WITHDRAWN: Single dose dipyrone for acute postoperative pain

Abstract

Background: Dipyrone (metamizole) is a non‐steroidal anti‐inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life‐threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought.

Objectives: To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain.

Search methods: The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010.

Selection criteria: Single dose, randomised, double‐blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs.

Data collection and analysis: Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected.

Main results: Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls.

Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30% with placebo in five studies (288 participants; NNT 2.4 (1.9 to 3.2)). Fewer participants needed rescue medication with dipyrone (7%) than with placebo (34%; four studies, 248 participants). There was no difference in participants experiencing at least 50% pain relief with 2.5 g intravenous dipyrone and 100 mg intravenous tramadol (70% vs 65%; two studies, 200 participants). No serious adverse events were reported.

Authors' conclusions: Based on very limited information, single dose dipyrone 500 mg provides good pain relief to 70% of patients. For every five individuals given dipyrone 500 mg, two would experience this level of pain relief who would not have done with placebo, and fewer would need rescue medication, over 4 to 6 hours.

Figure 1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

Figure 2

Forest plot of comparison: 1 Dipyrone 500 mg versus placebo, outcome: 1.1 Patients with ≥50% pain relief over 4 to 6 hours.

Analysis 1.1

Comparison 1 Dipyrone 500 mg versus placebo, Outcome 1 Patients with ≥50% pain relief over 4 to 6 hours.

Analysis 1.2

Comparison 1 Dipyrone 500 mg versus placebo, Outcome 2 Participants using rescue medication over 4 to 6 hours.

Analysis 2.1

Comparison 2 Dipyrone 2.5 g versus tramadol 100 mg (intravenous), Outcome 1 Patients with ≥50% pain relief over 4 to 6 hours.