Fluid resuscitation in malaria: the need for new randomised clinical trials.

Very little clinical research has been conducted on how to manage children with severemalaria, despite it accounting for the deaths of around 1 million children each year in Africa alone. Antimalarial drugs remain the mainstay of treatment (and are the subject of several current or planned clinical trials), but there is increasing debate around aspects of supportive care and the treatment of complications. No aspect of care has been more controversial in recent years than the initial fluid management of children with severe malaria, particularly given the resourcepoor health-care context in which most such children are treated. The debate centres around the role of hypovolaemia (i.e., insufficient circulating blood volume) in the pathophysiology of severe malaria. Hypovolaemia has been incriminated as an important cause of metabolic acidosis, which has been shown repeatedly to be associated with a poor prognosis. The key question is whether hypovolaemia contributes to impaired tissue perfusion in severe malaria, contributing to the anaerobic glycolysis and consequent acidosis. Some studies of severe malaria in children have supported this hypothesis by providing indirect evidence (e.g., capillary refill time, central venous p r e s s u r e mea su r emen t s , r a i s e d creatinine, and clinical dehydration) that severely ill patients are commonly hypovolaemic on admission, and that this contributes to the severity of the disease [1,2]. In febrile children hypovolaemia often results from dehydration, but a detailed study in Gabon showed that the children with severe malaria investigated had only a mild or moderate degree of dehydration (as measured by total body water, not necessarily synonymous with hypovolaemia) [3]. So, should children with severe malaria all receive rapid intravenous fluid rehydration? And if so, with what fluid? Proponents of rapid fluid repletion cite the standards of care applied in resourcerich settings for severely ill children with bacterial sepsis, whilst those advocating caution argue that malaria should be considered differently, particularly given the haemodynamic and circulatory differences from sepsis and the concerns of precipitating or worsening pulmonary or cerebral oedema [2,4]. It is clear that clinical trials are the only way forward to resolve the debate. There have been several previously published intervention studies, all conducted by Maitland and the Kilifi team on the Kenyan coast, but to date all have been too small and heterogenous to provide conclusive answers.