Jan Hau Lee, MBBS, MRCPCH. MCI

Children’s Intensive Care Unit

KK Women’s and Children's Hospital, Singapore

Pediatric severe sepsis:

What’s new and

controversial in fluid

strategies?

No conflict of interest

Overview

• Is there a controversy? Are there new stuff?

• Fluid resuscitation

• Fluid choice and fluid balance

• Clinical guidelines and quality improvement

• Future directions

Goldstein et al. Pediatr Crit Care Med 2005

• 20 ml/kg bolus of NS or 5% albumin vs. maintenance therapy

• 3141 children with clinical evidence of impaired perfusion

• Risk of mortality was significantly higher in patients receiving

bolus therapy (RR: 1.45; 95% CI 1.13 – 1.86)

Davis et al. Crit Care Med 2017

SSC 2012 SSC 2016 WHO 2016

Who gets fluid? Fluid resuscitation

recommended for

normotensive and

hypotensive children in

hypovolaemic shock

In children where

euvolemia

needs to be restored

Children with all 3 signs of

shock:

1) Cold extremities

2) capillary refill time > 3 s

3) weak and fast pulse

How much? Up to 20 ml/kg for

crystalloids (or albumin

equivalent) over 5 – 10

mins

No specific fluid or

volume

recommendations

10 – 20 ml/kg crystalloid

over 30 – 60 mins

Maximum? Up to 40 – 60 ml/kg for

initial resuscitation

No recommendations Further infusion of 10

ml/kg over 30 mins

for persistent shock.

Cessation? Hepatomegaly and/or

rales as signs of

hypervolemia

No recommendations Signs of fluid overload,

cardiac failure or

neurological deterioration

What do other guidelines say?

Glassford et al. Anaesth Intensive Care 2017

FBT: Fluid Bolus Therapy

Glassford et al. Anaesth Intensive Care 2017

Where Does Fluid Go?

Glassford et al. Anaesth Intensive Care 2017

• Single center RCT (N=96)

• 20ml/kg given in 15 – 20 mins vs 5 – 10 mins

• Primary outcome: Need for mechanical

ventilation and/or increase in OI of 5 points at 2

time points: 6 and 24 hours

• 6 hours: 36 vs. 57%. RR: 0.62; 95% CI: 0.39–0.99

• 24 hours: 43 vs. 68%. RR 0.63; 95% CI: 0.42–0.93

Sankar et al. Pediatric Critical Care Medicine 2017

Sankar et al. Pediatric Critical Care Medicine 2017

So how do you currently give

fluid bolus at your institution?

Would you change your practice

after the FEAST trial and recent

WHO guidelines?

Overview

• Is there a controversy? Are there new stuff?

• Fluid resuscitation

• Fluid choice and fluid balance

• Clinical guidelines and quality improvement

• Future directions

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

Type of Fluids

Long and Duke. Journal of Paediatrics and Child Health 2015

• Hyperchloremic acidosis – Worsen capillary leak

• Hyperchloremia – Renal dysfunction, AKI and need for CRRT

– Associated with mortality in critically ill adults

Cl-

154

111

98

N/S

LR/Hartmann’s

Plasmalyte

• 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)]

Weiss et al. Journal of Pediatrics 2017

• 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 score matching

• Matched for hospital, year, age, gender, septic shock, organ

dysfunction, and various comorbidities

Emrath et al. Critical Care Medicine 2017

Propensity-Matched Outcomes 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 but growing 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

Abulebda et al. Critical Care Medicine 2013

Abulebda et al. Critical Care Medicine 2013

• 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 2015

Bhaskar et al. Intensive Care Medicine 2015

Bhaskar et al. Intensive Care Medicine 2015

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.

Abstract at

PAS 2017

Fluid Balance per 10ml/kg Over First 5

Days of Severe Sepsis

Ho S et al. Abstract at 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

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. Abstract at PAS 2017

Overview

• Is there a controversy? Are there new stuff?

• Fluid resuscitation

• Fluid choice and fluid balance

• Clinical guidelines and quality improvement

• Future directions

Davis et al. Crit Care Med 2017

Nonadherence with timely fluid administration was

associated with both a longer ICU and hospital stay

Paul et al. Pediatrics 2012

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

Melendez et al. Curr Opin Pediatr 2015

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

Kissoon. Critical Care 2017

“The optimal approach to fluid administration in both high and low income countries

is not yet settled, with no rigorous study conducted in high income countries. The

FEAST trial, the largest and most rigorous attempt to address approaches to fluid

administration was done in low and middle income settings in Africa.”

“What is still unclear is how much fluid should be infused and

how fast to replenish intravascular volume deficits in children

with shock and complex co-morbidities. We need to

challenge our present dogma regarding approaches to

fluid resuscitation.”

Thank You lee.jan.hau@singhealth.com.sg