Severe and prolonged sedation in five neonates due to persistence of active diazepam metabolites.
Five neonates who suffered from an unexpected long period of respiratory failure, muscular hypotonia, and drowsiness were observed in a retrospective study. Prior to this general depression, unusually high doses of diazepam were administered to all patients via intravenous bolus injection. Serum levels of diazepam and its active metabolites were substantially elevated in the course of the disease. The persistence of the very long-acting N-desmethyldiazepam with considerable extension in neonates and even more exaggerated in premature infants is emphasized due to the reduced capacity of the hepatic biotransformation system.


CONCLUSIONS
The intravenous application of diazepam imposes a risk of marked and prolonged general depression in neonates. Pronounced adverse effects are to be expected for prematures even after a single diazepam intravenous bolus if the dosage is not appropriate. Diazepam should not be used for short sedation and is not the drug of choice for anticonvulsant therapy in neonates.
Peinemann
F
F
Zentrum für Kinderheilkunde, Heinrich-Heine-Universität, Düsseldorf, Germany. frank.peinemann@t-online.de
Daldrup
T
T
D001711:Biotransformation; D003975:Diazepam / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism
D006993:Hypnotics and Sedatives; D003975:Diazepam