Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian Medical University, Liaoning, China.
Chin Med J (Engl). 2010 Sep;123(18):2600-6.
Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is regarded as one of the worrisome complications of endoscopic retrograde cholangiopancreatography (ERCP). Results of randomized controlled trials evaluating the preventive effect of ulinastatin and gabexate mesylate (GM) on PEP are contradictory. The present study was designed to evaluate the prophylactic effect of ulinastatin and GM on PEP with meta-analyses of randomized controlled trials (RCTs).
Five electronic databases were searched for RCTs evaluating the preventive effect of ulinastatin and GM on PEP. Summary effects were assessed with the methods recommended by the Cochrane Collaboration.
Twelve studies involving 5105 participants were included in our meta-analyses. Administration of ulinastatin decreased the incidence of PEP only at sufficient doses (OR, 0.39; 95%CI, 0.19 to 0.81; P = 0.01). Number needed to treat (NNT) was 6. And administration of ulinastatin also reduced the incidence of post-ERCP hyperamylasemia (PEHA) (OR, 0.40; 95%CI, 0.28 to 0.58; P < 0.000 01). Slow infusion of high-dose GM was effective for PEP prevention (OR, 0.44; 95%CI, 0.25 to 0.79; P = 0.006), and rapid infusion of low-dose GM also showed efficacy for PEP prophylaxis (OR, 0.37; 95%CI, 0.20 to 0.69; P = 0.002). NNT was 7 and 6 respectively. However, administration of GM at low doses and by slow infusions was ineffective (OR, 0.99; 95%CI, 0.64 to 1.55; P = 0.98). Administration of GM had the tendency to reduce PEHA rate, but not to a statistical significance (OR, 0.86; 95%CI, 0.73 to 1.01; P = 0.06). When low-quality studies were excluded, the meta-analysis with two high-quality studies indicated that ulinastatin did not reduce the rate of PEP (OR, 0.63; 95%CI, 0.32 to 1.26; P = 0.19) and PEHA incidence (OR, 0.80; 95%CI, 0.31 to 2.07; P = 0.64). The meta-analysis with six high-quality studies showed that GM administration decreased PEP incidence (OR, 0.52; 95%CI, 0.29 to 0.91; P = 0.02), while was not efficacious for PEHA prevention (OR, 0.88; 95%CI, 0.74 to 1.04; P = 0.12).
Ulinastatin and GM may be of value for the prophylaxis of PEP. GM should be administered at high doses and by rapid infusions. And the doses of ulinastatin should be sufficient. However, the conclusions are not overwhelming. More large-sample size and high-quality RCTs are still needed to elucidate whether administrations of the two drugs really have prophylactic effect on PEP.
内镜逆行胰胆管造影术后胰腺炎（PEP）被认为是内镜逆行胰胆管造影术（ERCP）的一种令人担忧的并发症。评估乌司他丁和加贝酯（GM）预防 PEP 作用的随机对照试验（RCT）结果存在矛盾。本研究旨在通过荟萃分析评估乌司他丁和 GM 对 PEP 的预防作用。
检索了评估乌司他丁和 GM 预防 PEP 作用的 RCT 的五个电子数据库。使用 Cochrane 协作组织推荐的方法评估汇总效果。
12 项研究共纳入 5105 名参与者。乌司他丁只有在足够剂量时才能降低 PEP 的发生率（OR，0.39；95%CI，0.19 至 0.81；P = 0.01）。需要治疗的人数（NNT）为 6。乌司他丁还可降低 ERCP 后高淀粉酶血症（PEHA）的发生率（OR，0.40；95%CI，0.28 至 0.58；P < 0.000 01）。GM 的高剂量缓慢输注对预防 PEP 有效（OR，0.44；95%CI，0.25 至 0.79；P = 0.006），GM 的低剂量快速输注也显示出对 PEP 预防的疗效（OR，0.37；95%CI，0.20 至 0.69；P = 0.002）。NNT 分别为 7 和 6。然而，GM 低剂量和缓慢输注无效（OR，0.99；95%CI，0.64 至 1.55；P = 0.98）。GM 的给药有降低 PEHA 发生率的趋势，但无统计学意义（OR，0.86；95%CI，0.73 至 1.01；P = 0.06）。排除低质量研究后，两项高质量研究的荟萃分析表明，乌司他丁不能降低 PEP 发生率（OR，0.63；95%CI，0.32 至 1.26；P = 0.19）和 PEHA 发生率（OR，0.80；95%CI，0.31 至 2.07；P = 0.64）。六项高质量研究的荟萃分析表明，GM 给药可降低 PEP 的发生率（OR，0.52；95%CI，0.29 至 0.91；P = 0.02），但对预防 PEHA 无效（OR，0.88；95%CI，0.74 至 1.04；P = 0.12）。
乌司他丁和 GM 可能对预防 PEP 有效。GM 应高剂量和快速输注。乌司他丁的剂量应足够。然而，结论并不具有压倒性。仍然需要更多的大样本量和高质量的 RCT 来阐明这两种药物的给药是否真的对 PEP 具有预防作用。
