Mech-Sense and Centre for Pancreatic Diseases, Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Am J Gastroenterol. 2024 Nov 1;119(11):2307-2316. doi: 10.14309/ajg.0000000000002904. Epub 2024 Jun 25.
Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia.
This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers. Patients were randomized to receive 5 days of continuous intravenous methylnaltrexone (0.15 mg/kg/d) or placebo added to the standard of care. The primary end point was the Pancreatitis Activity Scoring System score after 48 hours of treatment. Main secondary outcomes included pain scores, opioid use, disease severity, and mortality.
In total, 105 patients (54% men) were randomized to methylnaltrexone (n = 51) or placebo (n = 54). After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points in the methylnaltrexone group and 130.5 points in the placebo group (difference 3.8, 95% confidence interval [CI] -40.1 to 47.6; P = 0.87). At 48 hours, we found no differences between the groups in pain severity (0.0, 95% CI -0.8 to 0.9; P = 0.94), pain interference (-0.3, 95% CI -1.4 to 0.8; P = 0.55), and morphine equivalent doses (6.5 mg, 95% CI -2.1 to 15.2; P = 0.14). Methylnaltrexone also did not affect the risk of severe disease (8%, 95% CI -11 to 28; P = 0.38) and mortality (6%, 95% CI -1 to 12; P = 0.11). The medication was well tolerated.
Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of AP.
在急性胰腺炎（AP）中使用阿片类药物来控制剧烈疼痛，可能会通过对胃肠道和免疫功能的影响使疾病恶化。美沙酮，一种外周作用的μ-阿片受体拮抗剂，可能在不改变镇痛效果的情况下对抗这些作用。
本项双盲、随机、安慰剂对照试验纳入了丹麦 4 个中心的患有 AP 和全身炎症反应综合征的成年患者。患者被随机分为接受 5 天连续静脉内美沙酮（0.15mg/kg/d）或安慰剂治疗，同时接受标准治疗。主要终点是治疗后 48 小时的胰腺炎活动评分系统评分。主要次要结局包括疼痛评分、阿片类药物使用、疾病严重程度和死亡率。
共有 105 名患者（54%为男性）被随机分为美沙酮组（n=51）或安慰剂组（n=54）。48 小时后，美沙酮组的胰腺炎活动评分系统评分为 134.3 分，安慰剂组为 130.5 分（差值 3.8，95%置信区间[CI]为-40.1 至 47.6；P=0.87）。48 小时时，我们发现两组之间的疼痛严重程度（0.0，95%CI 为-0.8 至 0.9；P=0.94）、疼痛干扰（-0.3，95%CI 为-1.4 至 0.8；P=0.55）和吗啡等效剂量（6.5mg，95%CI 为-2.1 至 15.2；P=0.14）均无差异。美沙酮也未影响严重疾病的风险（8%，95%CI 为-11 至 28；P=0.38）和死亡率（6%，95%CI 为-1 至 12；P=0.11）。药物耐受性良好。
美沙酮治疗并未优于安慰剂降低 AP 的严重程度。
