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      Propofol vs midazolam sedation for elective endoscopy in patients with cirrhosis: A systematic review and meta-analysis of randomized controlled trials

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          Abstract

          BACKGROUND

          Patients with cirrhosis frequently require sedation for elective endoscopic procedures. Several sedation protocols are available, but choosing an appropriate sedative in patients with cirrhosis is challenging.

          AIM

          To conduct a systematic review and meta-analysis to compare propofol and midazolam for sedation in patients with cirrhosis during elective endoscopic procedures in an attempt to understand the best approach.

          METHODS

          This systematic review and meta-analysis was conducted using the PRISMA guidelines. Electronic searches were performed using MEDLINE, EMBASE, Central Cochrane, LILACS databases. Only randomized control trials (RCTs) were included. The outcomes studied were procedure time, recovery time, discharge time, and adverse events (bradycardia, hypotension, and hypoxemia). The risk of bias assessment was performed using the Revised Cochrane Risk-of-Bias tool for randomized trials (RoB-2). Quality of evidence was evaluated by GRADEpro. The meta-analysis was performed using Review Manager.

          RESULTS

          The search yielded 3,576 records. Out of these, 8 RCTs with a total of 596 patients (302 in the propofol group and 294 in the midazolam group) were included for the final analysis. Procedure time was similar between midazolam and propofol groups (MD: 0.25, 95%CI: -0.64 to 1.13, P = 0.59). Recovery time (MD: -8.19, 95%CI: -10.59 to -5.79, P < 0.00001). and discharge time were significantly less in the propofol group (MD: -12.98, 95%CI: -18.46 to -7.50, P < 0.00001). Adverse events were similar in both groups (RD: 0.02, 95%CI: 0-0.04, P = 0.58). Moreover, no significant difference was found for bradycardia (RD: 0.03, 95%CI: -0.01 to 0.07, P = 0.16), hypotension (RD: 0.03, 95%CI: -0.01 to 0.07, P = 0.17), and hypoxemia (RD: 0.00, 95%CI: -0.04 to 0.04, P = 0.93). Five studies had low risk of bias, two demonstrated some concerns, and one presented high risk. The quality of the evidence was very low for procedure time, recovery time, and adverse events; while low for discharge time.

          CONCLUSION

          This systematic review and meta-analysis based on RCTs show that propofol has shorter recovery and patient discharge time as compared to midazolam with a similar rate of adverse events. These results suggest that propofol should be the preferred agent for sedation in patients with cirrhosis.

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          Most cited references46

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          Management of adult patients with ascites due to cirrhosis: an update.

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            The morphology of cirrhosis. Recommendations on definition, nomenclature, and classification by a working group sponsored by the World Health Organization.

            This memorandum provides guidelines on the definition, nomenclature, and classification of cirrhosis, chronic hepatitis, and hepatic fibrosis. These are considered according to morphological characteristics and aetiology. It is hoped that this system will serve as a standard for diagnostic, research, and epidemiological purposes. The relationship of cirrhosis to liver cell carcinoma is briefly discussed and the possible morphological markers of an increased risk of malignancy are defined.
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              The effects of age and liver disease on the disposition and elimination of diazepam in adult man.

              This study investigates the separate effects of age and hepatocellular liver disease on the disposition and elimination of diazepam (Valium) in man. The drug was given either by rapid intravenous injection (0.1 mg/kg) or orally (10 mg) to 33 normal volunteers rnaging in age from 15 to 82 yr as well as to 9 individuals with alcoholic cirrhosis, 8 with acute viral hepatitis, and 4 with chronic active hepatitis. In the normal individuals, the terminal plasma half-life of diazepam, (t 1/2 (B)) exhibited a striking age-dependence; at 20 yr the t 1/2 (beta) was about 20 h, but it increased linearly with age to about 90 h at 80 yr. The plasma clearance of diazepam in the majority of the normal subjects was between 20 and 32 ml/min and showed no significant age-dependence. Cigarette smoking did not affect the half-life or the clearance. Additionally, neither the plasma binding (97.4 plus or minus 1.2%, mean plus or minus SD) nor the blood/plasma concentration ratio (0.58 plus or minus 0.16) of diazepam showed any age-related changes (P greater than 0.05). By contrast, analysis of the intravenous data according to a two-compartment open model indicated that both the initial distribution space (V1) and the volume of distribution at steady state [Vd(ss)] of diazepam increased linearly with age (P less than 0.005). The increase in Vd(ss) was secondary to the change in V1. It appears then that the prolongation of t 1/2 (beta) of diazepam with age is primarily dependent on an increase in the initial distribution volume of the drug. The plasma concentration/time course of the metabolite, desmethyldiazepam, was also affected by age. In older individuals, the initial presence and the peak values of desmethyldiazepam were observed later and the metabolite was present in lower concentrations. Despite the profound prolongation of t 1/2 (theta) with age, the constancy of diazepam clearance indicates that drug plasma concentrations will not accumulate any more in the old than the young, and chronic dosage more in the old than the young, and chronic dosage modifications based on pharmacokinetic considerations are unnecessary. Data obtained in patients with liver disease were compared with those found in age-matched control groups. Patients with cirrhosis showed a more than twofold prolongation in the half-life of diazepam (105.6 plus or minus 15.2 vs. 46.6 plus or minus 14.2 h, P less than 0.001).
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                Author and article information

                Contributors
                Journal
                World J Gastrointest Endosc
                WJGE
                World Journal of Gastrointestinal Endoscopy
                Baishideng Publishing Group Inc
                1948-5190
                16 August 2020
                16 August 2020
                : 12
                : 8
                : 241-255
                Affiliations
                Gastrointestinal Endoscopy Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, Brazil
                Gastrointestinal Endoscopy Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, Brazil
                Gastrointestinal Endoscopy Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, Brazil. igorbraga1@ 123456gmail.com
                Gastrointestinal Endoscopy Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, Brazil
                Division of Gastroenterology, Department of Internal Medicine, West Virginia University, Charleston, WV 25304, United States
                Gastrointestinal Endoscopy Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, Brazil
                Gastrointestinal Endoscopy Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, Brazil
                Gastrointestinal Endoscopy Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo 05403-010, Brazil
                Author notes

                Author contributions: Guacho JAL and de Moura DTH contributed to acquisition of data, analysis, interpretation of data, drafting the article, revising the article, final approval; Ribeiro IB, da Ponte Neto AM and Singh S contributed to analysis and interpretation of data, revising the article; Tucci M contributed to acquisition of data drafting the article, final approval; Bernardo WM contributed to analysis and interpretation of data, drafting the article, final approval; de Moura EGH contributed to analysis and interpretation of data, drafting the article, revising the article, final approval.

                Corresponding author: Igor Braga Ribeiro, MD, Research Fellow, Surgeon, Gastrointestinal Endoscopy Unit, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr Enéas de Carvalho Aguiar, 225, 6 o andar, bloco 3, Cerqueira Cesar, São Paulo 05403-010, Brazil. igorbraga1@ 123456gmail.com

                Article
                jWJGE.v12.i8.pg241
                10.4253/wjge.v12.i8.241
                7443824
                32879659
                b0b438ce-63be-45ba-917e-29a3b74182f3
                ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 31 March 2020
                : 12 June 2020
                : 18 July 2020
                Categories
                Meta-Analysis

                sedation,midazolam,propofol,cirrhosis,endoscopic,endoscopy,meta-analysis

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