Brodner 2011.

Methods	Prospective, double‐blind, placebo‐ and active‐controlled study Multiple‐dose study, first dose administered 30 min before the end of surgery. Outcomes assessed for at least 48 h and up to 1 week in patients not discharged.
Participants	Type of surgery: plastic surgery (breast surgery, inguinal or axillary dissections), oral and maxillofacial surgery (correction of retrognathism and prognathism), gynecological (laparoscopy, breast surgery), and urological (cystoscopy, transurethral prostatectomy) surgery and orthopedic surgery (hip endoprosthesis for coxarthrosis) Paracetamol group Entered/completing: 49/45 Age (mean, SD): 50.5 ± 17.5 Sex (male, %): 26.5% Dipyrone group Entered/completing: 49/41 Age (mean, SD): 45.5 ± 17.9 Sex (male, %): 44.9% Parecoxib group Entered/completing: 49/44 Age (mean, SD): 49.4 ± 14.6 Sex (male, %): 26.5% Placebo group Entered/completing: 49/45 Age (mean, SD): 42.8 ± 16.8 Sex (male, %): 49.0%
Interventions	Paracetamol 1 g/100 ml NS over 15 min every 6 h for at least 48 h Dipyrone 1 g every 6 h, parecoxib 40 mg every 12 h (saline every 6 h between doses), or placebo (0.9% saline) every 6 h as above
Outcomes	Primary: dynamic VAS (0 to 100) for pain localized to the site of surgery Secondary: time to first piritramide PCA bolus and piritramide consumption as quantified by the number of boluses demanded and administered; satisfaction rated as 1, excellent; 2, good; 3, moderate; 4, insufficient; and 5, poor; adverse events (respiratory depression, N/V, sedation, itching sweating)
Source of funding	Bristol‐Myers Squibb, Munich, Germany, and Pfizer Pharma GmbH, Karlsruhe, Germany
Were treatment groups comparable at baseline?	Yes, with 3 exceptions: participants of group 3 parecoxib had a significantly shorter duration of anesthesia and needed significantly less intraoperative sufentanil compared to group 4 placebo, and there were more women in group 1 paracetamol and group 3 parecoxib than in group 2 dipyrone and group 4 placebo
Details of preoperative pain	Surgical area (0 to 100 VAS): paracetamol 9.2 ± 17.1, dipyrone 10.8 ± 17.2, parecoxib 13.3 ± 16.6, placebo 6.0 ± 13.2
Notes	Numbers completing based on number of participants discontinued after at least 2 doses of intervention. ITT analysis employed – no participants lost to follow‐up at 42 h.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	“assigned by random numbers”
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding (performance bias and detection bias) All outcomes	Low risk	“All study drugs were prepared by the hospital pharmacy in identical glass bottles as infusions of 100 ml. The bottles were labelled with patient number and time of administration. Infusions were administered by a blinded attending physician”.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups. ITT analysis performed, but no mention of how missing data imputed.
Selective reporting (reporting bias)	Unclear risk	Secondary outcome, patient satisfaction, reported as mean across all groups and statement that all participants were satisfied with their pain treatment. No mean data for each group and no details of what point on scale was defined as satisfied.
Size	High risk	Fewer than 50 participants per arm of the study (49 paracetamol, 49 dipyrone, 49 parecoxib, 49 placebo)