Pain Management in Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Abstract

Background: Pain management is an important priority in the treatment of acute pancreatitis (AP). Current evidence and guideline recommendations are inconsistent on the most effective analgesic protocol. This systematic review and meta-analysis of randomised controlled trials (RCTs) aimed to compare the safety and efficacy of analgesics for pain relief in AP.Methods: A literature search was performed to identify all RCTs assessing analgesics in patients with AP. The primary outcome was the number of participants who needed rescue analgesia. Study quality was assessed using Jadad score. Pooled odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CI) were analysed using a random-effects model.Results: Twelve studies comprising 699 patients with AP (83% mild AP) were analysed. The tested analgesics significantly decreased the need for rescue analgesia (3 studies, OR.36, 95% CI 0.21 to 0.60) vs. placebo or conventional treatment. The analgesics also improved the pain score [Visual Analogue Scale (Δ-VAS)] at 24 h (WMD 18.46, 0.84 to 36.07) and by the 3rd to 7th days (WMD 11.57, 0.87 to 22.28). Opioids vs. non-opioids were associated with a decrease in the need for rescue analgesia (6 studies, OR 0.25, 95% CI 0.07 to 0.86, p = 0.03) but without significance in pain score. In subgroup analyses, opioids were similar to non-steroidal anti-inflammatory drugs (NSAIDs) regarding the primary outcome (4 studies, OR 0.56, 95% CI 0.24 to 1.32, p = 0.18). There were no significant differences in other clinical outcomes and rate of adverse events. Other studies, comparing epidural anaesthesia vs. patient-controlled analgesia and opioid (buprenorphine) vs. opioid (pethidine) did not show significant difference in primary outcome. Study quality issues significantly contributed to overall study heterogeneity.Conclusions: NSAIDs and opioids are equally effective in decreasing the need for rescue analgesia in patients with mild AP. The relative paucity of trials and high-quality data in this setting is notable and the optimal analgesic strategy for patients with moderately severe and severe AP still requires to be determined.

Acute Pancreatitis: Diagnosis and Treatment

“…Abdominal pain can be profound in acute pancreatitis, and for most patients, strong opioid analgesia is appropriate, reducing the need for supplementary analgesia over other regimens; analgesia ladders can be used for those with less severe pain, mindful that early and effective relief is a priority [174]. NSAIDs are an opiate-sparing alternative for uncomplicated disease [175], but run the risk of renal injury in more severe disease.…”

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

“…To the best of our knowledge, this is the first RCT evaluating the safety and efficacy of intravenous hydromorphone PCA in AP patients. The strengths of this study include the following: 1) our treatment design the novel analgesic technology PCA versus the traditional analgesia in AP; 2) according to our inclusion criteria, 70% 2 (0-3) 2.5 (0-4) 0.564 2 (0-3) 2.5 (0-4) 0.475 24 h VAS, median (IQR) Frontiers in Pharmacology frontiersin.org of patients were MSAP to SAP, compared to a high proportion of MAP cases in the existing 12 RCTs (Cai et al, 2021); 3) the onset of symptoms of patients in the two groups was limited within 72 h, which maintained homogeneity between the groups; and 4) a VAS score for pain intensity greater than five on admission was one of the inclusion criteria to more accurately evaluate the analgesic effects of the drugs, which was not clearly defined in most of the previous RCTs.…”

“…However, these studies had relatively small sample sizes, included participants with mild acute pancreatitis (MAP), and adopted different diagnostic criteria for AP. In our recent systematic review and meta-analysis, NSAIDs and opioids are equally effective for analgesia in MAP, but the optimal analgesic strategy for moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) patients remains unclear ( Cai et al, 2021 ).…”

“…However, this notion has never been tested in the AP setting. Although the 2019 World Society of Emergency Surgery (WSES) recommended the use of PCA and hydromorphone in AP due to their superiority to morphine ( Leppäniemi et al, 2019 ), most AP guidelines lack a recommendation regarding optimal pain medications and analgesic approaches ( Cai et al, 2021 ).…”

Efficacy and Safety of Thoracic Epidural Analgesia in Patients With Acute Pancreatitis: A Narrative Review

“…The severity of abdominal pain in the early phase is more and needs to be managed using multi-modal analgesia. The drugs used are opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and thoracic epidural analgesia (TEA) in a few studies [ 10 ]. In the late phase, the problems encountered are pneumonia, bacteremia, intra-abdominal infections due to pancreatic necrosis, intra-abdominal collections, pseudocyst formation which increases the morbidity and mortality significantly [ 11 ].…”