Unidentified acids of strong prognostic significance in severe malaria*

Objective: To calculate, using the Stewart approach to acid-base disorders, the strong anion gap as an estimate for the contribution of unmeasured plasma anions other than lactate to the metabolic acidosis that characterizes severe falciparum malaria and to assess its relative prognostic significance. Design: Cohort study. Setting: The intensive care unit of an infectious diseases hospital in southern Vietnam. Patients: Consecutive adult patients (n = 268) with severe falciparum malaria. Interventions: The intervention was clinical management in a dedicated unit. We measured baseline venous lactate, electrolytes, biochemical variables, admission arterial blood pH, and gas tensions for calculation of the strong anion gap. Measurements and Main Results: The mean (95% confidence interval) admission strong anion gap was 11.1 (10.4–11.9) mEq/L, compared with lactate (geometric mean, 95% confidence interval) at 2.9 (2.7–3.2) mmol/L. Strong anion gap had a high predictive value for mortality (area under the receiver operating characteristic curve 0.73 (95% confidence interval, 0.65–0.82), which was independent of plasma lactate and creatinine concentrations. Renal failure and hepatic dysfunction were both associated with, but were not the sole determinants of, high levels of strong anion gap. Conclusions: In severe malaria, unidentified anions other than lactate are the most important contributors to metabolic acidosis, a major cause of death. The strong anion gap is a powerful prognostic indicator in patients with severe malaria.