Background: Methadone toxicity is one of the major causes of death in opioiddependent
Objective: We aimed to compare two different protocols of naloxone administration in terms of
reversal of overdose signs and symptoms and frequency of complications in opioid-dependent
Method: One-hundred opioid-dependent patients with signs/symptoms of methadone overdose
were included. The patients were consecutively assigned into Tintinalli (group 1) or Goldfrank
regimen protocol (group 2) of naloxone administration. Group 1 received naloxone with the dose
0.1 mg given every two to three minutes while group 2 received naloxone with the initial dose of
0.04 mg increasing to 0.4, 2, and 10 mg every two to three minutes to reverse respiratory depression.
They were then compared regarding reversal of toxicity and risk of development of complications.
Results: The time to reversal of the overdose signs/symptoms was significantly less in Goldfrank
regimen protocol (P<0.001). Frequency of withdrawal syndrome and recurrence of respiratory depression
were not significantly different between the two groups. Aspiration pneumonia and intubation
were more frequent in group 2, as well.
Conclusion: It seems that gradual titration of naloxone by Tintinalli protocol can reduce major
complications compared to the Goldfrank regimen. However, this protocol was not perfect in
opioid-dependent methadone-overdosed patients, either, since it could induce complications, as
well. We may need new protocols in overdosed opioid-dependent patients.