Fluid Resuscitation in Pediatric Falciparum Malaria Complicated by Acidosis

Michigan State University, East Lansing MI

Investigators

Linked publications & trials

Abstract

Fifty per cent of deaths in children hospitalized with severe pediatric malaria occur within 12 hours of admission to hospital. Rapidly acting interventions are required in order to address these early deaths. Metabolic acidosis has recently been recognized, by workers at the SMAC site in Kenya, as a complicating feature in patients with P. falciparum malaria. Acidosis may be the sole complication, in which case patients are fully alert, but present with deep breathing (an appropriate, involuntary, compensatory mechanism); the mortality rate in these patients is 24%. The mortality rate in patients with cerebral malaria and acidosis (32%) is significantly higher than in patients with cerebral malaria alone (19%). Clinical findings from this same site in Kenya suggest that many of the acidotic patients are hypovolemic, and that the acidosis improves quickly following, aggressive volume replacement (with intravenous fluids or blood). However, two of the SMAC sites (Kenya and Malawi) have data suggesting that brain swelling may be a cause of death. If this is tme, then the rapid administration of intravenous fluids might be harmful. Whether this particular intervention, the rapid administration of intravenous fluids, would be effective in terms of decreasing the mortality (early and late) in children with falciparum malaria complicated by acidosis, is the central question of this clinical trial. The clinical trial will be preceded by a pilot study, conducted in Kenya (the SMAC site most experienced in the required metabolic and hemodynamic monitoring). The purpose of the pilot study is to develop specific recommendations for fluid resuscitation which (a) are safe (b) can be evaluated in a multi-center study and (c) will be feasible in the district hospitals and health centers in which most of the African children with severe malaria are treated. Data regarding the safety and efficacy of various doses' of the intervention will be critical to our decision regarding the recommended regimen. In the intervention trial, parasitemic children with metabolic acidosis (plasma lactate concentration > 5.0 mmol\l or severe respiratory distress or pH and pCO2 measurements consisted with frank metabolic acidosis or compensated metabolic acidosis or base excess <-15) will be randomized to receive "resuscitation" or "regular care" (80 ml/'kg/24 hour of a crystalloid solution, dextrose > 5%). The execution of this study is the most difficult of the three studies contained in this proposal because the protocol must allow study clinicians to give fluid resuscitation to children who are obviously dehydrated. Data will be collected on other known predictors of outcome in severe malaria, in order to assess the comparability between treatment groups, but the sole measures of clinical efficacy will be clinical condition (dead or alive) at 12 hours, and overall outcome (survival or death). If rapid fluid administration is successful in decreasing mortality, especially the early mortality, then clinicians across Africa will have a new tool which can be deployed immediately in the treatment of severe pediatric malaria.