Perioperative intravenous acetaminophen and postcesarean pain control: a systematic review and meta-analysis of randomized controlled trials

OBJECTIVE: This study aimed to determine the efficacy of perioperative (pre- or intraoperative) intravenous acetaminophen in improving postcesarean pain control in healthy women receiving regional anesthesia. DATA SOURCES: MEDLINE, Ovid, ClinicalTrials.gov, and Scopus were searched from their inception to September 2019. STUDY ELIGIBILITY CRITERIA: A systematic review of the literature was performed to identify all randomized placebo-controlled trials examining the effect of perioperative intravenous acetaminophen on postcesarean pain control and other postoperative outcomes. Included trials examined women who were healthy and received regional anesthesia before cesarean delivery at term. STUDY APPRAISAL AND SYNTHESIS METHODS: The primary outcome was 24-hour postoperative pain scores with movement as measured by the individual studies. Secondary outcomes included intravenous morphine milligram equivalents used postoperatively. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of mean difference with 95% confidence interval. RESULTS: Notably, 4 randomized placebo-controlled trials were identified that met the inclusion criteria with a total of 190 in the intervention arm vs 174 women in the control group. Patients in the intervention group received 1000 mg intravenous acetaminophen in 3 of the studies and 2000 mg intravenous acetaminophen in 1 study. All patients received regional anesthesia before surgery. The medication was given anywhere from 1 hour before surgery to intraoperatively immediately after delivery of the fetus. Pain scores 24 hours after surgery were only available in 1 study. The use of opioids as measured by morphine milligram equivalents after surgery was similar for patients receiving perioperative intravenous acetaminophen and those receiving placebo (38.7 vs 42.55; mean difference, -2.54; 95% confidence interval, -9.24 to 4.16). Only 1 study showed decreased postoperative pain scores when using perioperative intravenous acetaminophen, and this was limited to the first 4 hours after surgery. Importantly, these patients did not receive long-acting neuraxial opioids, which may account for the finding of improved pain control in the early postoperative period. CONCLUSION: There are limited data available on the use of perioperative intravenous acetaminophen for cesarean delivery performed at term with regional anesthesia. The use of long-acting neuraxial opioids may make perioperative (pre- or intracesarean) intravenous acetaminophen unnecessary, whereas intravenous (or oral) acetaminophen may become more effective as neuraxial opioid analgesia wears off. More level-1 data are needed.