Effects of Combining Short- and Long-Acting Local Anaesthetics in Peripheral Nerve Blocks-A Systematic Review With Meta-Analysis and Trial Sequential Analysis

BACKGROUND: This systematic review aims to clarify how combining short- and long-acting local anaesthetics (LA) affects onset time and duration in peripheral nerve blocks.

METHODS: We included randomised controlled trials comparing adults undergoing peripheral nerve blocks with combined short- and long-acting LA with those receiving blocks performed with either a short- or long-acting LA. The primary outcome was the duration of analgesia. Secondary outcomes included the duration of onset time. We conducted meta-analyses, trial sequential analyses (TSA), risk of bias-2 and Grading Recommendations Assessment, Development and Evaluation (GRADE).

RESULTS: We included 21 trials with 1539 participants. The combination of short and long-acting LA reduced the duration of analgesia when compared with a long-acting LA (mean difference (MD) = -162 min, 95% CI: -246 to -79, p < 0.01, tau = 181 min, I2 = 96%, TSA-adj. 95% CI: -254 to -71, GRADE = moderate). The combination increased the duration of analgesia when compared with short-acting LA (MD = 216 min, 95% CI: 163-269, p < 0.01, TSA-adj. 95% CI: 150 to 282, GRADE = moderate). Combining short and long-acting LA reduced the duration of onset time (MD = -8.0 min, 95% CI: -11.5 to -4.6, p < 0.01, tau = 7.8 min, I2 = 98%, TSA-adj. 95% CI: -11.8 to -4.3, GRADE = low) when compared with long-acting LA. In contrast, the duration of onset time was increased (MD = 1.7 min, 95% CI: 0.2-3.3, p = 0.03, TSA-adj. 95% CI: 0.1-3.4, GRADE = low) when compared with short-acting LA.

CONCLUSION: Our assessment suggested that combining short and long-acting LA reduced block duration by 2½ h compared with long-acting LA and increased it by 3½ h compared with short-acting LA. The changes in duration of onset time were limited and likely not clinically relevant. Thus, using either long- or short-acting LA alone may generally be sufficient for peri- and postoperative pain management, making the need for combination unclear.

EDITORIAL COMMENT: This systematic review with meta-analysis presents updated results for different outcomes related to use of combined shorter and longer acting local anaesthetics for anaesthesia nerve blocks. The authors thoughtfully interpret the clinical relevance of the different outcomes in the meta-analysis.

TRIAL REGISTRATION: PROSPERO identifier: CRD4202346821, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=468211.