(treat) early & (reevaluate) oftenblogs.uw.edu/sepsis/files/2018/06/pediatric-sepsis... ·...
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Pediatric Sepsis Treatment:(treat) Early & (reevaluate) Often
June 11, 2018Leslie Dervan, MD MS
Pacific Northwest Sepsis Conference
Disclosures
• None
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Agenda
• Sepsis: pathophysiology at-a-glance• Pediatric differences impact treatment
• Treatment guidelines & evidence• Guideline-based treatment works!• Early antibiotics• Pathway care• Vasoactive support
• Late mortality SEPSIS: PATHOPHYSIOLOGYReevaluate often
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Sepsis, shock & septic shock
Sepsis: infection + inflammation• Fever, tachycardia, tachypnea, abnormal WBC,
abnormal MS
Shock: oxygen delivery does not meet demand
Updated Sepsis 3 definitions (in adults) - SOFA• qSOFA: Hypotension | altered MS | ↑ RR
Martin Minerva Pediatr 2015qsofa.org
Septic shock: 3 kinds of shock in one
Distributive shock
vasodilation+
endothelial dysfunctionHypovolemic shock
Cardiogenic shock
&
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Septic shock: 3 kinds of shock in one
Distributive shock
vasodilation+
endothelial dysfunctionHypovolemic shock
Cardiogenic shock
&
fluid & vasopressors
IV fluid
ionotropes
How are children different?
• Presentation: varies widely! • Common features: tachycardia, low urine output, lethargy• 80% cold shock: low cardiac output, ± low vascular tone
• Diminished pulses, delayed cap refill, narrow pulse pressure• 20% warm shock: normal/high cardiac output, + low vascular tone
• Bounding pulses, brisk cap refill, wide pulse pressure
• Why? • Young infants cannot increase stroke volume; only heart rate• Children can generate profound tachycardia (HR > 200)• This comes at a cost (↓ diastole = ↓ cardiac filling = ↓ cardiac output)• Tachypnea: robust compensatory efforts for acidosis• Hypoglycemia more common
Martin Minerva Pediatr 2015
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TREATMENT GUIDELINESTreat early:
Treatment guidelines work
Han Pediatrics 2003
92% 62%
Improved survival with guideline-directed therapy
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Multivariable model: odds of death increased w/ each missed treatment goal
# OR p0 1.0 -1 8.7 0.0012 34 <0.001
3+ 113 <0.001
Ninis BMJ 2005
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Treatment Guidelines
©2016 AHA; fromBrierley CCM 2009
Recognition
Treatment Guidelines
©2016 AHA; fromBrierley CCM 2009
IV AccessAntibiotics
Rapid IV fluid boluses
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Timing of antibiotics impacts mortality
Ferrer CCM 2014
% m
orta
lity
True in children too
Weiss CCM 2014
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Rapid IV fluid resuscitation
Carcillo JAMA 1991
N=14<20
ml/kg
N=1120-40 ml/kg
N=9>40
ml/kg
Pathways improve recognition & 1st hour therapy
• Computerized triage system & vital sign alert• Standardized orderset• Bedside presence of additional RN, RT, pharmacy
Cruz Pediatrics 2011
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Time to first bolus72 22 min
Time to third bolus280 61 min
Time to antibiotics143 38 min
patients pre | patients post
time
(min
utes
)
State-wide pathway implementation & outcomes
• 12-year-old Rory Staunton’s death from septic shock prompted NY state to mandate hospitals adopt sepsis screening & treatment protocols (2013)
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State-wide pathway implementation & outcomes State-wide pathway implementation & outcomes
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Treatment Guidelines
Vasoactive drugs
First hour!
Agent α1
Dopamine vasoconstriction(high dose)
Norepinephrine vasoconstriction
Epinephrine vasoconstriction(high dose)
Dobutamine
Agent α1 β1
Dopamine vasoconstriction(high dose)
ionotropychronotropy
Norepinephrine vasoconstriction
Epinephrine vasoconstriction(high dose)
ionotropychronotropy
Dobutamine ionotropychronotropy
Agent α1 β1 β2 other
Dopamine vasoconstriction(high dose)
ionotropychronotropy vasodilation dopamine receptors adrenalin,
noradrenalin
Norepinephrine vasoconstriction
Epinephrine vasoconstriction(high dose)
ionotropychronotropy
vasodilation(low dose)
Dobutamine ionotropychronotropy vasodilation
Vasopressors & ionotropes: many choices
Remember IV fluid (dehydration, losses, capillary leak)
cold shock
Agent
Dopamine
Norepinephrine
Epinephrine
Dobutamine
warm shock
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Why not dopamine? Is a peripheral vasopressor OK?
Start peripheral epinephrine earlyVentura CCM 2015
Epinephrine: Shorter resuscitation, less renal failure
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Epinephrine: Lower mortality, fewer HAI
Ventura CCM 2015
Similar to adult data
• Lower mortality with norepinephrine vs. dopamine Fewer adverse events & arrhythmias
• Similar mortality with norepinephrine vs. epinephrine
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Treatment Guidelines
©2016 AHA; fromBrierley CCM 2009
Hydrocortisone• History of chronic steroid therapy• History of panhypopituitarism• Consider if poor response to high-dose pressors
move to critical care
Treatment Guidelines
©2016 AHA; fromBrierley CCM 2009
Reassess &Titrate therapies
to exam
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• More ionotropes
• More fluid (4.9 vs 3.4 L)
• More PRBCs
• Higher MAP (95 vs 81)• Higher SVO2 (77 vs 66)• Less acidosis • Lower lactate (4.3 vs 4.9)
• Less MODS• Lower mortality
(40% vs 61%)
What about Early Goal-Directed Therapy? Since then…
NEJM 2017
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Since then…
EARLY & LATE MORTALITY
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Pediatric mortality after septic shock
0
5
10
15
20
25
30
35
40
45
Days 0-1 Days 2-3 Days 4-7 >7 days
Not related to sepsis
Resp/other
Neuro
MODS
Refractory shock
Weiss PCCM 2017
Post-sepsis immune suppression
Multiorgan failure in critical illness
Secondary infection & late mortality
ALC < 1000 x 7 days predicted mortality; deaths from HAI
Felmet J Imm 2005
“Immune paralysis”, lymphopenia
Low TNFα associated with increased & persistent HAI, mortality
Hall ICM 2011
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In summary…
• Focus on early identification of the septic patient & early resuscitation• Early IV access (IO)• IV fluid (20 ml/kg x 3) + antibiotics within 1 hour• Peripheral epinephrine (/norepinephrine) next• A protocol might help
• Reevaluate frequently! • Children recovering from septic shock are not out
of the woods • Multiorgan failure & immune suppression
Thank you!
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ReferencesAvni T1, et al. PLoS One. 2015 Aug 3;10(8). Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-
Analysis.Brierley J, et al. Crit Care Med. 2009 Feb;37(2):666-88. Clinical practice parameters for hemodynamic support of pediatric and
neonatal septic shock: 2007 update from the American College of Critical Care Medicine.Cruz AT1, et al. Pediatrics. 2011 Mar;127(3):e758-66. Implementation of goal-directed therapy for children with suspected sepsis
in the emergency department.Han YY1, et al. Pediatrics. 2003 Oct;112(4):793-9. Early reversal of pediatric-neonatal septic shock by community physicians is
associated with improved outcome.Hall MW1, et al. Intensive Care Med. 2011 Mar;37(3):525-32. Immunoparalysis and nosocomial infection in children with multiple
organ dysfunction syndrome.Hershey TB1, Kahn JM1. N Engl J Med. 2017 Jun 15;376(24):2311-2313. State Sepsis Mandates - A New Era for Regulation of
Hospital Quality.Davis AL1, , et al. Pediatr Crit Care Med. 2017 Sep;18(9):884-890. The American College of Critical Care Medicine Clinical Practice
Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock: Executive Summary.Felmet KA1, et al. J Immunol. 2005 Mar 15;174(6):3765-72.Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in
children with nosocomial sepsis and multiple organ failure.Ferrer R1, et al. Crit Care Med. 2014 Aug;42(8):1749-55. Empiric antibiotic treatment reduces mortality in severe sepsis and
septic shock from the first hour: results from a guideline-based performance improvement program.PRISM Investigators. N Engl J Med. 2017 Jun 8;376(23):2223-2234. Early, Goal-Directed Therapy for Septic Shock - A Patient-
Level Meta-Analysis.Rivers E1, et al. N Engl J Med. 2001 Nov 8;345(19):1368-77. Early goal-directed therapy in the treatment of severe sepsis and
septic shock.Ventura AM1,et al. Crit Care Med. 2015 Nov;43(11):2292-302. Double-Blind Prospective Randomized Controlled Trial of Dopamine
Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock.Weiss SL1 , et al. Crit Care Med. 2014 Nov;42(11):2409-17. Delayed antimicrobial therapy increases mortality and organ
dysfunction duration in pediatric sepsis.Weiss SL1, et al. Pediatr Crit Care Med. 2017 Sep;18(9):823-830. The Epidemiology of Hospital Death Following Pediatric Severe
Sepsis: When, Why, and How Children With Sepsis Die.