Safety Analysis of IV Methadone vs. IV Hydromorphone in Post-Procedural Adults

IV Methadone may be used post-procedurally to manage pain; however, it carries risks of respiratory depression and QTc prolongation. The purpose of this study is to compare safety profiles of multiple doses of intravenous (IV) methadone and IV hydromorphone in post-procedural patients. The primary outcome was incidence of respiratory event, defined as oxygen saturation (O₂Sat) less than 90%, respiratory rate less than 8 breaths per minute (bpm), increased supplemental oxygen, or naloxone administration within 24 h of IV methadone or hydromorphone. Secondary outcomes included incidence of QTc prolongation and additional opioid, benzodiazepine, or ketamine doses. After exclusion assessment, 154 patients met inclusion criteria. Patients were grouped by receiving methadone (n = 85) or hydromorphone (n = 69). The primary outcome occurred 111 times in the methadone group and 40 times in the hydromorphone group (p < 0.0001). Among patients who had a respiratory event, patients who received methadone had more respiratory events compared to those who received hydromorphone (IRR: 2.25, 95% CI (1.56-3.32), p < 0.0001). Patients who received methadone also received more opioid and ketamine doses (p < 0.0001). Post-procedural methadone may be unsafe due to increased incidence of respiratory events, possible because of methadone's long half-life causing drug accumulation.