ACIDOSIS IS A PRESENTING FEATURE OF CHLORAMPHENICOL TOXICITY

Abstract

Chloramphenicol (CAP) is an inhibitor of mitochondrial protein synthesis and impairs energy production through interference with oxidative phosphorylation. Metabolic acidosis associated with lactic acidemia has not been described as a presenting feature of CAP toxicity. Three critically ill children 6 mos to 11 y/o (congenital hypoaldosteronism, brain stem dysfunction, Reye's syndrome) received CAP (75-100 mg/kg/d) and had normal pH and stable cardiovascular, renal and pulmonary function for 48 hrs. Each developed profound acidosis (arterial pH 7.13-7.22) 60-108 hrs after beginning CAP. Initial CAP conc. were 61, 80, and 30 mcg/ml and subsequent levels decreased; CAP was 30 mcg/ml in the child with Reye's syndrome, a condition with recognized mitochondrial dysfunction. SGPT conc. were 386, 2,620, and 145 IU/1 when acidosis was recognized. Serum lactate was 6.6 and 8.8 mM in 2 patients prior to CAP and increased to 11.1 and 17.1 mM. Mean anion gap increased from 16.8 to 32.3 mM in the 3 patients. Hypotension followed acidosis by 6-19 hrs and was severe in one and mild in 2. Other signs of gray baby syndrome were absent. CAP was stopped in each patient and resolution of acidosis and hypotension paralleled the fall of serum CAP. 1) Unexplained metabolic acidosis is an early sign of CAP toxicity; 2) pre-existing lactic acidemia, hepatic dysfunction, and/or mitochondrial dysfunction may predispose to CAP toxicity; 3) toxicity may occur with CAP levels in a therapeutic range in Reye's syndrome.