Pediatric Sepsis Treatment:

Transcription

1 Disclosures Pediatric Sepsis Treatment: (treat) Early & (reevaluate) Often None June 11, 2018 Leslie Dervan, MD MS Pacific Northwest Sepsis Conference 1

2 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 Reevaluate often SEPSIS: PATHOPHYSIOLOGY 2

3 Sepsis, shock & septic shock Septic shock: 3 kinds of shock in one Sepsis: infection + inflammation Fever, tachycardia, tachypnea, abnormal WBC, abnormal MS Shock: oxygen delivery does not meet demand Distributive shock vasodilation + endothelial dysfunction Hypovolemic shock & Cardiogenic shock Updated Sepsis 3 definitions (in adults) - SOFA qsofa: Hypotension altered MS RR Martin Minerva Pediatr 2015 qsofa.org 3

4 Septic shock: 3 kinds of shock in one How are children different? Distributive shock fluid & vasopressors vasodilation + endothelial dysfunction Hypovolemic shock IV fluid & Cardiogenic shock ionotropes 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

5 Treatment guidelines work Improved survival with guideline-directed therapy Treat early: TREATMENT GUIDELINES 92% 62% Han Pediatrics

6 Ninis BMJ 2005 Multivariable model: odds of death increased w/ each missed treatment goal # OR p < <

7 Treatment Guidelines Treatment Guidelines Recognition IV Access Antibiotics Rapid IV fluid boluses 2016 AHA; from Brierley CCM AHA; from Brierley CCM

8 Timing of antibiotics impacts mortality True in children too Ferrer CCM 2014 Weiss CCM 2014 % mortality 8

9 Rapid IV fluid resuscitation Pathways improve recognition & 1 st hour therapy Cruz Pediatrics 2011 Computerized triage system & vital sign alert Standardized orderset Bedside presence of additional RN, RT, pharmacy N=14 <20 ml/kg N= ml/kg N=9 >40 ml/kg Carcillo JAMA

10 Time to first bolus min State-wide pathway implementation & outcomes time (minutes) Time to third bolus min Time to antibiotics min 12-year-old Rory Staunton s death from septic shock prompted NY state to mandate hospitals adopt sepsis screening & treatment protocols (2013) patients pre patients post 10

11 State-wide pathway implementation & outcomes State-wide pathway implementation & outcomes 11

12 Treatment Guidelines Vasopressors & ionotropes: many choices Agent α1 β1 β2 other Vasoactive drugs Dopamine Norepinephrine vasoconstriction (high dose) vasoconstriction ionotropy vasodilation chronotropy warm shock dopamine receptors adrenalin, noradrenalin Epinephrine vasoconstriction (high dose) ionotropy chronotropy vasodilation (low dose) cold shock First hour! Dobutamine ionotropy chronotropy vasodilation Remember IV fluid (dehydration, losses, capillary leak) 12

13 Why not dopamine? Is a peripheral vasopressor OK? Start peripheral epinephrine early Epinephrine: Shorter resuscitation, less renal failure Ventura CCM

14 Similar to adult data Ventura CCM 2015 Epinephrine: Lower mortality, fewer HAI Lower mortality with norepinephrine vs. dopamine Fewer adverse events & arrhythmias Similar mortality with norepinephrine vs. epinephrine 14

15 Treatment Guidelines Treatment Guidelines move to critical care Reassess & Titrate therapies to exam Hydrocortisone History of chronic steroid therapy History of panhypopituitarism Consider if poor response to high-dose pressors 2016 AHA; from Brierley CCM AHA; from Brierley CCM

16 What about Early Goal-Directed Therapy? Since then NEJM 2017 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%) 16

17 Since then EARLY & LATE MORTALITY 17

18 Pediatric mortality after septic shock Post-sepsis immune suppression Multiorgan failure in critical illness Weiss PCCM Days 0-1 Days 2-3 Days 4-7 >7 days Not related to sepsis Resp/other Neuro MODS Refractory shock ALC < 1000 x 7 days predicted mortality; deaths from HAI Low TNFα associated with increased & persistent HAI, mortality Immune paralysis, lymphopenia Felmet J Imm 2005 Hall ICM 2011 Secondary infection & late mortality 18

19 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! 19

20 References Avni T 1, et al. PLoS One Aug 3;10(8). Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta- Analysis. Brierley J, et al. Crit Care Med Feb;37(2): Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Cruz AT 1, et al. Pediatrics Mar;127(3):e Implementation of goal-directed therapy for children with suspected sepsis in the emergency department. Han YY 1, et al. Pediatrics Oct;112(4): Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Hall MW 1, et al. Intensive Care Med Mar;37(3): Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Hershey TB 1, Kahn JM 1. N Engl J Med Jun 15;376(24): State Sepsis Mandates - A New Era for Regulation of Hospital Quality. Davis AL 1,, et al. Pediatr Crit Care Med Sep;18(9): The American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock: Executive Summary. Felmet KA 1, et al. J Immunol Mar 15;174(6): Prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia in children with nosocomial sepsis and multiple organ failure. Ferrer R 1, et al. Crit Care Med Aug;42(8): 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 Jun 8;376(23): Early, Goal-Directed Therapy for Septic Shock - A Patient- Level Meta-Analysis. Rivers E 1, et al. N Engl J Med Nov 8;345(19): Early goal-directed therapy in the treatment of severe sepsis and septic shock. Ventura AM 1,et al. Crit Care Med Nov;43(11): Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Weiss SL 1, et al. Crit Care Med Nov;42(11): Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Weiss SL 1, et al. Pediatr Crit Care Med Sep;18(9): The Epidemiology of Hospital Death Following Pediatric Severe Sepsis: When, Why, and How Children With Sepsis Die. 20