Dexmedetomidine: present and future directions / 대한마취과학회지

Dexmedetomidine is a potent, highly selective α-2 adrenoceptor agonist, with sedative, analgesic, anxiolytic, sympatholytic, and opioid-sparing properties. Dexmedetomidine induces a unique sedative response, which shows an easy transition from sleep to wakefulness, thus allowing a patient to be cooperative and communicative when stimulated. Dexmedetomidine may produce less delirium than other sedatives or even prevent delirium. The analgesic effect of dexmedetomidine is not strong; however, it can be administered as a useful analgesic adjuvant. As an anesthetic adjuvant, dexmedetomidine decreases the need for opioids, inhalational anesthetics, and intravenous anesthetics. The sympatholytic effect of dexmedetomidine may provide stable hemodynamics during the perioperative period. Dexmedetomidine-induced cooperative sedation with minimal respiratory depression provides safe and acceptable conditions during neurosurgical procedures in awake patients and awake fiberoptic intubation. Despite the lack of pediatric labelling, dexmedetomidine has been widely studied for pediatric use in various applications. Most adverse events associated with dexmedetomidine occur during or shortly after a loading infusion. There are some case reports of dexmedetomidine-related cardiac arrest following severe bradycardia. Some extended applications of dexmedetomidine discussed in this review are promising, but still limited, and further research is required. The pharmacological properties and possible adverse effects of dexmedetomidine should be well understood by the anesthesiologist prior to use. Moreover, it is necessary to select patients carefully and to determine the appropriate dosage of dexmedetomidine to ensure patient safety.

Effect of dexmedetomidine on liver function, cytokine levels, and oxidative stress in patients undergoing hepatolobectomy / 临床肝胆病杂志

Objective To investigate the effect of dexmedetomidine on liver function,plasma cytokine levels,and oxidative stress due to ischemia/reperfusion injury in patients undergoing hepatolobectomy.Methods A total of 106 patients who underwent hepatolobectomy in General Hospital of Jizhong Energy Fengfeng Group Co.,Ltd.from January 2014 to January 2016 were enrolled and randomly divided into control group and observation group,with 53 patients in each group.The patients in the observation group were given 1 μg/kg/h dexmedetomidine within 10 minutes,followed by continuous intravenous infusion of 0.5 μg/kg/h dexmedetomidine,and those in the control group were given an equal volume of 0.9％ sodium chloride.The two groups were compared in terms of liver function parameters,plasma cytokine levels,and oxidative stress due to ischemia/reperfusion injury after anesthesia (T1),before abdominal closure (T2),and at 1,4,and 8 hours after surgery (T3,T4,and T5,respectively).The chi-square test was used for comparison of categorical data between groups;the t-test was used for comparison of indices between groups,the sphericity test was used for comparison of indices at different time points,and an analysis of variance was performed for repeated measurement data with P ＜ 0.05.Results The two groups had significantly higher alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at T2,T3,T4,and T5 than at T1 (ALT:F =43.72 and 44.16,both P ＜ 0.001;AST:F =53.87 and 65.44,both P ＜ 0.001),and the observation group had significantly lower levels than the control group atT2,T3,T4,andT5 (ALT:t =20.54,22.01,36.68,and 38.15,all P＜0.001;AST:t =32.27,41.08,52.82,and71.89,all P ＜ 0.001).The two groups had significantly higher levels of tumor necrosis factor α (TNFα) and interleukin-8 (IL-8) at T3,T4,and T5 than at T1 (TNFα:F =54.37 and 24.75,both P ＜ 0.001;IL-8:F =47.24 and 27.39,both P ＜ 0.001),and the observationgroup had significantly lower levels than the control group at T3,T4,and T5 (TNFα:t =59.39,86.32,and 83.16,all P ＜ 0.001;IL-8:t =74.47,72.29,and 76.67,all P ＜ 0.001).The two groups had a significantly higher level of malondialdehyde at T3,T4,and T5 than at T1 (F =37.65 and 17.44,both P ＜0.001),and the observation group had a significantly lower level than the control group at T3,T4,and T5 (t =17.35,19.11,and 24.12,all P ＜ 0.001).The two groups had a significantly lower level of superoxide dismutase at T3,T4,and T5 than at T1 (F =36.54 and 33.65,both P ＜0.001),and the observation group had a significantly higher level than the control group at T3,T4,and T5 (t =68.64,66.35,and 59.48,all P ＜0.001).Conclusion Dexmedetomidine can effectively inhibit liver injury,reduce the levels of cytokines,and alleviate ischemia/reperfusion injury in patients undergoing hepatectomy.

Effect of alpha‑2‑agonist premedication on intraocular pressure after selective laser trabeculoplasty.

Aim: To determine the effect of alpha‑2‑agonist (AA) premedication (PM) on intraocular pressure (IOP) following selective laser trabeculoplasty (SLT). Methods: Retrospective cohort study of all patients undergoing 360° SLT at an institution with two prevalent practice patterns consisting of SLT performed with PM and without premedication (NPM) with AA. The association between pre‑ and post‑operative IOP was evaluated using a linear regression model in 49 (59%) PM and 34 (41%) NPM eyes. Results: The prevalence of IOP elevations up to 5 mmHg 1 h postoperatively was similar in both groups, occurring in 18% of PM and in 15% of NPM. Elevations above 5 mmHg were seen in 4% of PM and 8% of NPM (P = 0.732). After correcting for age, gender, diagnosis, number of medications, and preoperative IOP, the presence or absence of AA PM had no significant association with any postoperative IOP (P > 0.5). Conclusion: The practice of using AAs before SLT and measuring IOP at 1 h has not been validated yet adds to expenses and workflow burden. Our retrospective study showed no significant correlation between PM and postoperative or longer‑term IOP. IOP at 1 h should be measured in patients who cannot tolerate transient pressure elevations. Further studies are needed to elucidate this relationship.

Effect of Alpha-1-Adrenergic Agonist, Midodrine for the Management of Long-Standing Neurogenic Shock in Patient with Cervical Spinal Cord Injury: A Case Report / 대한신경손상학회지

We report a rare case of a 71-year-old male patient who had suffered from long-lasting neurogenic shock for 13 weeks after cervical spinal cord injury (SCI) caused by a bicycle accident. The neurogenic shock was resolved dramatically 2 weeks after the administration of alpha-1-adrenergic agonist, midodrine hydrochloride. In usual cases, neurogenic shock tends to improve between 2 and 6 weeks after SCI; however, in a few cases, the shock lasts for several months. In our case, spinal shock lasted for 13 weeks and exhibited very sensitive decline of blood pressure for even a slight decrease of dopamine despite recovered bulbospongiosus reflex. Three days after midodrine hydrochloride was added, hypotension improved dramatically. We discuss our rare case with pertinent literatures.

Effect of dexmedetomidine on postoperative delirium in elderly patients with severe diseases / 中华老年医学杂志

Objective To observe the effect of dexmedetomidine anesthesia on postoperative delirium in elderly patients with severe diseases.Methods 67 elderly patients undergoing abdominal operation in our hospital from Jan.2014 to Oct.2014 were chosen as the research subjects,and randomly divided into the observation group (n =35) and the control group (n =32).In the observation group,35 cases were treated with dexmedetomidine in loading dose of 1 μg/kg and maintenance dose of 0.2 μg/kg.In the control group,32 cases were treated with the equal volume of saline instead of dexmedetomidine.The extubation time,recovery time and incidence of delirium were observed.Results The recovery time and extubation time were shorter in observation group than in control group[(18.4±6.9) min vs.(24.6± 7.4) min,(25.8 ±7.3) vs.(31.2±9.1) min,t=4.626,3.494,both P＜0.001].The incidence rate of postoperative delirium was lower in observation group much than in the control group (8.6％ vs.28.1％,x2 =7.063,P=0.008).Conclusions Dexmedetomidine anesthesia can significantly shorten the recovery time and extubation time,and reduce the incidence rate of postoperative delirium in elderly patients with severe diseases.

Effects of catecholamines on volemic replacement with saline solution and the impact on heart rate variability in rabbits subjected to hemorrhage. A study by spectral analysis

PURPOSE: To verify the effects of different catecholamines on volemic expansion and on the autonomic nervous system in rabbits that were subjected to hemorrhage. METHODS: Twenty four rabbits subjected to hemorrhage (with a 25% loss of blood volume) and were randomly divided into four experimental groups: 1) HEMO Group underwent replacement with their own blood in an equal volume; 2) SS Group underwent replacement with saline solution (SS) in a volume that corresponded to three times the removed blood volume; 3) ISP Group underwent replacement with SS and isoprenaline; 4) FNL Group underwent replacement with SS and phenylephrine. Spectral Analysis of the heart rate and heart rate variability were performed from the recorded data. Hematocrit was measured throughout the experiment. RESULTS: Replacement with SS and an α- or β-agonist did not produce differences in the intravascular retention compared to replacement with SS alone. An analysis of HRV showed that the FNL group maintained the LF/HF ratio better than ISP and SS. CONCLUSIONS: No difference in vascular retention when α- or β- agonists were added to SS during post-hemorrhagic recovery. The animals in the FNL group maintained the integrity of the autonomic response within normal physiological standards during hemorrhagic stress. .

Comparative study of nitric oxide production induced by selective estrogen receptors alpha and beta agonists in rats / Comparação da produção de óxido nítrico mediada por agonistas seletivos de receptores estrogênicos alfa e beta em ratos

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) is a potent vasodilator and estrogen-mediated vasodilation that increases NO production. The association of the vascular endothelium, gender and vasodilation induced by estrogen is due to the activation of two estrogen receptors, alpha (ERa) and beta (ERb). The aim of this study was to compare NO production stimulating receptors ERa and ERb with the use of selective agonists in thoracic aortas of rats. METHODS: Aortic rings were either treated with 17 ?-estradiol (17-BE2); acetylcholine (Ach); 4,4',4-[4-propil-(1H)-pirazol-1,3,5-triyl]tris-phenol (PPT), and 2,3-Bis(4-hydroxyphenyl)-propionitrile (DPN), or left untreated, and the concentration of NO was determined by spectrophotometry method. RESULTS: The females presented a higher basal concentration of nitrite than males. PPT determined increased production of nitrite in both females and males, compared to17-beta-estradiol (17-BE2). In males, the production of nitrite induced by DPN and PPT was higher than that induced by 17-BE2. The stimulation with 17-BE2 increased the production of nitrite in females compared to males. Regardless the gender, the stimulation of aortic rings by PPT caused a greater production of nitrite compared to that induced by 17-BE2. Interestingly, the stimulation of aortic rings from males with DPN provided an increase in the nitrite production compared to the levels induced by 17-BE2 incubation. CONCLUSION: The stimulation of estrogen receptor (ER) by PPT provides greater production of nitrite than 17-BE2 regardless of gender; in males, the stimulation of ER by DPN provides bigger production of nitrite than 17-BE2; the basal production of nitrite is higher in females compared to males.

JUSTIFICATIVA E OBJETIVOS: O óxido nítrico (NO) é um potente vasodilatador e o estrógeno promove vasodilatação aumentando a produção de NO. A associação entre endotélio vascular, gênero e vasodilatação induzida pelo estrógeno, é pela ativação de receptores estrogênicos, alfa (ERa) e (beta) ERb.O objetivo deste estudo foi comparar a produção de NO estimulando receptores estrogênicos, ERa e ERb, por agonistas seletivos em aorta torácica de ratos. MÉTODOS: Anéis aórticos foram tratados com 17 ?-estradiol (17-BE2), acetilcolina (Ach), 4,4',4-[4-propil-(1H)-pirazol-1,3,5-triyl]tris-fenol (PPT) e 2,3-Bis(4-hidroxifenil)-propionitrila (DPN) ou não tratados e a determinação de NO foi feita por método espectrofotométrico. RESULTADOS: As fêmeas apresentaram produção constitutiva basal de nitrito mais elevada do que os machos. O PPT causou elevação na produção de nitrito em ambos os sexos, em relação ao observado com 17-beta estradiol (17-BE2). Nos machos, PPT e DPN, aumentaram a produção de nitrito comparada àquela induzida por 17-BE2.A estimulação com 17-BE2 causou maior produção de nitrito em fêmeas que em machos. A incubação com PPT determinou maior produção de nitrito comparada àquela induzida por 17-BE2, independente do gênero. Interessantemente, em machos,a estimulação das artérias com DPN acarretou em elevação na produção de nitrito comparada ao efeito causado por 17-BE2.CONCLUSÃO: A estimulação de receptor estrogênico (ER) pelo PPT determina maior produção de nitrito do que 17-BE2 independente do gênero; a estimulação de ER pelo DPN determina maior produção de nitrito do que 17-BE2 em machos; a produção basal de nitrito é mais elevada em fêmeas comparada aos machos.

Evaluación de la efectividad y seguridad de los alfa agonistas para déficit atencional en población entre 6 y 19 años: revisión sistemática / Effectiveness and safety of alpha agonists for ADHD in population between 6 and 19 years: a systematic review

Introducción: el trastorno por déficit de atención e hiperactividad (TDAH) dispone de intervenciones farmacológicas y los psicoestimulantes son de primera opción; también se han usado otras alternativas como los alfa agonistas (clonidina), de las que es importante conocer su efectividad y seguridad. Objetivo: identificar, sintetizar y evaluar la mejor evidencia disponible sobre la efectividad y seguridad de los alfa agonistas en el tratamiento en déficit atencional en la población de 6 a 19 años. Métodos: se realizó una revisión sistemática de estudios de intervenciones, que evaluaron efectividad comparada entre alfa agonistas y metilfenidato, que se midió en términos de funcionamiento educacional, funcionamiento psicosocial, calidad de vida y efectos adversos, en las siguientes bases de datos hasta febrero de 2012 en inglés y castellano: PubMed, Lilacs, Cochrane, DARE y Guideline. Los artículos que cumplieron con criterios de inclusión, fueron evaluados por dos investigadores en forma independiente. Resultados: de los 34 estudios encontrados inicialmente, se incluyeron 3, entre ellos una revisión sistemática y 2 guías clínicas. Conclusiones: la clonidina puede ser un tratamiento eficaz de segundo y tercer nivel para los síntomas de TDAH, pero tiene un efecto menor que el de los estimulantes. Su uso se asocia con muchos efectos secundarios.

Introduction: Attention deficit hyperactivity disorder (ADHD) is generally treated with pharmacological interventions; psychostimulants are first choice. Other alternatives have been used such as alpha agonists (clonidine), hence it is important to know its effectiveness and safety. Purpose: To identify, synthesize and evaluate the best available evidence on the effectiveness and safety of alpha agonists in treating ADHD in the 6-19 year-old population. Methods: A systematic review of intervention studies that evaluated effectiveness comparing alpha agonists to methylphenidate was conducted. Outcomes measured were educational performance, psychosocial functioning, quality of life and adverse effects. The following databases were searched up to February 2012 in English and Spanish: PubMed/MEDLINE, Lilacs, Cochrane, DARE and National Guideline Clearinghouse. The articles that met the inclusion criteria were assessed by two researchers independently. Results: Of the 34 studies found initially, three were included, among which a systematic review and two clinical guidelines. Conclusions: Clonidine is considered an effective second and third line treatment for ADHD symptoms, but it is less effective than stimulants. Its use is associated with many side effects.

Efficacy of alpha-2 adrenergic agonists for prevention of postoperative cardiac adverse events in patients with coronary disease: a meta-analysis / 中华麻醉学杂志

Objective To evaluate the efficacy of α2 adrenergic agonists for the prevention of postoperative adverse cardiac events in patients with coronary disease.Methods MEDLINE,EMBASE,CINHAL,Web of Science,CBM and CNKI were searched to identify all randomized controlled trials on the efficacy of α2 adrenergic agonists for the prevention of postoperative cardiac complications following operation performed under general anesthesia in patients with coronary artery disease.The incidence of myocardial ischemia,myocardial infarction,bradycardia and hypotension were evaluated.Meta-analysis was conducted using the RevMan 5.1 software.Results Fifteen trials included 9 high-quality trials,4 medium-quality trials and 2 low-quality trials.A total of 3422 patients were included in this meta-analysis.1790 patients received α2 adrenergic agonists (clonidine and dexmedetomidine) and 1632 patients received placebo; 724 patients underwent non-cardiac surgery and 2698 patients underwent cardiac surgery.Meta-analysis indicated that α2 adrenergic agonists reduced incidence of myocardial infarction following non-cardiac surgery and myocardial ischemia following non-cardiac surgery and cardiac surgery.Alpha-2 adrenergic agonists significantly increased the incidence of postoperative bradycardia.Conclusion Alpha-2 adrenergic agonists can decrease postoperative cardiac adverse events in patients with coronary disease,but can induce bradycardia,and the efficacy of clonidine is consistent with that of dexmedetomidine.