title: Low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.
abstract: BACKGROUND
  Studies suggest that heparin has anti-inflammatory effects that could prevent acute post-ERCP pancreatitis. The aim of this investigator-initiated, prospective, randomized, double-blind, multicenter study was to determine whether low-molecular-weight heparin can prevent acute post-ERCP pancreatitis.
  
  
  METHODS
  Patients at increased risk for acute post-ERCP pancreatitis based on assessment of known risk factors were randomized to receive low-molecular-weight heparin (Certoparin 3000 IU subcutaneously) or placebo (saline solution 0.3 mL subcutaneously) the day before ERCP. The drug was given 2 hours before and 22 hours after ERCP. Documentation and follow-up included patient history, risk factors for acute post-ERCP pancreatitis, procedure-related data, assessment of pain (visual analogue scale, need for pain medication), laboratory findings before and after ERCP (0, 4, and 24 hours), as well as post-ERCP complications. The two-sided Fisher exact test was used for statistical comparison, and a p value < or =0.05 was considered significant.
  
  
  RESULTS
  A total of 458 patients were enrolled in the study. Data from 10 patients could not be evaluated, leaving 221 patients in the low-molecular-weight heparin group and 227 in the placebo group (total 448 patients; 135 men, 313 women; mean age 58 [15] years). Low-molecular-weight heparin and placebo groups were comparable with regard to risk factors for acute post-ERCP pancreatitis (gender distribution, age <65 years, history of pancreatitis, pancreas divisum, disorders of sphincter of Oddi) and procedure-related data (difficult cannulation, diagnostic or therapeutic ERCP, needle-knife papillotomy, endoscopic sphincterotomy, biliary or pancreatic procedure, pancreatic contrast injection, success and final diagnosis of ERCP). Acute post-ERCP pancreatitis occurred in 8.5% (38/448), with one death resulting from severe pancreatitis. Low-molecular-weight heparin offered no benefit compared with placebo based on the frequency of acute post-ERCP pancreatitis (low-molecular-weight heparin, 18/221 vs. placebo, 20/227; p=0.87) and the severity of acute post-ERCP pancreatitis (low-molecular-weight heparin, 14 mild, 3 moderate, one severe; placebo, 18 mild, two moderate, 0 severe). The 24-hour serum amylase values and 24-hour pain scores did not differ significantly between the low-molecular-weight heparin group and the placebo group. Bleeding complications occurred in two patients, both in the low-molecular-weight heparin group (one mild, one moderate).
  
  
  CONCLUSIONS
  Prophylactic subcutaneous administration of low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.
authors.affiliation: Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rabenstein
authors.forename: Bernhard
authors.initials: B
authors.lastname: Fischer
authors.forename: Volkmar
authors.initials: V
authors.lastname: Wiessner
authors.forename: Harald
authors.initials: H
authors.lastname: Schmidt
authors.forename: Martin
authors.initials: M
authors.lastname: Radespiel-Tröger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hochberger
authors.forename: Steffen
authors.initials: S
authors.lastname: Mühldorfer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Nusko
authors.forename: Helmut
authors.initials: H
authors.lastname: Messmann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schulz
authors.forename: Herbert
authors.initials: H
authors.lastname: Schönekäs
authors.forename: Eckhart Gustav
authors.initials: EG
authors.lastname: Hahn
authors.forename: Hans Thomas
authors.initials: HT
authors.lastname: Schneider
mesh_terms: D000208:Acute Disease; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects*; D015986:Confounding Factors, Epidemiologic; D004311:Double-Blind Method; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000893:Anti-Inflammatory Agents; D006495:Heparin, Low-Molecular-Weight; C403769:certoparin