FEAST and Paediatric Fluid Resuscitation

Reviewed and revised 8 July 2015

OVERVIEW

• FEAST stands for “Fluid Expansion As Supportive Therapy”
• The FEAST trial was a landmark study investigating the effects of fluid boluses in the resuscitation of febrile children with evidence of poor perfusion

FEAST TRIAL

Study design

• MC RCT from Africa
• n =3141 patients without ‘severe shock’ were studied in stratum A
• n = 29 patients with ‘severe shock’ were studied in stratum B

Patients

• children (ages: 60 days to 12 years) with shock; median age was 24 months (interquartile range 13-38 months)
• Inclusion criteria:
  Severe febrile illness AND
  Impaired consciousness or respiratory distress AND
  Impaired perfusion (including capillary refill time, tachycardia, thready radial pulse or lower limb temperature gradient)
• Exclusion criteria:
  Severe Malnutrition, Gastroenteritis, Non–infectious shock (trauma, burns, surgery)

Intervention and comparison

• Within stratum A, there were 3 arms, where each child was randomised to either:
  Bolus 0.9% Saline (20ml/kg over one hour) OR
  Bolus 5% Albumin (20ml/kg over one hour) OR
  Maintenance fluids (2.5—4ml/kg/hour)
•  in stratum B patients were randomised to 5% albumin boluses or 0.9% saline boluses

Outcomes

• Primary outcome: 48 hour mortality
• Secondary outcomes: 4 week mortality, neurological outcome at 4 and 24 weeks, hypotensive shock within 48 hours of randomization, adverse events related to fluid boluses (pulmonary oedema, brain oedema, and allergic reaction)

Results

• Maintenance fluids conferred a 3.3% survival benefit at 48 hours over EITHER bolus albumin OR bolus saline. (p=0.01)
• The mortality at 48 hours was 7.3% for those who were given no bolus, vs 10.5% for either bolus fluids
• There was no difference in outcome between albumin and saline
• Most deaths (87%) occurred within the first 24 hours
• no difference in other secondary endpoints
•  non-significant trend towards pulmonary oedema in the albumin bolus group
• no  sub-group in which bolus fluids were helpful

Commentary and criticisms:

• The trial was stopped early due to the results of the interim analysis, when 2995 patients had been analysed
• high percentage of patients with:
  • malaria
  • anaemia (one-third of children had hemoglobin <5 g/dl, fluid-induced hemodilution may be dangerous)
  • respiratory distress (80%), making fluid loading particularly problematic in the absence of rescue mechanical ventilation
• only a minority of children had severe hypotension and all such severely hypotensive children received fluid bolus resuscitation; and
• negative effects of fluids may have been ameliorated if First World intensive care facilities were available
• severely shocked patients in stratum B were not randomised to maintenance fluids for ethical reasons, ironic given the results for stratum A
• study protocol (by increasing the fluid bolus amounts from 20ml/kg to 40ml/kg) was changed 18 months into the 24 month trial, the initial study protocol used a low bolus (20ml/kg) due to concerns about the risk of pulmonary oedema without respiratory (i.e. intensive care) support immediately available
• only one sign of poor perfusion was needed, perhaps making the inclusion criteria less specific

External validity

• harms seen from fluid boluses in Africa may not be seen in settings with full intensive care available
• applicability to many African children may also be limited, due to the exclusion of protein malnutrition and gastroenteritis (both of which are common in many African settings)
• What does FEAST mean for adult fluid resuscitation, and pediatric fluid resuscitation in the developed world?

REANALYSIS

Maitland et al (2013) found:

• excess mortality from fluid boluses occurred in all subgroups of children
• no difference in outcomes between patients with malaria and those that did not have malaria
• no difference between patients who were fluid ‘responders’ (features of shock resolved at 1 hour) and those that were ‘non-responders’ (this is particularly worrying for the bedside clinician!)
• those patients classified as ‘severe shock’ had greater mortality associated with fluid boluses

REASONS FOR HARM FROM FLUID BOLUSES IN THE FEAST TRIAL

Proposed explanations include:

• haemodilution effects on patients with malaria (about half of FEAST patients) and anaemia (about one third of FEAST patients) — but subsequent analyses showed no difference in mortality for malaria and non-malarial patients
• hyperchloraemic acidosis from saline administration (also present in 5% albumin) worsening acidaemia
• fluid boluses may lead to release of natriuretic peptides (due to atrial stretch) resulting in vasodilation
• disruption of the glycocalyx, due to the effects of normal saline or natriuretic peptides, may cause vasodilation and capillary leak syndromes
• loss of physiological compensation (e.g. sympathetically mediated) leading to cardiovascular collapse (most FEAST patients had poor perfusion, not decompensated shock, and may have been maximally compensated
• repursion effects or direct cardiotoxicity of fluid boluses (fluid overload manifesting as respiratory distress did not occur in FEAST patients)

CONCLUSION

• the FEAST trial is a landmark study that causes us to reassess our assumptions about fluid resuscitation
• “shock may be an adaptive, time-dependent response sustaining children through a prolonged period prior to hospital admission” — Myburgh and Finfer, 2013
• early use of vasopressors in septic shock, while avoid excessive fluid resuscitation, may be a reasonable approach  (in both adults and children)
• more studies needed!

VIDEO

Short film about the FEAST trial:

References and Links

LITFL

• Ruling the Resus Room 005 — Own the FEAST! (2012)
• CCC — Fluid bolus therapy

Journal articles

• Ford N, Hargreaves S, Shanks L. Mortality after fluid bolus in children with shock due to sepsis or severe infection: a systematic review and meta-analysis. PLoS One. 2012;7(8):e43953. doi: 10.1371/journal.pone.0043953. Epub 2012 Aug 30. Review. PubMed PMID: 22952819; PubMed Central PMCID: PMC3431361.
• Maitland K, et al and the FEAST Trial Group. Mortality after Fluid Bolus in African Children with Severe Infection. N Engl J Med. 2011 May 26. [Epub ahead of print] PMID:21615299. [Free Full Text]
• Maitland K, et al; FEAST trial group. Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Med. 2013 Mar 14;11:68. doi: 10.1186/1741-7015-11-68. PubMed PMID: 23496872; PubMed Central PMCID: PMC3599745.
• Myburgh JA. Fluid resuscitation in acute illness – time to reappraise the basics. N Engl J Med. 2011 Jun 30;364(26):2543-4. doi: 10.1056/NEJMe1105490. Epub 2011 May 26. PubMed PMID: 21615300.
• Myburgh J, Finfer S. Causes of death after fluid bolus resuscitation: new insights from FEAST. BMC Med. 2013 Mar 14;11:67. doi: 10.1186/1741-7015-11-67. PubMed PMID: 23497460; PubMed Central PMCID: PMC3599713.

FOAM and web resources

• Emergucate — FEAST trial (2013)
• empem.org — Fluid controversies (2012)