Aubrun 2003.

Methods	Randomized, placebo‐controlled, double‐blind Medications administered at the beginning of skin closure
Participants	Type of surgery: orthopedic, abdominal, general, or gynecological surgery Propacetamol group Entered/completing: ?/275 Age (mean, SD): 44 (range 18 to 85) Sex (male, %): 46 Placebo group Entered/completing: ?/275 Age (mean, SD): 45 (18 to 72) Sex (male, %): 42
Interventions	Intervention: 2 g propacetamol over 15 min Placebo: 125 ml saline
Outcomes	Morphine related AEs Opioid consumption (morphine)
Source of funding	Not reported
Were treatment groups comparable at baseline?	Yes: patient characteristics, type and duration of surgery, expected postoperative pain, ASA status and type of anesthesia
Details of preoperative pain	Not mentioned, but anesthetists were asked to exclude patients who were expected to have no postoperative pain and those who were expected to have very severe postoperative pain requiring prolonged epidural and/or spinal postoperative analgesia or prolonged postoperative sedation and/or patient‐controlled analgesia (PCA).
Notes	Minor protocol violation occurred in 80 (15%) participants. There were no significant differences between the 2 groups.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Randomization was stratified according to centers
Allocation concealment (selection bias)	Unclear risk	Not described
Blinding (performance bias and detection bias) All outcomes	Low risk	Each vial was prepared immediately before administration by a nurse who was not involved in the care or pain assessment of the patient. Vials containing 2 g of propacetamol (yielding 1 g of acetaminophen) or saline were administered IV over 15 min.
Incomplete outcome data (attrition bias) All outcomes	Low risk	3% of randomized participants were not included in analysis, but reasons for exclusion suggest outcome would be unaffected
Selective reporting (reporting bias)	Unclear risk	Primary outcome, morphine‐related adverse events, reported in full, except for incidence of bronchospasm. All secondary outcomes reported, but VAS and pain relief only reported as "no significant difference" between groups.
Size	Low risk	>/= 200 participants in each arm of the study