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      The Median Effective Dose of Dexmedetomidine for the Inhibition of Emergence Delirium in Preschool Children Undergoing Tonsillectomy and/or Adenoidectomy: A Retrospective Dose-response Trial

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          Abstract

          The incidence of emergence delirium (ED) is higher in preschool children undergoing tonsillectomy and/or adenoidectomy. The purpose of this study was to determine the median effective dose (ED50) of dexmedetomidine (DEX) for the inhibition of ED in preschool children by using probit regression analysis. A total of 140 anesthesia records were retrieved and divided into seven groups based on the infusion rate of DEX: .2, .25, .3, .35, .4, .45, and .5 μg·kg −1·h −1. The Pediatric Anesthesia Emergence Delirium Scale (PAEDS) was used to assess ED in preschool children, and ED was defined as a PAEDS score ≥ 10. Probit regression analysis revealed that the ED50 and ED95 of DEX were .31 μg·kg −1·h −1 (95% CI: .29–.35) and .48 μg·kg −1·h −1 (95% CI: .44–.56), respectively. Probit(p) = −2.84 + 9.28 × ln (Dose), (χ 2 = 1.925, P = .859). The PAEDS score was significantly increased in the ED group, and the rate of bradycardia was significantly decreased in the ED group compared with the without ED group (27.3% vs 54.1%, P = .02). DEX can effectively inhibit the ED in preschool children undergoing tonsillectomy and/or adenoidectomy, however, bradycardia was the main complication.

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          Most cited references39

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          Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials.

          Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort. To determine the efficacy of dexmedetomidine vs midazolam or propofol (preferred usual care) in maintaining sedation; reducing duration of mechanical ventilation; and improving patients' interaction with nursing care. Two phase 3 multicenter, randomized, double-blind trials carried out from 2007 to 2010. The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia. Included were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours (midazolam, n = 251, vs dexmedetomidine, n = 249; propofol, n = 247, vs dexmedetomidine, n = 251). Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials. For each trial, we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation-Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were patients' ability to communicate pain (measured using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol population (midazolam, n = 233, vs dexmedetomidine, n = 227; propofol, n = 214, vs dexmedetomidine, n = 223). Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% CI, 0.97-1.18) and dexmedetomidine/propofol, 1.00 (95% CI, 0.92-1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours [IQR, 67-337]) vs midazolam (164 hours [IQR, 92-380]; P = .03) but not with dexmedetomidine (97 hours [IQR, 45-257]) vs propofol (118 hours [IQR, 48-327]; P = .24). Patients' interaction (measured using VAS) was improved with dexmedetomidine (estimated score difference vs midazolam, 19.7 [95% CI, 15.2-24.2]; P < .001; and vs propofol, 11.2 [95% CI, 6.4-15.9]; P < .001). Length of ICU and hospital stay and mortality were similar. Dexmedetomidine vs midazolam patients had more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001). Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients' ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine. clinicaltrials.gov Identifiers: NCT00481312, NCT00479661.
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            Emergence delirium in children: many questions, few answers.

            The introduction of a new generation of inhaled anesthetics into pediatric clinical practice has been associated with a greater incidence of ED, a short-lived, but troublesome clinical phenomenon of uncertain etiology. A variety of anesthesia-, surgery-, patient-, and adjunct medication-related factors have been suggested to play a potential role in the development of such an event. Restless behavior upon emergence causes not only discomfort to the child, but also makes the caregivers and parents feel unhappy with the quality of recovery from anesthesia. Although the severity of agitation varies, it often requires additional nursing care, as well as treatment with analgesics or sedatives, which may delay discharge from hospital. To reduce the incidence of this adverse event, it is advisable to identify children at risk and take preventive measures, such as reducing preoperative anxiety, removing postoperative pain, and providing a quiet, stress-free environment for postanesthesia recovery. More clinical trials are needed to elucidate the cause as well as provide effective treatment.
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              Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies.

              Emergence agitation (EA) in children is increased after sevoflurane anaesthesia. The efficacy of prophylactic treatment is controversial. The aim of this study was to provide a meta-analysis of the studies of the pharmacological prevention of EA in children. A comprehensive literature search was conducted to identify clinical trials that focused on the prevention of EA in children anaesthetized with sevoflurane, desflurane, or both. The data from each trial were combined using the Mantel-Haenszel model to calculate the pooled odds ratio (OR) and 95% confidence interval. I(2) statistics were used to assess statistics heterogeneity and the funnel plot and the Begg-Mazumdar test to assess bias. Thirty-seven articles were found which included a total of 1695 patients in the intervention groups and 1477 in the control ones. Midazolam and 5HT(3) inhibitors were not found to have a protective effect against EA [OR=0.88 (0.44, 1.76); OR=0.39 (0.12, 1.31), respectively], whereas propofol [OR=0.21 (0.16, 0.28)], ketamine [OR=0.28 (0.13, 0.60)], alpha(2)-adrenoceptors [OR=0.23 (0.17, 0.33)], fentanyl [OR=0.31 (0.18, 0.56)], and peroperative analgesia [OR=0.15 (0.07, 0.34)] were all found to have a preventive effect. Subgroup analysis according to the peroperative analgesia given does not affect the results. This meta-analysis found that propofol, ketamine, fentanyl, and preoperative analgesia had a prophylactic effect in preventing EA. The analgesic properties of these drugs do not seem to have a role in this effect.
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                Author and article information

                Journal
                Dose Response
                Dose Response
                spdos
                DOS
                Dose-Response
                SAGE Publications (Sage CA: Los Angeles, CA )
                1559-3258
                19 April 2024
                Apr-Jun 2024
                : 22
                : 2
                : 15593258241248919
                Affiliations
                [1-15593258241248919]Department of Anesthesiology, Ringgold 12485, universityThe Medical Center of AnQing of Anhui Medical University; , AnQing, China
                Author notes
                [*]WeiBing Wang, Department of Anesthesiology, The Medical Center of AnQing of Anhui Medical University, 87th, TianZhuShang East Road, AnQing, 246003, China. Email: w2bwang@ 123456sina.com
                [*]

                These authors have contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-6059-7916
                Article
                10.1177_15593258241248919
                10.1177/15593258241248919
                11032057
                38645383
                9a7d0778-bb80-4068-a4d1-13635f5e9580
                © The Author(s) 2024

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 21 November 2023
                : 6 April 2024
                Funding
                Funded by: Anhui Medical University, FundRef https://doi.org/10.13039/501100002947;
                Award ID: NO: 2022xkj247
                Funded by: Department of Anhui Education;
                Award ID: NO: 2022AH052555
                Categories
                Original Research Article
                Custom metadata
                ts10
                April-June 2024

                dexmedetomidine,median effective dose,emergence delirium,children,tonsillectomy

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