The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial

Abstract

Background: Surgical patients are vulnerable to opioid dependency and related risks. Clinical-translational data suggest that caffeine may enhance postoperative analgesia. This trial tested the hypothesis that intraoperative caffeine would reduce postoperative opioid consumption. The secondary objective was to assess whether caffeine improves neuropsychological recovery postoperatively.

Methods: This was a single-center, randomized, placebo-controlled trial. Participants, clinicians, research teams, and data analysts were all blinded to the intervention. Adult (≥18 years old) surgical patients (n = 65) presenting for laparoscopic colorectal and gastrointestinal surgery were randomized to an intravenous caffeine citrate infusion (200 mg) or dextrose 5% in water (40 mL) during surgical closure. The primary outcome was cumulative opioid consumption through postoperative day 3. Secondary outcomes included subjective pain reporting, observer-reported pain, delirium, Trail Making Test performance, depression and anxiety screens, and affect scores. Adverse events were reported, and hemodynamic profiles were also compared between the groups.

Results: Sixty patients were included in the final analysis, with 30 randomized to each group. The median (interquartile range) cumulative opioid consumption (oral morphine equivalents, milligrams) was 77 mg (33-182 mg) for caffeine and 51 mg (15-117 mg) for placebo (estimated difference, 55 mg; 95% confidence interval [CI], -9 to 118; P = .092). After post hoc adjustment for baseline imbalances, caffeine was associated with increased opioid consumption (87 mg; 95% CI, 26-148; P = .005). There were otherwise no differences in prespecified pain or neuropsychological outcomes between the groups. No major adverse events were reported in relation to caffeine, and no major hemodynamic perturbations were observed with caffeine administration.

Conclusions: Caffeine appears unlikely to reduce early postoperative opioid consumption. Caffeine otherwise appears well tolerated during anesthetic emergence.

Trial registration: ClinicalTrials.gov NCT03577730.

Figure 1.

Study flow diagram presented. CONSORT, Consolidated Standards of Reporting Trials.

Figure 2.

Mean opioid consumption presented over the first seven postoperative days. Error bars represent standard deviation. OME, oral morphine equivalents. POD, postoperative day.

Figure 3.

(A) Parietal electroencephalographic alpha power presented at preoperative baseline and in the postanesthesia care unit (PACU) for both groups. Parietal alpha power was significantly higher in the caffeine group (n=26) compared to placebo (n=26) during PACU assessment. (B) Frontal-parietal cortical connectivity, assessed via weighted phase lag index, presented over the same time period. The caffeine group demonstrated higher weighted phase lag index in the PACU, similar to parietal alpha power. Weighted phase lag index change from baseline (based on fold-change) was significantly higher in the caffeine group.