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Jan Hau Lee, MBBS, MRCPCH. MCI
Children’s Intensive Care Unit
KK Women’s and Children's Hospital, Singapore
1
Approach to Severe
Sepsis
No conflict of interest
2
Overview
• Epidemiology of Pediatric Severe Sepsis
• Fluid Resuscitation and Fluid Balance
• Clinical Guidelines and Quality Improvement
• Future Directions
3
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Goldstein et al. Pediatr Crit Care Med 2005
SPROUT
• Prospective cross-sectional study
• Point-prevalence using data from 5 days
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Weiss et al. ARJCCM 2015
• 128 PICUs – 59 North America
– 39 Europe
– 10 South America
– 10 Asia
– 7 Pacific
– 3 Africa
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
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Weiss et al. ARJCCM 2015
Outcomes from Severe Sepsis
• No difference in mortality across age groups
• Differences in mortality rates across regions
• Mortality risk factors identified were:
– Corticosteroids
– Albumin use
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Weiss et al. ARJCCM 2015
ĸ: 0.57 ± 0.02
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Weiss et al. Critical Care 2015
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 1·9–35·5)
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de Souza et al. Ped Crit Care Med 2016 Southeast Asia Infectious Disease Clinical Research Network. Lancet Glob Health 2017
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 2016.
• Hypothesis: A later year of study, developed
country status and randomised controlled trial
(RCT) design were associated with lower
mortality.
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Results
• 71 studies with a total of 5145 patients
– Developing countries: 26
– Developed countries: 45
• 65 observational studies
• Pooled PICU mortality: 27.9% (95%CI 24.0, 32.2)
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Time Period Adjusted Odds Ratio (95% CI)
1984 – 1990 Reference
1991 – 2000 0.48 (0.43, 0.53)
2001 – 2010 0.30 (0.28, 0.32)
2011 – 2016 0.53 (0.49, 0.57)
• Developed country status: lower mortality
• No difference between RCT and observational studies
Comparisons Between Continents
Continents Unadjusted OR p value Adjusted OR p value
Africa 3.27 (2.79 - 3.84) < 0.001 3.82 (3.24 - 4.50) < 0.001
Asia 3.31 (3.21 - 3.42) < 0.001 4.02 (3.84 - 4.22) < 0.001
Australia 1.43 (0.79 - 2.59) 0.152 2.22 (1.22 - 4.06) 0.807
Europe 1.63 (1.57 - 1.70) < 0.001 1.42 (1.36 - 1.50) < 0.001
South
America 2.96 (2.67 - 3.29) < 0.001 3.62 (3.23 - 4.05) < 0.001
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Reference: North America
Overview
• Epidemiology of Pediatric Severe Sepsis
• Fluid Resuscitation and Fluid Balance
• Clinical Guidelines and Quality Improvement
• Future Directions
13
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
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Type of Fluids
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Long and Duke. Journal of Paediatrics and Child Health 2015
• Hyperchloraemic acidosis – Worsen capillary leak
• Hyperchloraemia – Renal dysfunction, AKI and need for CRRT
– Associated with mortality in critically ill adults
Cl-
154
111
98
N/S
LR/Hartmann’s
Plasmalyte
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• 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 2017
• 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. 13.1 (4, 20)]
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Weiss et al. Journal of Pediatrics 2017
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• 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
Emrath et al. Critical Care Medicine 2017
Propensity-Matched Outcomes
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24-hour Fluid Groups
72-hour Fluid Groups
Emrath et al. Critical Care Medicine 2017
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
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Foland et al. Critical Care Medicine 2004
Sutherland et al. Am J Kidney Dis 2010
• 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
21
Bhaskar et al. Intensive Care Medicine 2015
22 Bhaskar et al. Intensive Care Medicine 2015
23 Bhaskar et al. Intensive Care Medicine 2015
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Characteristics Survivors (N=48) Non-survivors (N=23) P-value
Age, years 10.6 (4.9, 13.5) 8.0 (2.4, 12.6) 0.175
Male gender, n (%) 23 (48) 10 (43) 0.802
PIM 2 2.3 (1.1, 5.2) 4.7 (3.7, 14.3) 0.010
Source, n (%)
Respiratory 20 (42) 8 (35) 0.615
Central nervous system 3 (6.3) 4 (17.4) 0.203
Gastrointestinal 6 (13) 7 (30) 0.100
Bacteremia 2 (4) 2 (9) 0.591
Comorbidities, n (%) 21 (44) 18 (78) 0.010
Mechanical ventilation 18 (38) 22 (96) <0.001
Inotropes, n (%) 39 (81) 23 (100) 0.027
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) 0.013
Neurological 14 (29) 19 (83) <0.001
Hematological 17 (35) 10 (43) 0.604
Renal 12 (25) 8 (35) 0.411
Hepatic 16 (33) 12 (52) 0.194
Ho S et al. PAS 2017
25
Fluid Balance per 10ml/kg Over First 5
Days of Severe Sepsis
Ho S et al. PAS 2017
After adjusting for severity of illness,
organ failures and comorbidities,
each 10ml/kg positive fluid balance
increases mortality risk by 0.2%
Secondary Outcomes
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Outcomes β coefficient 95% confidence interval p value
VFD
Cumulative fluid balance -0.20 -0.25, -0.14 <0.001
IFD
Cumulative fluid balance -0.20 -0.24, -0.15 <0.001
InoFD
Cumulative fluid balance -0.16 -0.22, -0.11 0.007
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 2017
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 2017
29
Nonadherence with timely fluid administration was
associated with both a longer ICU and hospital stay
Paul et al. Pediatrics 2012
30 Paul et al. Pediatrics 2014
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
31
Melendez et al. Curr Opin Pediatr 2015
Overview
• Epidemiology of Pediatric Severe Sepsis
• Fluid Resuscitation and Fluid Balance
• Clinical Guidelines and Quality Improvement
• Future Directions
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Future Directions
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• 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
Thank You [email protected]
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