1 (SAS Institute, Cary, NC, USA).
56 | GAUDET-FERRAND
F I G U R E 3 Puncture of transperineal pudendal nerve block under
ultrasound guidance
F I G U R E 4 Ultrasound-guided pudendal nerve block: visualization
of local anesthetic spread in the ischiorectal fossa
3 | RESULTS
3.1 | Demographic data
During the study period, 120 US-guided pudendal nerve blocks were
performed on 60 patients (59 boys, 1 girl) consecutively included.
No refusal was registered. The mean weight was 20.8  12.4 kg.
Forty-eight (40%) children were younger than 3 years, 40 (33.3%)
were 3-6 years old and 32 (26.7%) were older than 6 years.
Surgical indications are detailed in Table 1. Most patients had
surgery for hypospadias (31.67%) or phimosis (33.33%). An additional
inguinal incision was indicated in 25% of children (Table 1).
Data on feasibility of the technique were extensively collected,
as well as data on intraoperative effectiveness. Day-case surgeries
were performed in 35 (58.3%) children. In these patients, 6 were lost
to the exit of the hospital: 4 families did not answer to the phone
ET AL.
T A B L E 1 Surgery indication and type of regional anesthesia
Surgery indication (regional anesthesia) n (%)
Perineal incision (PNB) 46 (76.67%)
Hypospadias 19 (31.67%)
Phimosis (posthectomy/circumcision) 20 (33.33%)
Other penis surgery 4 (6.66%)
Testicle surgery 2 (3.33%)
Hypertrophic minor labia 1 (1.66%)
Inguino-scrotal incision (PNB+TAPB or II/IHB) 14 (23.3%)
Orchidopexia 13 (21.66%)
Penis+testicle surgery 1 (1.66%)
Bold values indicate the sum of the perineal incision and the sum of the
ilioinguinal-scrotal incision. PNB, pudendal nerve block; TAPB, transver-
sus abdominis plane block; II/IHB, ilio-inguinal/ilio-hypogastric block.
call of the ambulatory department and 2 families were missed to call.
Data on postoperative pain control were lacking in these 6 patients.
3.2 | Feasibility of ultrasound-guided PNB
The US-guided blocks were performed by residents in 78.33% of case
and in 21.67% by senior practitioners. The quality of the picture was
judged “good” by the practitioner in 81.51% of cases, “intermediate” in
18.49%, and was never considered “bad”. The ischium and the rectum
were easily identified in more than 95% of cases (Table 2). Using Dop-
pler color, the pudendal artery identification was possible in 81.74% of
pictures. Localization of the tip of the needle was possible for all
blocks: directly in 17.8% of punctures or indirectly, by the movement
of adjacent anatomic structures, in 98.31% of cases. The mean depth
of injection was 20.3  9 mm, with no significant correlation to
patient’s weight (r = .3). The spread of local anesthetic was seen in
79.3% of cases. For 116 blocks (96.6%), a single puncture was neces-
sary. A second puncture was necessary in 4 cases. The first needle
placement was good in 68.7% of cases, whereas 1 reorientation
was noted in 24.35%, and more than 1 in 6.95% (maximum 3). The
mean duration of the technique from ultrasonographic identification
of anatomical structures to withdrawal of the needle was
139.6  78 seconds. Motor response was found in 23.7% of cases.
There was anal sphincter contraction (63% of cases), contraction of
the bulbospongious muscle (22%), and contraction of the deep
transverse perineal muscle (15%). Only one side effect was noted
(blood during aspiration test, despite visualization of pudendal artery
with Doppler), and no injection was performed. The needle was
relocated and injection of the local anesthetic was done without
complication.
3.3 | Efficacy of ultrasound-guided pudendal nerve
block
The surgical incision was performed an average of 39  21 minutes
after injection of the local anesthetic. The block was considered
effective in 88.33% of cases, with no increase in remifentanil
GAUDET-FERRAND ET AL.
T A B L E 2 Identification of anatomical landmarks on 120
ultrasound-guided pudendal nerve blocks
Visualization n (%)
Anatomical structures Easy Difficult Impossible
Ischium 116 (98.31%) 2 (1.69%) 0 (0%)
Rectum 114 (97.44%) 3 (2.56%) 0 (0%)
infusion rate during perineal incision. Mean maximum dose of
remifentanil was 0.06  0.03 lg/kg/min.
No relationship was found between successful pudendal nerve
block and visualization of anatomical structures, visualization of
spread of local anesthetic, or presence of a motor response to nerve
stimulation.
In the postoperative period, 60% of children received nalbuphine
in PACU. No rescue analgesia was required in 80% of hospitalized
children after PACU during the first 24 hours. In ambulatory patient,
acetaminophen and ketoprofen were sufficient in 76% of cases. No
relationship was found between successful PNB and need of rescue
analgesia in the postoperative period.
4 | DISCUSSION
The results of this prospective descriptive study show that the per-
formance of real-time US-guided transperineal approach of pudendal
nerve block is feasible and easy in children under general anesthesia.
This US-guided technique allows an efficient postoperative pain
management with low rate of patient requiring rescue analgesia
beyond the PACU.
As noted by our anesthesiologist team, the technique is easy to
learn because the puncture site using the US-guided approach was
sensibly unchanged in comparison with landmark technique.1-3 In
addition, the majority of blocks were performed by residents, under
the supervision of a senior anesthesiologist. The US visualization of
ischium and rectum was always possible. This is a crucial point in
improving safety. Also, the choice of puncture site and needle orien-
tation can be more suitable as to avoid a puncture of the rectum,
which is a septic risk situation.
This safety is enhanced by the visualization of the tip of the nee-
dle, which was indirect (movement of adjacent anatomic structures) in
a large part of blocks. The difficulties in the visualization of pudendal
artery are probably explained by its small diameter and sinuous path,
as described in anatomical studies. Even in case of artery visualization,
this sinuous path and the eventuality of multiple arteries in the
ischiorectal fossa,9 make its avoidance uncertain in this “out of plane”
approach. Aspiration test and visualization of the local anesthetic
spread are better ways to confirm lack of intravascular injection. This
spread has been seen in almost 80% of cases. The lack of spread visu-
alization can possibly be explained by the fat density that makes it
almost as anechoic as that of the local anesthetic, or by a too deep
injection. In our personal experience, direct visualization of the needle
and of local anesthetic spread seem to be improved with regular
| 57
practice of the technique, and better adaptation of needle inclination.
The aspiration test before local anesthetic injection remains essential
to avoid intravascular injection with real-time US. The use of
epinephrine is always contraindicated in pudendal nerve block due to
the risk of vasoconstriction on a terminal vascularization.
A surprising ascertainment in this study is the low rate of
responses to neurostimulation, possibly explained by the position of
the needle in the middle of the ischiorectal fossa, far from the emer-
gence of pudendal nerve from Alcock’s canal. The systematic motor
response was not mandatory for the injection of local anesthetic in
our study. Also, we noted that the lack of response was not corre-
lated with block failure. This can be explained because pudendal
nerve block is a spread block. Anatomical studies showed great vari-
ations of the pudendal nerve throughout its path, but the way of
terminal branches always goes through the ischiorectal fossa, which
is a fatty space allowing good diffusion of local anesthetic.10,11
Pudendal nerve and its branches in the ischiorectal fossa have a
small diameter.9 It is also difficult to identify them with US. Never-
theless, neurostimulation use in association with US guidance can be
safe to avoid direct nerve injury.
Alternative techniques are not desirable in children due to the
need for prone or lateral decubitus position. A transgluteal approach
for US-guided pudendal nerve block has been previously described
in adults.12-14 Tip of the needle was positioned in the interligamen-
tous plane between sacrospinous and sacrotuberous ligaments, medi-
ally to the pudendal internal artery, at the level of ischial spine. The
risk of associated blockade of sciatic nerve/sacral plexus is about
13%,14 which limits its use in ambulatory surgery. Another technique
is described with a pudendal nerve approach at the entrance of the
Alcock’s canal.15
The efficacy of US-guided PNB, as described in the present
study, is good in the perioperative period. Mean dose of remifentanil
was low.
Surprisingly, we found a discrepancy between the efficacy of the
nerve block intraoperatively and the use of nalbuphine in PACU. This
result could be partly explained by the high incidence of postopera-
tive delirium in children, which was not specifically distinguished
from pain. This discrepancy suggests inappropriate use of nalbuphine
for its sedative effects. Moreover, in 25% of children, an inguinal
incision was associated with the perineal incision, and evaluation of
the only perineal pain was not possible in PACU. At last, insufficient
analgesia can be underestimated under general anesthesia, due to
depression of the hemodynamic response to nociception.
Efficacy of pudendal nerve block in children was demonstrated
in hypospadias repair. In comparison with caudal analgesia, pudendal
nerve block provided more effective postoperative analgesia during
the first 24 hours, improving parent satisfaction.1,2 For pediatric cir-
cumcision, lower pain scores were noted with pudendal nerve block
compared to dorsal penile nerve block during the first 12 hours
postoperatively.6
There are a few limitations in this study, which examined the
feasibility of US-guided PNB in a transperineal approach. The spread
of local anesthetic in the ischiorectal fossa and its potential effect
58 | GAUDET-FERRAND
on success of pudendal nerve block were not evaluated, not allowing
to know if an injection too deep entailed a failure of the block. Our
results concerning postoperative pain should be the subject of fur-
ther investigations. Efficacy of the technique was not the primary
objective, and pain evaluation was based only on analgesic consump-
tion, and not on pain scores. The use of postemergence delirium
score would be necessary to better evaluate pain level in PACU. The
optimal volume of local anesthetic in the ischiorectal fossa remains
to be determined in children. Unfortunately, the study did not have
any control group, difficult to determine in view of the diversity of
surgical procedures. So, the efficacy, in each indication, of this new
US-guided technique has to be demonstrated in randomized studies.
5 | CONCLUSION
The aim of this study was to evaluate the feasibility of a new approach
of transperineal pudendal nerve block in children, under US guidance.
This technique is easy to learn and may improve safety of the puncture
by direct visualization of anatomical landmarks and of local anesthetic
spread, thus avoiding rectal puncture or intravascular injection. Bene-
fits of the technique about efficiency and safety, compared with
blinded techniques, must be further evaluated in randomized studies.
ETHICAL APPROVAL
Institutional Review Board approval was received from the South

diter-
Mediterranean IV Ethical Board on July 08, 2014 (CPP Sud Me
ranee IV, registration number: 2014-A00499-38).
DISCLOSURES
No authors have any conflicts of interest or disclosures with regard
to this study.
ORCID
Isabelle Gaudet-Ferrand http://orcid.org/0000-0002-3567-6460
Laurent Hertz http://orcid.org/0000-0001-9501-3434
Chrystelle Sola http://orcid.org/0000-0002-8375-9121
REFERENCES
1. Naja ZM, Ziade FM, Kamel R, El-Kayali S, Daoud N, El-Rajab MA. The
effectiveness of pudendal nerve block versus caudal block anesthesia
for hypospadias in children. Anesth Analg. 2013;117:1401-1407.
ET AL.
2. Kendigelen P, Tutuncu AC, Emre S, Altindas F, Kaya G. Pudendal
Versus Caudal Block in Children Undergoing Hypospadias Surgery: A
Randomized Controlled Trial. Reg Anesth Pain Med. 2016;41:610-
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3. Aissaoui Y, Bruye re R, Mustapha H, Bry D, Kamili ND, Miller C. A
randomized controlled trial of pudendal nerve block for pain relief
after episiotomy. Anesth Analg. 2008;107:625-629.
4. Naja Z, El-Rajab M, Al-Tannir M, et al. Nerve stimulator guided
pudendal nerve block versus general anesthesia for hemorrhoidec-
tomy. Can J Anaesth. 2006;53:579-585.
5. Naja Z, Ziade MF, Lo € nnqvist PA. Nerve stimulator guided pudendal
nerve block decreases posthemorrhoidectomy pain. Can J Anaesth.
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6. Naja Z, Al-Tannir MA, Faysal W, Daoud N, Ziade F, El-Rajab M. A
comparison of pudendal block vs dorsal penile nerve block for cir-
cumcision in children: a randomised controlled trial. Anaesthesia.
2011;66:802-807.
7. Polaner DM, Taenzer AH, Walker BJ, et al. Pediatric Regional Anes-
thesia Network (PRAN): a multi-institutional study of the use and
incidence of complications of pediatric regional anesthesia. Anesth
Analg. 2012;115:1353-1364.
8. Merkel SI, Voepel-Lewis T, Shayevitz JR, Malviya S. The FLACC: a
behavioral scale for scoring postoperative pain in young children.
Pediatr Nurs. 1997;23:293-297.
9. Fronho€ fer G, Niernberger T, Anderhuber F. Variations in the branch-
ing of the internal pudendal artery in the ischioanal fossa. Ann Anat.
1996;178:133-135.
10. Mahakkanukrauh P, Surin P, Vaidhayakarn P. Anatomical study of
the pudendal nerve adjacent to the sacrospinous ligament. Clin Anat.
2005;18:200-205.
11. Schraffordt SE, Tjandra JJ, Eizenberg N, Dwyer PL. Anatomy of the
pudendal nerve and its terminal branches: a cadaver study. ANZ J
Surg. 2004;74:23-26.
12. Kovacs P, Gruber H, Piegger J, Bodner G. New, simple, ultrasound-
guided infiltration of the pudendal nerve: ultrasonographic tech-
nique. Dis Colon Rectum. 2001;44:1381-1385.
13. Rofaeel A, Peng P, Louis I, Chan V. Feasibility of real-time ultrasound
for pudendal nerve block in patients with chronic perineal pain. Reg
Anesth Pain Med. 2008;33:139-145.
14. Bellingham GA, Bhatia A, Chan CW, Peng PW. Randomized con-
trolled trial comparing pudendal nerve block under ultrasound and
fluoroscopic guidance. Reg Anesth Pain Med. 2012;37:262-266.
15. Bendtsen TF, Parras T, Moriggl B, et al. Ultrasound-Guided Pudendal
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How to cite this article: Gaudet-Ferrand I, De La Arena P,
Bringuier S, et al. Ultrasound-guided pudendal nerve block in
children: A new technique of ultrasound-guided transperineal
approach. Pediatr Anesth. 2018;28:53-58. https://doi.org/
10.1111/pan.13286
Accepted: 13 October 2017

DOI: 10.1111/pan.13283

RESEARCH REPORT

Clinical implications of de Barsy syndrome

Lindsay L. Warner | David A. Olsen | Hugh M. Smith

Department of Anesthesiology, Mayo Clinic,

Rochester, MN, USA Summary
Background: De Barsy syndrome is a rare, autosomal recessive syndrome character-
Correspondence
Hugh M. Smith, Department of ized by cutis laxa, progeroid appearance, ophthalmic opacification, skeletal malfor-
Anesthesiology, Mayo Clinic, Rochester, MN, mations, growth delays, and intellectual disability.
USA.
Email: smith.hugh2@mayo.edu Aims: The aim of this case series is to identify the anesthetic considerations in the
clinical management of patients with de Barsy syndrome.
Funding information
The study was funded by departmental Methods: A retrospective case review from 1968 to 2016 was performed at a
resources. single tertiary medical center to identify patients with de Barsy syndrome who
Section Editor: Dr Francis Veyckemans underwent anesthesia for diagnostic and surgical procedures. We collected and
analyzed the perioperative records and following data: age, sex, American Society
of Anesthesiologists physical status, relevant comorbidities, surgical procedures,
anesthesia management, and observed complications.
Results: Three patients underwent 64 unique anesthetics for a diverse collection
of diagnostic and surgical procedures. An array of anesthetics and techniques
were successfully used. Observations of the perioperative period found 7 epi-
sodes of intraoperative hyperthermia (>38.3°), a single difficult airway requiring
fiberoptic bronchoscopic-guided intubation, and repeatedly difficult intravenous
access.
Conclusion: This expanded case series suggests that providers caring for patients
with de Barsy syndrome should be aware of potential challenges with airway man-
agement, vascular access, and temperature monitoring.

KEYWORDS
cutis laxa, fever, genetic diseases, rare diseases, syndrome

1 | INTRODUCTION The constellation of clinical manifestations of de Barsy syndrome

De Barsy syndrome is a rare genetic syndrome characterized by cutis
laxa III (ARCL3 OMIM# 219150, 614438), progeroid appearance,
ophthalmic opacification, skeletal malformations, growth delays, and
1-7
intellectual disability. Given the diverse array of ophthalmic and
skeletal malformations, de Barsy patients require frequent surgical
interventions.8 First described by de Barsy in 1967,1 only 100 cases
of the syndrome have been documented in the medical literature.
Several cases of de Barsy syndrome have been linked to mutations
of the PYCR1 or ALDH18A1 genes.9 The syndrome is inherited in
an autosomal recessive pattern.
include intrauterine growth retardation, postnatal growth delay,
motor delay, cognitive impairment, hypotonia, athetoid movements,
microcephaly, wormian bones, large fontanelles, facial dysmor-
phism, cataracts, corneal clouding, thin/wrinkled skin, easy bruis-
ing, sparse hair, joint laxity, osteopenia, and inguinal hernias.1-14 A
number of de Barsy syndrome manifestations are directly relevant
to perioperative patient management.3 Craniofacial abnormalities,
cognitive delays, and skin fragility (ie, “paper thin”) are all issues
requiring specific perioperative patient care consideration.
A single investigation relating to anesthetic management of de
Barsy syndrome patients was published in 2010 by authors of the

Pediatric Anesthesia. 2018;28:59–62. wileyonlinelibrary.com/journal/pan © 2017 John Wiley & Sons Ltd | 59
60 | WARNER
present study.3 This article reported on 2 patients and 35 anesthet-
ics associated with surgical and diagnostic procedures between 1968
and 2007. The present study identifies another patient with de
Barsy syndrome and 29 additional anesthetics performed between
2007 and 2016. Given the rarity of this condition, and limited pub-
lished data, this case series provides important information to provi-
ders encountering de Barsy syndrome patients for the first time or
during emergent situations.
2 | MATERIALS AND METHODS
After receiving Institutional Review Board (Rochester, MN, USA)
study approval, medical records prior to September 2016 were
searched to identify patients with de Barsy syndrome. As no single
longitudinal comprehensive medical index at our institution spans
this time frame, several medical databases were queried including
the Berkson Medical and Surgical Indexing Systema [1968-1975], the
Mayo Clinic Life Science System database [1996-2007] and the
Mayo Clinic Medical Index [1995-2016]. No exclusionary criteria
were applied. All available anesthetic and surgical records of de
Barsy syndrome patients were analyzed. Data collected included age,
gender, ASA physical status, relevant comorbid conditions, surgical
procedure, airway management, vascular access, monitoring, anes-
thetic induction and maintenance, intravenous and oral analgesics,
muscle relaxants, antibiotics, and blood product transfusions, PACU
information, and postoperative complications. Clinical observations
made by anesthesia providers were also recorded.
3 | RESULTS
In 3 different pediatric patients with genetically confirmed de Barsy
syndrome, a total of 64 anesthetics were reviewed. One female and 2
male patients had each undergone 14, 11, and 39 anesthetics, respec-
tively. With respect to airway management, 7 oral/nasal airways, 6
laryngeal mask airways, and 48 endotracheal tubes were placed. Of the
latter, 23 were placed by direct laryngoscopy, 24 by videolaryngoscopy,
and 1 by fiberoptic intubation for unanticipated difficult airway. In this
patient, although providers had been able to secure his airway easily by
direct laryngoscopy prior to 2012, subsequent airway management
required videolaryngoscopy with a maximum of 2 attempts for success-
ful intubation. This same patient, by the age of 15, also began requiring
2-handed mask ventilation. In the other 2 patients, no difficulties were
reported with mask ventilation or endotracheal intubation. A single inci-
dent of vomiting during preoxygenation was documented which
required rapid sequence intubation. The remaining airways were man-
aged with a mask or spontaneous breathing.
A wide range of inhalational agents and intravenous medication
were used throughout the 64 anesthetics. For induction, inhalational
a
An early epidemiologic database established by Dr. Joseph Berkson in 1935. Searchable
years: 1968-1975.
ET AL.
What is known
• In a previously published article on anesthetic manage-
ment of patients with de Barsy syndrome, no major peri-
operative adverse events were found in 35 separate
anesthetic cases.
What this article adds
• This article expands upon the previous series with 29
additional anesthetic cases, and offers management con-
siderations with respect to airway management, vascular
access, temperature monitoring and other issues unique
to de Barsy syndrome.
agents, propofol, or a combined technique were used in 54%, 39%,
and 8%, respectively. For analgesia, 2 caudal blocks and 1 peripheral
extremity block were performed. Fentanyl was the dominant opioid
administered and used in 59% of all anesthetics. No significant medi-
cation reactions or complications were observed. A comprehensive
list of medications used (number of times) is as follows:
• Induction: Propofol (25), sodium pentothal (2)
• Opioids: Fentanyl (38), oxymorphone (3), morphine (2), oxycodone
(2), sufentanil (1)
• Antibiotics: Cefazolin (25), piperacillin sodium/tazobactam sodium
(1), gentamicin (1), vancomycin (1)
• Antiemetics: Ondansetron (25), dexamethasone (10), droperidol
(3), granisetron (1)
• Vasoactive: Atropine (7), labetalol (1), phenylephrine (1), racemic
epinephrine (1)
• Other: Glycopyrolate (14), neostigmine (12), acetaminophen (11),
midazolam (6), albuterol (3), lidocaine (3), calcium gluconate (1),
clonidine (1), diazepam (1), heparin (1), ibuprofen (1), papaverine
(1), tranexamic acid (1)
• Neuraxial: Bupivacaine (2), hydromorphone(1)
• Regional: Bupivacaine(1)
In 7 distinct cases, intraoperative hyperthermia (tempera-
ture > 38°C) was noted. This represents 11% of total cases, and
occurred in more than 1 child. Difficulty was reported with peripheral
venous line placement due to the cutis laxa component of the syn-
drome. Eleven arterial lines (9 radial, 2 femoral) and 4 central lines (2
right internal jugular, 2 femoral) were placed without difficulty. Blood
products, albumin, neuromonitoring, central line placement, and periph-
eral blocks were all administered without recognized complications.
4 | DISCUSSION
Although basic science has begun to unravel the genetic basis of de
Barsy syndrome, the literature describing clinical management of
these patients remains exceedingly limited. Several known genetic
WARNER ET AL.
mutations are thought to explain the physical manifestations of de
Barsy syndrome. These include a mutation in the pyrroline-5-carbox-
ylate reductase gene (PYCR-1, known as type B) and the ALDH18A1
13,15
gene (type A). Malfunctioning of these genes leads to mito-
chondrial fragmentation with high apoptosis rates during oxidative
stress.4 A third mutation, ATP6V0A2-CDG, is also thought to be
possibly related to de Barsy syndrome.16 Two recent publications
have described additional clinical features in de Barsy syndrome
patients. In 2016, Dutta et al reported slowly progressive dilatation
of the aortic root, suggesting the need for cardiac evaluation and
longitudinal monitoring.4 Lin et al described glaucoma and idio-
pathic hypertrophic pyloric stenosis in patients with de Barsy syn-
drome.15
With regard to perioperative management, little is known about
Barsy syndrome patients. Extrapolating from known physical abnor-
malities, features such as joint hyperlaxity may pose positioning
issues, while pectus excavatum could present difficulty with ventila-
tion.15 Other features, such as developmental delay, present univer-
sal concern with regard to patient coping and cooperation during the
delivery of anesthesia. Given the rarity of this condition, and limited
published data, making available institutional experience pertaining
to clinical management offers providers of de Barsy syndrome
patients a basis of care. This study extends the published anesthesia
experience with de Barsy syndrome, including various anesthetic
techniques and pharmacologic agents safely utilized. Moreover, we
have highlighted clinical considerations and management concerns
associated with de Barsy syndrome including airway management,
vascular access, and monitoring for hyperpyrexia.
In this case series, 3 major concerns for de Barsy patients were
identified, ie, difficult vascular access, hyperthermia, and potential
for difficult airway. With cutis laxa, thin skin and minimal subcuta-
neous tissue contribute not only to challenging intravenous access
but also concerns for skin fragility and breakdown.7,10 Ultrasound or
other advanced imaging techniques may be useful in facilitating vas-
cular access in these patients.
In 11% of our cases, intraoperative hyperthermia occurred. A
review of these cases did not identify any direct etiology for hyper-
thermia from such causes as infection, neuroendocrine disorder,
anti-cholinergic use, or neuroleptic medication. Moreover, dantrolene
administration was not required in any case and no additional meta-
bolic derangements were reported. Previously published reports of
nonmalignant hyperthermia in such conditions as Costello syndrome,
Osteogenesis Imperfecta, and Arthrogryposis, have speculated that
central temperature control dysregulation occurs during general
anesthesia.16-18 To date, however, no defect has been identified and
no direct evidence supports such a mechanism. In fact, a recent
investigation at our institution specifically examined intraoperative
hyperthermia in 369 discrete anesthetic cases involving patients with
arthrogryposis multiplex congenital and distal arthrogryposis syn-
drome.19 In contrast to prior studies, this investigation found no
increased risk of intraoperative hyperthermia or hypermetabolic
events compared to control subjects without arthrogryposis. Similar
to our intraoperative hyperthermia rate of 11%, Gleich et al reported
| 61
10.3% of cases were associated with hyperthermia, all of which
responded to active cooling alone. Iatrogenic intraoperative over-
warming remains the most likely explanation of hyperthermia in our
case series. This explanation may be seen in the context of limited
subcutaneous insulation due to cutis laxa, and relatively low body
mass indexes (range: 11-19), both of which would increase suscepti-
bility to room warming, heating lamps, or forced air blankets.
Accordingly, close attention to temperature monitoring and the use
of warming devices constitutes prudent clinical care of de Barsy syn-
drome patients.
Providers should also consider having advanced airway manage-
ment equipment readily available. Although craniofacial abnormalities
are present in this syndrome, they did not present severe airway
management challenges in the overwhelming majority of anesthetics.
Difficulty with both mask ventilation and endotracheal intubation
were observed in our series but limited to clinical experience with 1
patient. In the era of videolaryngoscopy, safe airway management
would be anticipated.
While patient safety cannot be definitively established by any
case series, given the extreme rarity of the syndrome, this report
attempts to provide successful management options to potential
anesthesia providers of patients with de Barsy syndrome. And as
widespread genetic testing is capable of confirming new cases, fur-
ther research will enhance our understanding of the risks surgery
and anesthesia pose to these unique patients.
ETHICAL APPROVAL
This study was approved by Mayo Clinic IRB (16-007092).
CONFLICT OF INTEREST
Nothing to disclose.
ORCID
Lindsay L. Warner http://orcid.org/0000-0002-1473-7084
REFERENCES
1. De Barsy AM, Moens E, Dierckx L. Nanism, oligophrenia, and hypo-
plasia of the elastic tissue in the skin and the cornea. Arch Belg Der-
matol Syphiligr. 1967;23:411-412.
2. Aldave AJ, Eagle Jr RC, Streeten BW, Qi J, Raber IM. Congenital cor-
neal opacification in de Barsy syndrome. Arch Ophthalmol.
2001;119:285-288.
3. Aponte EP, Smith HM, Wanek BJ, Rettke SR. Anesthesia considera-
tions for patients with de Barsy syndrome. J Clin Anesth.
2010;22:499-504.
4. Dutta AK, Ekbote AV, Thomas N, Omprakash S, Danda S. De Barsy
syndrome type B presenting with cardiac and genitourinary abnor-
malities. Clin Dysmorphol. 2016;25:190-191.
5. Dutta A, Ghosh SK, Ghosh A, Roy S. A 5-year journey with cutis laxa
in an Indian child: the de Barsy syndrome revisited. Indian J Dermatol.
2016;61:81-84.
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6. Bartsocas CS, Dimitriou J, Kavadias A, Kyrzopoulos D. De Barsy syn-
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7. Arazi M, Kapicioglu MI, Mutlu M. The de Barsy syndrome. Turkish J
Pediatrics. 2001;43:79-84.
8. Al-Owain M, Alanazi S, Khalifa O, et al. A case of de Barsy syndrome
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9. Bicknell LS, Pitt J, Aftimos S, Ramadas R, Maw MA, Robertson SP. A
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boxylate synthase (P5CS), causes an autosomal recessive neurocuta-
neous syndrome. Eur J Hum Genet. 2008;16:1176-1186.
10. Hoekx J, Smeitink J, Brunner H, Monnens L. The de Barsy syndrome.
Tijdschrift Voor Kindergeneeskunde. 1989;57:53-57.
11. Pontz BF, Zepp F, Stoss H. Biochemical, morphological and immuno-
logical findings in a patient with a cutis laxa-associated inborn disor-
der (de Barsy syndrome). Eur J Pediatrics. 1986;145:428-434.
12. Karnes PS, Shamban AT, Olsen DR, Fazio MJ, Falk RE. De Barsy syn-
drome: report of a case, literature review, and elastin gene expres-
sion studies of the skin. Am J Med Genet. 1992;42:29-34.
13. Zampatti S, Castori M, Fischer B, et al. De Barsy syndrome: a geneti-
cally heterogeneous autosomal recessive cutis laxa syndrome related
to P5CS and PYCR1 dysfunction. Am J Med Genet. 2012;158:927-931.
ET AL.
14. Guerra D, Fornieri C, Bacchelli B, et al. The de Barsy syndrome.
J Cutaneous Path. 2004;31:616-624.
15. Lin DS, Chang JH, Liu HL, et al. Compound heterozygous mutations
in PYCR1 further expand the phenotypic spectrum of De Barsy syn-
drome. Am J Med Genet A. 2011;155A:3095-3099.
16. Leao-Teles E, Quelhas D, Vilarinho L, Jaeken J. De Barsy syndrome
and ATP6V0A2-CDG. Eur J Hum Genet. 2010;18:526.
17. Stanton RP, Rao N, Scott Jr CI. Orthopaedic manifestations in de
Barsy syndrome. J Pediatr Orthop. 1994;14:60-62.
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19. Dearlove O, Harper N. Costello syndrome. Paediatr Anaesth. 1997;7:
476-477.
How to cite this article: Warner LL, Olsen DA, Smith HM.
Clinical implications of de Barsy syndrome. Pediatr Anesth.
2018;28:59–62. https://doi.org/10.1111/pan.13283
Accepted: 24 October 2017
DOI: 10.1111/pan.13290
RESEARCH REPORT
Incidence and predictors of 30-day postoperative readmission
in children
Daniel Vo1 | David Zurakowski1 | David Faraoni2
1
Department of Anesthesiology,
Perioperative and Pain Medicine, Boston
Children’s Hospital, Harvard Medical
School, Boston, MA, USA
2 bursement without a clear understanding of the factors that contribute to readmission.
Department of Anesthesia and Pain
Medicine, The Hospital for Sick Children,
University of Toronto, Toronto, ON,
Canada
Correspondence
Daniel Vo, Department of Anesthesiology,
Perioperative and Pain Medicine, Boston
Children’s Hospital, Boston, MA, USA.
Email: daniel.vo@childrens.harvard.edu
Section Editor: Francis Veyckemans
Pediatric Anesthesia. 2018;28:63–70.
Summary
Background: Hospital readmissions are being used as a quality metric for hospital reim-
Objective: The objective of this study was to report the incidence of 30-day post-
surgical readmission in children, identify the predictors for readmission, and create
an algorithm to identify high-risk children.
Methods: Data from the 2012-2014 Pediatric database of the American College of
Surgeons National Surgical Quality Improvement Program were analyzed using uni-
variable and multivariable logistical regression analysis.
Results: Among 182 589 children included in the 2012-2014 American College of
Surgeons National Surgical Quality Improvement Program Pediatric database, 4.8%
(8815/182 589) experienced a readmission within 30 days. Four significant predic-
tors were retained in the multivariable logistic regression model: American Society
of Anesthesiologists physical status ≥ 3 (OR: 1.9, 95% CI: 1.8-2.0), presence of
congenital heart disease (OR: 1.66, 95% CI: 1.31-2.11), inpatient status at time of
surgery (OR: 3.5, 95% CI: 3.3-3.7), and at least 1 postoperative complication (neuro-
logic, renal, wound, cardiac, bleeding, or pulmonary) (OR: 3.14, 95% CI: 2.92-3.34).
The multivariable logistic regression model showed reasonably good discrimination
in predicting 30-day readmissions with receiver operating characteristic area under
the curve of 0.747 (95% CI: 0.73-0.75) and good calibration (Brier score: 0.044). We
created a predictive algorithm of 30-day readmission based on the 4 significant
predictors.
Conclusion: Children with congenital heart disease, high American Society of Anes-
thesiologist physical class, inpatient status, and at least 1 postoperative complication
of any kind are at high risk for postsurgical readmissions. We provide an algorithm
for quantifying this risk with the goal of reducing the number of readmissions,
improving the care of patients with complex chronic illnesses, and reducing hospital
costs.
KEYWORDS
congenital heart disease, hospital patient readmission, pediatrics, risk assessment, risk
management, specialties surgical
wileyonlinelibrary.com/journal/pan © 2017 John Wiley & Sons Ltd | 63
64 | VO
1 | INTRODUCTION
Hospital readmission rates are currently being used as quality indica-
tors by the Centers for Medicare & Medicaid Services (CMS). They
are being made public and tied to hospital reimbursements.1 As such,
they represent a potential target for hospital administrators and poli-
cymakers for improving the value returned from healthcare dollars.
Studies have estimated 9% to 48%2 of all readmissions were pre-
ventable at a cost of $12 billion annually.3 Not only do hospital
readmissions have economic consequences but they also place a
burden on the healthcare system, patients, and families and further
fragment a patient’s disease course. Reducing readmission is a means
for improving patient satisfaction and quality of life. It is unknown
whether these metrics truly represent substandard care or variations
in patient populations with differing disease progressions. Such
uncertainties only become more complex in pediatric populations
where the health of children is dependent on an “ecology of care,”
involving the social, economic, medical, and perioperative homes of
4
these patients. While reimbursement penalties have not been
applied to pediatric hospitals yet, the Pediatric Quality Measures
Program has begun to look at readmissions at children’s hospitals
nationally and the Children’s Health Insurance Reauthorization Act5
foreshadows that such penalties may be in the future for pediatric
hospitals.
Previous studies looking at postsurgical readmissions have largely
been restricted to specific populations such as patients with congen-
ital heart disease or specific procedures such as appendectomies7
6 Reviewer. To ensure the quality of the data collected, the ACS
8 NSQIP Pediatric conducts interrater reliability audits of selected par-
and ventriculo-peritoneal shunt revisions. These studies relied lar-
gely on internal, administrative databases intended for billing pur-
poses. This analysis of the American College of Surgeons National
Surgical Quality Improvement Program Pediatric Database (ACS
NSQIP Peds) is the largest retrospective database analysis looking at
hospital readmission for all pediatric surgical patients coming for all
types of noncardiac surgery. We looked at the incidence and predic-
tors of unplanned 30-day hospital readmission in postsurgical
patients. Our objective was to identify demographic, preoperative,
operative, and postoperative risk factors for 30-day readmission and
to develop a predictive algorithm for assessing readmission risk
based on these findings. The pediatric surgical population is growing
9
in volume and medical complexity. Unplanned postsurgical readmis-
sions remain a poorly characterized morbidity and emphasize that
the procedure is not the primary endpoint of the perioperative per-
iod but an episode of care in the lifecycle of a disease process.
2 | MATERIALS AND METHODS
2.1 | Data source
This study was performed using data from the 2012, 2013, and
2014 ACS NSQIP Pediatric database. The ACS NSQIP Pediatric col-
lects deidentified data on children less than 18 years of age under-
going noncardiac surgery, and includes over 150 variables, including
ET AL.
What’s known on this subject
• Hospital readmissions are responsible for an additional
$12 billion dollars in expenses to the healthcare system.
• Pediatric, unplanned postsurgical readmissions are poorly
characterized but often thought to be preventable.
What this study adds
• Using the 2012-2014 American College of Surgeons
National Surgical Quality Improvement Program Pediatric
database, we identified preoperative, intraoperative, and
postoperative risk factors for 30-day, unplanned readmis-
sion.
• We provide a novel risk stratification algorithm for identi-
fying pediatric patients at highest risk for postsurgical
readmission.
demographics, preoperative characteristics, 30-day readmission, and
mortality in both the inpatient and outpatient settings.10 A system-
atic sampling strategy is used to avoid bias in case selection and to
ensure a diverse surgical case mix. Data are entered by a combina-
tion of automatic extraction from the patient’s existing EMR and
data entered manually by a trained and certified Surgical Clinical
ticipating sites, and sites with an interrater reliability audit disagree-
ment rate > 5% are excluded from the data. The audits reveal an
overall disagreement rate of approximately 2% for all assessed pro-
gram variables. Additionally, cases coming from hospitals with a 30-
day follow-up rate < 80% were excluded. Exclusion criteria for the
ACS NSQIP Pediatric database include: age > 18 years old, trauma
cases, brain-dead organ donors, and solid organ transplantation. In
order to comply with the Hospital Participation Agreement between
ACS and participating hospitals, facility identifiers as well as
geographic information were removed for use in the ACS NSQIP
Pediatric.
2.2 | Variable selection
We included all children undergoing pediatric surgery recorded in
the 2012-2014 ACS NSQIP Pediatric database. Out of over 150
variables, 4 demographic, 6 preoperative variables, and 6 postopera-
tive complications were selected for univariable analysis. We
selected age, gender, race, BMI, American Society of Anesthesiolo-
gists physical status (ASA), elective vs emergent surgery, inpatient vs
outpatient admission status, surgical specialty (cardiothoracic, gen-
eral, orthopedic, ENT, plastics, and urogynecologic), congenital heart
disease, and prematurity. While there are many more variables
included in the database, many of the variables show correlation and
VO ET AL.
our objective was to construct a simple model consisting of a bal-
ance of demographic, preoperative, intraoperative, and postoperative
variables chosen for their clinical face-value and regular availability
before the procedures using Katz’s recommendations for multivari-
able logistic regression analysis in medical research.11 Many of the
variables selected have been shown in prior studies using smaller
datasets and differing methodologies to impact morbidity, mortality,
12-16
and readmission.
To standardize the univariable analysis (eg, variables are either
categorical or ordinal), children were stratified into 5 clinically rele-
vant age groups: <6 months, 6-12 months, 1-6 years, 6-12 years,
and >12 years old. Congenital heart disease was classified as mild,
major, and severe according to an ACS NSQIP classification system.
Minor CHD is defined as a lesion that does not require medical
maintenance or has been repaired resulting in normal cardiovascular
function. Major CHD is defined as a repaired lesion with a residual
hemodynamic abnormality with or without medications. Severe CHD
is defined as uncorrected cyanotic heart disease, pulmonary hyper-
tension, ventricular dysfunction requiring medications, or being listed
for a heart transplant. Gestational age was classified as full term
(>37 weeks), premature (≤37 weeks but greater than 24 weeks), and
extremely premature (<24 weeks). ASA class was divided into a high
acuity (ASA ≥ 3) and low acuity group (ASA 1-2).
Postoperative complications were aggregated by system into pul-
monary complications (pneumonia, pulmonary embolism, and re-intu-
bation), renal complications (acute renal failure, oliguria, and urinary
tract infection), wound complications (superficial and deep wound
infections and dehiscence), cardiac complications (ventricular fibrilla-
tion, cardiac arrest, and cardiopulmonary resuscitation), bleeding
requiring transfusion, and neurological complications (cerebral vascu-
lar accident, seizures, and stroke).
The primary outcome was unplanned readmission to the same or
another institution within 30 days of a primary surgery with the
cause for readmission suspected to be related to the procedure. The
patient had to be classified as an inpatient on his or her readmission.
Patients missing data on readmission were excluded from analysis.
Patients who met our readmission criteria but had missing data on
any of our 16 variables selected for regression were included in our
analysis as we chose to tolerate underestimates of the discriminative
ability of the model.
2.3 | Statistical analysis
Continuous data that were not normally distributed are expressed as
median and interquartile ranges (IQR), and categorical variables as
number and percentage. Demographic, preoperative risk factors, and
postoperative complications were compared using Wilcoxon rank-
sum test for continuous variables and the Pearson chi-square test
for categorical variables and proportions. To control for possible con-
founding among variables, we used univariable and multivariable
logistic regression using backward selection to determine the inde-
pendent predictors for 30-day readmission rates using a univariable
cutoff of P < .10 for inclusion and P > .05 for removal. The results
| 65
are expressed as regression coefficient (B), the odds ratio (OR) as a
measure of risk, the 95% confidence interval (CI), and P values were
obtained from the Wald test.
Two metrics to assess model performance were used. The AUC,
also known as the c-statistic, was constructed to assess the discrimi-
native ability of the set of multivariable predictors for 30-day read-
mission. In order to evaluate the internal validity of our predictive
algorithm of 30-day readmission, we applied the bootstrapping
method on the NSQIP 2012-2014 data. Bootstrap resampling draws
random samples with replacement from the entire sample (repeti-
tion = 500) and computes bias-corrected measures for model assess-
ment. Calibration was assessed graphically by plotting the observed
outcome against the predicted readmission rate. A smooth nonpara-
metric calibration line was created with the locally weighted scatter-
plot-smoothing algorithm to estimate the observed probabilities in
relation to the predicted probabilities.17
Statistical analysis was performed with IBM SPSS Statistics (ver-
sion 23.0, IBM Corporation, Armonk, NY). Bootstrapping was per-
formed with the lrm function in the R Design Package (R Core
Team, R: A language and environment for statistical computing. R
Foundation for Statistical Computing, Vienna, Austria, 2013) based
on a data-splitting (test and training set) approach.18
3 | RESULTS
The 2012-2014 ACS NSQIP Pediatric database includes 182 749
procedures. There were 160 patients missing data on readmission
who were excluded from our analyses. Of the patients remaining,
there were 77 907 female (42.7%) and 104 682 male patients
(57.3%). Neonates and infants under 1 year of age were the smallest
group (21%). All other age groups were equally represented. The
majority of procedures were performed by General Surgery (27.8%)
followed by ENT (20.3%) and Orthopedics (13.2%). The overall
unplanned 30-day readmission rate was 4.8% (8815/182 589).
Univariable analysis (Table 1) showed that inpatient status
(P < .001), extreme prematurity (P < .001), CHD (P < .001), higher
ASA physical status class ≥ 3 (P < .001), and the surgical specialty
(P < .001) were associated with a higher incidence of 30-day read-
mission (Table 1). After adjusting for surgical specialties, multivariable
logistic regression analysis shown in Table 2 revealed that ASA phys-
ical status class ≥ 3 (OR: 1.9, 95% CI: 1.8-2.0), inpatient admission
status (OR: 3.5, 95% CI: 3.3-3.7), and the presence of minor (OR:
1.2, 95% CI: 1.1-1.3), major (OR: 1.2, 95% CI: 1.1-1.3), or severe
(OR: 1.3, 95% CI: 1.2-1.7) CHD were significant and independent
predictors of 30-day hospital readmission. There was no difference
in rates of readmission observed based on patient gender, age, or
emergent vs elective surgery.
Postoperative complications were aggregated into 6 categories
by system: pulmonary complications, wound complications, renal
complications, neurological complications, cardiac complications, and
bleeding complications requiring transfusion. The overall complica-
tions rate was 9.8% (17 909/182 589). The most frequent
66 | VO ET AL.

T A B L E 1 Univariable analysis of preoperative risk factors T A B L E 2 Multivariable analysis of preoperative and postoperative
risk factors
Not readmitted Readmitted
Variable N = 173 774 (%) N = 8815 (%) P value Variable Beta coeff. OR 95% CI P value
Age ASA physical class
0-6 mo 7770 (4.5) 378 (4.3) <.001 ASA 1 or 2 Ref.
6-12 mo 28 841 (16.6) 1629 (18.5) ASA 3, 4, or 5 0.63 1.9 1.8-2.0 <.001*
1-6 y 46 383 (26.7) 2566 (29.1) CHD
6-12 y 45 709 (26.3) 1930 (21.9)
None Ref.
>12 y 45 071 (25.9) 2312 (26.2)
Mild 0.16 1.2 1.1-1.3 <.001*
ASA class
Major 0.14 1.2 1.1-1.3 .022*
ASA 1, 2 110 070 (63.3) 3549 (40.3) <.001
Severe 0.26 1.3 1.2-1.7 .011*
ASA 3, 4, 5 63 547 (36.6) 5263 (59.7)
Inpatient vs outpatient 1.25 3.5 3.3-3.7 <.001*
Gender
Bleeding complication 0.01 1.0 0.9-1.1 .864
Male 99 788 (57.4) 4894 (55.5) .04
Wound complication 2.13 8.4 7.8-9.1 <.001*
Female 73 986 (42.6) 3921 (44.5)
Pulmonary complication 0.62 1.9 1.6-2.2 <.001*
Race
Renal complication 1.79 6.0 5.2-6.9 <.001*
White 111 802 (64.3) 5592 (63.3) <.001
Neurologic complication 0.90 2.5 1.9-3.2 <.001*
Black 22 231 (12.8) 1090 (12.4)
Asian 5538 (3.2) 306 (3.5) ASA, American Society of Anesthesiologists; CHD, congenital heart dis-
ease; OR, odds ratio; CI, confidence interval.
Native American 858 (0.5) 65 (0.01)
Results are based on multivariable logistic regression, adjusted for age,
Other/Unknown 24 647 (14.2) 1087 (12.3) gender, prematurity, emergent vs elective procedure, and surgical spe-
Surgical specialty cialty.
Cardiothoracic 15 876 (9.1) 497 (5.6) <.001 *Statistically significant.

General surgery 47 132 (27.1) 3559 (40.5)

readmission to 10.3%. The frequency of a complication had no bear-
Neurosurgery 20 778 (12.0) 1567 (17.8)
ing on its impact on readmission. For example, bleeding was the
Orthopedics 23 597 (13.6) 578 (6.6)
most frequent complication, however, only 7% of patients experienc-
ENT 35 377 (20.4) 1753 (19.9)
ing a bleed required readmission. However, only 0.66% of patients
Urology/Gynecology 17 687 (10.2) 394 (4.5) experienced a renal complication, but 31.3% of those patients
Plastics 13 315 (7.7) 467 (5.3) required readmission. Figure 1 highlights the absence of relationship
Admission status between impact on readmission and frequency of a complication.
Inpatient 95 911 (55.2) 7456 (84.6) <.001 The incidence of readmission for each type of complication as well
Outpatient 77 863 (44.8) 1359 (15.4) as for patients experiencing no complications and at least 1 compli-
Urgency cation is represented as a bar graph. The number of patients experi-
Emergent 46 368 (26.7) 2607 (29.6) <.001 encing the complication is presented below the x-axis, and the
Elective 127 406 (73.3) 6208 (70.4) number of those patients readmitted is provided as “Events.”
Prematurity In Table 3, we combine the demographic variables, preoperative
Full term 133 172 (76.6) 6486 (73.6) <.001 risk factors, and postoperative complications retained in the multi-
28-38 wk 39 730 (22.9) 2240 (25.4) variable logistic regression model into a predictive algorithm. Risk of
<28 wk 872 (0.5) 89 (1.0) 30-day postoperative readmission is stratified according to the pres-
CHD ence or absence of any of the 4 variables. If a patient had a low
None 158 741 (91.3) 7450 (84.5) <.001 ASA physical status (1,2), no CHD, was an outpatient at the time of
Mild 8596 (5.0) 762 (8.6) surgery, and experienced no postoperative complications, the
Major 5281 (3.0) 474 (5.4) incidence of 30-day hospital readmission was 1.4% (95% CI: 1.3%-

Severe 1166 (0.7) 129 (1.5)
ASA class, American Society of Anesthesiology physical status; CHD,
congenital heart disease.
Data are presented as number and percentages (%).
complications were bleeding requiring transfusion (6.2%) and wound
complications (2.9%). If a patient had no complications, the absolute
risk of 30-day readmission was reduced to 1.1%. However, the
occurrence of 1 or more complication more than doubled the risk of
1.5%). The risk of readmission increased with the number of
variables retained in the final model. If a patient had all 4 variables
of ASA physical status ≥ 3, CHD, inpatient status, and a postopera-
tive complication, the incidence of readmission increased dramati-
cally to 20% (95% CI: 18.5%-21.0%).
Validation results for our predictive model of 30-day readmission
using the bootstrapping technique with 500 resamples indicated a
bias-corrected Somers’ D rank correlation measure of .454, corre-
sponding to a c-statistic or area under the curve (AUC) of 0.747.
VO ET AL. | 67

4 | DISCUSSION

Our results suggest several important risk factors associated with

F I G U R E 1 Frequency of postoperative complications and their
bearing on readmission. Each postoperative complication is listed as
a bar column. Patients experiencing no complications are listed as
“None” and patients experiencing 1 or more complications are
aggregated in the “At least 1” column. The number of patients
experiencing a complication are listed below each complication, and
the number of those patients readmitted are listed as “Events.” The
height of the bar graph is the number of patients experiencing a
complication who were readmitted expressed as a percentage
T A B L E 3 Multivariable predictive algorithm of 30-d readmission
among surgical patients: NSQIP 2012-2014
unplanned 30-day postoperative readmission in children undergoing
noncardiac surgery. Children with congenital heart disease, ASA
physical status class ≥ 3, inpatient status at the time of surgery, and
at least 1 postoperative complication of any system were at greatest
risk for 30-day postsurgical readmission. These findings are consis-
tent with previously known perioperative risk factors for morbidity
and mortality and help to complete a picture of the at-risk popula-
tion for unplanned pediatric hospital readmissions.19
Not surprisingly, medical complexity is a recurring theme in the
literature regarding postsurgical morbidity, mortality, and readmis-
sion. Looking at medical readmission to pediatric hospitals, Berry
et al examined 317 643 patients hospitalized and found an overall
readmission rate of 20% within 1 year. Characteristics of readmitted
children were older age, public insurance use, Black race, and com-
plex chronic conditions (CCCs) particularly dependence on medical
devices (g-tube, ventriculo-peritoneal shunts, and tracheostomies).20
Similarly, Burgonrappa et al21 looked at 2217 procedures performed
over 5 years at 2 tertiary care children’s hospitals within a single
health care system and found an unplanned postsurgical readmission
rate of 6.5%. The risk factors that they identified were patients with
CCCs and age less than 1 year.
Developed in 2000, the Pediatric Complex Chronic Conditions
Classification System is a comprehensive set of ICD-10 codes and

Without With CPT codes. The working definition of a CCC is any medical condition
postoperative postoperative that can be reasonably expected to last at least 12 months (unless
ASA 3, 4, complication complication death intervenes) and to involve either several different organ sys-
or 5 CHD Inpatient (%) (%)
tems or 1 system severely enough to require specialty pediatric care
No No No 1.4 (1.3-1.5) 3.7 (3.4-4.1) and probably some period of hospitalization in a tertiary care cen-
No Yes No 1.5 (1.4-1.7) 4.2 (3.7-4.6) ter.22 Children with CCCs are thought to make up 2.9% of the pedi-
Yes No No 2.4 (2.2-2.6) 6.4 (5.9-7.0) atric patient population but account for 18.8% of admissions, 23.4%
Yes Yes No 2.7 (2.4-2.9) 7.2 (6.4-7.8) of bed-days, and 23.2% ($3.42 billion) of aggregate charges.20
No No Yes 4.3 (4.0-4.6) 11.0 (10.3-12.0) Static definitions of medical complexity or comorbidity such as
No Yes Yes 4.8 (4.3-5.2) 12.2 (11.1-13.3) the CCC classification system or ASA physical status by themselves
Yes No Yes 7.4 (6.9-7.8) 18.0 (17.0-19.1) are inadequate for assessing postoperative risk of readmission. Peri-

Yes Yes Yes 8.1 (7.5-8.7) 20.0 (18.5-21.0)
ASA, American Society of Anesthesiologists; CHD, congenital heart dis-
ease.
Data represent probability of 30-d readmission, with 95% confidence
intervals based on logistic regression.
The Nagelkerke R2 measure was .295. The intercept and slope of an
overall logistic calibration equation were 0.002 and 1.00. The maxi-
mum absolute difference in predicted and calibrated probabilities, or
Emax, was .0006. The Brier quadratic probability score B was .044,
which is good evidence of prediction as a lower Brier score is better.
Thus, our internal validation results suggest that our predictive
model have good internal validity with a c-statistic approaching
0.750, and a bias-corrected Somers’ D rank correlation of .454. Our
multivariable algorithm performs reasonably well at predicting 30-
day readmission.
operative risk is an interaction between procedure, surgeon, disease,
and patient. The medical population and the surgical population dif-
fer in that the majority of surgeries are elective and ideally under-
taken when a patient is medically optimized. Thus, it is not only the
number of diagnoses or organ systems involved but also the func-
tional status of the patient that has bearing on risk of readmission.
Inpatient admission status indirectly captures aspects of medical
complexity, clinical function, and perioperative optimization at the
time of surgery missed by both the CCC classification and ASA phys-
ical class. It was in fact one of our most heavily weighted prognosti-
cators (OR: 3.5, 95% CI: 3.3-3.7) and increased the risk of 30-day
postoperative readmission across all analyses.
As an example, children with congenital heart disease are known
have higher rates of morbidity and mortality in the immediate intra-
and postoperative period.23,24 Our evidence suggests this vulnerabil-
ity extends to 30-day postsurgical readmissions. As shown in
68 | VO
Figure 2, the rate of readmission increased with lesion severity (Mild
3.8%, Major 5.1%, and Severe 6.0%). However, the impact of CHD
on readmission is still amplified by admission status. Compared to
outpatients with the same CHD classification, inpatients experienced
almost double the rate of readmission (Mild 6.9%, Major 9.0%, and
Severe 11.1%). Our interpretation of this finding is that the ACS
NSQIP Peds categories of mild, moderate, or severe CHD are static
definitions that fail to capture the variety of CHD lesions and an
individual’s performance. However, in-hospital admission declares
the functional status of a patient with CHD irrespective of disease
classification. Another possible explanation for why CHD by itself
was not more impactful on readmission is that often this population
is cared for by separate cardiac anesthesiologists and cardiac inten-
sive care units postoperatively which may make them perform more
like the general population.
Of the 4 variables identified, postoperative complications may be
most actionable. Studies using the ACS NSQIP data in the adult pop-
ulation have consistently found postoperative complications to be a
driver of hospital readmission.25,26 Tahiri et al used the ACS NSQIP
Peds to look at 30-day readmission in 5367 plastic surgery patients.
They found a lower overall readmission rate of 2.4% and the most
significant independent predicators of readmission were postopera-
27
tive medical and surgical complications. Other risk factors identi-
fied were medical comorbidities, contaminated wound classification,
higher ASA class, longer operative times, and longer length of stay.
In a preliminary analysis, we examined relative value units assigned
to procedures as a surrogate for procedural length and complexity
and did not find an association with increased readmissions. The dif-
ference in overall readmission rate and readmission risk factors
found in our 2 studies likely represents a different risk profile for
pediatric plastic surgery patients and the general cohort. In their
study of pediatric surgical readmission, Brown et al failed to find a
link between postoperative complications or length of stay and read-
mission. In an analysis of over 260 000 pediatric cases performed
nationwide, being a high volume surgical center was the only
F I G U R E 2 Thirty-day readmission rates for patients with mild,
moderate, severe congenital heart disease (CHD) stratified according
to inpatient or outpatient status. Error bars represent 95%
confidence intervals
ET AL.
variable significantly associated with higher readmission rates.28 This
led the authors to question whether pediatric surgical readmissions
are truly preventable. The dataset used in their study was an admin-
istrative dataset which likely lacked the granularity to model the
depth of preoperative and postoperative variables that the ACS
NSQIP Peds offers, leading to a paucity of identified risk factors and
counterintuitive findings.
Modifying postoperative complications is an ongoing challenge and
the subject of much research. Evidence for many proposed interven-
tions is lacking and beyond the scope of this manuscript. However,
while many individualized interventions have failed to show clear bene-
fit, the readmission risk model we propose in Table 3 can help identify
“red flags” early in the postoperative course which could triage at-risk
patients to more intensive discharge planning (eg, dedicated discharge
teams to ensure stability of therapy, assessment of home supports sys-
tems, care transition coaching, or postdischarge telephonic monitoring).
For example as seen in Figure 2, renal complications and wound infec-
tions while having varying incidence, both increase the risk of readmis-
sion above 30%. Currently, there is a lack of evidence regarding
intraoperative reno-protective or “rescue” strategies including fluid
management or the use of vasoactive agents, diuretics, or sodium
bicarbonate.29 However, Goldstein et al describe using automated
EMR screening and a decision support process to identify patients
exposed to nephrotoxic drugs and at risk for acute kidney injury leading
to daily serum creatinine monitoring decreasing both the exposure rate
and acute renal insufficiency rate by 64%.30 Similarly with wound
infections, while advances have been made in the operating room ven-
tilation, sterilization, barriers, surgical technique, and best practices for
perioperative antibiotics,31 the key to preventing readmissions may lie
in identifying the at-risk population and a team approach to plans of
care and community-based postdischarge surveillance.32-34
This study has several limitations. Retrospective database analy-
ses such as ours are inherently limited by the variables chosen to be
included in the database. Data may have been missing or incorrectly
entered. Hospital data in the ACS NSQIP Peds are deidentified so it
is unknown where and in what type of facility these surgeries were
performed. Geographic location has been shown to impact rates of
readmission.35 Surgical outcomes have been found to vary with vol-
ume and a hospital’s designation as “stand-alone children’s hospi-
tal.”36 As with any database, this sample may not be representative
of the national population of pediatric surgical patients. Despite
these limitations, the ACS NSQIP Peds represents a large dataset
which is case mix and risk adjusted from a variety of hospital set-
tings including but not limited to stand-alone children’s hospitals.
The database has rigorous quality control metrics and specifically
examines the surgical population using clinical data extracted from
the medical record as opposed to administrative/billing data.
5 | CONCLUSION
Children who have high ASA status, congenital heart disease, expe-
rience a postoperative complication, and are inpatients at the time
VO ET AL.
of surgery are at increased risk for 30-day postsurgical readmission.
We present a simplified prognostic model consisting of these 4
variables which shows good predictive discrimination and internal
calibration using the bootstrapping method. The next steps are to
validate these findings using the 2015, 2016 ACS NSQIP Pediatric
datasets. Preventing hospital readmission may prove to be a combi-
nation of improvements in perioperative care and the early identifi-
cation of patients at risk for complications, readmission, and
hospital-resource consumption. Further research is required to
determine whether triaging these patients to separate predischarge
care and postdischarge surveillance reduces unintended postopera-
tive readmissions.
ACKNOWLEDGMENTS
The authors thank the American College of Surgeons National Surgi-
cal Quality Improvement Program and the hospitals participating in
the ACS NSQIP, source of the data used herein. ACS NSQIP has not
verified and is not responsible for the statistical validity of the data
analysis or the conclusions derived by the authors.
CONFLICT OF INTEREST
The authors report no conflict of interest.
ORCID
Daniel Vo http://orcid.org/0000-0001-9176-9875
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3. Axon RN, Williams MV. Hospital readmission as an accountability
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4. Feudtner C, Levin J, Srivastava R, et al. How well can hospital read-
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5. Dougherty D, Schiff J, Mangione-Smith R. The Children’s Health
Insurance Program Reauthorization Act quality measures initiatives:
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cent outcomes. Acad Pediatr. 2011;11:S1-S10.
6. Mackie A, Ionescu-Ittu R, Pilote L, et al. Hospital readmissions in
children with congenital heart disease: a population-based study. Am
Heart J. 2008;155:577-584.
7. Newman K, Ponsky T, Kittle K, et al. Appendicitis 2000: variability in
practice, outcomes, and resource utilization at thirty pediatric hospi-
tals. J Pediatr Surg. 2003;38:372-379.
8. Tejerdor-Sojo J, Singleton L, McCormick K, et al. Preventability of
pediatric 30-day readmissions following ventricular shunt surgery. J
Peds. 2015;167:1327-1333.
9. Burns K, Casey P, Lyle R, et al. Increasing prevalence of medically
complex children in US hospitals. Pediatrics. 2010;126:638-646.
| 69
10. Anon. User Guide for the 2014 ACS NSQIP Pediatric Participant
Use Data File. 2014. http://www.pediatric.acsnsqip.org/acsNsqipDa
taPed/jsp/pdf/PEDS.ACS.NSQIP.PUF.UserGuide.2014.pdf. Accessed
November 10, 2015.
11. Katz M. Multivariable analysis: a primer for readers of medical
research. Ann Intern Med. 2003;138:644-650.
12. Faraoni D, Zurakowski D, Vo D, et al. Post-operative outcomes in
children with and without congenital heart disease undergoing non-
cardiac surgery. J Am Coll Cardiol. 2016;67:793-801.
13. Ramamoorthy C, Haberkern CM, Bhananker SM, et al. Anesthesia-
related cardiac arrest in children with heart disease: data from the
Pediatric Perioperative Cardiac Arrest (POCA) registry. Anest Analg.
2010;110:1376-1382.
14. Berry J, Toomey S, Zaslavsky A, et al. Pediatric readmission preva-
lence and variability across hospitals. JAMA. 2013;309:372-380.
15. Tsai T, Joynt K, Orav E, et al. Variation in surgical-readmission rates
and quality of hospital care. N Engl J Med. 2013;369:1134-1142.
16. Davenport D, Bowe E, Henderson W, et al. National Surgical Qual-
ity Improvement Program (NSQIP) risk factors can be used to vali-
date American Society of Anesthesiologists Physical Status
classification (ASA PS) levels. Ann Surg. 2006;243:636-641. discus-
sion 641–4.
17. Le Manach Y, Collins G, Rodseth R, et al. Preoperative score to pre-
dict postoperative mortality (POSPOM): derivation and validation.
Anesthesiology. 2016;124:570-579.
18. Miller M, Hui S, Tierney W. Validation techniques for logistic regres-
sion models. Stat Med. 1991;10:1213-1226.
19. Nakamura M, Toomey S, Zaslavsky A, et al. Measuring pediatric hos-
pital readmission rates to drive quality improvement. Acad Pediatr.
2016;14(5 suppl):S39-S246.
20. Berry J, Hall D, Kuo D, et al. Hospital utilization and characteristics
of patients experiencing recurrent readmissions within children’s
hospitals. JAMA. 2011;305:682-690.
21. Burjonrappa S, Theodorus A, Shah A, et al. Pediatric surgery
readmissions: a root cause analysis. Pediatr Surg Int. 2015;31:
551-555.
22. Simon T, Berry J, Feudtner C, et al. Children with complex chronic
conditions in inpatient hospital settings in the United States. Pedi-
atrics. 2010;126:647-655.
23. Baum V, Barton D, Gutgesell H. Influence of congenital heart disease
on mortality after noncardiac surgery in hospitalized children. Pedi-
atrics. 2000;105:332-335.
24. Islam S, Yasui Y, Kaul P, Mackie A. Hospital readmission of patients
with congenital heart disease in Canada. Can J Cardiol. 2016;32:987.
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readmission among general surgery patients. J Am Coll Surg.
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26. Glance L, Kellermann A, Osler T, et al. Hospital readmission after
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27. Tahiri Y, Fischer J, Wink J, et al. Analysis of risk factors associated
with 30-day readmissions following pediatric plastic surgery: a
review of 5376 procedures. Plast Reconstr Surg. 2015;135:521-
529.
28. Brown E, Anderson J, Burgess D, et al. Pediatric surgical readmis-
sions: are they truly preventable? J Pediatr Surg. 2017;52:161-165.
29. Sear J. Kidney dysfunction in the postoperative period. Br J Anaesth.
2005;95:20-32.
30. Goldstein S, Mottes T, Simpson K, et al. A sustained quality
improvement program reduces nephrotoxic medication-associated
acute kidney injury. Kidney Int. 2016;90:212-221.
31. Centers for Disease Control and Prevention (CDC). Surgical Site
Infection (SSI) Event: Procedure-associated Module. 2016. www.cdc.
gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf. Accessed July 19,
2017.
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32. McNaughton V, Orsted H. Surgical site infections in community care 36. Pasquali S, Gaies M, Jacobs J, et al. Centre variation in cost and out-
clients. Early detection and rational care through recognition of cli- comes for congenital heart surgery. Cardiol Young. 2012;22:796-799.
ent-specific risk factors. Wound Care Canada. 2005;3:10-13.
33. Huenger F, Schmachtenberg A, Haefner H, et al. Evaluation of post-
discharge surveillance of surgical site infections after total hip and
knee arthroplasty. AJIC. 2005;33:455-462. How to cite this article: Vo D, Zurakowski D, Faraoni D.
34. Kripalani S, Theobald C, Anctil B, et al. Reducing hospital readmis- Incidence and predictors of 30-day postoperative readmission
sion rates: current strategies and future directions. Annu Rev Med.
in children. Pediatr Anesth. 2018;28:63–70.
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35. Anderson G, Steinberg E. Hospital readmissions in the medicare pop- https://doi.org/10.1111/pan.13290
ulation. N Engl J Med. 1984;311:1349-1353.
Accepted: 18 October 2017

DOI: 10.1111/pan.13292

CASE REPORT

Nitroglycerin: An unusual solution to intraoperative

hypothermia in a 4-year-old burn patient

Eduardo J. Goenaga Dıaz1 | Jeffrey E. Carter2 | T. Wesley Templeton1

1
Department of Anesthesiology, Wake
Forest School of Medicine, Winston-Salem, Summary
NC, USA We describe the case of a 4-year-old child undergoing extensive burn surgery with
2
Department of Trauma Surgery, Wake
refractory intraoperative hypothermia. A low-dose nitroglycerin infusion was initi-
Forest School of Medicine, Winston-Salem,
NC, USA ated to reverse vasoconstriction and improve heat absorption, after which the
child’s temperature steadily improved. In hypothermic burn patients, topical vaso-
Correspondence
Eduardo J. Goenaga Dıaz, Department of constrictors may hinder surface warming efforts. A vasodilator infusion may aid in
Anesthesiology, Wake Forest School of
warming the pediatric patient undergoing extensive excision and grafting.
Medicine, Winston-Salem, NC, USA.
Email: egoenaga@wakehealth.edu
KEYWORDS
Funding information burns, hypothermia, nitroglycerin, pediatric, surgery, vasodilation
The study was funded by departmental
resources.

Section Editor: David Polaner

1 | INTRODUCTION
Burn patients are at risk for intraoperative hypothermia as a result
of increased heat loss through injured skin, increased evaporative
heat loss, and loss of normal thermal homeostatic mechanisms dur-
1
ing general anesthesia. Pediatric patients are even more susceptible
1
due to their increased body surface area to volume ratio. In adults,
perioperative hypothermia has been associated with acute lung
injury, coagulopathy, and impairments in the immune response and
wound healing.2,3 Aggressive warming and maintenance of normoth-
ermia are essential.
2 | CASE
A 4-year-old, 16.8 kg child with 49% total body surface area full-
thickness burns sustained in a house fire 5 days prior presented to
the operating room for initial excision and grafting. On arrival to the
operating room, his temperature was 37.7°C, saturating 97% on
Franklin Lakes, NJ, USA) fluid warming system. Anesthesia was main-
tained with isoflurane, 0.7%-1.2%, rocuronium, and hydromorphone.
One hour elapsed from OR arrival to draping of the patient for sur-
gery. Excision of full-thickness burns was performed using a combi-
nation of a Weck blade and the Versajet IIâ hydrosurgery system
(Smith & Nephew, Andover, MA, USA).
All burns were excised and covered with TelfaTM nonadherent
dressings (Covidien, Dublin, Ireland) soaked in a 1:10 000 epinephrine
solution for hemostasis before grafting with allograft (AlloDerm, Life-
Cell Corp-Allergan, Dublin, Ireland). During debridement, the patient’s
temperature by Foley probe dropped from 37°C to 35.7°C despite
warming of all fluids to 40°C, maintenance of the room temperature
at 103°F, and continuous forced air warming of all surfaces not
actively being debrided (Bair HuggerTM, 3M, St. Paul, MN)(Figure 1). At
this point, the operation was paused to allow the patient to rewarm.
He was completely covered with a sterile forced air warming blanket
and wrapped in plastic for approximately 45 minutes. Despite these
measures, we observed no change in the patient’s core temperature.
A low-dose nitroglycerin infusion was begun at 0.2 mcg
kg 1

min 1

ambient air. He underwent an IV induction with propofol and
rocuronium and was easily intubated via direct laryngoscopy. IV
catheters (16 Gauge) were placed in his right saphenous and right
external jugular veins, and a 3 Fr radial arterial catheter was placed.
Temperature was measured with a Foley catheter probe. All IV fluid
solutions were warmed using the enFlowâ (Becton Dikinson and Co,
to promote venodilation and improve peripheral perfusion. No
change was made to the maintenance anesthetic. Over the next
30 minutes, a gradual decrease in blood pressure was observed as
the temperature increased from 35.7°C to 36.3°C. At this point, the
operation was resumed with continued improvement in the patient’s
temperature. The nitroglycerin infusion was stopped when the

Pediatric Anesthesia. 2018;28:71–72. wileyonlinelibrary.com/journal/pan © 2017 John Wiley & Sons Ltd | 71
72 | GOENAGA DIAZ
F I G U R E 1 Patient’s intraoperative temperature and mean arterial
pressure (MAP). Lowest temperature is reached while surgery is
paused for warming (green arrow), and begins to rise during
nitroglycerin infusion (shaded box), while MAP gradually decreases
patient’s temperature reached 37°C, approximately 70 minutes after
initiation. The operation was completed with all surfaces grafted.
Postoperatively, he remained intubated and was taken to the pedi-
atric intensive care unit. He was extubated without event on the
second postoperative day.
3 | DISCUSSION
Despite aggressive warming efforts, this patient suffered signifi-
cant ambient heat loss during anesthesia induction, preparation,
and surgical excision of his burn wounds. Conventional warming
methods proved insufficient to maintain and eventually reestablish
normothermia. Given the total area excised and exposed to epi-
nephrine-soaked dressings, we considered the possibility that poor
skin and surface tissue perfusion was impeding the transfer of sur-
face heat to the patient’s core. Once the nitroglycerin infusion was
begun, vasodilation and improved perfusion of these exposed
areas allowed for the absorption and transfer of more heat from
the skin to deeper tissues throughout the body, increasing the
patient’s core temperature.
It is possible that the recovery of the patient’s temperature could
potentially have been due to other factors. Volatile anesthetics can
cause peripheral vasodilation as well, but in this patient, the endtidal
concentration of isoflurane remained essentially unchanged through-
out. Also, there was temporal correlation between the nitroglycerin
infusion, the rise in temperature, and the modest drop in mean arte-
rial pressure which would be expected in a child receiving a low-
dose nitroglycerin infusion (Figure 1).
ET AL.
4 | CONCLUSION
We present a case of refractory intraoperative hypothermia in a
pediatric burn patient who responded to vasodilation with low-dose
nitroglycerin. In this setting, great vigilance must be maintained to
appropriately manage the patient’s volume status as these patients
remain at high risk for hypovolemia and circulatory shock.
ETHICAL APPROVAL
Received written, signed consent for publication from patient’s mother.
CONFLICT OF INTEREST
No conflicts of interest.
Learning Points
• Children undergoing burn excision surgery are at high
risk for perioperative hypothermia.
• Topical vasoconstrictors may hinder heat transfer to
deeper tissues from surface warming techniques.
• Low-dose nitroglycerin may result in vasodilation and
improved surface heat absorption and distribution.
ORCID
Eduardo J. Goenaga Dıaz http://orcid.org/0000-0002-3479-7180
REFERENCES
1. Fuzaylov G, Fidkowski CW. Anesthetic considerations for major burn
injury in pediatric patients. Pediatr Anesth. 2009;19:202-211.
2. Oda J, Kasai K, Noborio M, Ueyama M, Yukioka T. Hypothermia dur-
ing burn surgery and postoperative acute lung injury in extensively
burned patients. J Trauma. 2009;66:1525-1529.
3. Rizzo JA, Rowan MP, Driscoll IR, Chan RK, Chung KK. Perioperative
temperature management during burn care. J Burn Care Res. 2017;38:
e277-e283.
How to cite this article: Goenaga Dıaz EJ, Carter JE,
Templeton TW. Nitroglycerin: An unusual solution to
intraoperative hypothermia in a 4-year-old burn patient. Pediatr
Anesth. 2018;28:71-72. https://doi.org/10.1111/pan.13292
DOI: 10.1111/pan.13287

CORRESPONDENCE

In response to “Interventions designed using quality

improvement methods reduce the incidence of serious airway
events and airway cardiac arrests during pediatric anesthesia”
Sir—As an anesthesia resident I read the article “Interventions Also, though they were observed to be immediately available
designed using quality improvement methods reduce the incidence more frequently following the intervention, did the use of succinyl-
of serious airway events and airway cardiac arrests during pediatric choline and atropine actually increase?
anesthesia” by James Spaeth et al from Cincinnati Children’s Hospi- Finally, and this may be difficult to quantify, what role do you
tal with great interest. believe having compensation tied to success of the quality improve-
While the article was a report on the successful implementation ment measures played in achieving the positive outcome?
of a quality improvement method, and I commend your group on
reducing these serious events, I am interested in the data surround-
ETHICAL APPROVAL
ing the decreased number of airway events and airway cardiac
arrests and have some questions regarding the methodology. First, No ethics approvals were necessary for this article.
how did you define whether an event was airway related or not?
Was a particular time frame used or was it classified based on CONFLICT OF INTEREST
the report of the provider involved? Also, did the rate of events
directly associated with airway management (direct laryngoscopy, The authors report no conflict of interest.
mask ventilation, etc.) in particular decrease with the described
interventions?
ORCID
What was the timing and location of occurrence of the serious
airway events and airway-related cardiac events, especially as Benjamin H. Cloyd http://orcid.org/0000-0003-3495-5190
regards the institutional preintervention practice for adenotonsillec-
tomy patients of extubation and airway management by post opera-
tive care unit nurses?1 These patients are at great risk of both Benjamin H. Cloyd

serious airway and cardiac events, and the presence of a trained Department of Anesthesiology, University of Michigan, Ann Arbor, MI,

anesthesia provider is required during their emergence, whether in USA

the operating room or post operative care unit at the Mott Chil- Email: bcloyd@med.umich.edu

dren’s Hospital at the University of Michigan.

The implementation of the use of neuromuscular blocking
agents in all cases longer than 30 minutes for patients 2 years of
age and under sparked significant discussion regarding clinical prac-
tice here at the Mott Children’s Hospital. I was surprised to find
that the incidence of residual neuromuscular blockade did not
change during the study period, despite the significantly increased
use of paralytics. The available evidence in both pediatric and adult
patients suggests that increased use of paralytics is associated with
increased residual neuromuscular blockade, approximately 40% of
the time in adults and 28% of the time in children.2,3 What was
your institution’s rate of residual neuromuscular blockade and how
did you assess it?
REFERENCES
1. Spaeth JP, Kreeger R, Varughese AM, Wittkugel E. Interventions
designed using quality improvement methods reduce the incidence of
serious airway events and airway cardiac arrests during pediatric
anesthesia. Pediatr Anesth. 2016;26:164-172.
2. Naguib M, Kopman A, Ensor J. Neuromuscular monitoring and post-
operative residual curarisation: a meta-analysis. Br J Anaesth.
2007;98:302-316.
3. Ledowski T, O’Dea B, Meyerkort L, Hegarty M, von Ungern-Stern-
berg BS. Postoperative residual neuromuscular paralysis at an Aus-
tralian tertiary children’s hospital. Anesthesiol Res Pract. 2015;2015:
1-4.

Pediatric Anesthesia. 2018;28:73–76. wileyonlinelibrary.com/journal/pan © 2017 John Wiley & Sons Ltd | 73
74 | CORRESPONDENCE

DOI: 10.1111/pan.13277

Continuous Erector Spinae Plane block for thoracic surgery in

a pediatric patient

Sir—Pediatric regional anesthesia has been gaining popularity since physiotherapy, SpO2 ranging from 80% to 90% (considered ade-
the introduction of ultrasound techniques,1 adding precision and quate for his cardiac pathology).
new blocks. Open thoracic surgery is considered a very painful procedure,
One newly described ultrasound-guided block in the adult popu- and thoracic epidural analgesia has been widely used with excellent
lation is the Erector Spinae Plane (ESP) block.2 results. In this patient, an alternative to epidural analgesia was
It is a facial plane block where local anesthetic is injected sought, because of the unknown effects of his chronic heart condi-
between the erector spinae muscle and the underlying transverse tion on epidural vessels. We believe, ESP block will become a useful
process, and was initially described at the T5 level for costal pain tool in regional anesthesia, potentially replacing epidural analgesia in
2
and thoracic surgery. many conditions. Obviously, prospective randomized controlled trials
There is a recent report of a single shot ESP block on a 7-year- comparing ESP block with current standard analgesic techniques are
old child.3 We would like to report the use of a continuous ESP block needed.
in a 3-year-old, 13 kg male patient for postoperative pain after open
thoracotomy.
The patient was a full-term newborn, with a hypoplastic left
heart syndrome. He already had several surgeries for his cardiac
defect. A postsurgical diaphragmatic paralysis after a Fontan proce-
dure was diagnosed and surgical treatment was indicated. A thora-
coscopic diaphragm plication attempt was unsuccessful and open
thoracotomy surgery was then scheduled. Balanced general anes-
thesia was given. Standard monitoring was placed and a radial arte-
rial line was inserted. Sevoflurane, fentanyl boluses, and
neuromuscular blocker were used. At the end of surgery, at the
surgical incision level (T9), an ESP block was done with the patient
still lying on his left side. A 6-13 MHz linear probe was used
(SonoSite Edge; SonoSite, Inc., Bothell, WA, USA). After skin clean-
ing, using a right sagittal paramedian probe orientation, transverse
processes were identified. A 5 cm 20G Tuohy needle was inserted
in-plane, caudal-cranial direction until the tip of the transverse pro-
cess was contacted (Figure 1). After negative aspiration, 8 mL of
0.25% levo-bupivacaine (Chirocaineâ 5 mg/mL; Abbvie, Elverum,
Norway) was injected. Immediately after injection, a 22G epidural
catheter was threaded 2 cm beyond the needle, fixed to the skin
and covered with a transparent dressing. The patient was extu-
bated and transferred to the pediatric intensive care unit. At PICU
arrival, the patient was awake, breathing smoothly, stable vital
signs, and 0/10 point CHIPPS4 score was measured. Two hours
later, a PCA pump with 0.1% levo-bupivacaine 3 mL/h continuous
infusion was started. A 1.5 mL rescue bolus, 30-minute lockout,
was programmed (to be used by a nurse or parent caring for the
child). Scheduled oral acetaminophen and intravenous ketorolac
were prescribed. On the 4th postoperative day, after chest tubes
were removed, the local anesthetic infusion was stopped and the
catheter was removed. During the postoperative period, only twice
F I G U R E 1 Patients’ position and US probe (upper); actual US
was a PCA bolus given. No other rescue medication was needed. image during block (middle), and anatomical sketch to understand US
The child never complained about pain and easily allowed chest image
CORRESPONDENCE
We hope this report will encourage others to follow on the use
and study of this block in the pediatric population.
CONFLICT OF INTEREST
Consent for report was sign by a parent. No funding involved.
Authors have no conflict of interest to declare.
ORCID
Juan Carlos De la Cuadra-Fontaine http://orcid.org/0000-0002-
3868-0764
Juan Carlos De la Cuadra-Fontaine1
Mario Concha1
Fernando Vuletin2
Hern
an Arancibia1
1
lica de Chile,
Department of Anesthesia, Pontificia Universidad Cato
Santiago, Chile
DOI: 10.1111/pan.13291
Mispositioning the end of a cuff inflating line in long-axis
ultrasound imaging of the pediatric larynx and trachea
Dear Editor,
When using pediatric cuffed endotracheal tubes (ETTs), cuff position
should be confirmed using safe anesthesia practice.1-3 Placing the
ETT tip in the optimal position may be difficult because of varying
1 4 2
tracheal lengths. Long-axis, in addition to short-axis, ultrasound
imaging of saline-inflated cuffs may help to confirm correct position-
ing of pediatric ETTs. In this letter, we describe long-axis ultrasound
imaging features of a saline-infiltrated cuff inflating line that was
mispositioned in the trachea or larynx. Informed written consent was
obtained from the patient’s parent for publication of anonymized
case details.
A 1-year-old boy (height, 66 cm; weight, 7.5 kg) was scheduled
for bilateral laparoscopic, total extraperitoneal inguinal hernia repair.
â
A 3.5 mm internal diameter cuffed ETT (Mallinckrodt , Dublin, Ire-
land) was successfully intubated to an oral depth of 12 cm from the
upper incisors. A long-axis view of the saline-infiltrated cuff inflating
line (Figure 1A) was obtained using an ultrasound apparatus
â
equipped with an L12-2 MHz probe (L441, Noblus ; Hitachi Aloka
Medical Ltd., Tokyo, Japan). We mistakenly assumed that the orifice
of the cuff inflating line opened and ended in the middle of the cuff:
it was believed that the cuff was positioned too deep and, accord-
ingly, the depth of the ETT was adjusted to 11 cm (Figure 1B). The
operation concluded uneventfully and the patient exhibited no
hoarseness.
| 75
2
Department of Pediatric Surgery, Pontificia Universidad Catolica de
Chile, Santiago, Chile
Email: juancarl@med.puc.cl
REFERENCES
1. Polaner DM, Taenzer AH, Walker BJ, et al. Pediatric Regional Anes-
thesia Network (PRAN): a multi-institutional study of the use and inci-
dence of complications of pediatric regional anesthesia. Anesth Analg.
2012;115:1353-1364.
2. Forero M, Adhikary SD, Lopez H, Tsui C, Chin KJ. The erector spinae
plane block: a novel analgesic technique in thoracic neuropathic pain.
Reg Anesth Pain Med. 2016;41:621-627.
3. Mun ~oz F, Cubillos J, Bonilla AJ, Chin KJ. Erector spinae plane block
for postoperative analgesia in pediatric oncological thoracic surgery.
Can J Anaesth. 2017;64:880-882.
4. Bu€ttner W, Finke W. Analysis of behavioural and physiological param-
eters for the assessment of postoperative analgesic demand in new-
borns, infants and young children: a comprehensive report on seven
consecutive studies. Paediatr Anaesth. 2000;10:303-318.
Postoperative investigation revealed that the end of the cuff
inflating line was positioned 4 mm from the tip of the ETT, and
the longitudinal cuff diameter was about 12 mm (Figure 1C). The
cephalad edge of the cuff appeared to be positioned approximately
2 mm from the caudal edge of the cricoid cartilage, judging by the
distance between the end of the cuff inflating line and the cuff
cephalad edge at an intubation depth of 12 cm (Figure 1A). The
ETT, however, appeared to be positioned too shallow at an intuba-
tion depth of 11 cm (Figure 1B). Misunderstanding the structure of
the ETT could have resulted in intralaryngeal malpositioning of the
ETT.
The midtracheal level is helpful in determining the optimal inser-
tion depth of the ETT in pediatric patients.1 The positions of the tra-
chea, cricoid cartilage, thyroid cartilage, and the cuff inflating line
may be better visualized in the long-axis than the short-axis view.4
Long-axis ultrasound images of the saline-inflated cuff in this case
could not be observed, probably because of hyperechoic shadows
created by cartilage formation in the perichondrium.5 However, we
were able to obtain images of the cuff inflating line where hypere-
choic shadows did not exist. Thus, long-axis ultrasound imaging of a
saline-infiltrated cuff inflating line may facilitate correct positioning of
a pediatric ETT cuff below the caudal edge of the cricoid cartilage.
Information regarding the position of the end of the cuff inflating line
is important for correct positioning. Many cuffed ETT designs are
CORRESPONDENCE
We hope this report will encourage others to follow on the use
and study of this block in the pediatric population.
CONFLICT OF INTEREST
Consent for report was sign by a parent. No funding involved.
Authors have no conflict of interest to declare.
ORCID
Juan Carlos De la Cuadra-Fontaine http://orcid.org/0000-0002-
3868-0764
Juan Carlos De la Cuadra-Fontaine1
Mario Concha1
Fernando Vuletin2
Hern
an Arancibia1
1
lica de Chile,
Department of Anesthesia, Pontificia Universidad Cato
Santiago, Chile
DOI: 10.1111/pan.13291
Mispositioning the end of a cuff inflating line in long-axis
ultrasound imaging of the pediatric larynx and trachea
Dear Editor,
When using pediatric cuffed endotracheal tubes (ETTs), cuff position
should be confirmed using safe anesthesia practice.1-3 Placing the
ETT tip in the optimal position may be difficult because of varying
1 4 2
tracheal lengths. Long-axis, in addition to short-axis, ultrasound
imaging of saline-inflated cuffs may help to confirm correct position-
ing of pediatric ETTs. In this letter, we describe long-axis ultrasound
imaging features of a saline-infiltrated cuff inflating line that was
mispositioned in the trachea or larynx. Informed written consent was
obtained from the patient’s parent for publication of anonymized
case details.
A 1-year-old boy (height, 66 cm; weight, 7.5 kg) was scheduled
for bilateral laparoscopic, total extraperitoneal inguinal hernia repair.
â
A 3.5 mm internal diameter cuffed ETT (Mallinckrodt , Dublin, Ire-
land) was successfully intubated to an oral depth of 12 cm from the
upper incisors. A long-axis view of the saline-infiltrated cuff inflating
line (Figure 1A) was obtained using an ultrasound apparatus
â
equipped with an L12-2 MHz probe (L441, Noblus ; Hitachi Aloka
Medical Ltd., Tokyo, Japan). We mistakenly assumed that the orifice
of the cuff inflating line opened and ended in the middle of the cuff:
it was believed that the cuff was positioned too deep and, accord-
ingly, the depth of the ETT was adjusted to 11 cm (Figure 1B). The
operation concluded uneventfully and the patient exhibited no
hoarseness.
| 75
2
Department of Pediatric Surgery, Pontificia Universidad Catolica de
Chile, Santiago, Chile
Email: juancarl@med.puc.cl
REFERENCES
1. Polaner DM, Taenzer AH, Walker BJ, et al. Pediatric Regional Anes-
thesia Network (PRAN): a multi-institutional study of the use and inci-
dence of complications of pediatric regional anesthesia. Anesth Analg.
2012;115:1353-1364.
2. Forero M, Adhikary SD, Lopez H, Tsui C, Chin KJ. The erector spinae
plane block: a novel analgesic technique in thoracic neuropathic pain.
Reg Anesth Pain Med. 2016;41:621-627.
3. Mun ~oz F, Cubillos J, Bonilla AJ, Chin KJ. Erector spinae plane block
for postoperative analgesia in pediatric oncological thoracic surgery.
Can J Anaesth. 2017;64:880-882.
4. Bu€ttner W, Finke W. Analysis of behavioural and physiological param-
eters for the assessment of postoperative analgesic demand in new-
borns, infants and young children: a comprehensive report on seven
consecutive studies. Paediatr Anaesth. 2000;10:303-318.
Postoperative investigation revealed that the end of the cuff
inflating line was positioned 4 mm from the tip of the ETT, and
the longitudinal cuff diameter was about 12 mm (Figure 1C). The
cephalad edge of the cuff appeared to be positioned approximately
2 mm from the caudal edge of the cricoid cartilage, judging by the
distance between the end of the cuff inflating line and the cuff
cephalad edge at an intubation depth of 12 cm (Figure 1A). The
ETT, however, appeared to be positioned too shallow at an intuba-
tion depth of 11 cm (Figure 1B). Misunderstanding the structure of
the ETT could have resulted in intralaryngeal malpositioning of the
ETT.
The midtracheal level is helpful in determining the optimal inser-
tion depth of the ETT in pediatric patients.1 The positions of the tra-
chea, cricoid cartilage, thyroid cartilage, and the cuff inflating line
may be better visualized in the long-axis than the short-axis view.4
Long-axis ultrasound images of the saline-inflated cuff in this case
could not be observed, probably because of hyperechoic shadows
created by cartilage formation in the perichondrium.5 However, we
were able to obtain images of the cuff inflating line where hypere-
choic shadows did not exist. Thus, long-axis ultrasound imaging of a
saline-infiltrated cuff inflating line may facilitate correct positioning of
a pediatric ETT cuff below the caudal edge of the cricoid cartilage.
Information regarding the position of the end of the cuff inflating line
is important for correct positioning. Many cuffed ETT designs are
76 | CORRESPONDENCE

(A)

F I G U R E 1 Long-axis ultrasound images

(B)
of the larynx and trachea, and a 3.5 mm
internal diameter cuffed Mallinckrodtâ
endotracheal tube. A, A long-axis
ultrasound image of the cuff inflating line
at a depth of 12 cm. B, The end of the
cuff inflating line moved as the ETT was
withdrawn to a depth of 11 cm. C, The
end of the cuff inflating line positioned
4 mm from the tip of the cuffed ETT; the
cuff inflating line opened 17 mm from the
(C)
tip

poorly suited for use in small children. Both manufacturers and REFERENCES
clinicians must consider the potential dangers of these designs.
1. Song IK, Kim SH, Ryu J, et al. Prediction of the midtracheal level
based on external anatomical landmarks: implication of the optimal
insertion depth of endotracheal tubes in pediatric patients. Pediatr
CONFLICT OF INTEREST
Anesth. 2016;26:1142-1147.
No conflicts of interest declared. 2. Weiss M, Dullenkopf A, Gysin C, Dillier CM, Gerber AC. Shortcomings
of cuffed paediatric tracheal tubes. Br J Anaesth. 2004;92:78-88.
3. Tessaro MO, Salant EP, Arroyo AC, Haines LE, Dickman E. Tracheal
rapid ultrasound saline test (T.R.U.S.T.) for confirming correct endotra-
ORCID
cheal tube depth in children. Resuscitation. 2015;89:8-12.
4. Kayashima K, Doi T, Yamasaki R, Imai K. Long-axis ultrasonic images
Kenji Kayashima http://orcid.org/0000-0003-3727-8746
of the pediatric larynx and trachea with a cuffed endotracheal tube.
Anesthesiology. 2017;127:1016.
5. Kraft M, Mende S, Arnoux A, Arens C. Anatomical landmarks for
Kenji Kayashima endosonography of the larynx. Head Neck. 2010;32:326-332.
Keiko Imai
Department of Anesthesiology, Japan Community Health Care
Organization Kyushu Hospital, Kitakyushu, Fukuoka, Japan
Email: ken5ji5ka5ya5shi5ma@nifty.com