Widespread adoption of intrathecal morphine into clinical practice is hampered by concerns about its potential side-effects. We undertook a systematic review, meta-analysis and trial sequential analysis with the primary objective of determining the efficacy and safety of intrathecal morphine. Our secondary objective was to determine the dose associated with greatest efficacy and safety. We also assessed the impact of intrathecal morphine on respiratory depression. We systematically searched the literature for trials comparing intrathecal morphine with a control group in patients undergoing hip or knee arthroplasty under spinal anaesthesia. Our primary efficacy outcome was rest pain score (0–10) at 8–12 hours; our primary safety outcome was the rate of postoperative nausea and vomiting within 24 hours. Twenty-nine trials including 1814 patients were identified. Rest pain score at 8–12 hours was significantly reduced in the intrathecal morphine group, with a mean difference (95%CI) of −1.7 (−2.0 to −1.3), p < 0.0001 (19 trials; 1420 patients; high-quality evidence), without sub-group differences between doses (p = 0.35). Intrathecal morphine increased postoperative nausea and vomiting, with a risk ratio (95%CI) of 1.4 (1.3–1.6), p < 0.0001 (24 trials; 1603 patients; high-quality evidence). However, a sub-group analysis by dose revealed that rates of postoperative nausea and vomiting within 24 hours were similar between groups at a dose of 100 µg, while the risk significantly increased with larger doses (p value for sub-group difference = 0.02). Patients receiving intrathecal morphine were no more likely to have respiratory depression, the risk ratio (95%CI) being 0.9 (0.5–1.7), p = 0.78 (16 trials; 1173 patients; high-quality evidence). In conclusion, there is good evidence that intrathecal morphine provides effective analgesia after lower limb arthroplasty, without an increased risk of respiratory depression, but at the expense of an increased rate of postoperative nausea and vomiting. A dose of 100 µg is a ‘ceiling’ dose for analgesia and a threshold dose for increased rate of postoperative nausea and vomiting.

中文翻译：

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鞘内注射吗啡用于下关节置换术后镇痛的疗效和安全性：系统评价和荟萃分析，荟萃回归和试验序贯分析

鞘内注射吗啡在临床实践中的广泛应用受到对其潜在副作用的担忧的阻碍。我们进行了系统评价、荟萃分析和试验序贯分析，主要目的是确定鞘内注射吗啡的有效性和安全性。我们的次要目标是确定与最大疗效和安全性相关的剂量。我们还评估了鞘内注射吗啡对呼吸抑制的影响。我们系统地检索了文献，以比较鞘内注射吗啡与对照组在脊柱麻醉下接受髋关节或膝关节置换术的患者。我们的主要疗效结果是 8-12 小时的静息疼痛评分（0-10）；我们的主要安全性结果是术后 24 小时内恶心和呕吐的发生率。确定了 29 项试验，包括 1814 名患者。鞘内注射吗啡组 8-12 小时的静息疼痛评分显着降低，平均差 (95%CI) 为 -1.7（-2.0 至 -1.3），p < 0.0001（19 项试验；1420 名患者；高质量证据），剂量之间没有亚组差异（p = 0.35）。鞘内注射吗啡可增加术后恶心和呕吐，风险比 (95%CI) 为 1.4 (1.3–1.6)，p < 0.0001（24 项试验；1603 名患者；高质量证据）。然而，按剂量进行的亚组分析显示，100 µg 剂量组间术后 24 小时内恶心和呕吐的发生率相似，而风险随着剂量的增加而显着增加（亚组差异的 p 值 = 0.02） . 接受鞘内注射吗啡的患者不再出现呼吸抑制，风险比 (95%CI) 为 0.9 (0.5–1.7)，p = 0.78（16 项试验；1173 名患者；高质量证据）。总之，有充分证据表明鞘内注射吗啡可在下肢关节置换术后提供有效镇痛，不会增加呼吸抑制的风险，但会增加术后恶心和呕吐的发生率。100 µg 的剂量是镇痛的“上限”剂量，也是增加术后恶心和呕吐率的阈值剂量。