Preventing pain after breast surgery: a systematic review with meta-analyses and trial-sequential analyses.

BACKGROUND AND OBJECTIVE The aim of this systematic review is to indirectly compare the efficacy of any intervention, administered perioperatively, on acute and persistent pain after breast surgery. DATABASES AND DATA TREATMENT We searched for randomised trials comparing analgesic interventions with placebo or no treatment in patients undergoing breast surgery under general anaesthesia. Primary outcome was intensity of acute pain (up to 6h postoperatively). Secondary outcomes were cumulative 24 hour morphine consumption, incidence of PONV, and chronic pain. We used an original three-step approach. First, meta-analyses were performed when data from at least three trials could be combined; secondly, trial sequential analyses were used to separate conclusive from unclear evidence. And thirdly, the quality of evidence was rated with GRADE. RESULTS Seventy-three trials (5512 patients) tested loco-regional blocks (paravertebral, pectoralis), local anaesthetic infiltrations, oral gabapentinoids or intravenous administration of glucocorticoids, lidocaine, NMDA antagonists or alpha2 agonists. With paravertebral blocks, pectoralis blocks, and glucocorticoids, there was conclusive evidence of a clinically relevant reduction in acute pain (VAS >1.0 cm). With pectoralis blocks, and gabapentinoids, there was conclusive evidence of a reduction in the cumulative 24 hour morphine consumption (≥5 mg). With paravertebral blocks and glucocorticoids, there was conclusive evidence of a relative reduction in the incidence of PONV of 70%. For chronic pain, insufficient data were available. CONCLUSIONS Mainly with loco-regional blocks, there is conclusive evidence of a reduction in acute pain intensity, morphine consumption, and PONV incidence after breast surgery. For rational decision-making, data on chronic pain are needed.