Low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.
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.
Rabenstein
Thomas
T
Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany.
Fischer
Bernhard
B
Wiessner
Volkmar
V
Schmidt
Harald
H
Radespiel-Tröger
Martin
M
Hochberger
Jürgen
J
Mühldorfer
Steffen
S
Nusko
Gerhard
G
Messmann
Helmut
H
Schölmerich
Jürgen
J
Schulz
Hans-Joachim
HJ
Schönekäs
Herbert
H
Hahn
Eckhart Gustav
EG
Schneider
Hans Thomas
HT
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
D000893:Anti-Inflammatory Agents; D006495:Heparin, Low-Molecular-Weight; C403769:certoparin