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      Effect of intrathecal lipophilic opioids on the incidence of shivering in women undergoing cesarean delivery after spinal anesthesia: a systematic review and bayesian network meta- analysis of randomized controlled trials

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          Abstract

          Background

          Shivering is a common side effect in women having cesarean delivery (CD) under spinal anesthesia, which can be bothersome to the patient, and it can also interfere with perioperative monitoring. In several studies, the intrathecal (IT) addition of a lipophilic opioid to local anesthetics has been shown to decrease the incidence of shivering.

          Objective

          We performed this network meta-analysis to evaluate the effects of intrathecal lipophilic opioids in preventing the incidence of shivering in patients undergoing CD.

          Methods

          This review was planned according to the PRISMA for Network Meta-Analysis (PRISMA-NMA) guidelines. An English literature search of multiple electronic databases was conducted. We included randomized controlled trials (RCTs) that reported on the incidence of shivering, with study groups receiving either IT fentanyl, sufentanil, or meperidine in women undergoing CD under spinal anesthesia. Quality of the studies was assessed using the modified Oxford scoring system. Using random-effects modeling, dichotomous data were extracted and summarized using odds ratio (OR) with a 95% credible interval (CrI). Statistical analysis was conducted using R studio version 1.0.153 - Inc.

          Results

          Twenty-one studies consisting of 1433 patients (Control group: 590 patients in twenty-one studies; Fentanyl group:199 patients in seven studies; Sufentanil group: 156 patients in five studies; Meperidine group: 488 patients in ten studies) met the inclusion criteria for this systematic review investigating the effect of intrathecal lipophilic opioids in preventing the incidence of shivering in women undergoing cesarean delivery under spinal anesthesia. Methodological validity scores ranged from 3 to 7. The Bayesian mixed network estimate showed the incidence of shivering was significantly lower with IT fentanyl (pooled odds ratio (OR): 0.13; 95% credible interval (CrI): 0.04 to 0.35; P = 0.0004) and IT meperidine (OR: 0.12; 95% CrI: 0.05 to 0.29; P < 0.00001), but not with IT sufentanil (OR: 0.37; 95% CrI: 0.11 to 1.22; P = 0.23). The IT fentanyl group had a significantly lower incidence of intraoperative discomfort [Risk Ratio (RR): 0.19; 95% CI: 0.10–0.35; P < 0.00001], the IT sufentanil group had a significantly higher incidence of pruritus (RR: 6.18; 95% CI: 1.18–32.46; P = 0.03) The IT meperidine group had a significantly lower incidence of intraoperative discomfort (2.7% vs. 13.6%; RR: 0.22; 95% CI: 0.09–0.55; P = 0.001), but there was a significant increase in nausea and vomiting (IT meperidine group vs. Control group: 42.7% vs. 19.4%; RR: 2.56; 95% CI: 1.14–5.75; P = 0.02). Meta-regression analysis based on the opioid dose and quality of the study did not impact the final inference of our result.

          Conclusion

          IT fentanyl significantly decreased the incidence of shivering in women undergoing CD under spinal anesthesia without increasing maternal adverse events, confirming that routine use in this patient population is a good choice. IT sufentanil did not decrease the incidence of shivering. IT meperidine decreased the incidence and severity of shivering, but its use was also associated with significant nausea and vomiting.

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          Most cited references55

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          Temperature monitoring and perioperative thermoregulation.

          Most clinically available thermometers accurately report the temperature of whatever tissue is being measured. The difficulty is that no reliably core-temperature-measuring sites are completely noninvasive and easy to use-especially in patients not undergoing general anesthesia. Nonetheless, temperature can be reliably measured in most patients. Body temperature should be measured in patients undergoing general anesthesia exceeding 30 min in duration and in patients undergoing major operations during neuraxial anesthesia. Core body temperature is normally tightly regulated. All general anesthetics produce a profound dose-dependent reduction in the core temperature, triggering cold defenses, including arteriovenous shunt vasoconstriction and shivering. Anesthetic-induced impairment of normal thermoregulatory control, with the resulting core-to-peripheral redistribution of body heat, is the primary cause of hypothermia in most patients. Neuraxial anesthesia also impairs thermoregulatory control, although to a lesser extent than does general anesthesia. Prolonged epidural analgesia is associated with hyperthermia whose cause remains unknown.
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            Reporting of results from network meta-analyses: methodological systematic review

            Objective To examine how the results of network meta-analyses are reported. Design Methodological systematic review of published reports of network meta-analyses. Data sources Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Medline, and Embase, searched from inception to 12 July 2012. Study selection All network meta-analyses comparing the clinical efficacy of three or more interventions in randomised controlled trials were included, excluding meta-analyses with an open loop network of three interventions. Data extraction and synthesis The reporting of the network and results was assessed. A composite outcome included the description of the network (number of interventions, direct comparisons, and randomised controlled trials and patients for each comparison) and the reporting of effect sizes derived from direct evidence, indirect evidence, and the network meta-analysis. Results 121 network meta-analyses (55 published in general journals; 48 funded by at least one private source) were included. The network and its geometry (network graph) were not reported in 100 (83%) articles. The effect sizes derived from direct evidence, indirect evidence, and the network meta-analysis were not reported in 48 (40%), 108 (89%), and 43 (36%) articles, respectively. In 52 reports that ranked interventions, 43 did not report the uncertainty in ranking. Overall, 119 (98%) reports of network meta-analyses did not give a description of the network or effect sizes from direct evidence, indirect evidence, and the network meta-analysis. This finding did not differ by journal type or funding source. Conclusions The results of network meta-analyses are heterogeneously reported. Development of reporting guidelines to assist authors in writing and readers in critically appraising reports of network meta-analyses is timely.
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              [3H]Sufentanil, a superior ligand for mu-opiate receptors: binding properties and regional distribution in rat brain and spinal cord.

              Stereospecific [3H]sufentanil binding, inhibited by dextromoramide, represents 90% of the total binding in membrane preparations of rat brain and spinal cord. Scatchard plots of the binding in the forebrain, at 37 degrees C in Tris-HCl buffer without and with 120 mM NaCl, were rectilinear; KD = 0.13 nM and 0.31 nM, Bmax = 13 fmol/mg tissue and 9.9 fmol/mg tissue in the absence and the presence of sodium ions respectively. The reduction in binding affinity in the presence of sodium ions was found to be due to a 9.7 fold enhancement of the initial dissociation rate from t1/2 = 2.1 min in the absence to 13 s in the presence of sodium ions. The [3H]sufentanil binding properties were superior to those of [3H]fentanyl, [3H]dihydromorphine and [3H]naloxone; [3H]sufentanil showed an unmatched favourable ratio of stereospecific versus non-specific binding; it had a 7.7, 20 and 40 fold binding affinity than the above ligands respectively. Due to its relatively slow dissociation rate, a more accurate estimation of the Bmax value was obtained with [3H]sufentanil than with the other, fast dissociating 3H-ligands (t1/2 less than 10 s). A total of 37 narcotic analgesic agonists and antagonists belonging to 5 different major structural classes all inhibited stereospecific [3H]sufentanil binding in a competitive way. There was no relationship between binding affinities and lipophilicity and degree of ionization of the compounds. Binding affinities correlated highly significantly with the analgesic potency measured in vivo, demonstrating that [3H]sufentanil labels mu-opiate receptor sites which mediate narcotic analgesia. Moreover, the binding affinity of sufentanil for delta-type binding sites labelled by [3H] [D-Ala2,D-Leu5]enkephalin was found to be 100 times lower than its binding affinity for the mu-receptor sites. [3H]Sufentanil was used for a detailed investigation of the regional distribution of mu-opiate receptor sites in the brain; Bmax and KD values were measured in the dorsal and ventral spinal cord.
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                Author and article information

                Contributors
                Yamini.subramani@lhsc.on.ca , yaminisrs@rediffmail.com
                Mahesh.Nagappa@lhsc.on.ca
                Kamal.Kumar@lhsc.on.ca
                LeeAnne.Fochesato@lhsc.on.ca
                mchohan6@uwo.ca
                yzhu422@uwo.ca
                Kevin.Armstrong@sjhc.london.on.ca
                indu.singh@sjhc.london.on.ca
                Journal
                BMC Anesthesiol
                BMC Anesthesiol
                BMC Anesthesiology
                BioMed Central (London )
                1471-2253
                26 August 2020
                26 August 2020
                2020
                : 20
                : 214
                Affiliations
                [1 ]GRID grid.39381.30, ISNI 0000 0004 1936 8884, Department of Anesthesia and Perioperative Medicine, Schulich School of Medicine, & Dentistry, Western University, , London Health Sciences Centre- University Hospital, (LHSC-UH) , ; London, Ontario, Canada
                [2 ]GRID grid.39381.30, ISNI 0000 0004 1936 8884, Department of Anesthesia and Perioperative Medicine, London Health Sciences Centre and St. Joseph’s Health Care, , Western University, ; London, Ontario, Canada
                [3 ]GRID grid.39381.30, ISNI 0000 0004 1936 8884, Department of Anesthesia and Perioperative Medicine, Schulich School of Medicine, & Dentistry, , Western University, London Health Sciences Centre- Victoria Hospital, (LHSC-VH) , ; London, Ontario, Canada
                Article
                1116
                10.1186/s12871-020-01116-5
                7448354
                32847522
                87546e82-b993-45d8-b427-1cec3f3a43c6
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 27 April 2020
                : 4 August 2020
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Anesthesiology & Pain management
                Anesthesiology & Pain management

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