In 2009, IV ibuprofen (IVIB) received FDA approval for the adult inpatient management of mild-to-moderate pain, moderate-to-severe pain in conjunction in opioids, and fever reduction. Nonetheless, there has been no comprehensive review of the evidence on the efficacy and safety of IVIB when administered as either multiple doses or a single dose for the management of pain and fever.

To help address this paucity of information, researchers conducted a systematic review (SR) and meta-analysis (MA) of randomized, controlled trials comparing IVIB with placebo or other analgesics and antipyretic medications for the management of pain and fever in the postoperative setting.

Investigators searched PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, WanFang Database, and SinoMed databases from their inception to June 2022 for information on IVIB used for the management of postoperative pain and fever. Additional sources searched included Clinicaltrials.gov, the World Health Organization clinical trials portal, and reference lists of relevant studies.

The outcomes of the study were twofold: pain relief and fever relief. The primary outcomes for pain relief were scores on the visual analogue scale (VAS) within the first 24 hours postoperative and the difference in cumulative opioid usage 24 and 48 hours postoperative. Secondary pain relief outcomes were the incidence of adverse events (AEs) and the usage rate of rescue analgesics. The primary outcome for fever relief was the body temperature change and the secondary outcome was the incidence of AEs.

A total of 32 studies were included in the SR, and 24 studies were included in the MA. Patients in this study underwent 18 different types of surgery, including laparoscopic cholecystectomy, orthopedic, abdominal, orthognathic, and third molar surgeries, septorhinoplasty, percutaneous nephrolithotomy, bunionectomy, and pancreaticoduodenectomy.

The authors also assessed the risk of bias and the quality of the evidence assessment.

For the primary pain relief outcome involving the VAS score differences at various postoperative times, the investigators found that nine studies involving 599 patients demonstrated that IVIB significantly reduced VAS scores at 0, 1, 2, 5, 9, 12, and 24 hours. However, the evidence was of low certainty at 0, 2, 4, 8, and 12 hours but of moderate certainty for 1 and 24 hours. A subgroup analysis found that lower VAS scores were associated with the preoperative administration of 800 mg IVIB followed by administration every 6 or 8 hours postoperative.

Use of single-dose IVIB was also examined and was associated with beneficial results. When IVIB was compared with IV acetaminophen (IA), there was no statistically significant difference in VAS scores at 1 hour and 24 hours (low-certainty evidence), although IVIB use was associated with lower pain intensity. Other studies comparing IVIB with placebo, IA or IV ketorolac using VAS pain curve, or the numeric rating scale yielded conflicting results.

Although IVIB was associated with lower rate of usage of rescue analgesia compared with placebo, this evidence was of low certainty. A subgroup analysis that was of moderate certainty did not demonstrate a significant difference between IVIB or IA groups with regards to the use of additional pain medications.

While use of IVIB was associated with a lower incidence of nausea and vomiting versus comparator groups, there were no differences in rates of pruritus, dizziness, headache, dyspepsia, or flatulence between the groups; this evidence was of moderate certainty.

IVIB was superior to placebo and was superior to IA at 14 minutes as an antipyretic, but there was no difference in fever reduction between IVIB and IA at 60 minutes. There were no drug-related AEs in the two antipyretic IVIB studies.

The authors cautioned that the study has a number of limitations, including that >70% of the trials included <60 patients; a funnel plot could not be performed to determine publication bias; and there was too much heterogeneity to adequately determine the effect of IVIB on some outcome measures.

This study provides pharmacists with evidence-based data on the safety and efficacy of IVIB use in the postoperative management of pain and fever and can help guide decision making for Pharmacy and Therapeutics Committees.

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