Acetate‐ Versus Lactate‐Buffered Crystalloids for Prevention of Post‐ERCP Pancreatitis in Patients Without Access to Rectal NSAIDs: A Multicentre Double‐Blind Randomized Trial

Background Aggressive peri‐procedural intravenous fluid (IVF) therapy with lactated Ringer's solution (LR) reduces the risk of post‐ERCP pancreatitis (PEP), but the standard 8‐h protocol is impractical in outpatient settings and the optimal fluid type remains uncertain. We compared LR with an acetate‐buffered balanced crystalloid (AC) using a symptom‐guided 4‐h aggressive IVF protocol. Methods This multicentre, double‐blind, randomized superiority trial was conducted at three academic hospitals in Korea where rectal NSAIDs are unavailable. Adults with native papillae and moderate‐to‐high PEP risk were randomized to receive LR or AC. The IVF protocol comprised 10 mL/kg boluses before and after ERCP, followed by 3 mL/kg/h for 4 hours and extended to 8 hours if abdominal pain developed or worsened. The primary outcome was PEP incidence; secondary outcomes included early post‐ERCP pain and adverse events. Results Of 813 patients (404 LR, 409 AC), PEP occurred in 12.4% of the LR group and 11.5% of the AC group (relative risk [RR] 0.93; 95% CI, 0.64–1.35; P = 0.70). Rates of mild (7.9% vs. 7.1%) and moderate (4.5% vs. 4.4%) PEP were similar, and no severe PEP or fluid overload occurred. Among the 68.3% of patients who remained asymptomatic at 4 hours and required only 4‐h IVF, PEP occurred in 7.4%, with no cases of severe PEP. Conclusion In this superiority trial, acetate‐buffered crystalloid did not reduce PEP compared with lactated Ringer's solution, and no significant safety differences were observed between the two agents. Lactated Ringer's remains the recommended first‐line crystalloid for aggressive hydration when rectal NSAIDs are unavailable. Trial Registration ClinicalTrials.gov (NCT05832047)