Evaluating the efficacy of N-acetyl-cysteine in combination with naloxone for the treatment of patients with methadone poisoning; a double-blind randomized clinical trial

Introduction: Methadone overdose is a severe and possibly fatal situation. Its routine treatment is naloxone therapy, meanwhile, N-acetylcysteine (NAC) may be effective in its clinical symptom improvement. Objectives: This study aimed to assess the effectiveness of combining NAC with naloxone in treating patients who have overdosed on methadone. Patients and Methods: This double-blind clinical trial was conducted on patients with methadone intoxication referred to Kashani Hospital in Shahrekord, Iran, from May to December 2021. Before the study began, written informed consent was obtained from the patients, and they were randomly assigned to two groups of intervention and control, with 32 patients in each group. In the control group, standard treatment with naloxone was administered, whereas in the intervention group, NAC was added to the standard treatment. The outcome measures included hemodynamic parameters, arterial blood gas analysis, and liver functional tests, which were assessed before and after the intervention, were compared between the two groups using statistical tests. Results: The study results indicated that the mean age of the control and intervention groups was 43.09 and 44.21 years, respectively. Demographic characteristics were similar between the two groups. The comparative analysis of the mean differences in changes in hemodynamic and biochemical parameters between the control and intervention groups revealed that the changes in mean arterial pressure (MAP), respiratory rate (RR), temperature (T), pH, and bicarbonate (HCO3 ) were not statistically significant (P>0.05). Conversely, the mean differences in changes of pulse rate (PR), partial pressure of carbon dioxide (PCO2 ), partial pressure of oxygen (PO2 ), alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were found to be statistically significant (P<0.05). This analysis demonstrated significant reductions in PR, PCO2 , and liver function tests (LFTs) including ALT, AST, and ALP in the intervention group compared to the control group. In contrast, the PO2 showed a positive change, with the intervention group exhibiting a greater increase compared to the control group. Conclusion: We conclude that NAC has a positive impact on the treatment of methadone intoxication, especially in improving liver function and respiratory parameters. Trial Registration: The trial protocol was approved by the Iranian Registry of Clinical Trials (IRCT20210222050462N1, https://irct.behdasht.gov.ir/trial/55313; ethical code from Shahrekord University of Medical Sciences; IR.SKUMS.REC.1399.244).