FEAST and FEAST Substudies

Maitland K., Kiguli S., Opoka R.O., S, Opoka RO, Engoru C., Olupot-Olupot P., Akech S.O., Nyeko R., Mtove G., Reyburn H., Lang T., Brent B., Evans J.A., Tibenderana J.K., Crawley J., Russell E.C., Levin M., Babiker A.G., Gibb D.M., for the FEAST Trial Group. Mortality after Fluid Bolus in African Children with Severe Infection.  N Engl J Med. 2011 Jun 30;364(26):2483-95. This paper is available here

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. Until this is resolved the rapid correction of intravascular volume deficits to restore perfusion by intravenous fluid resuscitation in children with severe malaria remains controversial.

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

• 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.