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Publications & References

FEAST Publications

The use of boluses (rapid fluid resuscitation) of children with shock caused by severe infections is standard practice in high-income countries. It is also recommended by WHO in low-income settings, but the evidence-base for this practice has been, until recently, very weak. Last year the results of the FEAST trial, examining fluid resuscitation in critically ill children with severe infections and shock (including children with WHO-defined shock), were published in the New England Journal of Medicine . The publication was fast tracked because of its importance, and subsequently received the BMJ Research Paper of the Year award because of the strength of the results, and implications for changing guidelines.

The FEAST trial was stopped early by the Data Monitoring Committee because results, even before the trial finished showed that fluid resuscitation with 20-40ml/kg 0.9% saline or albumin given rapidly over <1 hour (most received 20ml/kg) actually significantly increased mortality. The results of the trial were unexpected, and have raised important questions about the management of children critically ill with infections in Africa. Of note, the adverse effects of fluids did not appear to be related to the adverse effects of fluid overload.

 

Work leading up to FEAST trial

Evidence for intravascular volume depletion in children with severe malaria

Over the last 10 years the group at the Wellcome Trust Unit in Kilifi, Kenya, in collaboration with the paediatric intensive care group at Imperial College, London have used insights gained from paediatric critical illness to examine the pathophysiology of severe malaria in a series of physiological studies. These established that low central venous pressure (~0-3cm water), severe tachycardia, and a delayed capillary refilling time (CRT) -all features of compensated hypovolaemic shock – were common on admission. Up to 40% of those with severe acidosis (base deficit >15) were hypotensive – a feature of advanced, decompensated hypovolaemic shock. Three clinical trials in Kilfi, Kenya compared different fluids in children with severe malaria and signs of hypovolaemia. Up to 40mls/kg of 0.9% saline or HAS was found to be safe and corrected haemodynamic indices of hypovolaemia and when compared to huam albumin solution (HAS) mortality was lower (3.6%) in the HAS arm than saline arm  (18%).

What remains unresolved is whether rapid and early restoration of intravascular volume results in a superior outcome compared to slow corrections of deficits by low volume maintenance fluids. This was the question that the FEAST trial was designed to address

Relevant References

  • English M, Sauerwein R, Waruiru C, et al. Acidosis in severe childhood malaria. Q.J.Med. 1997; 90:263-70.
  • Maitland K, Levin M, English M, et al. Severe P. falciparum malaria in Kenyan children: evidence for hypovolaemia. Q.J.Med. 2003; 96:427-34.
  • Maitland K, Pamba A, Newton CR, Levin M. Response to volume resuscitation in children with severe malaria. Pediatr. Crit. Care Med. 2003;4:426-31.
  • Pamba A, Maitland K. Capillary refill: prognostic value in Kenyan children. Arch Dis Child 2004; 89:950-5.
  • Evans JA, May J, Ansong D, et al. Capillary refill time as an independant prognostic factor in children with severe and complicated malaria. Pediatrics 2006.
  • Maitland K, Newton CR. Acidosis of severe falciparum malaria: heading for a shock? Trends Parasitol 2005; 21:11-6.
  • Maitland K, Pamba A, English M, et al. Randomized trial of volume expansion with albumin or saline in children with severe malaria: preliminary evidence of albumin benefit. Clin Infect Dis 2005; 40:538-545.
  • Maitland K, Pamba A, English M, et al. Pre-transfusion management of children with severe malarial anaemia: a randomised controlled trial of intravascular volume expansion. Br J Haematol 2005; 128:393-400.
  • Akech S, Gwer S, Idro R, Fegan G, Eziefula AC, Newton CR, et al. Volume Expansion with Albumin Compared to Gelofusine in Children with Severe Malaria: Results of a Controlled Trial. PLoS Clin Trials 2006;1(5):e21
  • Akech SO, Jemutai J, Timbwa M, Kivaya E, Boga M, Fegan G, et al. Phase II trial on the use of Dextran 70 or starch for supportive therapy in Kenyan children with severe malaria. Crit Care Med 2010;38(8):1630-6.
  • Yacoub S, Lang HJ, Shebbe M, Timbwa M, Ohuma E, Tulloh R, et al. Cardiac function and hemodynamics in children in Africa with severe malaria. Crit Care Med 2010.

FEAST and FEAST sub-studies Publications

  1. Maitland K, Molyneux S, Boga M, Kiguli S, Lang T. Use of deferred consent for severely ill children in a multi-centre phase III trial. Trials. 2011;12:90
  2. Maitland K, Akech SO, Russell EC: Mortality after Fluid Bolus in African Children with Sepsis: Reply. The New England journal of medicine 2011, 365:1348-1353    http://www.nejm.org/doi/full/10.1056/NEJMc1108712
  3. Maitland K, Babiker A, Kiguli S, Molyneux E: The FEAST trial of fluid bolus in African children with severe infection. Lancet 2012, 379:613; author reply 613-614.
  4. Maitland K, George E, Evans J, Kiguli S, Olupot-Olupot P, Akech S, Opoka RO, Engoru C, Nyeko R, Mtove G, Reyburn H, Brent B, Nteziyaremye J, Mpoya A, Prevatt N, Dambisya CM, Semakula D, Ddungu A, Okuuny V, Wokulira R, Timbwa M, Otii B, Levin M, Crawley J, Babiker AG, DM G: Exploring mechanisms of excess mortality with early fluid resuscitation: insights from the FEAST trial. BMC Med 2013, in press.
  5. Molyneux S, Njue M, Boga M, Akello L, Olupot-Olupot P, Engoru C, Kiguli S, Maitland K: ‘The words will pass with the blowing wind’: staff and parent views of the deferred consent process, with prior assent, used in an emergency fluids trial in two african hospitals. PloS one 2013, 8:e54894 http://www.ncbi.nlm.nih.gov/pubmed/23408950

FEAST News

14 March 2014

FEAST investigators question why WHO have failed to change guidelines

  • Current septic shock treatment guidelines are putting children’s lives at risk in Africa
  • In a paper published in the British Medical Journal on 12th January the FEAST trial investigators called on the World Health Organisation to update their guidelines on how to treat children in shock in Africa urgently, warning that the World Health Organisation’s failure to update their guidelines is costing children’s lives.

19 February 2013