Safety and efficacy of intravenous hydromorphone patient-controlled analgesia versus intramuscular pethidine in acute pancreatitis: An open-label, randomized controlled trial

Zhiyao Chen; Kun Jiang; Fei Liu; Ping Zhu; Fei Cai; Yanqiu He; Tao Jin; Ziqi Lin; Qian Li; Cheng Hu; Qingyuan Tan; Xiaonan Yang; Jia Guo; Wei Huang; Lihui Deng; Qing Xia

doi:10.3389/fphar.2022.962671

Safety and efficacy of intravenous hydromorphone patient-controlled analgesia versus intramuscular pethidine in acute pancreatitis: An open-label, randomized controlled trial

Front Pharmacol. 2022 Aug 4:13:962671. doi: 10.3389/fphar.2022.962671. eCollection 2022.

Authors

Zhiyao Chen¹, Kun Jiang¹, Fei Liu², Ping Zhu¹, Fei Cai¹, Yanqiu He¹, Tao Jin¹, Ziqi Lin¹, Qian Li², Cheng Hu¹, Qingyuan Tan¹, Xiaonan Yang¹, Jia Guo¹, Wei Huang¹, Lihui Deng¹, Qing Xia¹

Affiliations

¹ Pancreatitis Center, Center of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
² Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Background: Hydromorphone patient-controlled analgesia (PCA) provides satisfactory postoperative pain therapy, but its effect has not been assessed in acute pancreatitis (AP). Aim: To assess the safety and efficacy of intravenous hydromorphone PCA for pain relief in AP. Methods: This open-label trial included AP patients admitted within 72 h of symptom onset, aged 18-70 years old, and with Visual Analog Scale (VAS) for pain intensity ≥5. They were randomized to receive intravenous hydromorphone PCA (0.05 mg/h with 0.2 mg on-demand) or intramuscular pethidine (50 mg as required) for three consecutive days. Intramuscular dezocine (5 mg on demand) was the rescue analgesia. The primary outcome was the change of VAS score recorded every 4 h for 3 days. Interim analysis was conducted by an Independent Data and Safety Monitoring Committee (IDSMC). Results: From 26 July 2019 to 15 January 2020, 77 patients were eligible for the intention-to-treat analysis in the interim analysis (39 in the hydromorphone group and 38 in the pethidine group). Baseline parameters were comparable between groups. No difference in VAS between the two groups was found. Hydromorphone PCA was associated with higher moderately severe to severe cases (82.1% vs. 55.3%, p = 0.011), acute peripancreatic fluid collections (53.9% vs. 28.9%, p = 0.027), more cumulative opioid consumption (median 46.7 vs. 5 mg, p < 0.001), higher analgesia costs (median 85.5 vs. 0.5 $, p < 0.001) and hospitalization costs (median 3,778 vs. 2,273 $, p = 0.007), and more adverse events (20.5% vs. 2.6%, p = 0.087). The per-protocol analysis did not change the results. Although a sample size of 122 patients was planned, the IDSMC halted further recruitment as disease worsening or worse clinical outcomes between the groups in the interim analysis. Conclusion: Hydromorphone PCA was not superior to pethidine in relieving pain in AP patients and might have worse clinical outcomes. Therefore, its use is not recommended. Clinical Trial Registration: Chictr.org.cn. ChiCTR1900025971.

Keywords: acute pancreatitis; hydromorphone; patient-controlled analgesia; pethidine; randomized controlled trial.