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      Subarachnoid and epidural dexmedetomidine for the prevention of post-anesthetic shivering: a meta-analysis and systematic review

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          Post-anesthetic shivering incurs discomfort to patients or even exacerbates their condition. However, no ideal drug has been well established for preventing post-anesthetic shivering. Currently, subarachnoid and epidural dexmedetomidine have demonstrated to have an anti-shivering effect.


          An electronic search was conducted to identify randomized placebo-controlled trials reporting shivering and then compared subarachnoid and epidural dexmedetomidine with placebo in adults undergoing selective surgery. Data assessment and pooling were analyzed by Review Manager 5.3, STATA 15.0 and GRADE-pro 3.6 software.


          Twenty-two studies (1389 patients) were subjected to this meta-analysis. The incidence of post-anesthetic shivering decreased from 20.10% in the placebo group to 10.30% in the dexmedetomidine group (RR, 0.48; 95% CI, 0.39–0.59; Z=6.86, P<0.00001, I 2=32%). Non-Indian, epidural-space route and cesarean subgroups indicated a better anti-shivering effect. In the subarachnoid-space route subgroup, a dosage of >5 μg showed significantly superior anti-shivering effects than that of ≤5 μg. Subarachnoid and epidural dexmedetomidine increased the incidence of bradycardia, had no impact on nausea and vomiting, shortened the onset of block and lengthened the duration of block and analgesia. However, its effect on hypotension and sedation remained uncertain. The overall risk of bias was relatively low. The level of evidence was high, and the recommendation of voting results was strong.


          Dexmedetomidine as a subarachnoid and epidural adjunct drug could decrease the incidence of post-anesthetic shivering in a dose-dependent manner. However, caution should be taken in patients with original bradycardia.

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          Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds.

          Clonidine decreases the vasoconstriction and shivering thresholds. It thus seems likely that the alpha2 agonist dexmedetomidine will also impair control of body temperature. Accordingly, the authors evaluated the dose-dependent effects of dexmedetomidine on the sweating, vasoconstriction, and shivering thresholds. They also measured the effects of dexmedetomidine on heart rate, blood pressures, and plasma catecholamine concentrations. Nine male volunteers participated in this randomized, double-blind, cross-over protocol. The study drug was administered by computer-controlled infusion, targeting plasma dexmedetomidine concentrations of 0.0, 0.3, and 0.6 ng/ml. Each day, skin and core temperatures were increased to provoke sweating and then subsequently reduced to elicit vasoconstriction and shivering. Core-temperature thresholds were computed using established linear cutaneous contributions to control of sweating, vasoconstriction, and shivering. The dose-dependent effects of dexmedetomidine on thermoregulatory response thresholds were then determined using linear regression. Heart rate, arterial blood pressures, and plasma catecholamine concentrations were determined at baseline and at each threshold. Neither dexmedetomidine concentration increased the sweating threshold from control values. In contrast, dexmedetomidine administration reduced the vasoconstriction threshold by 1.61 +/- 0.80 degrees C x ng(-1) x ml (mean +/- SD) and the shivering threshold by 2.40 +/- 0.90 degrees C x ng(-1) x ml. Hemodynamic responses and catecholamine concentrations were reduced from baseline values, but they did not differ at the two tested dexmedetomidine doses. Dexmedetomidine markedly increased the range of temperatures not triggering thermoregulatory defenses. The drug is thus likely to promote hypothermia in a typical hospital environment; it is also likely to prove an effective treatment for shivering.
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            Does Dexmedetomidine as a Neuraxial Adjuvant Facilitate Better Anesthesia and Analgesia? A Systematic Review and Meta-Analysis

            Background Neuraxial application of dexmedetomidine (DEX) as adjuvant analgesic has been invetigated in some randomized controlled trials (RCTs) but not been approved because of the inconsistency of efficacy and safety in these RCTs. We performed this meta-analysis to access the efficacy and safety of neuraxial DEX as local anaesthetic (LA) adjuvant. Methods We searched PubMed, PsycINFO, Scopus, EMBASE, and CENTRAL databases from inception to June 2013 for RCTs that investigated the analgesia efficacy and safety for neuraxial application DEX as LA adjuvant. Effects were summarized using standardized mean differences (SMDs), weighed mean differences (WMDs) or odds ratio (OR) with suitable effect model. The primary outcomes were postoperative pain intensity and analgesic duration, bradycardia and hypotension. Results Sixteen RCTs involving 1092 participants were included. Neuraxial DEX significantly decreased postoperative pain intensity (SMD, −1.29; 95% confidence interval (CI), −1.70 to −0.89; P<0.00001), prolonged analgesic duration (WMD, 6.93 hours; 95% CI, 5.23 to 8.62; P<0.00001) and increased the risk of bradycardia (OR, 2.68; 95% CI, 1.18 to 6.10; P = 0.02). No evidence showed that neuraxial DEX increased the risk of other adverse events, such as hypotension (OR, 1.54; 95% CI, 0.83 to 2.85; P = 0.17). Additionally, neuraxial DEX was associated with beneficial alterations in postoperative sedation scores and number of analgesic requirements, sensory and motor block characteristics, and intro-operative hemodynamics. Conclusion Neuraxial DEX is a favorable LA adjuvant with better and longer analgesia. The greatest concern is bradycardia. Further large sample trials with strict design and focusing on long-term outcomes are needed.
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              Dexmedetomidine as an intrathecal adjuvant for postoperative analgesia

              Background: Spinal anaesthesia is the most common approach which is used for lower limb surgery. Dexmedetomidine is the recent drug which acts on α2-adrenergic receptors in the dorsal horn of the spinal cord to produce analgesic effects. Aim: Efficacy and safety of intrathecal dexmedetomidine added to ropivacaine. Setting and Design: Randomised double blind trial. Methods: Sixty patients were randomly allocated to receive intrathecally either 3 ml of 0.75% isobaric ropivacaine + 0.5 ml normal saline (Group R) or 3 ml of 0.75% isobaric ropivacaine + 5 μg dexmedetomidine in 0.5 ml of normal saline (Group D). Results: The mean time of sensory regression to S2 was 468.3±36.78 minutes in group D and 239.33±16.8 minutes in group R. Duration of analgesia (time to requirement of first rescue analgesic) was significantly prolonged in group D (478.4±20.9 minutes) as compared to group R (241.67±21.67 minutes). The maximum visual analogue scale score for pain was less in group D (4.4±1.4) as compared to group R (6.8±2.2). Conclusion: The addition of dexmedetomidine to ropivacaine intrathecally produces a prolongation in the duration of the motor and sensory block.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                01 November 2019
                : 13
                : 3785-3798
                [1 ]Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University , Wenzhou, Zhejiang, People’s Republic of China
                [2 ]Department of Anesthesiology, Wenzhou Integrated Chinese and Western Hospital of Zhejiang Chinese Medical University , Wenzhou, Zhejiang, People’s Republic of China
                Author notes
                Correspondence: Han LinDepartment of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University , 109 Western Xueyuan Road, Lucheng, Wenzhou, Zhejiang325027, People’s Republic of ChinaTel +86 1 586 871 0831 Email nanlinhannansh@gmail.com
                © 2019 Li et al.

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                Page count
                Figures: 6, Tables: 1, References: 70, Pages: 14
                Original Research


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