Approach to Severe Sepsis. Jan Hau Lee, MBBS, MRCPCH. MCI Children s Intensive Care Unit KK Women s and Children's Hospital, Singapore

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1 Approach to Severe Sepsis Jan Hau Lee, MBBS, MRCPCH. MCI Children s Intensive Care Unit KK Women s and Children's Hospital, Singapore 1

2 2 No conflict of interest

3 Overview Epidemiology of Pediatric Severe Sepsis Fluid Resuscitation and Fluid Balance Clinical Guidelines and Quality Improvement Future Directions 3

4 4 Goldstein et al. Pediatr Crit Care Med 2005

5 Prospective crosssectional study Point-prevalence using data from 5 days SPROUT 128 PICUs 59 North America 39 Europe 10 South America 10 Asia 7 Pacific 3 Africa Weiss et al. ARJCCM

6 What did SPROUT show? Difference in point prevalence across regions 77% of children with severe sepsis had comorbid conditions Respiratory (40%) and bloodstream (19%) infections most common Common therapies used include Invasive mechanical ventilation Vasoactive medications Corticosteroids Gastric ulcer prophylaxis Weiss et al. ARJCCM

7 Outcomes from Severe Sepsis Weiss et al. ARJCCM 2015 No difference in mortality across age groups Differences in mortality rates across regions Mortality risk factors identified were: Corticosteroids Albumin use 7

8 Weiss et al. Critical Care 2015 ĸ: 0.57 ±

9 Since SPROUT South America 21 PICUs across 5 countries 464 sepsis; 282 severe sepsis; 216 septic shock Overall sepsis mortality: 14.2% Septic shock mortality: 23.1% Asia 13 hospitals across 3 countries 763 sepsis, no specific numbers for severe sepsis/septic shock Overall 28-day mortality: 2% Severe sepsis (adjusted OR 8 2, 95% CI ) 9 de Souza et al. Ped Crit Care Med 2016 Southeast Asia Infectious Disease Clinical Research Network. Lancet Glob Health 2017

10 Lack of cumulative data on pediatric severe sepsis and septic shock Aim: Determine the pooled PICU mortality rates in severe sepsis and septic shock from studies published from 1984 to Hypothesis: A later year of study, developed country status and randomised controlled trial (RCT) design were associated with lower mortality. 10

11 Results 71 studies with a total of 5145 patients Developing countries: 26 Developed countries: observational studies Pooled PICU mortality: 27.9% (95%CI 24.0, 32.2) Time Period Adjusted Odds Ratio (95% CI) Reference (0.43, 0.53) (0.28, 0.32) (0.49, 0.57) Developed country status: lower mortality No difference between RCT and observational studies 11

12 Comparisons Between Continents Continents Unadjusted OR p value Adjusted OR p value Africa 3.27 ( ) < ( ) < Asia 3.31 ( ) < ( ) < Australia 1.43 ( ) ( ) Europe 1.63 ( ) < ( ) < South America Reference: North America 2.96 ( ) < ( ) <

13 Overview Epidemiology of Pediatric Severe Sepsis Fluid Resuscitation and Fluid Balance Clinical Guidelines and Quality Improvement Future Directions 13

14 Fluid Choices in Pediatric Severe Sepsis Fluid resuscitation is the cornerstone of hemodynamic resuscitation Many studies on crystalloids vs. colloids 0.9%NS Albumin Semi-synthetic colloids (e.g. gelafundin) There is growing interest in chloride load in 0.9%NS and hence in the use of balanced solutions in fluid resuscitation Hartmann s/ Ringer s lactate Plasmalyte 14

15 Type of Fluids N/S LR/Hartmann s Plasmalyte Cl Hyperchloraemic acidosis Worsen capillary leak Hyperchloraemia Renal dysfunction, AKI and need for CRRT Associated with mortality in critically ill adults Long and Duke. Journal of Paediatrics and Child Health

16 Matched retrospective cohort study Administrative database Examined all patients that received LR or NS as fluid resuscitation during first 3 days Primary outcome: 30-day mortality Secondary outcomes: AKI, LOS Weiss et al. Journal of Pediatrics

17 30-day mortality (LR vs. NS): 7.2% vs. 7.9% No difference in AKI Median hospital LOS was longer in any LR group [15.5 (6, 22) vs (4, 20)] Weiss et al. Journal of Pediatrics

18 Observational cohort study Administrative database Examined all patients that received balanced and unbalanced solutions as fluid resuscitation during first 3 days Primary outcome: In-hospital mortality Secondary outcomes: AKI, LOS, vasoactive infusion days 18 Emrath et al. Critical Care Medicine 2017

19 Propensity-Matched Outcomes 24-hour Fluid Groups 72-hour Fluid Groups Emrath et al. Critical Care Medicine

20 20 Fluid Balance Fluid accumulation Fluid Overload Organ Dysfunction Fluid overload at time of CRRT was associated with mortality and morbidities Limited studies in children examining the impact of fluid balance on clinical outcomes Foland et al. Critical Care Medicine 2004 Sutherland et al. Am J Kidney Dis 2010

21 Matched case-control study Single-center study over 7 month period Cases: Children with fluid accumulation > 10% of admission weight Controls: Without these early fluid accumulation Primary outcome: PICU mortality Bhaskar et al. Intensive Care Medicine

22 Bhaskar et al. Intensive Care Medicine

23 Bhaskar et al. Intensive Care Medicine

24 Characteristics Survivors (N=48) Non-survivors (N=23) P-value Age, years 10.6 (4.9, 13.5) 8.0 (2.4, 12.6) Male gender, n (%) 23 (48) 10 (43) PIM (1.1, 5.2) 4.7 (3.7, 14.3) Source, n (%) Respiratory 20 (42) 8 (35) Central nervous system 3 (6.3) 4 (17.4) Gastrointestinal 6 (13) 7 (30) Bacteremia 2 (4) 2 (9) Comorbidities, n (%) 21 (44) 18 (78) Mechanical ventilation 18 (38) 22 (96) <0.001 Inotropes, n (%) 39 (81) 23 (100) Cumulative balance*, (x10ml/kg) 2.1 (-0.9, 9.8) 15.6 (5.5, 42.1) <0.001 Multi-organ dysfunction 28 (58) 23 (100) <0.001 Cardiovascular 37 (77) 23 (100) Neurological 14 (29) 19 (83) <0.001 Hematological 17 (35) 10 (43) Ho S et al. PAS 2017 Renal 12 (25) 8 (35) Hepatic 16 (33) 12 (52)

25 Fluid Balance per 10ml/kg Over First 5 Days of Severe Sepsis After adjusting for severity of illness, organ failures and comorbidities, each 10ml/kg positive fluid balance increases mortality risk by 0.2% Ho S et al. PAS

26 Secondary Outcomes Outcomes β coefficient 95% confidence interval p value VFD Cumulative fluid balance , <0.001 IFD Cumulative fluid balance , <0.001 InoFD Cumulative fluid balance , Adjusted for weight, PIM-2 score, PELOD score, comorbidities, multiorgan dysfunction VFD- 28-day ventilator-free day IFD- 28-day intensive care-free day InoFD- 28-day inotrope free day Ho S et al. PAS

27 Overview Epidemiology of Pediatric Severe Sepsis Fluid Resuscitation and Fluid Balance Clinical Guidelines and Quality Improvement Future Directions 27

28 Davis et al. Crit Care Med

29 Nonadherence with timely fluid administration was associated with both a longer ICU and hospital stay Paul et al. Pediatrics

30 Paul et al. Pediatrics

31 Quality Improvement in Severe Sepsis Understand local barriers Adapt and individualize intervention Multidisciplinary approach Some strategies to consider: - Recognize abnormal vital signs of sepsis - Delay in securing vascular access Melendez et al. Curr Opin Pediatr

32 Overview Epidemiology of Pediatric Severe Sepsis Fluid Resuscitation and Fluid Balance Clinical Guidelines and Quality Improvement Future Directions 32

33 Future Directions Pressing need for an updated pediatric severe sepsis and septic shock definition Increasing studies on balanced solutions and attention to fluid balance after the resuscitative phase Quality improvement and standardization of management of severe sepsis is important in improving overall outcomes 33

34 Thank You 34

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