See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/235648907

Anesthetic Considerations in Infants With Hypoplastic Left Heart Syndrome

Article in Seminars in Cardiothoracic and Vascular Anesthesia · February 2013

DOI: 10.1177/1089253213476958 · Source: PubMed

CITATIONS READS
10 434

2 authors:

Mark Twite Richard John Ing

University of Colorado Children's Hospital Colorado
105 PUBLICATIONS 878 CITATIONS 103 PUBLICATIONS 1,142 CITATIONS

SEE PROFILE SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Kawasaki Disease View project

Editorial View project

All content following this page was uploaded by Mark Twite on 05 April 2017.

The user has requested enhancement of the downloaded file.

476958
ars in Cardiothoracic and Vascular AnesthesiaTwite and Ing
SCVXXX10.1177/1089253213476958Semin
Congenital Cardiac Forum
Anesthetic Considerations in Infants With
Hypoplastic Left Heart Syndrome
Mark D.Twite, MA, MB, BChir, FRCP1,2, and
Richard J. Ing, MB, BCh, FCA (SA)1,2
Abstract
Hypoplasia of the left ventricle is a congenital cardiac lesion that is almost universally fatal if left untreated. Six decades
of improved diagnostic modalities, greater understanding of single ventricle physiology, and earlier surgical and palliative
options have given many of these patients an opportunity of surviving well into adulthood. This review will summarize
these advances and focus on the anesthetic implications of this challenging disease from diagnosis to beyond the first
palliative surgery.
Keywords
hypoplastic left heart syndrome, congenital heart disease, anesthesia
Introduction
The term hypoplasia of the aortic tract complexes, initially
introduced by Lev in 1952, describes an almost uniformly
lethal group of congenital heart malformations with small
left-sided cardiac chambers.1 The diagnosis is seen in
1.2% to 1.5% of all congenital heart defects.2 Without
surgical intervention, approximately 90% of infants with
left ventricular hypoplasia will die when the ductus arte-
riosus closes spontaneously, usually within the first month
of life.2 In these early descriptions, small left-sided heart
chambers were associated with a diminutive ascending
and transverse aortic arch, large pulmonary artery, and
normally related great vessels.1,3 Subsequently, authors
have used the term hypoplastic left heart syndrome
(HLHS) interchangeably with Lev’s initial description of
hypoplasia of the aortic tract complexes.4,5 The early pal-
liative surgical attempts were associated with a very high
mortality. However, over the past 20 years, there have
been significant improvements in surgical outcomes, with
the current expectation that 70% of newborns born today
with HLHS may reach adulthood.6 Nomenclature for con-
genital heart lesions is important and today the term
HLHS is used to describe a hypoplastic left ventricle asso-
ciated with hypoplasia of the aortic arch. The aortic and
mitral valves may either be too small to allow adequate
blood flow or atretic (closed) with no antegrade blood
flow across them.6
The option of orthotopic heart transplantation for every
child presenting with HLHS has not been possible because
of limited donor organ availability.7 Therefore, building on
Seminars in Cardiothoracic and
Vascular Anesthesia
17(2) 137–145
© The Author(s) 2013
Reprints and permissions:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/1089253213476958
scv.sagepub.com
the surgical knowledge that has been acquired from treat-
ing children with tricuspid atresia, a surgical strategy to
palliate children with HLHS has been developed.8-11 Today
most children diagnosed with HLHS in the developed
world undergo a well-established series of 3-staged car-
diac operations before they are 4 years old. Survivors are
equipped with a single right ventricle supplying the entire
cardiac output to the body. Deoxygenated venous blood
returns to the lungs via a total cavopulmonary connection
or Fontan circulation without a ventricular pump to aug-
ment pulmonary blood flow.4,9,10,12 In many patients, right
ventricular dysfunction develops over time, and some of
these patients may require orthotopic heart transplantation
later in life.13
Despite these technical advances, there is often great
variability in the severity of left ventricular hypoplasia at
presentation, and there are still differences in the therapeu-
tic approach in centers of pediatric cardiovascular surgical
excellence throughout the world.6,14 For example, in less
severe forms of left ventricular hypoplasia with mild aortic
stenosis, it may be possible to surgically correct the left
ventricular outflow tract obstruction, and the systemic cir-
culation may then be supported with a biventricular
repair.15 Therefore, in this form of left ventricular
1
Children’s Hospital Colorado, Aurora, CO, USA
2
University of Colorado, Anschutz Medical Campus, Denver, CO, USA.
Corresponding Author:
Mark D. Twite, Department of Anesthesiology, Children’s Hospital
Colorado, 13123 East 16th Avenue, B090, Aurora, CO 80045, USA.
Email: mark.twite@childrenscolorado.org
138
hypoplasia, the term HLHS inadequately describes the
anatomy. The importance of early anatomical diagnosis to
the pediatric cardiac anesthesiologist is that by defining
the aortic outflow tract integrity and the severity of left
ventricular hypoplasia, adequate anesthetic planning is
facilitated. This review will focus on the current neonatal
anesthetic management of patients with HLHS for the first
staged cardiac palliation and noncardiac surgery.
Fetal Considerations of
Hypoplastic Left Heart Syndrome
As with other congenital heart defects, HLHS has been
shown to be heritable within families and it has also been
linked to other genetic abnormalities, such as Turner’s
syndrome, Jacobsen syndrome, trisomy 13, trisomy 18,
and Smith–Lemli–Opitz syndrome.16 The etiology of left
ventricular hypoplasia has long been considered multi-
factorial. Ventricular hypoplasia is known to occur sec-
ondary to left ventricular inflow or outflow tract
obstruction, changes in phasic blood flow patterns, endo-
thelial sheer stress from altered blood flow patterns, and
therefore, changes in signal transduction factors in the
developing heart.17-20 Recently, a study of pathological
heart specimen in HLHS, found a frame shift mutation
(A126fs) in early ventricular development helix loop
transcription factor, HAND-1, in 77% of hypoplastic left
ventricular tissue.20,21 HAND-1 and HAND-2 play a role
in ventricular development and left–right axis determina-
tion in the developing heart.20
Although the heart is almost fully developed at 8 weeks
of gestation, the continued normal growth of the heart
depends on normal fetal circulation. Any interruption to
this fetal circulation, such as a restrictive atrial septum or
abnormal development of the left sided cardiac valves,
may result in underdevelopment of the left sided heart
structures and HLHS. The normal fetal circulation allows
communications between the pulmonary and systemic cir-
culations via the foramen ovale and the ductus arteriousus,
which allows both ventricles to contribute to the work of
supplying blood to the developing fetus. In HLHS, in utero
shunting of blood across the atrial septum is reversed from
the normal pattern as the small amount of blood returning
to the left atrium from the pulmonary veins predominantly
crosses the atrial septum into the right atrium. The major-
ity of blood leaving the right ventricle passes through the
ductus arteriosus to supply the lower body. In extreme
cases of HLHS with aortic atresia, the myocardial and
cerebral circulations are supplied by the ductus in a retro-
grade manner.
About 60% of children with HLHS are diagnosed pre-
natally because of the widespread availability of ultra-
sound screening.22 Infants without a prenatal diagnosis of
HLHS may be detected because of a murmur or cyanosis
Seminars in Cardiothoracic and Vascular Anesthesia 17(2)
discovered in the newborn nursery prior to discharge
home. Occasionally, some infants are diagnosed only
after cardiovascular collapse following closure of the
ductus arteriousus. The advantages of prenatal diagnosis
are to give the parents information and counseling on
HLHS and to refer them to a congenital cardiac program
that has expertise to manage their newborn child. It also
allows for genetic testing and evaluation of extracardiac
anomalies, which, in association with a diagnosis of
HLHS, carries a worse prognosis.23,24 In this situation,
counseling may also provide the option to terminate preg-
nancy or provide comfort care only after birth. Although
prenatal diagnosis of HLHS allows for parental prepara-
tion and the coordination of health care teams, it is not
associated with a survival advantage, fewer postoperative
complications, or shorter length of hospital stay following
stage 1 surgery.25
However, prenatal diagnosis does allow for potential
fetal cardiac intervention.26 There are 2 possible in utero
interventions depending on the underlying condition.
First, in a fetus with an intact or highly restrictive atrial
septum, an atrial septal defect may be created and, if nec-
essary, a stent placed in the septum to keep it open.
Approximately 10% to 20% of fetuses with HLHS have
some degree of atrial restriction. Prenatal detection of this
restriction is possible using fetal echocardiography and a
pulmonary venous Doppler forward/reverse time–velocity
integral ratio. In a fetus with HLHS and a Doppler forward/
reverse time–velocity integral ratio of 3 or less, it is very
likely an emergency atrial septostomy will be required
after delivery unless an in utero fetal atrial septostomy is
performed.27 The prenatal presence of atrial septal restric-
tion in the setting of HLHS confers a survival disadvan-
tage, with increases in both early and late mortality.28 The
mechanism of this is likely due to the chronic in utero left
atrial hypertension adversely affecting the development of
the pulmonary vasculature. Whether fetal cardiac inter-
vention creating an atrial septal communication could
potentially reduce the pathologic pulmonary process and
thus improve outcomes is not known.
The second scenario for fetal cardiac intervention is in
the fetus with aortic stenosis and evolving HLHS. On
echocardiogram, the ventricle often appears bright
because of endocardial fibroelastosis, and the systolic
function is usually poor. Prenatal balloon aortic valvulo-
plasty may improve left heart growth and function, pos-
sibly preventing evolution to HLHS. Technical success,
defined as the ability to perform the balloon valvuloplasty,
is currently around 80% in experienced centers. Moderate
to severe postdilation aortic regurgitation occurs in 40%
of technically successful procedures.26 Fetal aortic valvu-
loplasty carries a risk of fetal demise of about 10%.29
Whether fetal aortic valvuloplasty results in increased
chances of biventricular repair remains unclear. In cases
Twite and Ing
where biventricular circulation is not achieved, a func-
tioning left ventricle will contribute to improved cardiac
output in the single ventricle patient.
Most fetal cardiac interventions require an obstetric
anesthesia team, to provide general anesthesia for the
mother, and a fetal anesthesia team. The main limitations
to developments in this field are inadequacies in equip-
ment and imaging for the procedure and our lack of under-
standing of fetal–maternal physiology.30
Preoperative Management
Regardless of presentation, infants with HLHS require
careful management during the interim period between
diagnosis and surgery. The management goals at this time
include clinical stabilization, complete definition of car-
diac anatomy, and diagnosis of extracardiac problems.
Preoperative medical management varies widely among
different centers.31 One therapy common to all centers car-
ing for neonates with HLHS is the use of prostaglandin E1
to maintain ductal patency for adequate systemic blood
flow. As pulmonary vascular resistance (PVR) falls after
birth, balancing the systemic and pulmonary circulations
becomes essential. There are many strategies to achieve
this balanced circulation, including the use of intubation
and mechanical ventilation. The ventilation techniques
used include ventilation in room air or a hypoxic gas mix-
ture, or using inhaled carbon dioxide, all of which will
increase PVR.32 Other management strategies aim to
increase cardiac output with inotropic support and/or
reduce afterload.33 However, what may be most important
for all these strategies is how to effectively monitor them.
The use of near-infrared spectroscopy (NIRS) on the fore-
head and flank of patients with HLHS awaiting palliation
provides noninvasive assessment of oxygen delivery and
has been shown to reduce the use of controlled ventilation
and inspired gas mixtures.34
In addition to transthoracic echocardiography to
delineate accurate cardiac anatomy, the use of cardiac
magnetic resonance imaging (cMRI) is increasing. cMRI
may be used to assist surgical planning, including the
decision for a single versus 2-ventricle repair.35 In a study
of 20 neonates with borderline left ventricle hypoplasia,
it was found that echocardiography consistently underes-
timated left ventricular volumes compared with MRI and
may unfairly preclude some patients from a biventricular
repair.36 Many of these infants will require general anes-
thesia for a successful cMRI. Patient immobility, and in
some centers, patient breath holds are important factors
for high quality studies. These patients with complex car-
diac physiology are at increased risk of adverse events in
the MRI scanner compared with healthy infants and
require the attention of a dedicated cardiac anesthesia
team.37,38
139
Three strategies for the postnatal management of HLHS
exist—hybrid palliation, stage 1 Norwood procedure, and
orthotopic heart transplantation. This review will only dis-
cuss the first 2 strategies. The common objectives for both
of these strategies are to provide an unobstructed systemic
cardiac output, a controlled source of pulmonary blood
flow, a reliable source of coronary blood flow, and unob-
structed outflow of the pulmonary veins.
Hybrid Palliation
An alternative postdelivery intervention strategy advo-
cated by some centers almost routinely, and in others for
high-risk HLHS children with coexisting disease, is a
hybrid approach with cardiologist and cardiac surgeon
working side by side in the cardiac catheterization labora-
tory.39 Following sternotomy, direct access is made to the
right atrium with a purse string secured sheath. This
approach is safer than accessing small femoral vessels that
are prone to thrombosis and occlusion when large intra-
vascular sheaths are placed in newborn children.40 First,
the cardiologists may perform an interatrial balloon sep-
tostomy if inadequate mixing of atrial blood is present.
Second, the cardiologist will place a stent in the ductus
arteriosus to ensure a stable source of systemic blood
flow. Finally, to complete the procedure, a cardiac surgeon
performs bilateral pulmonary artery banding. This hybrid
palliation procedure is performed without the need for
cardiopulmonary bypass (CPB). A study from a large
hybrid palliation center, reports the average age of patients
undergoing hybrid palliation as 11.8 days with an average
weight of 2.98 kg. Fentanyl was used for analgesia at an
average dose of 5.7 µg/kg. Twenty-seven percent of
patients received a blood transfusion during the proce-
dure, and the majority of patients were extubated within
24 hours of the procedure. The study authors report that
the patients had stable intraoperative and early postopera-
tive hemodynamics.41 This hybrid palliation procedure
defers the risks of anesthesia, CPB, hypothermia, and
prolonged postoperative sedation and may confer devel-
opmental advantages to patients born with HLHS who are
known to have abnormal brain development.39,42 However,
current literature does not indicate better outcomes with
this hybrid approach beyond the second stage palliated
Glenn surgery for HLHS.43
Stage I Norwood Procedure
The classic surgical approach to HLHS and its variants
was developed by Norwood and colleagues in 1980 fol-
lowing on from the report in 1970 by Cayler et al.8
Currently, the first stage surgery consists of an atrial sep-
tectomy to improve mixing of oxygenated blood and
relieve pulmonary venous hypertension, reconstruction of
140
the aortic arch, and the creation of a controlled source of
pulmonary blood flow either with a modified Blalock–
Tausig shunt (MBT) or a right ventricle to pulmonary
artery (RV-PA) Sano shunt. These 3 procedures are carried
out on CPB and are commonly referred to as a stage I
Norwood procedure.11 The diastolic runoff associated
with the MBT shunt may result in poor coronary perfusion
during diastole, so-called “coronary steal.”44 This problem
had previously been addressed with the RV-PA shunt in
1981, however, it was decades later that it was popularized
once more and successful results with it were reported.12,45
The anesthetic approach to the Norwood procedure is
similar to the setup for most cardiac surgeries on CPB.
Arterial pressure line monitoring is used, and the indwell-
ing catheter should preferably be placed in the right radial
artery to ensure cerebral perfusion pressures are monitored
during selective anterograde cerebral perfusion through-
out the aortic arch reconstruction. Central venous access is
required and usually femoral vessels or an existing umbili-
cal venous catheter are preferred to avoid the internal jug-
ular vein. This minimizes venous complications and
preserves the patency of the internal jugular vein and supe-
rior vena cava for the next surgical stage, the modified
Glenn procedure or cavopulmonary anastomosis.46
However, subsequent femoral vessel occlusion may make
future cardiac catheterizations difficult.
In patients with a single ventricle, the most important
anesthetic principle is to maintain the balance of pulmo-
nary: systemic blood flow (Qp:Qs) as close to 1:1 as pos-
sible. To achieve this, maintaining a good cardiac output is
essential, and inotropic support is used as required.
Peripheral oxygen saturation should be close to 80% with
as low an inspired oxygen concentration as feasible. It is
essential to avoid hyperventilation with a high inspired
oxygen concentration as this causes hypocarbia and hyper-
oxia, both of which lower the PVR and increase the Qp:Qs
ratio >1. The consequence of a high pulmonary blood flow
is a low systemic cardiac output resulting in decreased
oxygen delivery to the vital organs and subsequently a
metabolic acidosis quickly ensues. In other words, in this
parallel circulation, for every red cell that preferentially
passes through the pulmonary vascular bed, there is one
less red cell passing though the systemic circulation and
delivering oxygen, which results in anaerobic metabolism
and lactic acidosis. Early studies found preoperative meta-
bolic acidosis to be a risk factor for greater mortality fol-
lowing surgical repair.47 This unique pathophysiological
state of increased pulmonary blood flow at the expense of
systemic blood flow unwittingly places the infant at risk of
sudden cardiac arrest in the perioperative period despite
excellent oxygen saturations.47
One of the earliest reports on the successful use of an
intraoperative anesthetic agent in children undergoing the
Norwood procedure highlighted the safety of fentanyl
Seminars in Cardiothoracic and Vascular Anesthesia 17(2)
administered at 50 µg/kg during the procedure.48 Today, a
balanced anesthetic approach, using fentanyl and low con-
centrations of inhaled anesthetic agent, such as isoflurane,
is the technique utilized by most anesthesiologists intraop-
eratively. A recent systematic review on brain protective
strategies during CPB in children found that avoiding
extreme hemodilution on CPB is the only current recommen-
dation.49 There are many investigators who are concerned
with the use of benzodiazepines, ketamine, isoflurane,
nitrous oxide, and propofol in small children because of
the compelling findings of accelerated neuro-apoptosis in
neonatal primate studies.50,51 Dexmedetomidine has been
shown to have opiate sparing properties and minimal
hemodynamic effects on postoperative single ventricle
patients in the intensive care unit.52
Stage I surgery requires periods of regional low-flow
cerebral perfusion or deep hypothermic cardiac arrest at
18°C to 20°C to reconstruct the aortic tract. The child’s
head should be cooled slowly and uniformly to prevent
cerebral vasoconstriction and to ensure hypothermic pro-
tection of all cerebral structures.53 This operation creates
systemic blood flow without ventricular outflow obstruc-
tion and prevents pressure loading of the single ventricle.
Surgery is completed with a MBT shunt or RV-PA shunt.45
Either option for surgical shunt ensures stable pulmonary
blood flow while the infant grows. The RV-PA shunt has
been shown to confer greater postoperative hemodynamic
stability with a higher diastolic blood pressure and greater
heart transplantation–free survival at 12 months of age
compared with the Norwood procedure with the MBT
shunt.54 Recently, it has been found that single ventricle
anatomy preterm infants with a patent aortic valve benefit
more from a MBT shunt compared with a RV-PA shunt.55
Some investigators consider that the right ventricular
function and anatomy, but not shunt type, determines the
need for subsequent heart transplantation.55
It has recently been shown that a greater requirement
for vasoactive inotropes in the first 48 hours post cardiac
surgery is a good predictor of poor clinical outcomes,
including death, cardiac arrest, mechanical circulatory
support, renal replacement therapy, and/or neurologic
injury.56 Although inotropic use varies at different centers,
milrinone, epinephrine, and dopamine are extensively
used.57 Milrinone has been shown to safely avoid a low
cardiac output state in children following cardiac sur-
gery.57,58 Some investigators have found a deleterious
increase in oxygen consumption in neonates following the
Norwood procedure, with the use of dopamine.59
Therefore, planning the choice of inotropic agent and the
dose to be administered is essential to good clinical out-
comes in patients following the Norwood operation.59
Ideally, if surgical anatomical repair has been achieved,
and myocardial function has been preserved, the postop-
erative recovered, extubated, HLHS patient should achieve
Twite and Ing
a Qp:Qs ratio close to 1 in room air. Intensive, early post-
operative monitoring of high-risk patients has been shown
to achieve good outcomes.60,61
Postoperative Intensive Care
Management
The pre-, intra-, and postoperative management strategies
for infants with HLHS are a continuum of care. However,
following open heart surgery with CPB, there is the prob-
lem of low cardiac output, which is characterized by
reduced systemic oxygen delivery, high systemic oxygen
extraction, and anaerobic end-organ dysfunction. The
cause of this low cardiac output state is multifactorial but
includes the systemic inflammatory response syndrome to
surgery and CPB.62,63 Infants with single ventricle anat-
omy have the added burden that the total ventricular mass
available to generate cardiac output is reduced and the
parallel pulmonary and systemic circulations result in the
need for double the normal total cardiac output from a
single ventricle. Achieving normal systemic oxygen deliv-
ery at the lowest total cardiac output requires an arteriove-
nous oxygen saturation difference of 20% to 50% and a
Qp:Qs ratio of close to 1.0.64,65 However, with single
ventricle physiology, standard monitoring provides inad-
equate information resulting in a high rate of cardiac arrest
and organ dysfunction. In a multicenter randomized con-
trolled trial of HLHS patients who were postoperative
from stage 1 Norwood palliation, 10% were placed on
extracorporeal membrane oxygenation and 15% required
cardiopulmonary resuscitation.54 There is also a wide vari-
ability in hemodynamics and oxygen transport following
the stage 1 Norwood procedure. Li et al66 found that a
decrease in oxygen consumption (VO2) during the first 24
hours postoperatively was the main contributor to improv-
ing the balance of oxygen delivery. Systemic oxygen
delivery (DO2) was most closely correlated to systemic
vascular resistance and hemoglobin and weakly correlated
to PaO2, and it was not correlated with Qp. The study
authors concluded that postoperative management strate-
gies aimed at decreasing VO2, maintaining a high hemo-
globin level and a low systemic vascular resistance may
improve outcomes.66 The routine use of venous oximetry
(SvO2) during the first 48 hours after surgery has been
associated with improved early and intermediate survival,
fewer complications, and improved neurodevelopment at
4 to 6 years of age, particularly when SvO2 is >50%.65,67,68
Many centers now routinely use NIRS for a continuous
and noninvasive estimate of SvO2. Monitoring NIRS in
both cerebral and flank locations has been shown to pro-
vide closer estimates of SvO2 and to be a good predictor
of outcomes.60,69,70 Another postoperative early indicator
of low cardiac output and decreased systemic oxygen
delivery is blood lactate level. Murtuza et al71 showed that
141
the inability to clear blood lactate levels to <6.8 mmol/L
within the first 24 hours following stage 1 Norwood pro-
cedure with a Sano shunt was a strong predictor of periop-
erative mortality.71 However, it is usually not a single
parameter but a combination of parameters that have the
strongest influence on postoperative decisions made by
the intensive care unit team. In a prospective study of 52
high-risk children following open-heart surgery, Seear
et al72 found that lactate levels and SvO2 were the only
postoperative measurements with predictive power for
major adverse events and that a combination of the 2
parameters increased this predictive power.
Anesthetic Considerations for
Noncardiac Surgery Following
Stage I Surgical Palliation
Some children with HLHS may have pulmonary venous
abnormalities or associated parenchymal lung disease.
Children often convalesce for a few weeks on the ward
before being discharged from hospital. During this period
of increased inspired oxygen requirements, meticulous
monitoring of postoperative oxygen saturations and
weight gain has become essential to good clinical inter-
stage surgical outcomes.73,74
Following the first stage palliative surgery for HLHS,
3% to 45% of children have been shown to have laryngo-
pharyngeal dysfunction. Forty-eight percent of these
patients develop dysphagia, and 9% to 26% have gastro-
esophageal reflux disease.75,76 These medical problems are
known to increase patient mortality and morbidity and
often result in delayed growth.77 Because of the changes in
hemodynamics following the Norwood procedure, blood
can be shunted away from the splanchnic bed toward the
brain. This places the bowel at risk for ischemia.78,79 The
median incidence of necrotizing enterocolitis in children
undergoing the Norwood procedure is 11% to 20%.80
Because of the high incidence of feeding difficulties in
these children, pediatric anesthesiologists are often
requested to provide general anesthesia for aerodigestive
work-up, including flexible and rigid bronchoscopy, and
laparoscopic Nissen fundoplication and gastrostomy tube
insertion.81-83 The anesthetic challenges include the single
ventricle physiology and a patient who often has difficult
peripheral intravenous access, which may be further exac-
erbated secondary to dehydration due to prolonged fasting
and diuretic use. Acute patient decompensation may be
due to systemic-to-pulmonary artery shunt occlusion, and
this may require emergent intervention in the cardiac cath-
eterization laboratory and/or placement on extracorporeal
membrane oxygenation support.84 These noncardiac sur-
geries in children with congenital heart disease have a
perioperative cardiac arrest incidence of 22% to 27%.85 In
142
a recent series, 18% of stage 1 completed HLHS patients
required post noncardiac surgery intensive care unit
admission.86 In another series, there was a postoperative
complication rate of 50%,81 and in another report, 19%
died during hospitalization for noncardiac surgery.87 These
studies highlight the need for experienced cardiac anesthe-
sia providers during these procedures. Following stage I
surgery, single ventricle children should ideally only
undergo surgeries at centers adequately equipped and
trained to care for these children.
Conclusion
The therapy for HLHS, once an almost uniformly lethal
disease, has progressed extensively over the last 6 decades.
Currently, a far better understanding of the physiological
implications of the single ventricle patient exists than was
ever possible before. The strides made in cardiology and
diagnostic modalities, surgical intervention techniques,
pharmacology, bedside monitoring, anesthesiology, and
intensive care therapy have all played a role in creating the
expectation that 70% of children born today with HLHS
in the developed world, may reach adulthood.6
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
References
1. Lev M. Pathologic anatomy and interrelationship of hypopla-
sia of the aortic tract complexes. Lab Invest. 1952;1:61-70.
2. Morris CD, Outcalt J, Menashe VD. Hypoplastic left heart
syndrome: natural history in a geographically defined popu-
lation. Pediatrics. 1990;85:977-983.
3. Sinha SN, Rusnak SL, Sommers HM, Cole RB, Muster AJ,
Paul MH. Hypoplastic left ventricle syndrome. Analysis of
thirty autopsy cases in infants with surgical considerations.
Am J Cardiol. 1968;21:166-173.
4. Noonan JA, Nadas AS. The hypoplastic left heart syn-
drome: an analysis of 101 cases. Pediatr Clin North Am.
1958;5:1029-1056.
5. Lumb G, Dawkins WA. Congenital atresia of mitral and aor-
tic valves with vestigial left ventricle (three cases). Am Heart
J. 1960;60:378-387.
6. Feinstein JA, Benson DW, Dubin AM, et al. Hypoplastic left
heart syndrome: current considerations and expectations. J
Am Coll Cardiol. 2012;59(1 suppl):S1-S42.
7. Irving C, Parry G, Cassidy J, Hasan A, Griselli M, Kirk R.
Outcomes following infant listing for cardiac transplantation: the
Seminars in Cardiothoracic and Vascular Anesthesia 17(2)
impact of strategies introduced to counteract limited donor
availability. Arch Dis Child. 2010;95:883-887.
8. Cayler GG, Smeloff EA, Miller GE Jr. Surgical pal-
liation of hypoplastic left side of the heart. N Engl J Med.
1970;282:780-783.
9. Glenn WW, Gardner TH Jr, Talner NS, Stansel HC Jr,
Matano I. Rational approach to the surgical manage-
ment of tricuspid atresia. Circulation. 1968;37(4 suppl):
II62-II67.
10. Fontan F, Baudet E. Surgical repair of tricuspid atresia. Tho-
rax. 1971;26:240-248.
11. Norwood WI, Lang P, Casteneda AR, Campbell DN. Experi-
ence with operations for hypoplastic left heart syndrome. J
Thorac Cardiovasc Surg. 1981;82:511-519.
12. Norwood WI, Kirklin JK, Sanders SP. Hypoplastic left heart
syndrome: experience with palliative surgery. Am J Cardiol.
1980;45:87-91.
13. Murtuza B, Dedieu N, Vazquez A, et al. Results of orthotopic
heart transplantation for failed palliation of hypoplastic left
heart [published online July 3, 2012]. Eur J Cardiothorac
Surg. doi:10.1093/ejcts/ezs326.
14. Schidlow DN, Anderson JB, Klitzner TS, et al. Variation in
interstage outpatient care after the Norwood procedure: a
report from the Joint Council on Congenital Heart Disease
National Quality Improvement Collaborative. Congenit
Heart Dis. 2011;6:98-107.
15. Tchervenkov CI. Indications, criterions, and principles
for biventricular repair. Cardiol Young. 2004;14(suppl 1):
97-100.
16. Natowicz M, Chatten J, Clancy R, et al. Genetic disorders
and major extracardiac anomalies associated with the hypo-
plastic left heart syndrome. Pediatrics. 1988;82:698-706.
17. Harh JY, Paul MH, Gallen WJ, Friedberg DZ, Kaplan S.
Experimental production of hypoplastic left heart syndrome
in the chick embryo. Am J Cardiol. 1973;31:51-56.
18. Groenendijk BC, Van der Heiden K, Hierck BP, Poelmann
RE. The role of shear stress on ET-1, KLF2, and NOS-3
expression in the developing cardiovascular system of
chicken embryos in a venous ligation model. Physiology
(Bethesda). 2007;22:380-389.
19. Chintala K, Tian Z, Du W, Donaghue D, Rychik J. Fetal pul-
monary venous Doppler patterns in hypoplastic left heart
syndrome: relationship to atrial septal restriction. Heart.
2008;94:1446-1449.
20. Hickey EJ, Caldarone CA, McCrindle BW. Left ventricular
hypoplasia: a spectrum of disease involving the left ventricu-
lar outflow tract, aortic valve, and aorta. J Am Coll Cardiol.
2012;59(1 suppl):S43-S54.
21. Reamon-Buettner SM, Ciribilli Y, Inga A, Borlak J. A loss-
of-function mutation in the binding domain of HAND1
predicts hypoplasia of the human hearts. Hum Mol Genet.
2008;17:1397-1405.
22. Stumper O. Hypoplastic left heart syndrome. Heart.
2010;96:231-236.
Twite and Ing
23. Stasik CN, Gelehrter S, Goldberg CS, Bove EL, Devaney EJ,
Ohye RG. Current outcomes and risk factors for the Norwood
procedure. J Thorac Cardiovasc Surg. 2006;131:412-417.
24. Baker K, Sanchez-de-Toledo J, Munoz R, et al. Critical con-
genital heart disease: utility of routine screening for chromo-
somal and other extracardiac malformations. Congenit Heart
Dis. 2012;7:145-150.
25. Kipps AK, Feuille C, Azakie A, et al. Prenatal diagnosis of
hypoplastic left heart syndrome in current era. Am J Cardiol.
2011;108:421-427.
26. McElhinney DB, Tworetzky W, Lock JE. Current status of
fetal cardiac intervention. Circulation. 2010;121:1256-1263.
27. Divanović A, Hor K, Cnota J, Hirsch R, Kinsel-Ziter M,
Michelfelder E. Prediction and perinatal management of
severely restrictive atrial septum in fetuses with critical left heart
obstruction: clinical experience using pulmonary venous Dop-
pler analysis. J Thorac Cardiovasc Surg. 2011;141:988-994.
28. Lowenthal A, Kipps AK, Brook MM, Meadows J, Azakie A,
Moon-Grady AJ. Prenatal diagnosis of atrial restriction in
hypoplastic left heart syndrome is associated with decreased
2-year survival. Prenat Diagn. 2012;32:485-490.
29. Kohl T, Breuer J, Heep A, Wenningmann I, Weinbach J,
Gembruch U. Fetal transesophageal echocardiography dur-
ing balloon valvuloplasty for severe aortic valve stenosis
at 28+6 weeks of gestation. J Thorac Cardiovasc Surg.
2007;134:256-257.
30. Bacha EA. Impact of fetal cardiac intervention on congenital
heart surgery. Semin Thorac Cardiovasc Surg Pediatr Card
Surg Annu. 2011;14:35-37.
31. Brown DW, Connor JA, Pigula FA, et al. Variation in pre-
operative and intraoperative care for first-stage palliation of
single-ventricle heart disease: a report from the Joint Council
on Congenital Heart Disease National Quality Improvement
Collaborative. Congenit Heart Dis. 2011;6:108-115.
32. Ramamoorthy C, Tabbutt S, Kurth CD, et al. Effects of
inspired hypoxic and hypercapnic gas mixtures on cerebral
oxygen saturation in neonates with univentricular heart
defects. Anesthesiology. 2002;96:283-288.
33. Krushansky E, Burbano N, Morell V, et al. Preoperative man-
agement in patients with single-ventricle physiology. Conge-
nit Heart Dis. 2012;7:96-102.
34. Johnson BA, Hoffman GM, Tweddell JS, et al. Near-infrared
spectroscopy in neonates before palliation of hypoplastic left
heart syndrome. Ann Thorac Surg. 2009;87:571-577.
35. Dillman JR, Dorfman AL, Attili AK, et al. Cardiovascular
magnetic resonance imaging of hypoplastic left heart syn-
drome in children. Pediatr Radiol. 2010;40:261-274.
36. Grosse-Wortmann L, Yun TJ, Al-Radi O, et al. Border-
line hypoplasia of the left ventricle in neonates: insights
for decision-making from functional assessment with
magnetic resonance imaging. J Thorac Cardiovasc Surg.
2008;136:1429-1436.
37. Stockton E, Hughes M, Broadhead M, Taylor A, McEwan A.
A prospective audit of safety issues associated with general
143
anesthesia for pediatric cardiac magnetic resonance imaging.
Paediatr Anaesth. 2012;22:1087-1093.
38. Dorfman AL, Odegard KC, Powell AJ, Laussen PC, Geva T.
Risk factors for adverse events during cardiovascular mag-
netic resonance in congenital heart disease. J Cardiovasc
Magn Reson. 2007;9:793-798.
39. Kutty S, Burke RP, Hannan RL, Zahn EM. Hybrid aortic
reconstruction for treatment of recurrent aortic obstruction
after stage 1 single ventricle palliation: medium term out-
comes and results of redilation. Catheter Cardiovasc Interv.
2011;78:93-100.
40. Dumond AA, da Cruz E, Almodovar MC, Friesen RH. Femo-
ral artery catheterization in neonates and infants. Pediatr Crit
Care Med. 2012;13:39-41.
41. Naguib AN, Winch P, Schwartz L, et al. Anesthetic manage-
ment of the hybrid stage 1 procedure for hypoplastic left
heart syndrome (HLHS). Paediatr Anaesth. 2010;20:38-46.
42. Hinton RB, Andelfinger G, Sekar P, et al. Prenatal head
growth and white matter injury in hypoplastic left heart syn-
drome. Pediatr Res. 2008;64:364-369.
43. Photiadis J, Sinzobahamvya N, Hraška V, Asfour B. Does
bilateral pulmonary banding in comparison to norwood
procedure improve outcome in neonates with hypoplas-
tic left heart syndrome beyond second-stage palliation? A
review of the current literature. Thorac Cardiovasc Surg.
2012;60:181-188.
44. Ohye RG, Ludomirsky A, Devaney EJ, Bove EL. Com-
parison of right ventricle to pulmonary artery conduit
and modified Blalock-Taussig shunt hemodynamics
after the Norwood operation. Ann Thorac Surg. 2004;78:
1090-1093.
45. Sano S, Ishino K, Kawada M, et al. Right ventricle-pul-
monary artery shunt in first-stage palliation of hypoplastic
left heart syndrome. J Thorac Cardiovasc Surg. 2003;126:
504-509.
46. Wu ET, Takeuchi M, Imanaka H, Higuchi T, Kagisaki K.
Chylothorax as a complication of innominate vein thrombo-
sis induced by a peripherally inserted central catheter. Anaes-
thesia. 2006;61:584-586.
47. Bando K, Turrentine MW, Sun K, et al. Surgical manage-
ment of hypoplastic left heart syndrome. Ann Thorac Surg.
1996;62:70-76.
48. Hansen DD, Hickey PR. Anesthesia for hypoplastic left heart
syndrome: use of high-dose fentanyl in 30 neonates. Anesth
Analg. 1986;65:127-132.
49. Hirsch JC, Jacobs ML, Andropoulos D, et al. Protecting the
infant brain during cardiac surgery: a systematic review. Ann
Thorac Surg. 2012;94:1365-1373.
50. Brambrink AM, Back SA, Riddle A, et al. Isoflurane-induced
apoptosis of oligodendrocytes in the neonatal primate brain.
Ann Neurol. 2012;72:525-535.
51. Brambrink AM, Evers AS, Avidan MS, et al. Ketamine-
induced neuroapoptosis in the fetal and neonatal rhesus
macaque brain. Anesthesiology. 2012;116:372-384.
144
52. Lam F, Bhutta AT, Tobias JD, Gossett JM, Morales L,
Gupta P. Hemodynamic effects of dexmedetomidine in
critically ill neonates and infants with heart disease. Pediatr
Cardiol. 2012;33:1069-1077.
53. Greeley WJ, Kern FH, Ungerleider RM, et al. The effect of
hypothermic cardiopulmonary bypass and total circulatory
arrest on cerebral metabolism in neonates, infants, and chil-
dren. J Thorac Cardiovasc Surg. 1991;101:783-794.
54. Ohye RG, Sleeper LA, Mahony L, et al. Comparison of shunt
types in the Norwood procedure for single-ventricle lesions.
N Engl J Med. 2010;362:1980-1092.
55. Tweddell JS, Sleeper LA, Ohye RG, et al. Intermediate-term
mortality and cardiac transplantation in infants with single-
ventricle lesions: risk factors and their interaction with shunt
type. J Thorac Cardiovasc Surg. 2012;144:152-159.
56. Gaies MG, Gurney JG, Yen AH, et al. Vasoactive-inotropic
score as a predictor of morbidity and mortality in infants
after cardiopulmonary bypass. Pediatr Crit Care Med.
2010;11:234-238.
57. Baker-Smith CM, Neish SR, Klitzner TS, et al. Variation
in postoperative care following stage I palliation for sin-
gle-ventricle patients: a report from the Joint Council on
Congenital Heart Disease National Quality Improvement
Collaborative. Congenit Heart Dis. 2011;6:116-127.
58. Hoffman TM, Wernovsky G, Atz AM, et al. Efficacy
and safety of milrinone in preventing low cardiac out-
put syndrome in infants and children after corrective sur-
gery for congenital heart disease. Circulation. 2003;107:
996-1002.
59. Li J, Zhang G, Holtby H, et al. Adverse effects of dopamine
on systemic hemodynamic status and oxygen transport in
neonates after the Norwood procedure. J Am Coll Cardiol.
2006;48:1859-1864.
60. Ghanayem NS, Hoffman GM, Mussatto KA, et al. Periopera-
tive monitoring in high-risk infants after stage 1 palliation of
univentricular congenital heart disease. J Thorac Cardiovasc
Surg. 2010;140:857-863.
61. Li J. Systemic oxygen transport derived by using continu-
ous measured oxygen consumption after the Norwood pro-
cedure-an interim review. Interact Cardiovasc Thorac Surg.
2012;15:93-101.
62. Levy JH, Tanaka KA. Inflammatory response to cardiopul-
monary bypass. Ann Thorac Surg. 2003;75:S715-S720.
63. Brix-Christensen V. The systemic inflammatory response
after cardiac surgery with cardiopulmonary bypass in chil-
dren. Acta Anaesthesiol Scand. 2001;45:671-679.
64. Hoffman GM, Ghanayem NS, Kampine JM, et al. Venous
saturation and the anaerobic threshold in neonates after the
Norwood procedure for hypoplastic left heart syndrome. Ann
Thorac Surg, 2000;70:1515-1520.
65. Tweddell JS, Hoffman GM, Mussatto KA, et al. Improved
survival of patients undergoing palliation of hypoplastic
left heart syndrome: lessons learned from 115 consecutive
patients. Circulation. 2002;106:I82-I89.
Seminars in Cardiothoracic and Vascular Anesthesia 17(2)
66. Li J, Zhang G, McCrindle BW, et al. Profiles of hemodynam-
ics and oxygen transport derived by using continuous mea-
sured oxygen consumption after the Norwood procedure. J
Thorac Cardiovasc Surg. 2007;133:441-448.
67. Tweddell JS, Ghanayem NS, Mussatto KA, et al. Mixed
venous oxygen saturation monitoring after stage 1 pallia-
tion for hypoplastic left heart syndrome. Ann Thorac Surg.
2007;84:1301-1310.
68. Hoffman GM, Mussatto KA, Brosig CL, et al. Systemic
venous oxygen saturation after the Norwood procedure and
childhood neurodevelopmental outcome. J Thorac Cardio-
vasc Surg. 2005;130:1094-1100.
69. Chakravarti SB, Mittnacht AJ, Katz JC, Nguyen K, Joashi U,
Srivastava S. Multisite near-infrared spectroscopy predicts
elevated blood lactate level in children after cardiac surgery.
J Cardiothorac Vasc Anesth. 2009;23:663-667.
70. Kaufman J, Almodovar MC, Zuk J, Friesen RH. Correlation
of abdominal site near-infrared spectroscopy with gastric
tonometry in infants following surgery for congenital heart
disease. Pediatr Crit Care Med. 2008;9:62-68.
71. Murtuza B, Wall D, Reinhardt Z, et al. The importance of
blood lactate clearance as a predictor of early mortality fol-
lowing the modified Norwood procedure. Eur J Cardiotho-
rac Surg. 2011;40:1207-1214.
72. Seear MD, Scarfe JC, LeBlanc JG. Predicting major adverse
events after cardiac surgery in children. Pediatr Crit Care
Med. 2008;9:606-611.
73. Ghanayem NS, Hoffman GM, Mussatto KA, et al. Home
surveillance program prevents interstage mortality after
the Norwood procedure. J Thorac Cardiovasc Surg.
2003;126:1367-1377.
74. Petit CJ, Fraser CD, Mattamal R, Slesnick TC, Cephus CE,
Ocampo EC. The impact of a dedicated single-ventricle
home-monitoring program on interstage somatic growth,
interstage attrition, and 1-year survival. J Thorac Cardiovasc
Surg. 2011;142:1358-1366.
75. Davis D, Davis S, Cotman K, et al. Feeding difficulties and
growth delay in children with hypoplastic left heart syn-
drome versus d-transposition of the great arteries. Pediatr
Cardiol. 2008;29:328-333.
76. Skinner ML, Halstead LA, Rubinstein CS, Atz AM,
Andrews D, Bradley SM. Laryngopharyngeal dysfunction
after the Norwood procedure. J Thorac Cardiovasc Surg.
2005;130:1293-1301.
77. Golbus JR, Wojcik BM, Charpie JR, Hirsch JC. Feeding
complications in hypoplastic left heart syndrome after the
Norwood procedure: a systematic review of the literature.
Pediatr Cardiol. 2011;32:539-552.
78. Cheung YF, Ho MH, Cheng VY. Mesenteric blood flow
response to feeding after systemic-to-pulmonary arterial
shunt palliation. Ann Thorac Surg. 2003;75:947-951.
79. Wolovits JS, Torzone A. Feeding and nutritional challenges
in infants with single ventricle physiology. Curr Opin Pedi-
atr. 2012;24:295-300.
 Twite and Ing
80. Jeffries HE, Wells WJ, Starnes VA, Wetzel RC, Moromisato
DY. Gastrointestinal morbidity after Norwood palliation
for hypoplastic left heart syndrome. Ann Thorac Surg.
2006;81:982-987.
81. Slater B, Rangel S, Ramamoorthy C, Abrajano C, Alba-
nese CT. Outcomes after laparoscopic surgery in neonates
with hypoplastic heart left heart syndrome. J Pediatr Surg.
2007;42:1118-1121.
82. Mariano ER, Boltz MG, Albanese CT, Abrajano CT,
Ramamoorthy C. Anesthetic management of infants with pal-
liated hypoplastic left heart syndrome undergoing laparoscopic
nissen fundoplication. Anesth Analg. 2005;100:1631-1633.
83. Garcia X, Jaquiss RD, Imamura M, Swearingen CJ, Dassinger
MS 3rd, Sachdeva R. Preemptive gastrostomy tube placement
after Norwood operation. J Pediatr. 2011;159:602.e1-607.e1.
View publication stats
145
84. Zahn EM, Chang AC, Aldousany A, Burke RP. Emergent
stent placement for acute Blalock-Taussig shunt obstruction
after stage 1 Norwood surgery. Cathet Cardiovasc Diagn.
1997;42:191-194.
85. Ramamoorthy C, Haberkern CM, Bhananker SM, et al.
Anesthesia-related cardiac arrest in children with heart dis-
ease: data from the Pediatric Perioperative Cardiac Arrest
(POCA) registry. Anesth Analg. 2010;110:1376-1382.
86. Christensen RE, Gholami AS, Reynolds PI, Malviya S.
Anaesthetic management and outcomes after noncardiac
surgery in patients with hypoplastic left heart syndrome: a
retrospective review. Eur J Anaesthesiol. 2012;29:425-430.
87. Torres A Jr, DiLiberti J, Pearl RH, et al. Noncardiac surgery
in children with hypoplastic left heart syndrome. J Pediatr
Surg. 2002;37:1399-1403.