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      Re: Role of dexmedetomidine as adjuvant in postoperative sciatic popliteal and adductor canal analgesia in trauma patients: a randomized controlled trial

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      1 , 1 , 2
      The Korean Journal of Pain
      The Korean Pain Society

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          Abstract

          To the editor Dexmedetomidine (DMED), a highly selective alpha-2 adrenergic agonistic agent, is one of the preferred sedatives due to its outstanding characteristics including sympatholytic, sedative, hypnotic, and analgesic efficacy [1]. And it can achieve an appropriate level of sedation without respiratory depression. Especially, the efficacy of dexmedetomidine when combined with regional anesthesia includes increasing the quality of regional anesthesia, prolongation of the duration of analgesia, and having an opioid-sparing effect postoperatively [2]. We have carefully read with great concern the article entitled “Role of dexmedetomidine as adjuvant in postoperative sciatic popliteal and adductor canal analgesia in trauma patients: a randomized controlled trial.” published in The Korean Journal of Pain by Ahuja et al. [2]. Their results showed that perineurally or intravenously administered dexmedetomidine reduced postoperative tramadol consumption in patients undergoing lower extremity surgery when combined with sciatic popliteal and adductor canal analgesia. And they reported that hemodynamic parameters were within the normal physiologic range during the 48 hours of follow-up, even though they didn’t show the raw results. However, in clinical practice, the patients who received intravenous dexmedetomidine often experience hypotension or bradycardia, even postoperatively. As investigated in a few studies, the hemodynamic effects of dexmedetomidine such as hypotension and bradycardia are well known in the perioperative period, as well as in intensive care unit (ICU) settings [3–6]. We are working on ways to identify the incidence and risk factors for dexmedetomidine-induced hemodynamic instability in perioperative settings. We conceived that body composition, such as fat percentage to total body weight, is one of the contributing factors, which can affect the volume of distribution of the drug, because dexmedetomidine is a highly lipophilic drug [7]. Indeed, in the clinical practice, we are often faced with the overdosing of anesthetic drugs with high lipophilicity by dosing based on total body weight, especially in female patients having a high body mass index. The dosing scheme of dexmedetomidine may be modified in the susceptible populations. Advancing the quality of care and patient safety could be achieved by individualized anesthetic and risk management. Moreover, safety concerns regarding perineural administration of dexmedetomidine, such as neurotoxicity, should be further investigated in future studies.

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          Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine

          Dexmedetomidine is an α2-adrenoceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects, and minimal depression of respiratory function. It is potent and highly selective for α2-receptors with an α2:α1 ratio of 1620:1. Hemodynamic effects, which include transient hypertension, bradycardia, and hypotension, result from the drug’s peripheral vasoconstrictive and sympatholytic properties. Dexmedetomidine exerts its hypnotic action through activation of central pre- and postsynaptic α2-receptors in the locus coeruleus, thereby inducting a state of unconsciousness similar to natural sleep, with the unique aspect that patients remain easily rousable and cooperative. Dexmedetomidine is rapidly distributed and is mainly hepatically metabolized into inactive metabolites by glucuronidation and hydroxylation. A high inter-individual variability in dexmedetomidine pharmacokinetics has been described, especially in the intensive care unit population. In recent years, multiple pharmacokinetic non-compartmental analyses as well as population pharmacokinetic studies have been performed. Body size, hepatic impairment, and presumably plasma albumin and cardiac output have a significant impact on dexmedetomidine pharmacokinetics. Results regarding other covariates remain inconclusive and warrant further research. Although initially approved for intravenous use for up to 24 h in the adult intensive care unit population only, applications of dexmedetomidine in clinical practice have been widened over the past few years. Procedural sedation with dexmedetomidine was additionally approved by the US Food and Drug Administration in 2003 and dexmedetomidine has appeared useful in multiple off-label applications such as pediatric sedation, intranasal or buccal administration, and use as an adjuvant to local analgesia techniques.
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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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              Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate.

              Dexmedetomidine (DMED) is a highly selective centrally acting alpha 2-adrenergic agonist thought to provide significant sedation without appreciable ventilatory effects. This double-blind, placebo-controlled experiment evaluated four dose levels of DMED (0.25, 0.5, 1.0, and 2.0 micrograms/kg intravenously over 2 min) in 37 healthy male volunteers. Measurements of sedation, arterial blood gases, resting ventilation, hypercapnic ventilatory response (HVR), and metabolic rate (O2 consumption and CO2 production) were performed at baseline, 10 min after DMED infusion, and thereafter at the end of each subsequent 45-min period. DMED caused sedation resulting in loss of responsiveness in most of the subjects administered 1.0 and 2.0 micrograms/kg; sedation was evident for 195 min following 2.0 micrograms/kg (P < .05). Ten minutes following infusion of 1.0 and 2.0 micrograms/kg, PaCO2 had increased by 5.0 and 4.2 mmHg, respectively (P < .05), and 60 min following 2.0 micrograms/kg, VE had decreased by 28% (P < .05). The placebo group showed a progressive increase in the HVR slope (50% increase by 330 min following the infusion; P < .05). Overall, across all the DMED doses, the slope was decreased (P < .05) at all times after DMED. The calculated ventilation at a PaCO2 of 55 mmHg was decreased (39%; P < .05) 10 min following 1.0 and 2.0 micrograms/kg, returning to control values by 285 min following 2.0 micrograms/kg. O2 consumption increased 16% (P < .05) at 10 min following 2.0 micrograms/kg; CO2 production decreased (22% at 60 min). By 5 h postinfusion, both had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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                Author and article information

                Journal
                Korean J Pain
                Korean J Pain
                The Korean Journal of Pain
                The Korean Pain Society
                2005-9159
                2093-0569
                1 July 2020
                1 July 2020
                : 33
                : 3
                : 284-285
                Affiliations
                [1 ]Department of Anesthesiology and Pain Medicine, Jeonbuk National University Medical School, Jeonju, Korea
                [2 ]Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea
                Author notes
                Correspondence Ki-Jae Lee, Department of Anesthesiology and Pain Medicine, Jeonbuk National University Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea, Tel: +82-63-250-1241, Fax: +82-63-250-1240, E-mail: lovingij1@ 123456gmail.com

                Handling Editor: Jee Youn Moon

                Author information
                https://orcid.org/0000-0002-2591-455X
                https://orcid.org/0000-0003-1310-790X
                Article
                KJP-33-284
                10.3344/kjp.2020.33.3.284
                7336344
                32606273
                60a6a648-4752-4726-9b0e-ae14d32712f6
                © The Korean Pain Society, 2020

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 3 April 2020
                : 8 May 2020
                : 28 May 2020
                Categories
                Letter to the Editor

                Anesthesiology & Pain management
                Anesthesiology & Pain management

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