Randomized Trial of Volume Expansion with Albumin or Saline in Children with SevereMalaria: Preliminary Evidence of Albumin Benefit

Kathryn Maitland,1,2 Allan Pamba,1 Michael English,1,4 Norbert Peshu,1 Kevin Marsh,1,5 Charles Newton,1,3 and Michael Levin21The Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya; 2Department of Paediatrics, Facultyof Medicine and the Wellcome Trust Centre for Clinical Tropical Medicine, Imperial College, and 3Neurosciences Unit, Institute of Child Health, University College, London, and 4Department of Paediatrics and 5Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom



Metabolic acidosis is the best predictor of death in children with severe falciparum malaria;however, its treatment presents a therapeutic dilemma, because acidosis and hypovolemia may coexist with coma, which can be associated with elevated intracranial pressure. We postulated that volume resuscitation with albuminmight correct acidosis and hypovolemia with a lower risk of precipitating cerebral edema than crystalloid. In anopen-label, randomized, controlled trial, we compared the safety of resuscitation with albumin to saline in Kenyan children with severe malaria.

Methods. We randomly assigned children with severe malaria and metabolic acidosis (base deficit, 18 mmol/L) to receive fluid resuscitation with either 4.5% albumin or normal saline. A control (maintenance only) group was only included for patients with a base deficit of !15 mmol/L.

The primary outcome measure was the percentagereduction in base deficit at 8 h. Secondary end points included death, the requirement for rescue therapies, andneurological sequelae in survivors.
Results. Of 150 children recruited for the trial, 61 received saline, 56 received albumin, and 33 served as control subjects. There was no significant difference in the resolution of acidosis between the groups; however, the mortalityrate was significantly lower among patients who received albumin (3.6% [2 of 56 patients]) than among those whoreceived saline (18% [11 of 61]; relative risk, 5.5; 95% confidence interval, 1.2–24.8; Pp.013).

Conclusions. In high-risk children with severe malaria and acidosis, fluid resuscitation with albumin may reduce mortality. Our study design did not enable us to determine whether saline administration is preferable tofluid restriction or whether saline administration is actually hazardous. Further studies are needed to confirm ourfindings before definitive treatment recommendations can be made.

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