High-dose naloxone: pharmacokinetics in patients in septic shock

Naloxone, a commonly used narcotic antagonist, may be beneficial in reversing the hemodynamic alterations seen in septic shock. In normal subjects, naloxone pharmacokinetics are characterized by rapid distribution and elimination. We investigated the pharmacokinetics of high-dose naloxone in four patients with septic shock and multiorgan failure. The pharmacokinetics of naloxone in these patients can be described by a two-compartment model with a rapid alpha distribution similar to that observed in normal humans. However, in these critically ill patients there was virtually no drug elimination as levels were followed for 5 h post-termination of a 6-h infusion of 2.4 mg/kg X h. This dramatic accumulation of naloxone may explain why responses have been reported by others to small doses of naloxone in septic shock patients. No significant side-effects were seen in our patients with plasma naloxone levels as high as 3.78 micrograms/ml. Caution is warranted when one administers naloxone to patients whose ability to eliminate this drug is minimal.