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

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

Update on the management of acute pancreatitis

“…A recent retrospective analysis of 352 patients with severe acute pancreatitis admitted to the ICU of a Chinese hospital suggests thoracic epidural analgesia may provide protection against adult respiratory distress syndrome (ARDS), acute kidney injury (AKI), and even mortality [18 ▪ ]. An unblinded trial has randomized patients between hydromorphone patient-controlled analgesia (PCA) and intramuscular pethidine and showed no difference in pain relief, but an overall worse outcome in the hydromorphone-PCA group resulting in premature termination of the trial [19].…”

Analgesia for the treatment of acute pancreatitis: a protocol for a systematic review and network meta-analysis

“… 17 20 Furthermore, newer, randomised controlled trials have become available since the publication of the last systematic review. 21 For these reasons, we aim to conduct an updated systematic review, in which we will include a network meta-analysis in addition to the traditional pairwise meta-analysis. Finally, we will report the certainty of the overall evidence for each analgesic intervention used in acute pancreatitis by using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.…”

Molecular mechanisms of pain in acute pancreatitis: recent basic research advances and therapeutic implications

“…The characteristic abdominal pain has been adopted by the revised Atlanta classification as a diagnostic criterion for AP ( Banks et al, 2013 ) and its intensity was associated with increased severity and mortality ( Foldi et al, 2022 ). Opioid analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for the management of pain in AP patients but are accompanied with side effects ( Cai et al, 2021 ) and sometimes may even worsen the severity of AP ( Barlass et al, 2018 ; Chen et al, 2022 ). Therefore, the development of new drugs and regimens for the treatment of pain in AP is required.…”

“…worsen the severity of AP (Barlass et al, 2018;Chen et al, 2022). Therefore, the development of new drugs and regimens for the treatment of pain in AP is required.…”