Abstract:
Background
The role of fluid resuscitation in the treatment of children with shock and lifethreatening
infections who live in resource-limited settings is not established.
Methods
We randomly assigned children with severe febrile illness and impaired perfusion to
receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9%
saline solution (saline-bolus group) per kilogram of body weight or no bolus (control
group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum
A); children with severe hypotension were randomly assigned to one of the bolus groups
only (stratum B). All children received appropriate antimicrobial treatment, intravenous
maintenance fluids, and supportive care, according to guidelines. Children with malnutrition
or gastroenteritis were excluded. The primary end point was 48-hour mortality;
secondary end points included pulmonary edema, increased intracranial
pressure, and mortality or neurologic sequelae at 4 weeks.
Results
The data and safety monitoring committee recommended halting recruitment after
3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57%
overall) and clinical severity were similar across groups. The 48-hour mortality was
10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044
children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative
risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90;
P = 0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29;
P = 0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P = 0.003).
The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively
(P = 0.004 for the comparison of bolus with control). Neurologic sequelae occurred
in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P = 0.92), and
pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7%
(P = 0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albuminbolus
group and 56% (9 of 16) in the saline-bolus group died (P = 0.45). The results
were consistent across centers and across subgroups according to the severity of
shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia.
Conclusions
Fluid boluses significantly increased 48-hour mortality in critically ill children with
impaired perfusion in these resource-limited settings in Africa.