Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis

doi:10.1016/S0016-5107(00)70377-4

Gastrointestinal Endoscopy

Volume 51, Issue 1, January 2000, Pages 1-7

https://doi.org/10.1016/S0016-5107(00)70377-4 Get rights and content

Abstract

Background: The identification of therapeutic agents that can prevent the pancreatic injury after endoscopic retrograde cholangiopancreatography (ERCP) is of considerable importance. Methods: We performed a meta-analysis including 28 clinical trials on the use of somatostatin (12 studies), octreotide (10 studies), and gabexate mesilate (6 studies) after ERCP. Outcome measures evaluated were the incidence of acute pancreatitis, hyperamylasemia, and pancreatic pain. Three analyses were run separately: for all available studies, for randomized trials only, and for only those studies published as complete reports. Results: When all available studies were analyzed, somatostatin and gabexate mesilate were significantly associated with improvements in all three outcomes. Odds ratios (OR) for gabexate mesilate were 0.27 (95% CI [0.13, 0.57], p = 0.001) for acute pancreatitis, 0.66 (95% CI [0.48, –0.89], p = 0.007) for hyperamylasemia, and 0.33 (95% CI [0.18, 0.58], p = 0.0005) for post-procedural pain. Somatostatin reduced acute pancreatitis (OR 0.38: 95% CI [0.22, 0.65], p < 0.001), pain (OR 0.24: 95% CI [0.14, 0.42], p < 0.001), and hyperamylasemia (OR 0.65: 95% CI [0.48, 0.90], p = 0.008). Octreotide was associated only with a reduced risk of post-ERCP hyperamylasemia (OR 0.51: 95% CI [0.31, 0.83], p = 0.007) but had no effect on acute pancreatitis and pain. The statistical significance of data did not change after analyzing randomized trials only or studies published as complete reports. For each considered outcome, the publication bias assessment and the number of patients that need to be treated to prevent one adverse effect were, respectively, higher and lower for somatostatin than for gabexate mesilate. Conclusions: The pancreatic injury after ERCP can be prevented with the administration of either somatostatin or gabexate mesilate, but the former agent is more cost-effective. Additional studies comparing the efficacy of short-term infusion of somatostatin versus gabexate mesilate in patients at high risk for post-ERCP complications seem warranted. (Gastrointest Endosc 2000;51:1-7.)

Section snippets

Review of the published reports

We searched primarily the Medline database (1978 to 1998) under the following headings: somatostatin, octreotide, gabexate mesilate, ERCP, amylase, and acute pancreatitis. The reference lists of pertinent reviews and retrieved articles were also checked to identify additional studies. In the meta-analysis we included exclusively controlled trials comparing active treatment with placebo that were published as complete reports or in abstract form. A total of 28 trials were identified: 6 trials

Acute pancreatitis

Data were derived from 10 trials of SS, 8 of OCT, and 4 of FOY. These studies included 321 patients treated with SS versus 325 control patients, 423 patients treated with OCT versus 430 control patients, and 311 patients treated with FOY versus 369 control patients. AP developed in 13.5% of control patients versus 5.6% of treated cases with SS, in 5.6% versus 7.6% with OCT, and in 6.5% versus 1.6% with FOY. The results of the meta-analysis for each agent are shown in Table 4: SS and FOY

Discussion

Acute pancreatitis is the most frequent and serious complication of ERCP and endoscopic sphincterotomy. This complication cannot always be avoided and the search for drugs to prevent pancreatitis remains of considerable importance. After a careful review of published data we identified 28 clinical trials that evaluated the effect of administration of SS, OCT or FOY in the prevention of AP. The limited number of studies together with their low precision warrants further research in this

Disclosure statement

The present meta-analysis was not supported by pharmaceutical companies or private or institutional grants.

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To perform a meta-analysis of all available studies on the effect of prophylactic somatostatin administration on prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) and post-ERCP hyperamylasemia (PEHA).
Electronic databases, including PubMed, EMBASE, the Cochrane library, and the Science Citation Index were searched to retrieve relevant trials. Randomized, placebo-controlled trials in adult patients that compared somatostatin versus placebo in prevention of PEP were included. Meta-analysis was performed using a random-effects model to assess the ratios of PEP, PEHA and post-ERCP abdominal pain.
Total ratio of PEP of somatostatin group was significantly lower than that of placebo group. For the short-term injection or bolus injection there were no heterogeneity and no significance between the ratio of PEP of somatostatin group and placebo group. For the long-term injection subgroup there was heterogeneity, and the ratio of PEP of somatostatin group was significantly lower than that of placebo group. There was no significance between the ratio of PEP of somatostatin group and placebo group for the low-risk PEP subgroup, while the ratio of PEP of somatostatin group was significantly lower than that of placebo group for the high-risk PEP subgroup. The ratio of PEP of somatostatin group was significantly lower than that of placebo group for the long-term injection high-risk PEP subgroup. There was no significance between the ratio of PEHA of somatostatin group and placebo group for the short-term injection subgroup or bolus injection subgroup. The ratio of PEHA of somatostatin group was significantly lower than that of placebo group for the long-term injection subgroup. The total ratio of post-ERCP abdominal pain of somatostatin group was significantly lower than that of placebo group. The funnel plot of incidence of PEP and PEHA showed no asymmetry with a negative slope.
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On the basis of a systematic review, NSAIDs are appropriate for use in prevention of PEP, especially for high-risk cases. Additional research is necessary to clarify the role of other pharmacologic agents. These findings could inform future research and guide clinical decision-making and policy.
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^☆: Reprint requests: Angelo Andriulli, MD, Division of Gastroenterology, “CSS Hospital,” 71013 San Giovanni Rotondo, Rome, Italy; fax: 39-882-411-879.

^☆☆: 0016-5107/2000/$12.00 + 0 37/1/101044

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Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis☆,☆☆

Abstract

Section snippets

Review of the published reports

Acute pancreatitis

Discussion

Disclosure statement

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Gastrointest Endosc

Complications of endoscopic biliary sphincterotomy

N Engl J Med

ERCP and endoscopic sphincterotomy-induced pancreatitis

Pancreas

Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography

N Engl J Med

Study on prevention of complication associated with endoscopic retrograde cholangiopancreatography (ERCP): a controlled trial of a new protease inhibitor, FOY, in hyperamylasemia following endoscopic retrograde cholangiopancreatography

Gendai Iryo

Effect of FOY on hyperamylasemia after endoscopic retrograde cholangiopancreatography

Gendai Iryo

Prophylactic effects of preoperative administration of Gabexate Mesilate (FOY) on post-ERCP pancreatitis

Gendai Iryo

Wirkung des synthetischen proteinase-inhibitors FOY auf die hyperamylasamie nach ERP

Effect of a new enzyme inhibitor (Gabexate Mesilate- FOY) on hyperenzymemia induced by ERCP. A double blind study

Digestion

Der einfluß von somatostatin auf die amylasespiegel und pankreatitistrate nach ERCP

Med Welt

Effect of somatostatin on clinical, biochemical and morphological changes following ERCP

Ital J Gastroenterol

Effect of somatostatin on hyperamylasemia following endoscopic pancreatography

Acta Chir Scand

Prevention of pancreatic reactions by bolus somatostatin administration in patients undergoing endoscopic retrograde cholangio-pancreatography and endoscopic sphincterotomy

Hormone Res

Endoscopic papillo-sphincterotomy: prevention of pancreatic reaction by somatostatin

Ital J Gastroenterol