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

ABSTRACT: 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.

SUBMITTER: Koning MV

PROVIDER: S-EPMC7497029 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Koning Mark V MV Klimek Markus M Rijs Koen K Stolker Robert J RJ Heesen Michael A MA

British journal of anaesthesia 20200711 3

<h4>Background</h4>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.<h4>Methods</h4>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 me ...[more]

PMID: 32660719

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Project description: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.

Project description:BackgroundFluid loading is one of the recognised measures to prevent hypotension due to spinal anaesthesia in women scheduled for a caesarean section.ObjectiveWe aimed to evaluate the current evidence on fluid loading in the prevention of spinal anaesthesia-induced hypotension.DesignSystematic review and network meta-analysis with trial sequential analysis and meta-regression.Data sourcesMedline, Epub, Embase.com (Embase and Medline), Cochrane Central, Web of Science and Google Scholar were used.Eligibility criteriaOnly randomised controlled trials were used. Patients included women undergoing elective caesarean section who received either crystalloid or colloid fluid therapy as a preload or coload. The comparator was a combination of either a different fluid or time of infusion.ResultsA total of 49 studies (4317 patients) were included. Network meta-analysis concluded that colloid coload and preload offered the highest chance of success (97 and 67%, respectively). Conventional meta-analysis showed that crystalloid preload is associated with a significantly higher incidence of maternal hypotension than colloid preload: risk ratio 1.48 (95% CI 1.29 to 1.69, P < 0.0001, I = 60%). However, this result was not supported by Trial Sequential Analysis. There was a significant dose-response effect for crystalloid volume preload (regression coefficient = -0.073), which was not present in the analysis of only double-blind studies. There was no dose-response effect for the other fluid regimes.ConclusionUnlike previous meta-analysies, we found a lack of data obviating an evidence-based recommendation. In most studies, vasopressors were not given prophylactically as is recommended. Studies on the best fluid regimen in combination with prophylactic vasopressors are needed. Due to official european usage restrictions on the most studied colloid (HES), we recommend crystalloid coload as the most appropriate fluid regimen.Trial registrationCRD42018099347.

Project description:BackgroundFollowing abdominal surgery, postoperative ileus is a common complication significantly increasing patient morbidity and cost of hospital admission. This is the first systematic review aimed at determining the average global hospital cost per patient associated with postoperative ileus.MethodsA systematic search of electronic databases was performed from January 2000 to March 2023. Studies included compared patients undergoing abdominal surgery who developed postoperative ileus to those who did not, focusing on costing data. The primary outcome was the total cost of inpatient stay. Risk of bias was assessed using the Newcastle-Ottawa assessment tool. Summary meta-analysis was performed.ResultsOf the 2071 studies identified, 88 papers were assessed for full eligibility. The systematic review included nine studies (2005-2022), investigating 1 860 889 patients undergoing general, colorectal, gynaecological and urological surgery. These studies showed significant variations in the definition of postoperative ileus. Six studies were eligible for meta-analysis showing an increase of €8233 (95 per cent c.i. (5176 to 11 290), P < 0.0001, I2 = 95.5 per cent) per patient with postoperative ileus resulting in a 66.3 per cent increase in total hospital costs (95 per cent c.i. (34.8 to 97.9), P < 0.0001, I2 = 98.4 per cent). However, there was significant bias between studies. Five colorectal-surgery-specific studies showed an increase of €7242 (95 per cent c.i. (4502 to 9983), P < 0.0001, I2 = 86.0 per cent) per patient with postoperative ileus resulting in a 57.3 per cent increase in total hospital costs (95 per cent c.i. (36.3 to 78.3), P < 0.0001, I2 = 85.7 per cent).ConclusionThe global financial burden of postoperative ileus following abdominal surgery is significant. While further multicentre data using a uniform postoperative ileus definition would be useful, reducing the incidence and impact of postoperative ileus are a priority to mitigate healthcare-related costs, and improve patient outcomes.

Dataset Information

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

Publications

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

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