Regional analgesia techniques for postoperative pain after breast cancer surgery: a network meta-analysis.

Rationale: Postoperative pain is an important outcome for individuals undergoing breast cancer surgery. Regional analgesia techniques are considered integral to postoperative pain management, but are not without risks.

Objectives: To assess the analgesic benefits and harms of different regional analgesia techniques in women undergoing breast cancer surgery.

Search methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, Scopus, and Web of Science from inception to 6 June 2023 without restrictions on language, publication year, or publication status.

Eligibility criteria: We included randomised controlled trials (RCTs) comparing two or three of the following regional analgesia techniques in women undergoing breast cancer surgery: paravertebral block (PVB), erector spinae plane block (ESPB), pectoral nerve block (PEC), and serratus anterior plane block (SAPB).

Outcomes: Our critical outcomes were postoperative pain (rated on a visual analogue scale (VAS) or numeric rating scale (NRS) of 0-10) and rates of regional analgesia-related complications. Our important outcomes were quality of recovery, time to first analgesic request, postoperative opioid and nonsteroidal anti-inflammatory drug (NSAID) use, and postoperative nausea and vomiting (PONV).

Risk of bias: We used the Cochrane risk of bias tool (RoB 2) to assess risk of bias.

Synthesis methods: We conducted network meta-analyses (NMAs) using multivariate frequentist random-effects models to calculate mean differences (MDs), standardised mean differences (SMDs), or risk ratios (RRs), each with its 95% confidence interval (CI). We used CINeMA to rate the certainty of evidence. We only included studies with an overall low risk of bias in the primary analysis. For postoperative pain, we considered one point difference as the minimal clinically important difference (MCID).

Included studies: We included 39 RCTs with a total of 2348 participants. The studies were conducted between 2013 and 2023 in Egypt, India, Turkey, China, Japan, USA, and Thailand. Most used single-shot long-acting anaesthetics administered with ultrasound guidance. In 35 studies, the surgery was modified radical mastectomy. All studies performed surgery under general anaesthesia in the hospital. Our primary analysis for postoperative pain included 16 studies.

Synthesis of results: Critical outcomes Postoperative pain at rest at two hours This NMA included seven studies (384 participants). PEC is slightly more effective than PVB in reducing postoperative pain at rest at two hours (MD -0.47, 95% CI -0.73 to -0.22; P < 0.001, I² = 0%; high-certainty evidence), but this difference is smaller than the MCID. Compared with PVB, ESPB is similarly effective (MD -0.12, 95% CI -0.31 to 0.07; P = 0.21, I² = 0%; high-certainty evidence), and SAPB probably has similar effectiveness (MD -0.50, 95% CI -1.09 to 0.09; P = 0.094, I² = 0%; moderate-certainty evidence). Postoperative pain during movement at two hours This NMA included four studies (246 participants). PEC may be more effective than PVB in reducing postoperative pain during movement at two hours (MD -1.06, 95% CI -1.98 to -0.14; P = 0.024, I² = 79.6%; low-certainty evidence). ESPB compared with PVB may be similarly effective (MD -0.46, 95% CI -1.24 to 0.33; P = 0.25, I² = 79.6%; low-certainty evidence). Postoperative pain at rest at 24 hours This NMA included 13 studies (793 participants). PEC is slightly more effective than PVB in reducing postoperative pain at rest at 24 hours (MD -0.32, 95% CI -0.61 to -0.03; P = 0.029, I² = 38.7%; high-certainty evidence), but the difference is smaller than the MCID. Compared with PVB, ESPB is similarly effective (MD -0.15, 95% CI -0.35 to 0.05; P = 0.14, I² = 38.7%; high-certainty evidence), and SAPB is similarly effective (MD -0.16, 95% CI -0.42 to 0.10; P = 0.23, I² = 38.7%; high-certainty evidence). Postoperative pain during movement at 24 hours This NMA included eight studies (545 participants). Compared with PVB, ESPB probably has similar effectiveness for reducing postoperative pain during movement at 24 hours (MD -0.09, 95% CI -0.48 to 0.31; P = 0.67, I² = 74.1%; moderate-certainty evidence), PEC may be similarly effective (MD 0.08, 95% CI -0.48 to 0.64; P = 0.78, I² = 74.1%; low-certainty evidence), and SAPB may be similarly effective (MD 0.16, 95% CI -0.38 to 0.69; P = 0.57, I² = 74.1%; very low-certainty evidence), although the evidence from the last analysis is very uncertain. Postoperative pain at rest at 48 hours One study (44 participants) reported postoperative pain at rest at 48 hours and found little or no difference in effectiveness between PVB and ESPB, though the evidence is very uncertain (MD 0.18, 95% CI -0.31 to 0.67; P = 0.47; very low-certainty evidence). Postoperative pain during movement at 48 hours This NMA included two studies (104 participants). Compared with PVB, ESPB may be similarly effective for reducing postoperative pain during movement at 48 hours (MD 0.13, 95% CI -0.55 to 0.81; P = 0.71, I² = 0%; very low-certainty evidence) and PEC may be similarly effective (MD -0.07, 95% CI -0.43 to 0.29; P = 0.71, I² = 0%; very low-certainty evidence), although the evidence from both analyses is very uncertain. Complications Three studies (170 participants) recorded complications, but there were no reported events of block failure, local anaesthetic systemic toxicity, hypotension, nerve damage, intraneural injection, accidental vascular puncture, bleeding at puncture site, infection, or pneumothorax. Certainty of evidence We frequently downgraded the certainty of the evidence for imprecision due to small sample sizes and wide CIs, particularly for complications and analgesic use. Heterogeneity also affected certain pain outcomes. Limited data availability further reduced certainty, with outcomes based on one or two studies rated as very low.

Authors' conclusions: Overall, the regional analgesia techniques included in our NMAs seem comparable in reducing postoperative pain and rates of complications.

Funding: This Cochrane review had no dedicated funding.

Registration: Protocol (2022): doi.org/10.1002/14651858.CD014818.