title: Randomized trial of volume expansion with albumin or saline in children with severe malaria: preliminary evidence of albumin benefit.
abstract: BACKGROUND
  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 albumin might correct acidosis and hypovolemia with a lower risk of precipitating cerebral edema than crystalloid. In an open-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, >8 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 percentage reduction in base deficit at 8 h. Secondary end points included death, the requirement for rescue therapies, and neurological 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 mortality rate was significantly lower among patients who received albumin (3.6% [2 of 56 patients]) than among those who received saline (18% [11 of 61]; relative risk, 5.5; 95% confidence interval, 1.2-24.8; P=.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 to fluid restriction or whether saline administration is actually hazardous. Further studies are needed to confirm our findings before definitive treatment recommendations can be made.
authors.affiliation: The Centre for Geographic Medicine Research, Coast, Kenya Medical Research Institute, Kilifi, Kenya. kmaitland@kilifi.mimcom.net
authors.forename: Kathryn
authors.initials: K
authors.lastname: Maitland
authors.forename: Allan
authors.initials: A
authors.lastname: Pamba
authors.forename: Michael
authors.initials: M
authors.lastname: English
authors.forename: Norbert
authors.initials: N
authors.lastname: Peshu
authors.forename: Kevin
authors.initials: K
authors.lastname: Marsh
authors.forename: Charles
authors.initials: C
authors.lastname: Newton
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
mesh_terms: D000138:Acidosis / Q000150:complications*; D000418:Albumins / Q000627:therapeutic use*; D002675:Child, Preschool; D005440:Fluid Therapy; D006801:Humans; D020896:Hypovolemia; D007223:Infant; D016778:Malaria, Falciparum / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D012720:Severity of Illness Index; D012965:Sodium Chloride / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D012965:Sodium Chloride