The effects of selected sedatives on basal and stimulated serum cortisol concentrations in healthy dogs.

Background: Hormone assessment is typically recommended for awake, unsedated dogs. However, one of the most commonly asked questions from veterinary practitioners to the endocrinology laboratory is how sedation impacts cortisol concentrations and the adrenocorticotropic hormone (ACTH) stimulation test. Butorphanol, dexmedetomidine, and trazodone are common sedatives for dogs, but their impact on the hypothalamic-pituitary-adrenal axis (HPA) is unknown. The objective of this study was to evaluate the effects of butorphanol, dexmedetomidine, and trazodone on serum cortisol concentrations. Methods: Twelve healthy beagles were included in a prospective, randomized, four-period crossover design study with a 7-day washout. ACTH stimulation test results were determined after saline (0.5 mL IV), butorphanol (0.3 mg/kg IV), dexmedetomidine (4 µg/kg IV), and trazodone (3-5 mg/kg PO) administration. Results: Compared to saline, butorphanol increased basal (median 11.75 µg/dL (range 2.50-23.00) (324.13 nmol/L; range 68.97-634.48) vs 1.27 µg/dL (0.74-2.10) (35.03 nmol/L; 20.41-57.93); P < 0.0001) and post-ACTH cortisol concentrations (17.05 µg/dL (12.40-26.00) (470.34 nmol/L; 342.07-717.24) vs 13.75 µg/dL (10.00-18.90) (379.31 nmol/L; 275.96-521.38); P ≤ 0.0001). Dexmedetomidine and trazodone did not significantly affect basal (1.55 µg/dL (range 0.75-1.55) (42.76 nmol/L; 20.69-42.76); P = 0.33 and 0.79 µg/dL (range 0.69-1.89) (21.79 nmol/L; 19.03-52.14); P = 0.13, respectively, vs saline 1.27 (0.74-2.10) (35.03 nmol/L; 20.41-57.93)) or post-ACTH cortisol concentrations (14.35 µg/dL (range 10.70-18.00) (395.86 nmol/L; 295.17-496.55); (P = 0.98 and 12.90 µg/dL (range 8.94-17.40) (355.86 nmol/L; 246.62-480); P = 0.65), respectively, vs saline 13.75 µg/dL (10.00-18.60) (379.31 nmol/L; 275.86-513.10). Conclusion: Butorphanol administration should be avoided prior to ACTH stimulation testing in dogs. Further evaluation of dexmedetomidine and trazodone's effects on adrenocortical hormone testing in dogs suspected of HPA derangements is warranted to confirm they do not impact clinical diagnosis.

Prospective, randomised comparison of two intravenous sedation methods for magnetic resonance imaging in children.

BACKGROUND: Children usually need sedation or even anaesthesia for magnetic resonance imaging (MRI) studies. As there is no universally accepted method for this purpose we undertook a prospective, randomised comparison of propofol and dexmedetomidine in children aged 1 to 10 years. METHODS: After Institutional Board approval and parents' informed consent 64 ASA status I or II children scheduled for MRI scan were enrolled. Patients were premedicated with intravenous (IV) midazolam (0.1 mg kg -1 ) and ketamine (1 mg kg -1 ) and randomised to propofol (P) or dexmedetomidine (D) group. A propofol bolus of 1 mg kg -1 followed by infusion of 4 mg kg -1 h -1 , or dexmedetomidine 1 µg kg -1 followed by 2 µg kg -1 h-1 infusion were used. Heart rate, SpO 2 and non-invasive blood pressure were monitored and recorded at 5 min intervals. Results were compared by means of standard statistical methods. RESULTS: Both dexmedetomidine and propofol after premedication with ketamine and midazolam are suitable for MRI sedation, although propofol use results in shorter recovery time. Less interventions are needed when dexmedetomidine is used.

Recovery of driving skills after endoscopy under propofol sedation: a prospective pilot study to assess the driving skills after endoscopic sedation using driving simulation.

BACKGROUND: Patients are recommended not to drive for at least the first 24 h after endoscopy with propofol sedation. However, the evidence underlying these recommendations is scarce. We hypothesized that after endoscopic procedures performed under propofol sedation, the subject's driving ability was restored in less than 24 h. METHODS: We prospectively enrolled thirty patients between 20 and 70 years possessing a legitimate driver's license scheduled for endoscopy at our hospital. The sample chosen was a convenience sample. Gastroscopy or colonoscopy was performed with propofol sedation. Before and after endoscopy, the investigator drove the subjects to the laboratory to assess their driving skills using a driving simulation system, which employs 3 driving scenarios designed by professional transportation researchers. The blood propofol concentration was estimated before endoscopy, and 2 and 4 h after endoscopy. The primary outcome was the time required for subjects to recover their driving ability after propofol sedation. The secondary outcome was the blood propofol concentration before and after endoscopic procedures under propofol anesthesia. RESULTS: Thirty volunteers participated in the study and 18 of them completed all the interventions. In the low-risk S-curve scene, the mean acceleration, lane deviation, and number of deviations from the path at baseline (0.016 cm/s2, 42.50 cm, and 0.83, respectively) were significantly less than that at post-2 h (0.029 cm/s2, P = 0.001; 53.80 cm, P = 0.014; 2.06, P = 0.022). In the moderate-(overtaking) and high-risk (emergency collision avoidance) scenes, the tested parameters at baseline and post-2 h were statistically comparable. In the low-, moderate-, and high-risk scenes the tested parameters at baseline and post-4 h were statistically comparable. The total range of propofol was 120-280 mg.The mean blood concentration of propofol at post-2 h was 0.81 ± 0.40 µg/mL, and at post-4 h was below the limit of detection. CONCLUSION: After endoscopy performed under propofol sedation, subjects' driving abilities were completely restored at 4 h when tested on a simulator.

Safety, Pharmacokinetics, and Pharmacodynamics of Midazolam Gel After Rectal Administration in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVES: Midazolam rectal gel is a novel rectal formulation that may be a promising and potential alternative to oral administration for pediatric sedation. The objective of this study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and absolute bioavailability of midazolam rectal gel in healthy Chinese subjects. METHODS: An open-label, single-dose, randomized, two-period, two-treatment, crossover clinical study was conducted in 22 healthy subjects (16 males and six females), each receiving 2.5 mg intravenous midazolam in one period and 5 mg midazolam rectal gel in another period (the dosages here were calculated as active midazolam). Safety, pharmacokinetic, and pharmacodynamic assessments were conducted throughout the study. RESULTS: All of the subjects completed both treatment periods. The formulation of rectal gel was well tolerated, with no serious adverse events occurring. After a single rectal dose of 5 mg midazolam rectal gel, it was absorbed rapidly with a median value of time to peak concentration (Tmax) of 1.00 h, and mean values of the peak concentration (Cmax) and area under the concentration-time curve (AUC0-t) of 37.2 ng/mL and 137 h·ng/mL, respectively. The absolute bioavailability of rectal gel was 59.7%. The rectal gel exhibited a relatively delayed onset but a more stable sedative effect and a longer duration when compared with intravenous midazolam. CONCLUSION: Midazolam rectal gel may be a feasible alternative with a high level of acceptance in pediatric sedation and enhanced bioavailability compared to an oral formulation. The modeling results may help to disclose out the exposure-response relationship of midazolam rectal gel and support the design of an escalating-doses study and pediatric extrapolation study. CLINICAL TRIAL REGISTRATION: The study was registered at http://www.chinadrugtrials.org.cn (No. CTR20192350).

Halogenated anesthetics vs intravenous hypnotics for short and long term sedation in the intensive care unit: A meta-analysis / Anestésicos halogenados vs. hipnóticos intravenosos para sedación a corto y largo plazo en la unidad de cuidados intensivos: un metaanálisis

Objective To comprehensively assess peer-reviewed studies using volatile (VA) or intravenous (i/v) anesthetics for sedation in intensive care units (ICUs), with the hypothesis that the type of sedation may have an impact on survival and other clinically relevant outcomes. Design Systematic review and meta-analysis of randomized and non-randomized trials. Setting ICUs. Participants Critically ill and postoperative patients. Interventions None. Measurements and main results Studies comparing VA versus i/v anesthetics used in the ICU settings were independently systematically searched. Finally, 15 studies (1520 patients of predominantly surgical profile needed VA sedation for less than 96h) were included. VA had no impact on all-cause mortality (very low quality of evidence, Odds Ratio=0.82 [0.60–1.12], p=0.20). However, VA were associated with a reduction in duration of mechanical ventilation (p=0.03) and increase in ventilator-free days (p<0.001). VA also reduced postoperative levels of cardiac troponin (24h), time to extubation (p<0.001) and awakening (p=0.04). Conclusions In this meta-analysis, volatile sedation vs propofol caused the increase in ventilator-free days, the reduction in the duration of mechanical ventilation, time to extubation and the troponin release in medical or surgical ICU patients, while in surgical ICU patients the time to awakening was shortened (AU)

Objetivos Evaluar exhaustivamente los estudios revisados por pares que utilizan anestésicos volátiles (AV) o intravenosos (iv) para sedación en unidades de cuidados intensivos (UCI), con la hipótesis de que el tipo de sedación puede tener un impacto en la supervivencia y otros resultados clínicamente relevantes. Diseño Revisión sistemática y metaanálisis de ensayos aleatorizados y no aleatorizados. Ámbito UCI. Pacientes Se incluyeron críticamente enfermos y postoperatorios. Intervenciones Ninguna. Mediciones y resultados principales Los estudios que comparaban los AV vs. los anestésicos iv utilizados en la UCI se buscaron de forma independiente y sistemática. Finalmente, se incluyeron 15 estudios (1.520 pacientes de perfil predominantemente quirúrgico necesitaron sedación de AV durante menos de 96h). El AV no tuvo impacto en la mortalidad por cualquier causa (calidad de los datos probatorios muy baja, Odds Ratio=0,82 [0,60-1,12], p=0,20). Sin embargo, el AV se asoció con una reducción de la duración de la ventilación mecánica (p=0,03) y aumento de los días sin ventilación mecánica (p<0,001). La AV también redujo los niveles postoperatorios de troponina cardíaca (24 horas), el tiempo hasta la extubación (p<0,001) y el despertar (p=0,04). Conclusiones En este metaanálisis, la sedación volátil vs. propofol causó el aumento de los días sin ventilación, la reducción de la duración de la ventilación mecánica, el tiempo hasta la extubación y la liberación de troponina en pacientes de la UCI médica o quirúrgica, mientras que en pacientes de la UCI quirúrgica el tiempo hasta el despertar se acortó (AU)

Racial disparities in the pharmacological treatment of insomnia: A time-to-event analysis using real-world data.

OBJECTIVE: Examine the association between race and time to pharmacologic treatment of insomnia in a large multi-institutional cohort. METHODS: Retrospective analysis of electronic medical records from a regional health information exchange. Eligible patients included adults with at least one healthcare visit per year from 2010 to 2019, a new insomnia diagnosis code during the study period, and no prior insomnia diagnosis codes or medications. A Cox frailty model was used to examine the association between race and time to an insomnia medication after diagnosis. RESULTS: In total, 9557 patients were analyzed, 7773 (81.3%) of whom where White, 1294 (13.5%) Black, 238 (2.5%) Other, and 252 (2.6%) unknown race. About 6.2% of Black and 8% of Other race patients received an order for a Food and Drug Administration-approved insomnia medication after diagnosis compared with 13.5% of White patients. Black patients were significantly less likely to have an order for a Food and Drug Administration-approved insomnia medication at all time points (adjusted hazard ratio [aHR] range: 0.37-0.73), and patients reporting Other race were less likely to have received an order at 2 (aHR 0.51, 95% confidence interval [CI] 0.28-0.94), 3 (aHR 0.33, 95% CI 0.13-0.79), and 4 years (aHR 0.21, 95% CI 0.06-0.71) of follow-up. Similar results were observed in a sensitivity analysis including off-label medications. CONCLUSIONS: Patients belonging to racial minority groups are less likely to be prescribed an insomnia medication than White patients after accounting for sociodemographic and clinical factors. Further research is needed to determine the extent to which patient preferences and physician perceptions affect these prescribing patterns and investigate potential disparities in nonpharmacologic treatment.

The sedative effect of intranasal administration of medetomidine using a mucosal atomization device in Japanese White rabbits.

To prevent aspiration in Japanese White (JW) rabbits, the maximum single volume of medetomidine administered intranasally is 0.3 mL per nostril using a mucosal atomization device (MAD). This study aimed to examine the sedative effect of intranasal administration of medetomidine using MAD in eight healthy female JW rabbits. Each rabbit received intranasal atomization (INA) of saline (Control treatment) along with three doses of 1 mg/mL medetomidine (0.3 mL to one nostril [MED0.3 treatment]; 0.3 mL each to both nostrils [MED0.6 treatment]; 0.3 mL twice to both nostrils [MED1.2 treatment]), with a washout period of at least 7 days between treatments. The actual doses of medetomidine were 82 (75-84) µg/kg (median [25th-75th percentile]), 163 (156-168) µg/kg, and 323 (295-343) µg/kg for the MED0.3, MED0.6, and MED1.2 treatments, respectively. A medetomidine-dose dependent sedative effect was detected, and the loss of righting reflex (LRR) was achieved in one rabbit at 18 min, seven rabbits at 11 (9-18) min, and eight rabbits at 7 (4-18) min after the MED0.3, MED0.6, and MED1.2 treatments, respectively. The LRR was maintained for 63 (29-71) min and 83 (68-101) min after the MED0.6 and MED1.2 treatments, respectively. Additionally, the INA of medetomidine produced a significant dose-dependent cardiorespiratory depression including a decrease in pulse rate, respiratory rate, percutaneous oxygen saturation, and arterial partial pressure of oxygen, and an increase in arterial partial pressure of carbon dioxide in the rabbits.

Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration: A Randomized Clinical Trial.

Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent. Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation. Design, Setting, and Participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021. Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 µg/kg; n = 575) immediately after injection of a hypnotic. Main Outcomes and Measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%. Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%). Conclusions and Relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03960801.

Two-center randomized controlled trial comparing oral chloral hydrate and intranasal combination of dexmedetomidine and ketamine for procedural sedation in children: study protocol.

BACKGROUND: Oral chloral hydrate is widely used in pediatric sedation. Intranasal dexmedetomidine has been increasingly used for pediatric sedation; however, its improvement is warranted. The combination of dexmedetomidine with ketamine can improve onset and hemodynamic stability while maintaining sedative efficacy. This study aims to determine the efficacy and safety of intranasal combination of dexmedetomidine and ketamine compared to oral chloral hydrate. METHODS: This is a prospective, parallel-arm, single-blinded, two-center, superiority randomized controlled trial with 1:1 allocation, designed to compare the effects of intranasal combination of dexmedetomidine and ketamine with those of oral chloral hydrate. We shall enroll 136 patients aged < 7 years old in this study. Prior to the procedure, we shall randomize each patient into the control group (oral chloral hydrate 50 mg/kg) or study group (intranasal dexmedetomidine 2 µg/kg and ketamine 3 mg/kg). The primary outcome will be the rate of achieving an adequate sedation level (6-point Pediatric Sedation State Scale 1, 2, or 3) within 15 min. In addition, we shall measure the sedation time, sedation failure rate, completion of procedure, adverse events, patient acceptance, and physician satisfaction. DISCUSSION: This study will provide evidence of the efficacy and safety of the intranasal combination of dexmedetomidine and ketamine in comparison with oral chloral hydrate. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04820205. Registered on 19th March 2021.

Sedative use and incidence of falls and hip fractures among older adults in an outpatient geriatric clinic / Perfil de uso de sedativos e ocorrência de quedas e fratura de fêmur entre idosos em um ambulatório de geriatria

OBJECTIVE: To investigate the use of sedatives by older adults attending a private outpatient geriatric clinic in Belo Horizonte (MG), Brazil, and its association with falls and hip fractures. METHODS: Using a longitudinal design, the prevalence of benzodiazepine and nonbenzodiazepine ("z-drugs") intake by older adults was described and their association with the incidence of falls and fractures (30 days after the initial visit) was evaluated through logistic regression. RESULTS: A total of 7821 older adults were included in the study, most of them women (72.50%), with a mean age of 77.5 years and a mean Clinical-Functional Vulnerability Index (IVCF-20) score of 16.5. The overall prevalence of sedative use (any sedative) was 6.19%, with 4.48% benzodiazepines and 1.98% z-drugs. The most widely used sedatives were clonazepam (29.04%), zolpidem (28.65%), and alprazolam (23.44%). Falls were reported for 182 patients (2.33%), with a higher incidence among users of any sedatives (4.34; p = 0.002; OR = 1.94, adjusted for sex, age, and IVCF-20) and benzodiazepines (5.14%; p < 0.001; OR = 2.28) than among non-users (2.19%). Hip fractures occurred in 33 patients (0.42%), and again were more frequent among users of sedatives (1.03%; p = 0.032; OR = 2.57) and benzodiazepines (1.43%; p = 0.003; OR = 3.45) than among non-users (0.38%). CONCLUSIONS: The use of sedatives, especially benzodiazepines, is associated with an increased incidence of falls and hip fractures in older adults

OBJETIVO: Investigar a utilização de sedativos entre idosos atendidos em ambulatório privado de geriatria em Belo Horizonte (MG), bem como sua associação com quedas e fraturas de fêmur. METODOLOGIA: Trata-se de estudo longitudinal, no qual foi descrita a prevalência de uso de benzodiazepínicos e drogas Z entre idosos (60 anos ou mais) e avaliada sua associação com a incidência de queda e fratura (30 dias após consulta inicial) por meio de regressão logística. RESULTADOS: Foram incluídos no estudo 7821 idosos, com maioria feminina (72,50%), idade média de 77,5 anos e Índice de Vulnerabilidade Clínico Funcional (IVCF-20) médio de 16,5 pontos. A prevalência de uso de sedativos em geral foi de 6,19%, sendo 4,48% de benzodiazepínicos e 1,98% de drogas Z. Os medicamentos sedativos mais utilizados foram clonazepam (29,04%), zolpidem (28,65%) e alprazolam (23,44%). Relatou-se queda para 182 idosos (2,33%), com incidência maior entre usuários de sedativos (4,34; p = 0,002; OR = 1,94 ajustada por sexo, idade e IVCF-20) e de benzodiazepínicos (5,14%; p < 0,001; OR = 2,28) do que entre não usuários (2,19%). Identificou-se fratura de fêmur em 33 idosos (0,42%), sendo mais frequente entre usuários de sedativos (1,03%; p = 0,032; OR = 2,57) e de benzodiazepínicos (1,43%; p = 0,003; OR = 3,45) do que entre não usuários (0,38%). CONCLUSÃO: Concluiu-se que a incidência de quedas e fraturas de fêmur em idosos possui associação com o uso de medicamentos sedativos, em especial os benzodiazepínicos

Cardiopulmonary and propofol-sparing effects of dexmedetomidine in total intravenous anesthesia in cats undergoing ovariohysterectomy.

OBJECTIVES: This study aimed to assess the effect of dexmedetomidine on the propofol-based anesthesia of cats subjected to ovariohysterectomy. METHODS: Twenty-eight cats were randomly allocated to four groups (seven cats in each) and premedicated with either 5 µg/kg dexmedetomidine (groups Dex 1, Dex 3 and Dex 5) or 0.05 ml saline (Prop group) intramuscularly. After the induction of anesthesia with propofol, total intravenous anesthesia was initiated with 300 µg/kg/min propofol plus 3 ml/kg/h NaCl 0.9% (Prop), or 200 µg/kg/min propofol plus dexmedetomidine at the rates of 1 µg/kg/h (Dex 1), 3 µg/kg/h (Dex 3) or 5 µg/kg/h (Dex 5). Cardiorespiratory variables were assessed 5 mins after induction and every 10 mins thereafter, until the end of anesthesia. The propofol infusion rate was adjusted every 10 mins (± 50 µg/kg/min) to maintain anesthetic depth. The times to extubation, sternal recumbency, ambulation and total recovery were recorded. Pain scoring was performed 1, 2, 4, 8, 12 and 24 h after the end of anesthesia. RESULTS: Dexmedetomidine produced a propofol-sparing effect of 72.8%, 71.1% and 74.6% in the Dex 1, Dex 3 and Dex 5 groups, respectively. Cats in the Prop group maintained higher heart rate values than the other groups, and the mean arterial pressure remained higher in the Dex 3 and Dex 5 groups. Rescue intraoperative analgesia (fentanyl bolus) was most frequent in the Prop group. There was no significant difference in the time of extubation. Cats in the Dex 1 and Dex 3 groups had a faster anesthetic recovery, with shorter times to achieving sternal recumbency, regaining ambulation and reaching full recovery. Cats in the Dex 1 and Dex 5 groups presented the best recovery quality scores, with 4 (range 4-5) and 4 (range 3-5), respectively, while the Prop group scored 1 (range 1-3), the worst anesthetic recovery score among the groups. CONCLUSIONS AND RELEVANCE: The use of dexmedetomidine as a total intravenous anesthesia adjuvant, especially at doses of 1 and 3 µg/kg/h, reduces propofol consumption and improves cardiorespiratory stability and intraoperative analgesia, while promoting a better and quicker recovery from anesthesia.

Preoperative sedation in children with congenital heart disease: 50% and 95% effective doses, hemodynamic effects, and safety of intranasal dexmedetomidine.

STUDY OBJECTIVE: To determine the 50% and 95% effective doses (ED50 and ED95, respectively), hemodynamic effects, and safety of intranasal dexmedetomidine for preoperative sedation in pediatric patients with congenital heart disease (CHD) with a left-to-right shunt. DESIGN: Double-blind sequential allocation trial. SETTING: Pediatric preoperative waiting area. PATIENTS: 86 pediatric patients ASA physical status II-III scheduled for cardiac surgery, aged1-month to 6-years-old with left-to-right type CHD. INTERVENTIONS: Children were divided into three groups according to age: infants (1 month-1 year), toddlers (1-3 years), and preschoolers (3-6 years). The first patient in all groups received intranasal dexmedetomidine (2 µg/kg), using the up-and-down Dixon method, and the and the next patient's dose was dependent on the previous patient's response. MEASUREMENTS: Assessment using the Modified Observer's Assessment of Alertness/Sedation Scale and the Mask Acceptance Scale was performed before and every 5 min after treatment. Pulse oxygen saturation and heart rate were recorded at baseline, at 10-min intervals, and after admission to the operating room. Systolic pulmonary artery pressure was measured before anesthesia induction. MAIN RESULTS: The respective ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for preoperative sedation using intranasally administered dexmedetomidine were 3.1 (2.8-3.3) and 3.5 (3.3-4.0) µg/kg for infants; 3.4 (3.2-3.6) and 3.9 (3.7-4.4) µg/kg for toddlers; and 2.4 (2.2-2.6) and 2.9 (2.6-3.3) µg/kg for preschoolers. ED50 was lower for preschoolers than for toddlers (p < 0.001) and infants (p = 0.044). No obvious difference in ED50 was found between infants and toddlers. There was no significant difference in sedation onset time among the groups, and no adverse events were observed during sedation in all patients. CONCLUSIONS: Intranasal dexmedetomidine can be safety used for preoperative sedation in children with CHD and is effective for sedation when dosed appropriately. Trial registrationclinicaltrials.gov (ChiCTR2100047472); registered 20 June 2021.

A pilot study of ADRA2A genotype association with doses of dexmedetomidine for sedation in pediatric patients.

STUDY OBJECTIVE: Dexmedetomidine is titrated to achieve sedation in the pediatric and cardiovascular intensive care units (PICU and CVICU). In adults, dexmedetomidine response has been associated with an ADRA2A polymorphism (rs1800544); CC genotype is associated with an increased sedative response compared with GC and GG. To date, this has not been studied in children. DESIGN: We conducted a pilot study to determine whether ADRA2A genotype is associated with dexmedetomidine dose in children. MEASUREMENTS AND MAIN RESULTS: Forty intubated PICU or CVICU patients who received dexmedetomidine as a continuous infusion for at least 2 days were genotyped for ADRA2A with a custom-designed TaqMan® Assay. Ten (25%) subjects were wildtype (GG), 15 (37.5%) were heterozygous (GC), and 15 (37.5%) were homozygous (CC) variant. The maximum dexmedetomidine doses (mCg/kg/h) were not different between genotype groups CC (1, 0.3-1.2), GC (1, 0.3-1.3), and GG (0.8, 0.3-1.2), (p = 0.37); neither were mean dexmedetomidine doses for these respective genotype groups 0.68 (0.24-1.07), 0.72 (0.22-0.98), 0.58 (0.3-0.94), (p = 0.67). CONCLUSIONS: These findings did not confirm the results from adult studies where ADRA2A polymorphisms correlate with dexmedetomidine response, therefore highlighting the need for pediatric studies to validate PGx findings in adults prior to implementation in pediatrics.