摘要
Background 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）. Methods 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. Results 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% C/, 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% C/, 0.28 to 0.58; P〈0.000 01）. Slow infusion of high-dose GM was effective for PEP prevention （OR, 0.44; 95% Cl, 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% C/, 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% Cl, 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% Cl, 0.32 to 1.26; P=0.19） and PEHA incidence （OR, 0.80; 95% Cl, 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% C/, 0.74 to 1.04; P=0.12）. Conclusions 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.
Background 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）. Methods 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. Results 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% C/, 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% C/, 0.28 to 0.58; P〈0.000 01）. Slow infusion of high-dose GM was effective for PEP prevention （OR, 0.44; 95% Cl, 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% C/, 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% Cl, 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% Cl, 0.32 to 1.26; P=0.19） and PEHA incidence （OR, 0.80; 95% Cl, 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% C/, 0.74 to 1.04; P=0.12）. Conclusions 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.
