Abstract: We included 75 studies (36 from the original review and 39 from our updated review) enrolling a total of 7200 participants. Among primary outcomes, 36% of participants receiving IV paracetamol/propacetamol experienced at least 50% pain relief over four hours compared with 16% of those receiving placebo (number needed to treat to benefit (NNT) = 5; 95% confidence interval (CI) 3.7 to 5.6, high quality evidence). The proportion of participants in IV paracetamol/propacetamol groups experiencing at least 50% pain relief diminished over six hours, as reflected in a higher NNT of 6 (4.6 to 7.1, moderate quality evidence). Mean pain intensity at four hours was similar when comparing IV paracetamol and placebo, but was seven points lower on a 0 to 100 visual analog scale (0 = no pain, 100 = worst pain imaginable, 95% CI -9 to -6, low quality evidence) in those receiving paracetamol at six hours. For secondary outcomes, participants receiving IV paracetamol/propacetamol required 26% less opioid over four hours and 16% less over six hours (moderate quality evidence) than those receiving placebo. However, this did not translate to a clinically meaningful reduction in opioid-induced adverse events. Meta-analysis of efficacy comparisons between IV paracetamol/propacetamol and active comparators (e.g., opioids or nonsteroidal anti-inflammatory drugs) were either not statistically significant, not clinically significant, or both. Adverse events occurred at similar rates with IV paracetamol or IV propacetamol and placebo. However, pain on infusion occurred more frequently in those receiving IV propacetamol versus placebo (23% versus 1%). Meta-analysis did not demonstrate clinically meaningful differences between IV paracetamol/propacetamol and active comparators for any adverse event. Since the last version of this review, we have found 39 new studies providing additional information. Most included studies evaluated adults only. We reanalyzed the data but the results did not substantially alter any of our previously published conclusions. This review provides high quality evidence that a single dose of either IV paracetamol or IV propacetamol provides around four hours of effective analgesia for about 36% of patients with acute postoperative pain. Low to very low quality evidence demonstrates that both formulations are associated with few adverse events, although patients receiving IV propacetamol have a higher incidence of pain on infusion than both placebo and IV paracetamol.

Plain-language summary: Our updated review included data from 75 studies of 7200 patients with moderate-to-severe pain after an operation. We found high quality evidence that IV paracetamol or IV propacetamol provided pain relief for four hours for about 36% of people versus 16% of those receiving placebo. Direct comparisons with other painkillers, such as morphine and anti-inflammatories, did not show large differences (if any) in effectiveness, although this may have been due to the small numbers of patients studied. Low quality evidence showed that IV paracetamol and IV propacetamol produced few side effects. However, patients receiving IV propacetamol complained of pain at the site their medication was infused at more often than those receiving placebo or IV paracetamol. Due to the amount of data already included in our review, we think it is unlikely that any new studies will change our conclusions. However, we found very few studies that included children, so this is an area that requires further investigation.