Controversies in the management of acute pancreatitis: An update

Table 7 Important randomized controlled trials on analgesics in acute pancreatitis

Ref.	Country	Comparison drugs	Study design	Patients, n	Rescue agent	Primary outcome	Results	Conclusion
Blamey et al[74], 1984	United Kingdom	IM buprenorphine vs IM pethidine	RCT, blinding not mentioned	32	Pethidine	Pain relief at 24 h	No significant difference in pain relief at 24 h and no significant difference in pain-free period	No superiority established
Ebbehøj et al[75], 1985	Denmark	Indomethacin suppository vs placebo	Placebo-controlled, double-blind RCT	30	Opiate not specified	Pain relief using VAS; Pain-free days	Indomethacin provided better pain control, a lesser number of painful days and lesser need for rescue analgesia	Indomethacin suppository favored over placebo
Jakobs et al[76], 2000	Germany	IV buprenorphine vs IV procaine	Open-label RCT	39	Procaine group–pethidine; buprenorphine group–pethidine	Pain relief: VAS ever 8 hr for 3 d; rescue demand	Buprenorphine provided better pain relief on days 1 and 2 with lesser need for rescue analgesia; comparable side effects, complications, mortality	Buprenorphine favored
Stevens et al[77], 2002	United States	Transdermal fentanyl IM pethidine vs placebo and IM pethidine	Double-blind placebo-controlled RCT	32	IM pethidine	Pain relief: Self-reported 0-5 scale; self-reported satisfaction 1-5 at discharge	Fentanyl provided no significant difference in pain relief at 24 h but better pain relief at 36 h and a shortened hospital stay	Fentanyl favored
Kahl et al[78], 2004	Germany	Infusion procaine vs IV pentazocine	Open RCT	101	IM pethidine	Pain relief based on VAS and rescue analgesia	Pentazocine provided better pain relief until day 3 and required fewer rescue doses	Pentazocine favored
Peiró et al[79], 2008	Spain	IV metamizole vs SC morphine	Open RCT	16	Pethidine	Pain relief based on VAS and time to pain relief	Metamizole showed better pain relief at 24 h and faster pain relief, which was nonsignificant	A favorable trend towards metamizole but a small sample size
Wilms et al[80], 2009	Germany	IV procaine vs IV placebo	Double-blind placebo-controlled RCT	42	Buprenorphine	Pain relief and need for rescue analgesia over 3 d	Failed to show better pain relief as compared to placebo, and the need for rescue analgesia was similar in both groups	Procaine is not superior to placebo
Layer et al[81], 2011	Germany	IV procaine vs IV placebo	Double-blind placebo-controlled RCT	44	Metamizole or buprenorphine	Pain relief at 3 d; rescue analgesia; proportion achieving > 67% drop in VAS	Procaine showed higher analgesic superiority with greater pain relief at 72 h, lesser need for rescue analgesia and more patients achieving VAS drop > 67%	Procaine favored over placebo
Sadowski et al[82], 2015	Switzerland	Epidural analgesia vs PCA	Open RCT	35	Not applicable	Safety and efficacy of EA; pancreatic perfusion on CT; pain relief VAS	EA was safe, provided faster pain relief and increased pancreatic perfusion	EA favored over PCA
Gülen et al[83], 2016	Turkey	Tramadol vs paracetamol + dexketoprofen	Single-blind RCT	90	Morphine	Pain relief at 30 min	No significant drop in VAS at 30 min for both agents and a similar need for rescue analgesia for both groups	No superior analgesia
Mahapatra et al[84], 2019	India	IV pentazocine vs IV diclofenac	Double blind RCT	50	Fentanyl PCA	Pain relief; pain-free period; rescue analgesia	Higher rescue analgesia needed with diclofenac; longer pain-free period and lower need for PCA with pentazocine	Pentazocine favored
Kumar et al[85], 2019	India	IV diclofenac vs IV tramadol	Double-blind RCT	41	IV morphine	Pain relief VAS over 7 d; painful days; rescue demand; time for significant VAS drop	No significant difference among both groups except time to a significant drop in VAS was quicker with diclofenac	No superior agent
Chen et al[86], 2022	China	Hydromorphone PCA vs IM pethidine	Open-label RCT	77	IM dezocine	Change in VAS score over 72 h; rescue analgesia; organ failures; local complications; ICU admission LOH; mortality	No significant difference in VAS score deduction was noted with PCA as compared to pethidine, but a higher dose of hydromorphone needed for similar pain relief; need for rescue analgesia similar	No superior agent

CT: Computed tomography; EA: Epidural analgesia; ICU: Intensive care unit; IM: Intramuscular; IV: Intraveneous; LOH: Loss of heterozygosity; PCA: Patient-controlled analgesia; RCT: Randomized controlled trial; SC: Synovial chondromatosis; VAS: Visual analog scale.