Interpretation of excessive serum concentrations of digoxin in children

Between January 1981 and April 1984, excessive serum concentrations of digoxin (5 ng/ml or higher) were recorded in 47 children, aged 2 days to 16 years. In 10 patients, the high concentrations were measured 9.25 to 48 hours after death and were significantly higher than antemortem levels in all cases (8.3 ± 2.4 (± standard deviation) postmortem vs 3.3 ±1.5 antemortem, <0.0001). In 15 patients (40.5% of the living patients) serum concentrations of 5 ng/ml or higher reflected sampling errors; drug levels were monitored too closely to the administration of a dose. None of these children had toxic manifestations of digoxin. In 10 patients, the excessive concentrations were associated with renal failure and a prolonged elimination half-life (T 1 2) of digoxin; in 3 of these patients, there were signs of digoxin toxicity. Six cases were caused by digoxin overdose (accidental ingestions, pharmacy error and a suicide attempt). In 6 additional cases, the existence of an endogenous digoxin-like substance (EDLS) was shown to contribute to the excessive levels of the drug. One case could be attributed to digoxin-amiodarohe interaction. In 10 of 37 living patients, digoxin toxicity was diagnosed. After excluding the 15 sampling errors and 6 cases with EDLS, this represents 63% of the cases. There was a good correlation between digoxin elimination T 1 2 and serum creatinine concentrations (r = 0.71, p <0.01). The above observations suggest that excessive serum concentrations of digoxin may not necessarily reflect potentially toxic levels. Sampling errors, postmortem determinations and circulating EDLS should be considered as explanations when toxic levels of digoxin are found.