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Many children with autism spectrum disorder (ASD) also have attention-deficit/hyperactivity disorder (ADHD). ADHD in children is associated with increased risk of negative outcomes, and early intervention is critical. Current guidelines recommend psychosocial interventions such as behavioral training as the first line of therapy in managing ADHD symptoms in children with or without ASD. Where symptoms are refractory to these interventions, medications such as stimulants, α2-adrenergic agonist inhibitors, selective norepinephrine reuptake inhibitors, and second-generation antipsychotics are recommended. However, these pharmacotherapies do not have regulatory approval for use in children of preschool age, and evidence on their safety and efficacy in this population has historically been very limited. Since publication of the current guidelines in 2020, several new randomized controlled trials and real-world studies have been published that have investigated the efficacy and tolerability of these medications in preschool children with ADHD, with or without comorbid ASD. Here, we provide a review of the key findings of these studies, which suggest that there is growing evidence to support the use of pharmacological interventions in the management of ADHD in preschool children with comorbid ASD.

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Hallucinogen-persisting perception disorder (HPPD), also known as acute hallucinogen-induced psychosis or informally known as "flashbacks," is an unusual condition experienced by patients due to the use of different hallucinogenic substances. Hallucinogen-persisting perception disorder causes many symptoms, predominantly persistent visual perception distortion instead of intermittent distortion. Although different hallucinogens could cause HPPD, lysergic acid diethylamide (LSD) and LSD-like properties seem to be the most common hallucinogens causing the symptoms. In our case report, the patient is a 28-year-old Caucasian male with a long psychiatric and social history of polysubstance use using LSD and cannabis. He started experiencing many of the classic symptoms of HPPD seven months after stopping LSD. The diagnosis is suspected by ruling out all other possible underlying causes with the help of several laboratory and imaging tests. Despite having an extensive psychiatric history of illnesses, the patient's symptoms failed to improve with antipsychotics, confirming that the symptoms were not only due to mental illness. Although supposedly the first-line treatment for HPPD is the use of alpha-2 adrenergic drugs such as clonidine and benzodiazepines, we started to witness improvement in patient's symptoms with the use of lamotrigine, which is the gold standard in treating perceptual disturbance in time and space.

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INTRODUCTION: Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent condition that causes persistent problems with attention and/or hyperactivity-impulsivity and often results in significant impairment when left untreated. Medications for this disorder continue to evolve and provide new treatment options. Ongoing review of related medication safety and tolerability remains an important task for prescribers. AREAS COVERED: This manuscript provides an updated safety review of medications used to treat ADHD in children and adolescents. PubMed and OneSearch online databases were utilized to search for literature relevant to the topic of ADHD medications and safety. Clinical trials of medications used to treat ADHD, systematic reviews and meta-analyses, and articles covering specific safety issues (adverse or unfavorable events) such as cardiovascular effects, seizures, impact on growth, depression, suicidal ideation, substance use disorders, psychosis, and tics are described. EXPERT OPINION: Available pharmacologic treatments for ADHD have favorable efficacy, safety and tolerability and allow many patients to achieve significant improvement of their symptoms. Despite the availability of multiple stimulant and non-stimulant formulations, some individuals with ADHD may not tolerate available medications or attain satisfactory improvement. To satisfy unmet clinical needs, ADHD pharmaceutical research with stimulant and nonstimulant formulations targeting dopamine, norepinephrine, and novel receptors is ongoing.

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Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Adolescente , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/efectos adversos , Metilfenidato/efectos adversos , Clorhidrato de Atomoxetina/uso terapéutico

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Background There is a need for improved strategies for managing abrupt opioid withdrawal when transitioning patients with opioid use disorder to comprehensive longitudinal care strategies such as naltrexone maintenance treatment. In addition, alpha-2 adrenergic agonists are used to ameliorate withdrawal symptoms, but current data characterizing real-world treatment are lacking. Methods A retrospective chart review was conducted in outpatients undergoing abrupt opioid withdrawal managed with lofexidine (0.18 mg, 1-4 tablets 4x daily for 7 days, pro re nata [PRN or as needed]) or clonidine (0.2 mg, 1 tablet 3x daily for 10 days, PRN). Withdrawal outcomes were characterized at 30 days of follow-up. Binomial logistic regression was used to assess a potential association of the two treatments with different likelihoods of opioid cessation success in this real-world outpatient practice. Results In cases treated with lofexidine (n=166) and clonidine (n=432), respectively, 40% and 10% were opioid-free, 6% and 2% continued long-term buprenorphine or methadone, 17% and 36% relapsed, and 37% and 52% were lost to follow-up at 30 days post-withdrawal. Among patients returning for follow-up care, 63% of patients treated with lofexidine and 21% treated with clonidine were opioid-free. Lofexidine was associated with a higher likelihood of opioid cessation success relative to clonidine (OR=6.47; Wald Chi-square=53.79, p<0.001). Conclusion Among outpatients returning for follow-up care, nearly two-thirds of those managed with lofexidine reached opioid-free status at 30 days post-withdrawal, which was a higher likelihood than those managed with clonidine, thus allowing their transition to comprehensive care, including naltrexone.

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Objectives: To determine whether conditions coexisting with attention-deficit/hyperactivity disorder (ADHD) in preschool-age children are associated with choice of stimulants or alpha-2 adrenergic agonists (A2As) and/or likelihood of improvement in ADHD symptoms. Methods: A retrospective electronic health record review of 497 children from 7 Developmental Behavioral Pediatrics Research Network (DBPNet) sites. Children were <72 months when treated with medication for ADHD from January 1, 2013 to July 1, 2017. We abstracted coexisting conditions, initial medication prescribed, and whether the medication was associated with improvement in symptoms. Analysis of improvement was adjusted for clustering by clinician and site. Results: The median (interquartile range) child age at the time of initiation of ADHD medication was 62 (54-67) months. The most common coexisting conditions included language disorders (40%), sleep disorders (28%), disruptive behavior disorders (22.7%), autism spectrum disorder (ASD; 21.8%), and motor disorders (19.9%). No coexisting conditions were present in 17.1%; 1 in 36.8%, 2 in 26.8%, and ≥3 in 19.3%. Stimulants were initially prescribed for 322 (64.8%) and A2A for 175 (35.2%) children. Children prescribed stimulants were more likely to have no coexisting conditions than those prescribed A2A (22.3% vs. 7.4%; p < 0.001). Coexisting ASD and sleep disorder were associated with increased likelihood of starting A2As versus stimulants (p < 0.0005; p = 0.002). The association between medication treatment and improvement varied by number of coexisting conditions for 0, 1, 2, or ≥3, respectively (84.7%, 73.8%, 72.9%, 64.6%; p = 0.031). Children with ≥3 coexisting conditions were less likely to respond to stimulants than children with no coexisting conditions (67.4% vs. 79.9%; p = 0.037). Conclusions: Among preschool-age children with ADHD, those with ≥3 coexisting conditions were less likely to respond to stimulants than those with no coexisting conditions. This was not found for A2A, but further research is needed as very few children with no coexisting conditions were treated with A2A.

Asunto(s)

Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Estimulantes del Sistema Nervioso Central , Trastornos del Sueño-Vigilia , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/tratamiento farmacológico , Estimulantes del Sistema Nervioso Central/uso terapéutico , Niño , Preescolar , Humanos , Estudios Retrospectivos , Trastornos del Sueño-Vigilia/tratamiento farmacológico

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BACKGROUND: We report a case of lorazepam-induced agitated delirium treated with haloperidol, which in turn triggered the onset of neuroleptic malignant syndrome (NMS). The latter condition, a medical emergency, was effectively treated with medical treatment and dexmedetomidine, a versatile and highly selective short-acting alpha-2 adrenergic agonist with sedative-hypnotic and anxiolytic effects. CASE SUMMARY: A 65-year-old man with a history of bipolar disorder presented to the emergency department with severe abdominal discomfort after binge eating. During his hospital stay, he received intravenous lorazepam for insomnia. On the next day, he became delirious and was thus treated with seven doses (5 mg each) of haloperidol over a 48 h period. Signs of NMS (hyperthermia, rigidity, myoclonus of upper limbs, impaired consciousness, tachypnea, and dark urine) became apparent and haloperidol was immediately suspended and brisk diuresis was initiated. On intensive care unit admission, he was confused, disoriented, and markedly agitated. Dexmedetomidine infusion was started with the goal of achieving a Richmond Agitation-Sedation Scale score of -1 or 0. NMS was resolved gradually and the patient stabilized, permitting discontinuation of dexmedetomidine after 3 d. CONCLUSION: Dexmedetomidine may be clinically helpful for the management of NMS, most likely because of its sympatholytic activity.

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BACKGROUND: The potent sedative medetomidine is a commonly used adjunct for the immobilisation of non-domestic mammals. However, its use is associated with pronounced cardiovascular side effects, such as bradycardia, vasoconstriction and decreased cardiac output. We investigated the effects of the peripherally-acting alpha-2-adrenoceptor antagonist vatinoxan on cardiovascular properties in medetomidine-tiletamine-zolazepam anaesthetised wild boar (Sus scrofa). METHODS: Twelve wild boars, anaesthetised twice with medetomidine (0.1 mg/kg) and tiletamine/zolazepam (2.5 mg/kg) IM in a randomised, crossover study, were administered (0.1 mg/kg) vatinoxan or an equivalent volume of saline IV (control). Cardiovascular variables, including heart rate (HR), mean arterial blood pressure (MAP), pulmonary artery pressure (PAP), pulmonary artery occlusion pressure (PAOP) and cardiac output (CO), were assessed 5 min prior to vatinoxan/saline administration until the end of anaesthesia 30 min later. RESULTS: MAP (p < 0.0001), MPAP (p < 0.001) and MPAOP (p < 0.0001) significantly decreased from baseline after vatinoxan until the end of anaesthesia. HR increased significantly (p < 0.0001) from baseline after vatinoxan administration. However, the effect on HR subsided 3 min after vatinoxan. All variables remained constant after saline injection. There was no significant effect of vatinoxan or saline on CO. CONCLUSION: Vatinoxan significantly reduced systemic and pulmonary artery hypertension, induced by medetomidine in wild boar.

Asunto(s)

Medetomidina , Zolazepam , Animales , Estudios Cruzados , Frecuencia Cardíaca , Hipnóticos y Sedantes/farmacología , Medetomidina/farmacología , Quinolizinas , Sus scrofa , Porcinos , Tiletamina/farmacología , Zolazepam/farmacología

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RESUMO O manejo cardíaco, ventilatório e renal no ambiente de terapia intensiva tem melhorado nas últimas décadas. Cognição e sedação representam dois dos últimos desafios a vencer. Como a sedação convencional não é ideal, e a sedação evocada por agonistas adrenérgicos alfa-2 (sedação "cooperativa" com dexmedetomidina, clonidina ou guanfacina) representa uma alternativa valiosa, este artigo abrange três tópicos práticos para os quais há lacunas na medicina baseada em evidência. O primeiro deles é a mudança de sedação convencional para sedação cooperativa ("mudança"): a resposta curta consiste em retirada abrupta de sedação convencional, implantação imediata de infusão de um agonista alfa-2 e uso de "sedação de resgate" (bolos de midazolam) ou "sedação agressiva" (haloperidol em bolos) para estabilizar a sedação cooperativa. O segundo tópico é a mudança de sedação convencional para sedação cooperativa em pacientes instáveis (por exemplo: delirium tremens refratário, choque séptico, síndrome do desconforto respiratório agudo etc.), pois, para evitar a hipotensão e a bradicardia provocadas por desativadores simpáticos, a resposta curta é manter o volume sistólico por administração de volume, vasopressores e inotrópicos. Por fim, para evitar essas mudanças e dificuldades associadas, os agonistas alfa-2 podem ser sedativos de primeira linha. A resposta curta é administrar agonistas alfa-2 lentamente desde a admissão ou intubação endotraqueal, até estabilização da sedação cooperativa. Dessa forma, conclui-se que os agonistas alfa-2 são, ao mesmo tempo, agentes desativadores simpáticos e sedativos, bem como a desativação simpática implica na manutenção do volume sistólico e na avaliação persistente da volemia. A medicina baseada em evidência deve documentar esta proposta.

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ABSTRACT Cardiac, ventilatory and kidney management in the critical care setting has been optimized over the past decades. Cognition and sedation represent one of the last remaning challenges. As conventional sedation is suboptimal and as the sedation evoked by alpha-2 adrenergic agonists ("cooperative" sedation with dexmedetomidine, clonidine or guanfacine) represents a valuable alternative, this manuscript covers three practical topics for which evidence-based medicine is lacking: a) Switching from conventional to cooperative sedation ("switching"): the short answer is the abrupt withdrawal of conventional sedation, immediate implementation of alpha-2 agonist infusion and the use of "rescue sedation" (midazolam bolus[es]) or "breakthrough sedation" (haloperidol bolus[es]) to stabilize cooperative sedation. b) Switching from conventional to cooperative sedation in unstable patients (e.g., refractory delirium tremens, septic shock, acute respiratory distress syndrome, etc.): to avoid hypotension and bradycardia evoked by sympathetic deactivation, the short answer is to maintain the stroke volume through volume loading, vasopressors and inotropes. c) To avoid these switches and associated difficulties, alpha-2 agonists may be considered first-line sedatives. The short answer is to administer alpha-2 agonists slowly from admission or endotracheal intubation up to stabilized cooperative sedation. The "take home" message is as follows: a) alpha-2 agonists are jointly sympathetic deactivators and sedative agents; b) sympathetic deactivation implies maintaining the stroke volume and iterative assessment of volemia. Evidence-based medicine should document our propositions.

Asunto(s)

Humanos , Clonidina , Dexmedetomidina , Cuidados Críticos , Agonistas de Receptores Adrenérgicos alfa 2 , Hipnóticos y Sedantes

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We focused on tweets containing hashtags related to ADHD pharmacotherapy between 20 September and 31 October 2019. Tweets were classified as to whether they described medical issues or not. Tweets with medical content were classified according to the topic they referred to: side effects, efficacy, or adherence. Furthermore, we classified any links included within a tweet as either scientific or non-scientific. We created a dataset of 6568 tweets: 4949 (75.4%) related to stimulants, 605 (9.2%) to non-stimulants and 1014 (15.4%) to alpha-2 agonists. Next, we manually analyzed 1810 tweets. In the end, 481 (48%) of the tweets in the stimulant group, 218 (71.9%) in the non-stimulant group and 162 (31.9%) in the alpha agonist group were considered classifiable. Stimulants accumulated the majority of tweets. Notably, the content that generated the highest frequency of tweets was that related to treatment efficacy, with alpha-2 agonist-related tweets accumulating the highest proportion of positive consideration. We found the highest percentages of tweets with scientific links in those posts related to alpha-2 agonists. Stimulant-related tweets obtained the highest proportion of likes and were the most disseminated within the Twitter community. Understanding the public view of these medications is necessary to design promotional strategies aimed at the appropriate population.

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Introduction: To assess drug plasma levels, preanesthetic sedation, cardiopulmonary effects during anesthesia and recovery in horses anesthetized with isoflurane combined with medetomidine or xylazine. Study design: Prospective blinded randomized clinical study. Animals: Sixty horses undergoing elective surgery. Methods: Thirty minutes after administration of antibiotics, flunixine meglumine or phenylbutazone and acepromazine horses received medetomidine 7 µg kg-1 (group MED) or xylazine 1.1 mg kg-1 (group XYL) slowly intravenously (IV) and sedation was assessed 3 min later. Anesthesia was induced with ketamine/diazepam and maintained with isoflurane in oxygen/air and medetomidine 3.5 µg kg-1 h-1 or xylazine 0.69 mg kg-1 h-1. Ringer's acetate 10 mL kg-1 h-1 and dobutamine were administered to maintain normotension. All horses were mechanically ventilated to maintain end-tidal carbon dioxide pressures at 45 ± 5 mmHg (5.3-6.7 kPa). Heart rate (HR), invasive arterial blood pressures, inspired and expired gas compositions, pH, arterial blood gases, electrolytes, lactate and glucose were measured. For recovery all horses received intramuscular morphine 0.1 mg kg-1 and medetomidine 2 µg kg-1 or xylazine 0.3 mg kg-1 IV. Recovery was timed and scored using three different scoring systems. Plasma samples to measure medetomidine and xylazine concentrations were collected at predetermined timepoints. Repeatedly measured parameters were analyzed using a two-way repeated-measures analysis of variance for differences between groups and over time; p < 0.05 was considered statistically significant. Results: Mean arterial blood pressures (MAP) stayed within normal ranges but were higher (p = 0.011) in group XYL despite significant lower dobutamine doses (p = 0.0003). Other measured parameters were within clinically acceptable ranges. Plasma levels were at steady state during anesthesia (MED 2.194 ± 0.073; XYL 708 ± 18.791 ng mL-1). During recovery lateral recumbency (MED 42.7 ± 2.51; XYL 34.3 ± 2.63 min; p = 0.027) and time to standing (MED 62.0 ± 2.86; XYL 48.8 ± 3.01 min; p = 0.002) were significantly shorter in group XYL compared to group MED. Recovery scores did not differ significantly between groups. Conclusion and Clinical Relevance: In horses anesthetized with isoflurane and medetomidine or xylazine, xylazine maintained higher MAP, reduced the dobutamine consumption and recovery time, whilst overall recovery quality was unaffected.

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Alpha2 -adrenergic agonists have been implicated in the development of pulmonary edema (PE) and sustained hypoxemia that lead to life-threatening pulmonary distress in ruminants, especially with sensitive and compromised animals. Recently, there is limited understanding of exact mechanism underlying pulmonary alterations associated with α2 -adrenergic agonist administration. Ruminants have a rich population of pulmonary intravascular macrophages (PIMs) in the pulmonary circulation, which may be involved in the development of pulmonary alveolo-capillary barrier damage. Hence, the central thesis of this review is overviewing the literatures regarding the systemic use of α2 -adrenergic agonists in domestic ruminants, focusing on their pulmonary side effects, especially on the influence of PIMs on the lung. At this moment, further studies are needed to provide a clear emphasis and better understanding of the potential role of PIMs in the lung pathophysiology associated with α2 -adrenergic agonists. These preliminary studies would be potentially to develop future medications and intervention targets that may be helpful to alleviate or prevent the critical striking pulmonary effects, and thereby improving the safety of α2 -agonist application in ruminants.

Asunto(s)

Anestésicos , Edema Pulmonar , Agonistas de Receptores Adrenérgicos alfa 2/efectos adversos , Animales , Hipoxia/inducido químicamente , Hipoxia/veterinaria , Macrófagos , Edema Pulmonar/inducido químicamente , Edema Pulmonar/veterinaria , Rumiantes

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A presente pesquisa comparou os efeitos cardiorrespiratórios, hemogasométricos e sedativos da associação midazolam (0,41mg/kg) e butorfanol (0,31mg/kg) acrescida de detomidina (157µg/kg) (DTMB) ou dexmedetomidina (36µg/kg) (DXMB) em catetos. Catetos adultos (n=20) foram distribuídos em dois grupos, DTMB ou DXMB. As variáveis (FC, f, PAM, SpO2, EtCO2 e TR) foram avaliadas após aplicação dos fármacos. A sedação foi avaliada por meio de escala analógica visual, relaxamento muscular, postura e resposta auditiva. Foi realizada ANOVA, seguida de teste t pareado (paramétricos) e teste de Mann-Whitney rank-sum test (não paramétricos), com P<0,05. Não foi observada diferença estatística entre os grupos para o período de latência. Observou-se diferença significativa entre grupos para as variáveis f, PAM e SpO2, com maiores valores para DTMB, e EtCO2, com maiores valores para DXMB. Os dois grupos apresentaram redução da FC e da concentração de lactato, bem como aumento da concentração de bicarbonato. A SpO2 permaneceu abaixo de 90%, durante todo o período experimental, nos dois grupos estudados. Os animais dos dois grupos apresentaram sedação profunda e relaxamento muscular máximo. Conclui-se que os dois protocolos testados proporcionaram adequada sedação, podendo ser indicados para contenção química de catetos adultos.(AU)

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The study compared the cardiorespiratory, hemogasometric and sedative effects of the combination of midazolam (0.41mg/kg) and butorphanol (0.31mg/kg) plus detomidine (157µg/kg) (DTMB) or dexmedetomidine (36µg/kg) (DXMB) in collared peccaries. Collared peccaries (n= 20) were divided into two groups, either DTMB or DXMB. The variables (FC, f, PAM, SpO2, EtCO2 and TR) were evaluated after application of the drugs. Sedation was assessed by visual analogue scale, muscle relaxation, posture and auditory response. ANOVA followed by paired t-test (parametric) and Mann Whitney Rank Sum Test (non-parametric) with P< 0.05 were performed. No statistical difference was observed for the latency period. A significant increase was observed between groups for the variables f, PAM and SpO2 with higher values for DTMB and EtCO2 with higher values for DXMB. The two groups presented a reduction in HR and lactate concentration, and an increase in bicarbonate concentration. SpO2 remained below 90% throughout the experiment in both groups. The animals of the two groups presented deep sedation and maximum muscle relaxation. It is concluded that the two protocols tested provided adequate sedation and could be indicated for chemical containment of collared peccaries.(AU)

Asunto(s)

Animales , Artiodáctilos/fisiología , Midazolam/administración & dosificación , Butorfanol/administración & dosificación , Dexmedetomidina/administración & dosificación , Capacidad Cardiovascular , Anestésicos Combinados/análisis , Agonistas de Receptores Adrenérgicos alfa 2

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Aim: To evaluate the sedative and clinical effects of I/V xylazine, detomidine, medetomidine and dexmedetomidine in miniature donkeys.Methods: Seven clinically healthy, male adult miniature donkeys with a mean age of 6 years and weight of 105 kg, were assigned to five I/V treatments in a randomised, cross-over design. They received either 1.1 mg/kg xylazine, 20 µg/kg detomidine, 10 µg/kg medetomidine, 5 µg/kg dexmedetomidine or saline, with a washout period of ≥7 days. The degree of sedation was scored using a 4-point scale by three observers, and heart rate (HR), respiration rate (RR), rectal temperature and capillary refill time (CRT) were recorded immediately before and 5, 10, 15, 30, 60, 90 and 120 minutes after drug administration.Results: All saline-treated donkeys showed no sedation at any time, whereas the donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine had mild or moderate sedation between 5 and 60 minutes after treatment, and no sedation after 90 minutes. All animals recovered from sedation without complication within 2 hours. The mean HR and RR of saline-treated donkeys did not change between 0 and 120 minutes after administration, but the mean HR and RR of donkeys treated with xylazine, detomidine, medetomidine and dexmedetomidine declined between 5 and 60 minutes after drug administration. The mean rectal temperature of all treated donkeys did not change between 0 and 120 minutes after administration. The CRT for all donkeys was ≤2 seconds at all times following each treatment.Conclusions and clinical relevance: Administration of xylazine at 1.1 mg/kg, detomidine at 20 µg/kg, medetomidine at 10 µg/kg and dexmedetomidine at 5 µg/kg resulted in similar sedation in miniature donkeys. Therefore any of the studied drugs could be used for sedation in healthy miniature donkeys.

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Equidae/fisiología , Hipnóticos y Sedantes/farmacología , Imidazoles/farmacología , Xilazina/farmacología , Animales , Dexmedetomidina/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Irán , Masculino , Medetomidina/farmacología , Frecuencia Respiratoria/efectos de los fármacos

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The high number of patients infected with the SARS-CoV-2 virus requiring care for ARDS puts sedation in the critical care unit (CCU) to the edge. Depth of sedation has evolved over the last 40 years (no-sedation, deep sedation, daily emergence, minimal sedation, etc.). Most guidelines now recommend determining the depth of sedation and minimizing the use of benzodiazepines and opioids. The broader use of alpha-2 adrenergic agonists ('alpha-2 agonists') led to sedation regimens beginning at admission to the CCU that contrast with hypnotics+opioids ("conventional" sedation), with major consequences for cognition, ventilation and circulatory performance. The same doses of alpha-2 agonists used for 'cooperative' sedation (ataraxia, analgognosia) elicit no respiratory depression but modify the autonomic nervous system (cardiac parasympathetic activation, attenuation of excessive cardiac and vasomotor sympathetic activity). Alpha-2 agonists should be selected only in patients who benefit from their effects ('personalized' indications, as opposed to a 'one size fits all' approach). Then, titration to effect is required, especially in the setting of systemic hypotension and/or hypovolemia. Since no general guidelines exist for the use of alpha-2 agonists for CCU sedation, our clinical experience is summarized for the benefit of physicians in clinical situations in which a recommendation might never exist (refractory delirium tremens; unstable, hypovolemic, hypotensive patients, etc.). Because the physiology of alpha-2 receptors and the pharmacology of alpha-2 agonists lead to personalized indications, some details are offered. Since interactions between conventional sedatives and alpha-2 agonists have received little attention, these interactions are addressed. Within the existing guidelines for CCU sedation, this article could facilitate the use of alpha-2 agonists as effective and safe sedation while awaiting large, multicentre trials and more evidence-based medicine.

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PURPOSE: To determine the effect of topical brimonidine tartrate prophylaxis on intraocular pressure (IOP) spikes following intravitreal injection of antivascular endothelial growth factor (anti-VEGF) agents. METHODS: This is a randomised crossover trial of consecutive non-glaucomatous eyes receiving intravitreal anti-VEGF injections between December 2016 and July 2017. All eyes were randomly assigned to no prophylaxis or topical brimonidine tartrate 0.15 % administered 20 min prior to injection in one of two consecutive visits. Measurements of IOP were obtained immediately (T0), 10 min (T10) and 20 min (T20) after injection during the visits with and without prophylaxis. RESULTS: Among the 58 eyes of 55 patients (116 visits), the mean (SD) age was 74.3 (11.6), and 62% were female. The mean baseline IOP was 15.3 (2.3) mm Hg (range: 11-20). On average, the immediate postinjection IOP during the visit without prophylaxis was 41.6 (12) mm Hg (range: 17-81). Compared with no prophylaxis, the visit with preadministered topical brimonidine tartrate had a lower IOP at T0 (p<0.001), T10 (p=0.001) and T20 (p=0.043), and a smaller proportion of eyes with IOP elevation of greater than 20 mm Hg from preinjection (p=0.002) and IOP greater than 50 mm Hg at T0 (p=0.036). Without prophylaxis, two eyes (two patients) had an IOP of greater than 70 mm Hg at T0 and thus underwent anterior chamber paracentesis. CONCLUSION: Topical brimonidine tartrate prophylaxis for intravitreal injection of anti-VEGF agents effectively reduces IOP spikes in non-glaucomatous eyes and may be easily incorporated into ophthalmologists' current practice. TRIAL REGISTRATION NUMBER: NCT03513172.

Asunto(s)

Inhibidores de la Angiogénesis/efectos adversos , Antihipertensivos/uso terapéutico , Tartrato de Brimonidina/uso terapéutico , Presión Intraocular/efectos de los fármacos , Hipertensión Ocular/prevención & control , Administración Oftálmica , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Bevacizumab/efectos adversos , Bevacizumab/uso terapéutico , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Inyecciones Intravítreas , Degeneración Macular/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Hipertensión Ocular/inducido químicamente , Soluciones Oftálmicas , Estudios Prospectivos , Ranibizumab/efectos adversos , Ranibizumab/uso terapéutico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Tonometría Ocular , Resultado del Tratamiento

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OBJECTIVE: To study the effect of clonidine administrated as a co-analgesic during scoliosis surgery, on the neuromonitoring of spinal motor pathways. METHODS: Using standardized intraoperative monitoring, we compared the time course of peripherally and transcranially electrically evoked motor potentials (TcEMEPs) before and after injection of a single bolus of clonidine in children under total intravenous anesthesia (TIVA). MEP data were obtained from 9 patients and somatosensory evoked potentials (SSEPs) were obtained from 2 patients. The potential effect of clonidine on mean blood pressure (BP) was controlled. RESULTS: TcEMEPs from upper and lower limbs rapidly showed significant drops in amplitude after the injection of clonidine. Amplitudes reached minimal values within five minutes and remained very weak for at least 10-20minutes during which monitoring of the central motor pathways was severely compromised. SSEPs were not altered during maximal amplitude depression of the TcEMEPS. CONCLUSIONS: This is the first report showing that clonidine severely interferes with neuromonitoring of the spinal cord motor pathways. The results are discussed in light of the literature describing the effects of dexmedetomidine, another α-2 adrenergic agonist. The experimental and literature data point to central mechanisms taking place at both the spinal and cerebral levels. Therefore, clonidine as well as other α-2 adrenergic agonists should be used with extreme caution in patients for whom neuromonitoring of the motor pathways is required during surgery.

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Clonidina/uso terapéutico , Potenciales Evocados Motores/efectos de los fármacos , Potenciales Evocados Somatosensoriales/efectos de los fármacos , Monitoreo Intraoperatorio , Escoliosis/cirugía , Adolescente , Niño , Clonidina/administración & dosificación , Potenciales Evocados Motores/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Femenino , Humanos , Masculino , Monitoreo Intraoperatorio/métodos , Estudios Retrospectivos , Escoliosis/tratamiento farmacológico

RESUMEN

The use of sheep in experiments is widespread and is increasing worldwide, and so is the need to develop species-specific anaesthetic techniques to ensure animal safety. Previous studies have mentioned several protocols involving the administration of alpha-2 adrenergic agonists in sheep; however, assessment of the efficacy and safety of these infusion techniques is still relatively new. Thus, the aim of the present study is to assess the effectiveness of detomidine constant rate infusion (CRI) in sheep by measuring the cardiovascular and respiratory parameters, blood gas variables and sedation scores. Eight adult female Santa Inês sheep received 20 µg/kg of detomidine hydrochloride intravenously as a bolus loading dose, followed by an infusion rate of 60 µg/kg/h. The heart rates and respiratory rates changed continuously during the CRI period. No arrhythmias were observed. The reduction in arterial partial pressure of oxygen (PaO2) was not significant, but one animal showed signs of hypoxaemia (minimum PaO2 of 66.9 mmHg). The arterial partial pressure of carbon dioxide (PaCO2) increased, but the animals did not become hypercapnic. The bicarbonate (HCO3-), pH and base excess (BE) tended towards metabolic alkalosis. The cardiac output (CO), stroke volume (SV), cardiac index (CI) and ejection fraction (EF%) showed no significant changes. The fractional shortening (FS%) decreased slightly, starting at T45min. Sedation scores varied between 3 (0/10) after sedation and during recovery and 7 (0/10) during CRI. We concluded that administering detomidine at an infusion rate of 60 µg/kg/h in Santa Inês sheep is a simple technique that produces satisfactory sedation for minimally invasive procedures.

Asunto(s)

Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes/efectos adversos , Imidazoles/efectos adversos , Frecuencia Respiratoria/efectos de los fármacos , Ovinos/fisiología , Animales , Análisis de los Gases de la Sangre , Sedación Consciente , Femenino , Infusiones Intravenosas

RESUMEN

Objetivou-se comparar as alterações cardiorrespiratórias e a analgesia pós-operatória promovidas pela dexmedetomidina e pelo tramadol, quando associados ao midazolam, em felinas. Para tal, foram selecionadas 18 gatas hígidas, divididas em dois grupos randomizados: GDM, tratadas com dexmedetomidina (10µg/kg) e GTM, tratadas com tramadol (2mg/kg), ambos associados a midazolam (0,2mg/kg,) IM. Após 15 minutos, procedeu-se à indução anestésica com propofol (1,46±0,79mL), mantendo-se a anestesia com isoflurano. As felinas foram submetidas à ovário-histerectomia, registrando-se as variáveis cardiorrespiratórias 15 minutos após a MPA (M0), 15 minutos após a indução (M15) e sequencialmente a cada cinco minutos, até o término do procedimento cirúrgico (M20, M25, M30, M35 e M40). A avaliação da dor iniciou-se 30 minutos após o término do procedimento cirúrgico (MP30) e sequencialmente em intervalos de 30 minutos (MP60, MP90, MP120). A partir do MP120, as avaliações foram registradas a cada hora (MP180, MP240 e MP360). A associação dexmedetomidina-midazolam infere diminuição inicial de frequência cardíaca (FC) sem significado clínico e está relacionada à sedação mais pronunciada, à analgesia menor e menos duradoura e a episódios de êmese, quando comparada à associação tramadol-midazolam. Ambos os protocolos denotaram estabilidade cardiorrespiratória e podem ser considerados seguros em felinas submetidas à ovário-histectomia.(AU)

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The aim of this study was to compare cardiorespiratory changes and post-operative analgesia provided by dexmedetomidine or tramadol, associated with midazolam, in female cats. For that purpose, 18 healthy cats were assigned to two randomized groups: GDM, which received dexmedetomidine (10 µg/kg) and GTM, which received tramadol (2 mg/kg), both associated with midazolam (0.2 mg/kg) IM. After 15 minutes, anesthesia was induced with propofol (1.46±0.79 mL) and maintained with isofluorane. Ovariohysterectomy was performed and cardiorespiratory variables were registered 15 minutes after pre-anesthetic medication (M0), 15 minutes after anesthetic induction (M15), and every five minutes until the end of the surgical procedure (M20, M25, M30, M35 e M40). Pain evaluation started 30 minutes after the surgery (MP30) and sequentially at thirty-minute intervals (MP60, MP90, MP120). After MP120, each evaluation was registered at every hour (MP180, MP240 e MP360). Dexmedetomidine-midazolam association results in decreases on initial heart rate (HR) without clinical relevance and it is related to pronounced sedation, poor and less durable antinociception and vomiting events, when compared to tramadol-midazolam association. Both protocols indicate cardiorespiratoy stability and safety in cats undergoing ovariohysterectomy.(AU)

Asunto(s)

Animales , Femenino , Gatos , Dexmedetomidina/análisis , Isoflurano/uso terapéutico , Midazolam/análisis , Tramadol/análisis , Anestésicos Combinados/uso terapéutico , Histerectomía/veterinaria , Ovariectomía/veterinaria , Frecuencia Respiratoria

RESUMEN

OBJECTIVE: To compare the effects of two balanced anaesthetic protocols (isoflurane-dexmedetomidine versus medetomidine) on sedation, cardiopulmonary function and recovery in horses. STUDY DESIGN: Prospective, blinded, randomized clinical study. ANIMALS: Sixty healthy adult warm blood horses undergoing elective surgery. METHODS: Thirty horses each were sedated with dexmedetomidine 3.5 µg kg-1 (group DEX) or medetomidine 7 µg kg-1 (group MED) intravenously. After assessing and supplementing sedation if necessary, anaesthesia was induced with ketamine/diazepam and maintained with isoflurane in oxygen/air and dexmedetomidine 1.75 µg kg-1 hour-1 or medetomidine 3.5 µg kg-1 hour-1. Ringer's lactate (7-10 mL kg-1 hour-1) and dobutamine were administered to maintain normotension. Controlled mechanical ventilation maintained end-tidal expired carbon dioxide pressures at 40-50 mmHg (5.3-6.7 kPa). Heart rate, invasive arterial blood pressure, inspired and expired gas composition and arterial blood gases were measured. Dexmedetomidine 1 µg kg-1 or medetomidine 2 µg kg-1 was administered for timed and scored recovery phase. Data were analysed using two-way repeated-measures analysis of variance and chi-square test. Significance was considered when p≤0.05. RESULTS: In group DEX, significantly more horses (n=18) did not fulfil the sedation criteria prior to induction and received one or more supplemental doses, whereas in group MED only two horses needed one additional bolus. Median (range) total sedation doses were dexmedetomidine 4 (4-9) µg kg-1 or medetomidine 7 (7-9) µg kg-1. During general anaesthesia, cardiopulmonary parameters did not differ significantly between groups. Recovery scores in group DEX were significantly better than in group MED. CONCLUSIONS AND CLINICAL RELEVANCE: Horses administered dexmedetomidine required more than 50% of the medetomidine dose to reach equivalent sedation. During isoflurane anaesthesia, cardiopulmonary function was comparable between the two groups. Recovery scores following dexmedetomidine were better compared to medetomidine.

Asunto(s)

Anestesia por Inhalación/veterinaria , Anestésicos por Inhalación , Sedación Profunda/veterinaria , Dexmedetomidina , Hipnóticos y Sedantes , Isoflurano , Medetomidina , Anestesia por Inhalación/métodos , Animales , Sedación Profunda/métodos , Dexmedetomidina/administración & dosificación , Femenino , Caballos , Hipnóticos y Sedantes/administración & dosificación , Inyecciones Intravenosas/veterinaria , Masculino , Medetomidina/administración & dosificación

RESUMEN

BACKGROUND AND AIMS: Alpha (α-2) adrenergic agonists have both analgesic and sedative properties when used as an adjuvant in regional anesthesia. A prospective randomized double-blind study was carried out to evaluate the efficacy of epidural route and to compare the efficacy and clinical profile of dexmedetomidine and clonidine as an adjuvant to bupivacaine with special emphasis on their quality of analgesia, sedation and the ability to provide the smooth intra-operative and postoperative course. MATERIAL AND METHODS: The study was conducted in prospective, randomized and double-blind manner. It included 60 American Society of Anesthesiologists Class I and II patients undergoing lower limb surgery under epidural anesthesia. Patients were randomly divided into Group A receiving 0.5% isobaric bupivacaine 15 ml with dexmedetomidine 1 µg/kg and Group B receiving 0.5% isobaric bupivacaine 15 ml with clonidine 2 µg/kg epidurally. Onset and duration of sensory and motor blocks, duration of analgesia, sedation, and adverse effects were assessed. RESULTS: Demographic data, surgical characteristics cardio-respiratory parameters, side-effect profile were comparable and statistically not significant in both the groups. However, sedation scores with dexmedetomidine were better than clonidine and turned out to be statistically significant. The onset times for sensory and motor blocks were significantly shorter in Group A as compared to Group B. The duration of analgesia and motor block was significantly longer in A Group as compared to Group B. CONCLUSION: Dexmedetomidine is a superior neuraxial adjuvant to bupivacaine when compared to clonidine for early onset of analgesia, superior intra-operative analgesia, stable cardio-respiratory parameters, prolonged postoperative analgesia and providing patient comfort.