Intrathecal hydrophilic opioids for abdominal surgery: a meta-analysis, meta-regression, and trial sequential analysis. 2020

Mark V Koning, and Markus Klimek, and Koen Rijs, and Robert J Stolker, and Michael A Heesen
Department of Anaesthesiology, Erasmus University Medical Centre, Rotterdam, the Netherlands; Department of Anaesthesiology and Critical Care, Rijnstate Hospital, Arnhem, the Netherlands. Electronic address: Markkoning66@hotmail.com.

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. 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. 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. 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. PROSPERO-registry: CRD42018090682.

UI MeSH Term Description Entries
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D012131 Respiratory Insufficiency Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed) Acute Hypercapnic Respiratory Failure,Acute Hypoxemic Respiratory Failure,Hypercapnic Acute Respiratory Failure,Hypercapnic Respiratory Failure,Hypoxemic Acute Respiratory Failure,Hypoxemic Respiratory Failure,Respiratory Depression,Respiratory Failure,Ventilatory Depression,Depressions, Ventilatory,Failure, Hypercapnic Respiratory,Failure, Hypoxemic Respiratory,Failure, Respiratory,Hypercapnic Respiratory Failures,Hypoxemic Respiratory Failures,Respiratory Failure, Hypercapnic,Respiratory Failure, Hypoxemic,Respiratory Failures
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000005 Abdomen That portion of the body that lies between the THORAX and the PELVIS. Abdomens
D000701 Analgesics, Opioid Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Opioid,Opioid Analgesic,Opioid Analgesics,Opioids,Full Opioid Agonists,Opioid Full Agonists,Opioid Mixed Agonist-Antagonists,Opioid Partial Agonists,Partial Opioid Agonists,Agonist-Antagonists, Opioid Mixed,Agonists, Full Opioid,Agonists, Opioid Full,Agonists, Opioid Partial,Agonists, Partial Opioid,Analgesic, Opioid,Full Agonists, Opioid,Mixed Agonist-Antagonists, Opioid,Opioid Agonists, Full,Opioid Agonists, Partial,Opioid Mixed Agonist Antagonists,Partial Agonists, Opioid
D015360 Analgesia, Epidural The relief of pain without loss of consciousness through the introduction of an analgesic agent into the epidural space of the vertebral canal. It is differentiated from ANESTHESIA, EPIDURAL which refers to the state of insensitivity to sensation. Epidural Analgesia

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