Journal Club 18/04/13

“Mortality after fluid bolus in African children with severe

infection”

Maitland K et al ,N Engl J Med 2011;364:2483-95

Robert Morton

Clinical scenario

• Called to resus to see an 18 month old boy admitted with fever & lethargy.

• On arrival, child is very quiet, respiratory distress and agitated.

• Cool peripheries and mottled limbs.

• Cap refill 3 seconds

Observations

• HR 160

• BP 95/50

• O2 sats 98% in 15L via non re-breathe

• Temp 39.5°C

• RR 40

• BM 5.3

Management (APLS)• A• B - high flow 02• C - Gain IV/IO access

• Take blood for FBC, U/E ,LFTs, culture, clotting, cross match

• Give 20ml/kg rapid bolus of crystalloid to all patients except those with signs of heart failure as their primary pathology.

• Apart from septic shock, it is uncommon to need more than one or two 20ml/kg boluses of fluid.

• In septic shock, the first bolus of fluid may be given as 4.5% Human albumin solution.

• Give 80ml/kg 3rd generation cephalosporin

?

Background

• Due to lack of intensive care facilities in Africa, WHO recommends reserving the practice of fluid resuscitation for children with advanced shock (CR> 3 seconds, weak fast pulse). Therefore most children admitted with shock in Africa receive no specific fluid management.

• Study was designed to investigate the practice of early resuscitation with a saline bolus or albumin bolus to improve outcomes.

FEAST trial

• Fluid Expansion as Supportive Therapy• Population- Children with severe

febrile illness & impaired perfusion• Intervention- 20-40ml/kg N. saline

or 5% albumin solution• Control- No bolus• Outcome- Mortality at 48 hrs

Methods

• Multi centre RCT (Kenya, Tanzania, Uganda.

• Children with septic shock assigned to early intervention with 20ml/kg N. saline or 5% albumin or no bolus.

• 2 strata, with/ without hypotension

Outcomes

• Primary outcomeMortality at 48hrs

• Secondary outcomesMortality at 4 weeksNeurological sequelae 4 & 24 weeksEpisodes of hypotensive shockAdverse reactions to fluids (PO, ICP,

allergy)

Results

• Study stopped early due to excess mortality in the bolus groups.

• 10.6% vs 10.5% vs 7.3%

CASP

1.

Did the trial address a clearly focused issue?

• Yes- Are 48 hr mortality rates increased in children with septic shock who receive fluid boluses?

Are the results valid?

2.

Was the assignment of patients to treatments randomized?

• Yes

Permuted blocks to achieve 1:1:1 ratio

Are the results valid?

3.Were all the patients who entered the trial

properly accounted for at its conclusion?

• Yes• Only 17 (0.5%) children lost to follow up

at 48hrs• 97, 98 & 98% f/u at 4 weeks

Are the results valid?

4.

Were patients, health workers and study personnel “blind” to the treatment?

• No

Are the results valid?

5.

Were the groups similar at the start of the trial?

Yes

Are the results valid?

6.

Aside from the clinical intervention, were the groups treated equally?

• Yes

What are the results?

Will the results help locally?

• ??

• Different population, intensive care facilites available.

• Different level of assessment post fluids

• Different causes of sepsis, 57% malaria in study (but equal across all groups)-can cause haemodilution and anaemia

Criticism of study

• Impaired perfusion rather than shock studied

- Only 26% cap refill > 3 secs

- Only 52% 2 signs of shock

- Only 67 children (2%) fulfilled WHO criteria for shock (cold hands, weak peripheral pulse and CR >3 seconds)

• Is cap refill a reliable sign of shock?

• Is tachycardia?

• Final diagnoses not published

• ? SIADH- Na levels not reported

Further analysis

• Further results published in 2013 showed excess mortality from boluses occurred in all subgroups of children.

• Mode of death cardiovascular collapse rather than fluid overload