Approach to Severe Sepsis - slacip.org

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

4

Goldstein et al. Pediatr Crit Care Med 2005

SPROUT

• Prospective cross-sectional study

• Point-prevalence using data from 5 days

5

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

6


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

7


ĸ: 0.57 ± 0.02

8

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)

9

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.

10

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)

11

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

12

Reference: North America

Overview





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

14

Type of Fluids

15

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

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 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)]

17

Weiss et al. Journal of Pediatrics 2017

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

Emrath et al. Critical Care Medicine 2017

Propensity-Matched Outcomes

19

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

20

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

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) 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


After adjusting for severity of illness,

organ failures and comorbidities,

each 10ml/kg positive fluid balance

increases mortality risk by 0.2%

Secondary Outcomes

26

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


Overview





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





32

Future Directions

33

• 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]

34

Approach to Severe Sepsis - slacip.org

Documents

Transcript of Approach to Severe Sepsis - slacip.org