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      The efficacy and safety of dexmedetomidine in cardiac surgery patients: A systematic review and meta-analysis

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          Abstract

          This study aimed to evaluate the efficacy and safety of dexmedetomidine versus any other treatment without dexmedetomidine in patients who have undergone cardiac surgery. Electronic databases including PubMed, Embase, and Cochrane Library were systematically searched without limitations of language and publication time. Randomized controlled trials (RCTs) aiming to evaluate the efficacy and safety of dexmedetomidine versus any other treatment without dexmedetomidine in patients that have undergone cardiac surgery were selected. Endpoints such as hemodynamic indexes and adverse events in eligible studies were extracted by two researchers, independently. The data was analyzed using RevMan 5.3 and Stata 11.0 software. A total of 18 RCTs met the inclusion criteria, involving 1730 patients. Compared to control (any treatment without dexmedetomidine), dexmedetomidine showed a pooled mean difference (MD) of -14.46 [95% confidence interval(CI): -24.69, -4.23; p<0.01] for systolic arterial pressure, a standardized mean difference (SMD) of -1.74 for mean arterial blood pressure (95% CI: -2.80, -0.68; P < 0.01), -2.12 (95%CI: -3.23, -1.00; p<0.01) for heart rate, and combined odds ratio (OR) of 0.22 (95%CI: 0.11, 0.44; p<0.01) for tachycardia, 3.44 (95%CI: 1.95, 5.96; p<0.01) for bradycardia, 0.74 (95%CI: 0.49, 1.12; p>0.05) for atrial fibrillation, and 0.99 (95%CI: 0.51, 1.90; p>0.05) for hypotension. In addition, dexmedetomidine could reduce time of surgery and stay in intensive care units, improve delirium with good safety. Our study shows clinical application of dexmedetomidine in cardiac surgery patients can reduce risks of abnormal hemodynamics with good safety.

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          Most cited references42

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          Dexmedetomidine and the reduction of postoperative delirium after cardiac surgery.

          Delirium is a neurobehavioral syndrome caused by the transient disruption of normal neuronal activity secondary to systemic disturbances. The authors investigated the effects of postoperative sedation on the development of delirium in patients undergoing cardiac-valve procedures. Patients underwent elective cardiac surgery with a standardized intraoperative anesthesia protocol, followed by random assignment to one of three postoperative sedation protocols: dexmedetomidine, propofol, or midazolam. The incidence of delirium for patients receiving dexmedetomidine was 3%, for those receiving propofol was 50%, and for patients receiving midazolam, 50%. Patients who developed postoperative delirium experienced significantly longer intensive-care stays and longer total hospitalization. The findings of this open-label, randomized clinical investigation suggest that postoperative sedation with dexmedetomidine was associated with significantly lower rates of postoperative delirium and lower care costs.
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            Prevalence of delirium with dexmedetomidine compared with morphine based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study).

            Commonly used sedatives/analgesics can increase the risk of postoperative complications, including delirium. This double-blinded study assessed the neurobehavioral, hemodynamic, and sedative characteristics of dexmedetomidine compared with morphine-based regimen after cardiac surgery at equivalent levels of sedation and analgesia. A total of 306 patients at least 60 yr old were randomized to receive dexmedetomidine (0.1-0.7 microg x kg(-1) x h(-1)) or morphine (10-70 microg x kg(-1) x h(-1)) with open-label propofol titrated to a target Motor Activity Assessment Scale of 2-4. Primary outcome was the prevalence of delirium measured daily via Confusion Assessment Method for intensive care. Secondary outcomes included ventilation time, additional sedation/analgesia, and hemodynamic and adverse effects. Of all sedation assessments, 75.2% of dexmedetomidine and 79.6% (P = 0.516) of morphine treatment were in the target range. Delirium incidence was comparable between dexmedetomidine 13 (8.6%) and morphine 22 (15.0%) (relative risk 0.571, 95% confidence interval [CI] 0.256-1.099, P = 0.088), however, dexmedetomidine-managed patients spent 3 fewer days (2 [1-7] versus 5 [2-12]) in delirium (95% CI 1.09-6.67, P = 0.0317). The incidence of delirium was significantly less in a small subgroup requiring intraaortic balloon pump and treated with dexmedetomidine (3 of 20 [15%] versus 9 of 25 [36%]) (relative risk 0.416, 95% CI 0.152-0.637, P = 0.001). Dexmedetomidine-treated patients were more likely to be extubated earlier (relative risk 1.27, 95% CI 1.01-1.60, P = 0.040, log-rank P = 0.036), experienced less systolic hypotension (23% versus 38.1%, P = 0.006), required less norepinephrine (P < 0.001), but had more bradycardia (16.45% versus 6.12%, P = 0.006) than morphine treatment. Dexmedetomidine reduced the duration but not the incidence of delirium after cardiac surgery with effective analgesia/sedation, less hypotension, less vasopressor requirement, and more bradycardia versus morphine regimen.
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              ICU sedation after coronary artery bypass graft surgery: dexmedetomidine-based versus propofol-based sedation regimens.

              To compare dexmedetomidine-based to propofol-based sedation after coronary artery bypass graft (CABG) surgery in the intensive care unit (ICU). Randomized, open label. Twenty-five centers in the United States and Canada. Two hundred ninety-five adults undergoing CABG surgery. At sternal closure, patients in group A received 1.0 microg/kg of dexmedetomidine over 20 minutes and then 0.2 to 0.7 microg/kg/h to maintain a Ramsay sedation score > or =3 during assisted ventilation and > or =2 after extubation. Patients could be given propofol for additional sedation if necessary; group B patients received propofol-based care according to each investigator's standard practice. Mean sedation levels were within target ranges in both groups. Mean times to weaning and extubation were similar, although fewer dexmedetomidine patients remained on the ventilator beyond 8 hours. Morphine use was significantly reduced in the dexmedetomidine group. Only 28% of the dexmedetomidine patients required morphine for pain relief while ventilated versus 69% of propofol-based patients (p < 0.001). Propofol patients required 4 times the mean dose of morphine while in the ICU. Mean blood pressure increased initially in both groups, then decreased to 3 mmHg below baseline in dexmedetomidine patients; mean arterial pressure remained at 9 mmHg above baseline in propofol patients. No ventricular tachycardia occurred in the dexmedetomidine-sedated patients compared with 5% of the propofol patients (p = 0.007). Respiratory rates and blood gases were similar. Fewer dexmedetomidine patients received beta-blockers (p = 0.014), antiemetics (p = 0.015), nonsteroidal anti-inflammatory drugs (p < 0.001), epinephrine (p = 0.030), or high-dose diuretics (p < 0.001). Dexmedetomidine provided safe and effective sedation for post-CABG surgical patients and significantly reduced the use of analgesics, beta-blockers, antiemetics, epinephrine, and diuretics.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: Project administrationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 September 2018
                2018
                : 13
                : 9
                : e0202620
                Affiliations
                [001]Department of Surgical Intensive Care Unit, The First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou, Zhejiang, P.R. China
                University of Notre Dame Australia, AUSTRALIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-4824-3904
                http://orcid.org/0000-0003-2629-6404
                http://orcid.org/0000-0003-3783-8328
                Article
                PONE-D-18-17045
                10.1371/journal.pone.0202620
                6145508
                30231052
                45cf1cbd-9ebe-4846-ae54-e4b2a67f0914
                © 2018 Wang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 6 June 2018
                : 7 August 2018
                Page count
                Figures: 9, Tables: 2, Pages: 18
                Funding
                Funded by: Zhejiang Provincial Natural Science Foundation of China
                Award ID: LY15H150001
                This research was supported by Grants from Zhejiang Provincial Natural Science Foundation of China (Project No. LY15H150001).
                Categories
                Research Article
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Cardiac Surgery
                Medicine and Health Sciences
                Vascular Medicine
                Blood Pressure
                Medicine and Health Sciences
                Cardiology
                Heart Rate
                Bradycardia
                Medicine and Health Sciences
                Cardiology
                Heart Rate
                Medicine and Health Sciences
                Cardiology
                Heart Rate
                Tachycardia
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Coronary Artery Bypass Grafting
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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                Uncategorized

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