title: Perforated peptic ulcer and short-term mortality among tramadol users.
abstract: BACKGROUND
  * Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is a strong risk and prognostic factor for peptic ulcer perforation, and alternative analgesics are needed for high-risk patients. * Pain management guidelines propose tramadol as a treatment option for mild-to-moderate pain in patients at high risk of gastrointestinal side-effects, including peptic ulcer disease. * Tramadol may mask symptoms of peptic ulcer complications, yet tramadol's effect on peptic ulcer prognosis is unknown.
  
  
  CONCLUSIONS
  * In this population-based study of 1271 patients hospitalized with peptic ulcer perforation, tramadol appeared to increase mortality at least as much as NSAIDs. * Among users of tramadol, alone or in combination with NSAIDs, adjusted 30-day mortality rate ratios were 2.02 [95% confidence interval (CI) 1.17, 3.48] and 1.32 (95% CI 0.89, 1.95), compared with patients who used neither tramadol nor NSAIDs.
  
  
  OBJECTIVE
  Use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases risk and worsens prognosis for patients with complicated peptic ulcer disease. Therefore, patients who are at high risk of peptic ulcer often use tramadol instead of NSAIDs. Tramadol's effect on peptic ulcer prognosis is unknown. The aim was to examine mortality in the 30 days following hospitalization for perforated peptic ulcer among tramadol and NSAID users compared with non-users.
  
  
  METHODS
  The study was based on data on reimbursed prescriptions and hospital discharge diagnoses for the 1993-2004 period, extracted from population-based healthcare databases. All patients with a first-time diagnosis of perforated peptic ulcer were identified, excluding those with previous ulcer diagnoses or antiulcer drug use. Cox regression was used to estimate 30-day mortality rate ratios for tramadol and NSAID users compared with non-users, adjusting for use of other drugs and comorbidity.
  
  
  RESULTS
  Of 1271 patients with perforated peptic ulcers included in the study, 2.4% used tramadol only, 38.9% used NSAIDs and 7.9% used both. Thirty-day mortality was 28.7% overall and 48.4% among users of tramadol alone. Compared with the 645 patients who used neither tramadol nor NSAIDs, the adjusted mortality rate in the 30 days following hospitalization was 2.02-fold [95% confidence interval (CI) 1.17, 3.48] higher for the 31 'tramadol only' users, 1.41-fold (95% CI 1.12, 1.78) higher for the 495 NSAID users and 1.32-fold (95% CI 0.89, 1.95) higher for the 100 patients who used both drugs.
  
  
  CONCLUSIONS
  Among patients hospitalized for perforated peptic ulcer, tramadol appears to increase mortality at a level comparable to NSAIDs.
authors.affiliation: Department of Clinical Epidemiology, Aarhus University Hospital, University of Aarhus, Aarhus, Denmark. mlt@alm.au.dk
authors.forename: Marie L
authors.initials: ML
authors.lastname: Tørring
authors.forename: Anders
authors.initials: A
authors.lastname: Riis
authors.forename: Steffen
authors.initials: S
authors.lastname: Christensen
authors.forename: Reimar W
authors.initials: RW
authors.lastname: Thomsen
authors.forename: Peter
authors.initials: P
authors.lastname: Jepsen
authors.forename: Jens
authors.initials: J
authors.lastname: Søndergaard
authors.forename: Henrik T
authors.initials: HT
authors.lastname: Sørensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D003718:Denmark; D004334:Drug Administration Schedule; D004381:Duodenal Ulcer / Q000139:chemically induced* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D010439:Peptic Ulcer Perforation / Q000139:chemically induced* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000401:mortality; D015996:Survival Rate; D014147:Tramadol / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014147:Tramadol