Efficacy and safety of intrathecal adjuvants in lower limb orthopaedic surgery: a systematic review and network meta-analysis of randomised controlled trials.

Abstract

Background: Intrathecal adjuvants are frequently used in spinal anaesthesia for lower-limb surgery to enhance block quality and prolong postoperative analgesia. However, evidence remains fragmented across individual agents. This systematic review with frequentist network meta-analysis aimed to compare the efficacy and safety of intrathecal adjuvants in patients undergoing lower limb orthopaedic surgery to evaluate the effectiveness and safety of intrathecal adjuvants combined with long-acting local anaesthetics for lower limb orthopaedic surgery.

Methods: A systematic search of PubMed, CENTRAL, and Embase was conducted to retrieve English-language RCTs involving adult patients undergoing lower limb orthopaedic surgery under single-shot spinal anaesthesia. We included trials evaluating any intrathecal drug or placebo added to a long-acting local anaesthetic. Our primary outcome was the duration of effective analgesia, defined as the time to the first analgesic requirement, in hours. We selected randomised controlled trials (RCTs) reported in English.

Results: We included 183 RCTs, for a total of 14,431 patients and 27 interventions. Morphine combined with ketorolac, morphine alone followed by diamorphine, clonidine combined with morphine and ketamine combined with midazolam provided the greatest prolongation of effective analgesia. Morphine also significantly reduced pain at 12 h and postoperative opioid consumption with no impact on motor block duration. Dexmedetomidine reduced pain intensity at 12 h but substantially prolonged motor block duration and increased the incidence of bradycardia. Morphine and neostigmine showed an increased risk of postoperative nausea and vomiting, while several interventions increased the risk of pruritus. The certainty of evidence ranged from low to very low due to within-study bias, reporting bias, high heterogeneity, imprecision and incoherence.

Conclusions: Considering the body of evidence in an NMA framework, intrathecal morphine appears to offer a potentially favourable efficacy-safety balance. Dexmedetomidine may prolong motor block and increase the risk of bradycardia. The certainty of the evidence was low to very low and needs caution interpretation.

Systematic review registration: PROSPERO CRD42024557751.