BACKGROUND: The role of fluid resuscitation in the treatment of children
with shock and life-threatening 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
albumin-bolus 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.
This paper won the prestigious BMJ Research Paper of the Year award, May
Maitland, K.; Kiguli, S.; Opoka, R.O.; Engoru, C.; Olupot-Olupot, P.; Akech, S.O.; Nyeko, R.; Mtove, G.; Reyburn, H.; Lang, T.; Brent, B.; Evans, J.A.; Tibenderana, J.K.; Crawley, J.; Russell, E.C.; Levin, M.; Babiker, A.G.; Gibb, D.M.; Feast Trial Group. Mortality after Fluid Bolus in African Children with Severe Infection. New England Journal of Medicine (2011) 364 (26) 2483-2495. [DOI: 10.1056/NEJMoa1101549]
Mortality after Fluid Bolus in African Children with Severe Infection.