(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



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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Vasoactive drugs

First hour!

Agent α1

Dopamine vasoconstriction(high dose)

Norepinephrine vasoconstriction

Epinephrine vasoconstriction(high dose)

Dobutamine

Agent α1 β1


ionotropychronotropy




Dobutamine ionotropychronotropy

Agent α1 β1 β2 other


ionotropychronotropy vasodilation dopamine receptors adrenalin,

noradrenalin




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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Hydrocortisone• History of chronic steroid therapy• History of panhypopituitarism• Consider if poor response to high-dose pressors

move to critical care



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.

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