American College of Critical Care Medicine Clinical Practice Parameters

for Hemodynamic Support of Pediatric and Neonatal Septic Shock.

Davis AL, Carcillo JA, Aneja RK, Deymann AJ, Lin JC, Nguyen TC,
Okhuysen-Cawley RS, Relvas MS, Rozenfeld RA, Skippen PW,
Stojadinovic BJ, Williams EA, Yeh TS, Balamuth F, Brierley J, de Caen AR,
Cheifetz IM, Choong K, Conway E Jr, Cornell T, Doctor A, Dugas MA,
Feldman JD, Fitzgerald JC, Flori HR, Fortenberry JD, Graciano AL,
Greenwald BM, Hall MW, Han YY, Hernan LJ, Irazuzta JE, Iselin E,
van der Jagt EW, Jeffries HE, Kache S, Katyal C, Kissoon NT, Kon AA,
Kutko MC, MacLaren G, Maul T, Mehta R, Odetola F, Parbuoni K, Paul R,
Peters MJ, Ranjit S, Reuter-Rice KE, Schnitzler EJ, Scott HF, Torres A Jr,
Weingarten-Abrams J, Weiss SL, Zimmerman JJ, Zuckerberg AL.
Crit Care Med. 2017 Jun;45(6):1061-1093.
doi: 10.1097 / CCM.0000000000002425. PMID:28509730
2
 Infection
with
Fever Many 1000s of
children per year
scarlet fever with infection
strep throat that gets better
in a few days
but ….
3
3
 INFECTION

SEPSIS

4
 SEPTIC
SHOCK

Prolonged Capillary Refill Time

5 Painful Legs
 Sepsis
MODS is
Serious

Sometimes
MOF
Lethal

6
6
 IF SEPTIC SHOCK IS PREVENTABLE THEN WHY NOT HAVE

HOSPITAL PROTOCOLS FOR EARLY RECOGNITION

AND TREATMENT OF SEPSIS?
7
 INDEED, IF SEPTIC SHOCK IS PREVENTABLE THEN WHY NOT HAVE

HOSPITAL PROTOCOLS FOR EARLY RECOGNITION

AND TREATMENT OF SEPSIS?

WE ALREADY HAVE THEM FOR HEART ATTACKS,

BRAIN ATTACKS, TRAUMA, etc.
8
 THE 2014
ACCM
Recognition
SOLUTION:

PROVIDE
‘THREE ELEMENT’
BUNDLE
Resuscitation
EXAMPLES

MEANT TO BE
INSTITUTION
Stabilization
AND CONTEXT
SPECIFIC

Performance

9
 Recognition Bundle Example

• Screen patient for septic shock

• Clinician assessment within 15 minutes for any
patient who screens positive
• Initiate Resuscitation Bundle within 15 minutes for
patient identified by the trigger tool whom the
assessing clinician confirms suspicion of septic
shock

10
On Recognition Trigger Tools
and Emergency Department
Sepsis Initiatives…….
 A, Statistical process control charts of time to first bolus for children
identified at triage.

Mortality reduction from

4% to 2.4% at TCH

Andrea T. Cruz et al. Pediatrics

2011;127:e758-e766

13

©2011 by American Academy of Pediatrics

 Statistical process control charts demonstrating gains in achieving
predefined goals for our ED septic shock project.

Reduces LOS in Salt Lake City Utah

Gitte Y. Larsen et al. Pediatrics

2011;127:e1585-e1592

14

©2011 by American Academy of Pediatrics

 Also Successful in DCH

Triage sepsis alert and sepsis protocol lower times to fluids and
antibiotics in the ED ☆ ☆☆

Geoffrey E. Hayden, Rachel E. Tuuri, Rachel Scott, Joseph D. Losek, Aaron M.

Blackshaw, Andrew J. Schoenling, Paul J. Nietert, Greg A. Hall

15
The American Journal of Emergency Medicine, Volume 34,
Issue 1, 2016, 1–9
 Resuscitation Bundle in Pediatric Shock Decreases Acute Kidney Injury and Improves
Outcomes
Portions of this study were presented orally at the meeting of the European Society of
Intensive Care Medicine, Paris, France, October 5-9, 2013. Ayse Akcan Arikan, MD1, 2, Eric A.
Williams, MD, MS1, Jeanine M. Graf, MD1, Curtis E. Kennedy, MD, PhD1, Binita Patel, MD3,
Andrea T. Cruz, MD, MPH3, 4

Multivariate analyses of risk factors for the development of AKI

Variables aOR (95% CI) P value

Shock protocol 0.27 (0.13-0.56) <.001
PELOD 1.08 (1.03-1.12) .002
Age 1.01 (0.96-1.07) .47
Sex 0.99 (0.54-1.84) .99

The Journal of Pediatrics

Volume 167, Issue 6, December 2015, Pages
1301–1305.e1
16
 Restricted fluid bolus versus current practice in children with septic shock: the FiSh feasibility study and pilot RCT.
Health Technol Assess. 2018 Sep;22(51):1-106.
Potential outcome Treatment group Effect estimate (95% CI) p-value
measures 10 ml/kg (n = 39) 20 ml/kg (n = 34)
Hospital mortality, n/N 0/39 (0.0) 0/34 (0.0) Not estimable
(%)
a
Length of hospital stay 4 (3–7) [39] 5 (4–8) [34] 0.225
(days), median (IQR) [n]
b
Transferred to PICU, n/N 10/39 (25.6) 11/34 (32.4) –6.7 (–27.6 to 14.1) 0.354
(%) c
0.79 (0.38 to 1.63)
a
Length of stay in PICU 45 (18–143) [10] 119 (52–228) [11] 0.091
(hours), median (IQR)
[n]
e
Days alive and free of 28.9 (2.4) [39] 27.9 (3.6) [34] 1.0 (–0.4 to 2.4) 0.160
d
PICU up to 30 days,
mean (SD) [n]
b
Receipt of mechanical 4/36 (11.1) 8/32 (25.0) –13.9 (–32.1 to 4.3) 0.119
ventilation, n/N (%) c
0.44 (0.15 to 1.34)
Duration of mechanical 6 (4–8) [4] 5.5 (4–8.5) [8] 0.797
f
ventilation (days),
median (IQR) [n]
e
Days alive and free of 29.3 (2.1) [36] 28.5 (2.7) [32] 0.8 (–0.4 to 2.0) 0.192
mechanical ventilation
d
up to 30 days, mean
(SD) [n]
d
Mortality at 30 days, 0/39 (0.0) 0/34 (0.0) Not estimable
n/N (%)
17
First bolus 20 mL/kg in both treatment arms followed by 10 mL / kg vs 20 mL /kg thereafter
 Antibiotics are the CURE!

Pathogens Doubling Time is

less than 30 minutes!!!!!!!!!

SO WHY WAIT????????????
 Systematic Bias in Meta-Analyses of Time
to Antimicrobial in Sepsis Studies.
Kumar, Anand; MD, FCCM

Critical Care Medicine. 44(4):e234-e235,

April 2016.
DOI: 10.1097/CCM.0000000000001512

Figure 1 . Previously unpublished pilot data for

the relationship of time to antimicrobial and
mortality in septic shock among emergency
department (ED) patients (n = 192). In this
pilot analysis, the index time represents the
first documented hypotension in ED, but does
not include pre-ED arrival data. The
subsequent full study (4) utilized pre-ED data
whenever available inclusive of ambulance
and nursing home records. CATSS =
Cooperative Antimicrobial Therapy of Septic
Shock.
19
Copyright © by 2016 by the Society of Critical Care Medicine and Wolters Kluwer 2
Health, Inc. All Rights Reserved. Published by Lippincott Williams & Wilkins, Inc.
 Timing of Correct Parenteral Antibiotic
Initiation and Outcomes From Severe
Bacterial Community-acquired Pneumonia
in Children.
Muszynski, Jennifer; Knatz, Nina; Sargel,
Cheryl; Fernandez, Soledad; Marquardt,
David; Hall, Mark

Pediatric Infectious Disease Journal.

30(4):295-301, April 2011.
DOI: 10.1097/INF.0b013e3181ff64ec
FIGURE 1. Time to correct parenteral antibiotic initiation and
clinical outcomes for all study subjects (n = 45) and those
without acute comorbidities (n = 23). For the cohort as a
whole, longer time to correct parenteral antibiotic initiation
was not significantly associated with duration of mechanical
ventilation (A), though it was significantly associated with
longer durations of ICU (B) and hospital (C) lengths of stay by
simple linear regression. In children without acute
comorbidities, longer time to correct antibiotic initiation was
significantly associated with longer durations of mechanical
ventilation (D), ICU (E), and hospital (F) lengths of stay by
simple linear regression. Children with complex chronic
conditions are identified by solid symbols.

20
© 2011 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams &
3
Wilkins, Inc.
 Weiss, Scott; Fitzgerald, Julie; MD, PhD;
Balamuth, Fran; MD, PhD; Alpern, Elizabeth;
MD, MSCE; Lavelle, Jane; Chilutti, Marianne;
Grundmeier, Robert; Nadkarni, Vinay; MD,
MS; Thomas, Neal; MD, MSc

Critical Care Medicine. 42(11):2409-2417,

Evaluation only.
Created with Aspose.PowerPoint.
November 2014.
DOI: 10.1097/CCM.0000000000000509
Delayed Antimicrobial Therapy Increases
Mortality and Organ Dysfunction Duration in
Pediatric Sepsis

Copyright 2004 Aspose Pty Ltd.

21
© 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. 8
Published by Lippincott Williams & Wilkins, Inc.
Figure 1. Pediatric intensive care unit empiric antibiotic pathway including risk factors for infection due to healthcare-associated bacteria. aMinimum 7
days in previous 6 weeks. bMalignancy, chemotherapy, chronic steroid/immunosuppressants, organ transplant, immunodeficiency, or acute steroids
>5 days in the past month. cPiperacillin-tazobactam, cefepime, and meropenem. dGentamicin, tobramycin, and amikacin.

Annals ATS, 2014

http://www.atsjournals.org/doi/abs/10.1513/AnnalsATS.201408-389OC

Published in: Todd J. Karsies; Cheryl L. Sargel; David J. Marquardt; Nadeem Khan; Mark W. Hall; Annals ATS 11, 1569-1575.
DOI: 10.1513/AnnalsATS.201408-389OC
Copyright © 2014 by the American Thoracic Society
 Resuscitation Bundle
• Attain IV/IO access within 5 minutes
• Appropriate fluid resuscitation begun within 30 minutes
• Initiation of broad spectrum antibiotics within 60 minutes
• Begin peripheral (adrenaline) or central inotrope infusion therapy
for fluid refractory shock within 60 minutes.

23
 Figure 3 . Kaplan-Meyer survival function according to
group.

Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock.
Ventura, Andrea; Shieh, Huei; Bousso, Albert; Goes, Patricia; Fernandes, Iracema; de Souza, Daniela; Paulo, Rodrigo; Chagas, Fabiana; Gilio, Alfredo

Critical Care Medicine. 43(11):2292-2302, November 2015.

DOI: 10.1097/CCM.0000000000001260

24
Copyright © by 2015 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. 10
Published by Lippincott Williams & Wilkins, Inc.
 Ventura, Andrea; Shieh, Huei;
Bousso, Albert; Goes, Patricia;
Fernandes, Iracema; de Souza,
Daniela; Paulo, Rodrigo; Chagas,
Fabiana; Gilio, Alfredo Double-Blind
Prospective Randomized Controlled
Trial of Dopamine Versus
Epinephrine as First-Line Vasoactive
Drugs in Pediatric Septic Shock.
Critical Care Medicine. 43(11):2292-
25 2302, November 2015.
Copyright © by 2015 by the Society of Critical Care Medicine and Wolters Kluwer 7
Health, Inc. All Rights Reserved. Published by Lippincott Williams & Wilkins, Inc.
 SVRI and cardiac index (CI) in 30 cases of fluid-resistant septic shock.

Joe Brierley, and Mark J. Peters Pediatrics

2008;122:752-759
26

©2008 by American Academy of Pediatrics

 Five time points evaluated for adherence from 2006 PALS algorithm.

Raina Paul et al. Pediatrics 2012;130:e273-

e280

27

©2012 by American Academy of Pediatrics

 Percent adherence to 5 algorithm time points and median time to
intervention (with goal time displayed). *Error bars represent IQRs for
median times.

Raina Paul et al. Pediatrics 2012;130:e273-

e280

28

©2012 by American Academy of Pediatrics

 Ishikawa fishbone diagram for fluid delivery.

Raina Paul et al. Pediatrics 2014;133:e1358-

e1366

29

©2014 by American Academy of Pediatrics

 Statistical process control charts for outcome measures.

Mortality 4% to 1.7%

Raina Paul et al. Pediatrics 2014;133:e1358-

e1366

30

©2014 by American Academy of Pediatrics

Pediatric Septic Shock Collaborative
Initial Clinical Assessment Compliance Time to First Fluid Bolus (wi 20 min)

Fluid within First Hour (2 or 3 boluses) Timely Antibiotic Administration (1 hr)

 CHA Rapid
Cycle
Collaborative

Phase II: 22 participating Children’s Hospital Emergency Departments

Mortality
Outcomes
*

Severe Sepsis
30 day mortality:
11%3%
(p<0.03)
Association Between the New York Sepsis Care Mandate and In-Hospital Mortality for
Pediatric Sepsis. JAMA. 2018 Jul 24;320(4):358-367. Evans IVR et al

Question Following statewide mandated care for pediatric sepsis, was the
prompt completion of a 1-hour bundle associated with lower risk-adjusted
in-hospital mortality?

Findings Among 1179 pediatric patients with sepsis at 54 adult and

pediatric specialty hospitals in New York State, the completion of a 1-hour
sepsis bundle that included blood cultures, broad spectrum antibiotics, and
a 20-mL/kg fluid bolus was significantly associated with lower risk-adjusted
in-hospital mortality compared with not completing the bundle within 1
hour (odds ratio, 0.59).

Meaning Timely completion of a 1-hour bundle of care may improve

outcomes in pediatric sepsis
Association Between the New York Sepsis Care Mandate and In-Hospital Mortality for
Pediatric Sepsis. JAMA. 2018 Jul 24;320(4):358-367. Evans IVR et al
Association Between the New York Sepsis Care Mandate and In-Hospital Mortality for
Pediatric Sepsis. JAMA. 2018 Jul 24;320(4):358-367. Evans IVR et al
 Stabilization (PICU) Bundle Example
• Use multimodal monitoring to optimize fluid, hormonal , and
cardiovascular therapies to attain hemodynamic goals.
• Confirm administration of appropriate antimicrobial therapy and
source control

36
 PICU GOALS

1) MAP-CVP or MAP-ICP
2) ScVO2 > 70%, CI 3.3-6
L/min/m2

3) Confirm Source Control

 ACCM/PALS haemodynamic support guidelines for paediatric septic shock: an outcomes comparison with and
without monitoring central venous oxygen saturation Intensive Care Med (2008) 34:1065–1075
DOI 10.1007/s00134-008-1085-9 Cláudio F. de Oliveira et al

Reduced
Mortality
From
40% to 11%

38
 Reduced
Mortality
54% to 33%
Early Goal-Directed Therapy in Pediatric
Septic Shock: Comparison of Outcomes
"With" and "Without" Intermittent Superior
Venacaval Oxygen Saturation Monitoring: A
Prospective Cohort Study*. Sankar, Jhuma;
Sankar, M; Suresh, C; Dubey, Nandkishore;
Singh, Archana Pediatric Critical Care
Medicine. 15(4):e157-e167, May 2014. DOI:
10.1097/PCC.0000000000000073

39
©2014The Society of Critical Care Medicine and the World Federation of Pediatric 3
Intensive and Critical Care Societies. Published by Lippincott Williams & Wilkins, Inc.
 2014 Aug;42(8):1775-87. doi:
10.1097/CCM.0000000000000298.
Randomized controlled trial comparing
cerebral perfusion pressure-targeted therapy
versus intracranial pressure-targeted therapy
for raised intracranial pressure due to acute
CNS infections in children.
Kumar R1, Singhi S, Singhi P, Jayashree M,
Bansal A, Bhatti A.
40
 Intensive Care Med. 2013 Sep;39(9):1602-9. doi:
10.1007/s00134-013-3003-z. Epub 2013 Jun 28.
Evolution of haemodynamics and outcome of fluid-
refractory septic shock in children.
Deep A1, Goonasekera CD, Wang Y, Brierley J.

41
 Front Pediatr. 2018 Oct 23;6:314. doi: 10.3389/fped.2018.00314. eCollection 2018.
Oxygen Delivery and Oxygen Consumption in Pediatric Fluid Refractory Septic Shock During the First 42 h
of Therapy and Their Relationship to 28-Day Outcome.
Goonasekera CDA1, Carcillo JA2, Deep A3.

42
 Front Pediatr. 2018 Oct
23;6:314. doi:
10.3389/fped.2018.00314.
eCollection 2018.
Oxygen Delivery and Oxygen
Consumption in Pediatric Fluid
Refractory Septic Shock
During the First 42 h of
Therapy and Their
Relationship to 28-Day
Outcome.
Goonasekera CDA1, Carcillo
JA2, Deep A3.

43
 CHILDREN

RESUSCITATION
ALGORITHM
EXAMPLE

STABILIZATION
ALGORITHM
EXAMPLE

44
 NEWBORNS

RESUSCITATION
ALGORITHM
EXAMPLE

STABILIZATION
ALGORITHM
EXAMPLE

45
 Let us not forget that SOURCE CONTROL is paramount in sepsis!

N Mortality Mortality
With Xigris Without Xigris

28-Day source
control
Adequate 204 4.9% 1.0
Inadequate 48 95.5% 92.3
Indeterminate 107 37.0% 56.6

Benefit/risk profile of drotrecogin alfa (activated) in surgical patients with severe sepsis.
Barie PS1, Williams MD, McCollam JS, Bates BM, Qualy RL, Lowry SF, Fry DE; PROWESS Surgical
Evaluation Committee. Am J Surg. 2004 Sep;188(3):212-20.

46
 Performance Bundle Example
• Measure adherence to Trigger, Resuscitation, and Stabilization
Bundles
• Perform root cause analysis to identify barriers to adherence
• Provide an action plan to address identified barriers

47
 Previously
CONTEXT Healthy

SPECIFIC Hematocrit = 34
Mortality 2% with
GUIDELINES Fluid Bolus
ESSENTIAL Appropriate timely Abx
Inotropes
TO BEST
OUTCOMES

Chronic High
Previously Output, Anemia
Healthy Malnutrition
Hematocrit = 50 Hematocrit = 18
Mortality 0% with Mortality 7%
Fluid Boluses with Blood
Wills et al. Maintenance IVF
Ngo et al Antimalarials
48
Maitland et al.
 LET’S GET IT STARTED!

49 www.cdc.gov/vitalsigns/sepsis
 American College of Critical Care Medicine Clinical Practice Parameters
for Hemodynamic Support of Pediatric and Neonatal Septic Shock.

Davis AL, Carcillo JA, Aneja RK, Deymann AJ, Lin JC, Nguyen TC,
Okhuysen-Cawley RS, Relvas MS, Rozenfeld RA, Skippen PW,
Stojadinovic BJ, Williams EA, Yeh TS, Balamuth F, Brierley J, de Caen AR,
Cheifetz IM, Choong K, Conway E Jr, Cornell T, Doctor A, Dugas MA,
Feldman JD, Fitzgerald JC, Flori HR, Fortenberry JD, Graciano AL,
Greenwald BM, Hall MW, Han YY, Hernan LJ, Irazuzta JE, Iselin E,
van der Jagt EW, Jeffries HE, Kache S, Katyal C, Kissoon NT, Kon AA,
Kutko MC, MacLaren G, Maul T, Mehta R, Odetola F, Parbuoni K, Paul R,
Peters MJ, Ranjit S, Reuter-Rice KE, Schnitzler EJ, Scott HF, Torres A Jr,
Weingarten-Abrams J, Weiss SL, Zimmerman JJ, Zuckerberg AL.
Crit Care Med. 2017 Jun;45(6):1061-1093.
doi: 10.1097 / CCM.0000000000002425. PMID:28509730
50
Q&A
RECOGNITION
TRIGGER
TOOL
EXAMPLE
 CHILDREN

RESUSCITATION
ALGORITHM
EXAMPLE

STABILIZATION
ALGORITHM
EXAMPLE

53
 NEWBORNS

RESUSCITATION
ALGORITHM
EXAMPLE

STABILIZATION
ALGORITHM
EXAMPLE

54