Intrathecal hydrophilic opioids for abdominal surgery: a meta-analysis, meta-regression, and trial sequential analysis

BACKGROUND: Intrathecal hydrophilic opioids decrease systemic opioid consumption after abdominal surgery and potentially facilitate enhanced recovery. A meta-analysis is needed to quantify associated risks and benefits. METHODS: A systematic search was performed to find RCTs investigating intrathecal hydrophilic opioids in abdominal surgery. Caesarean section and continuous regional or neuraxial techniques were excluded. Several subgroup analyses were prespecified. A conventional meta-analysis, meta-regression, trial sequential analysis, and provision of GRADE scores were planned. RESULTS: The search yielded 40 trials consisting of 2500 patients. A difference was detected in ‘i.v. morphine consumption’ at Day 1 {mean difference [MD] −18.4 mg, (95% confidence interval [CI]: −22.3 to −14.4)} and Day 2 (MD −25.5 mg [95% CI: −30.2 to −20.8]), pain scores at Day 1 in rest (MD −0.9 [95% CI: −1.1 to −0.7]) and during movement (MD −1.2 [95% CI: −1.6 to −0.8]), length of stay (MD −0.2 days [95% CI: −0.4 to −0.1]) and pruritus (relative risk 4.3 [95% CI: 2.5–7.5]) but not in nausea or sedation. A difference was detected for respiratory depression (odds ratio 5.5 [95% CI: 2.1–14.2]) but not when two small outlying studies were excluded (odds ratio 1.4 [95% CI: 0.4–5.2]). The level of evidence was graded as high for morphine consumption, in part because the required information size was reached. CONCLUSIONS: This study showed important opioid-sparing effects of intrathecal hydrophilic opioids. Our data suggest a dose-dependent relationship between the risk of respiratory depression and the dose of intrathecal opioids. Excluding two high-dose studies, intrathecal opioids have a comparable incidence of respiratory depression as the control group. CLINICAL TRIAL REGISTRATION: PROSPERO-registry: CRD42018090682.