Novel Use of Clonidine Patch to Treat Tizanidine Withdrawal.

Tizanidine is commonly prescribed for muscle spasticity and pain. Yet, withdrawal is rarely reported. Tizanidine stimulates presynaptic α-2 adrenergic and imidazoline receptors decreasing norepinephrine release. Abrupt cessation can cause withdrawal. Current treatment strategies include tapering oral tizanidine or substituting oral clonidine. A 52-year-old male with a history of hypertension, diabetes, coronary artery disease, and chronic back pain presented with altered mental status, agitation, hypertensive emergency (blood pressure: 250/145 mmHg), and tachycardia. The patient had been prescribed tizanidine for chronic back pain for two years and had recently run out with suspicion of misuse. Tizanidine withdrawal was diagnosed, and he improved with 0.1 mg oral clonidine three times daily weaned over five days while hospitalized. One month later the patient was admitted for persistent hypertension, tachycardia, diaphoresis, and anxiety. Alpha-2 agonist withdrawal was again diagnosed. Utilizing a clonidine patch taper may offer a reasonable approach in patients with tizanidine withdrawal.

Sedative and cardiorespiratory effects of dexmedetomidine alone or combined with acepromazine in healthy cats.

The purpose of this study was to assess sedation, emesis and cardiovascular effects of dexmedetomidine alone or combined with acepromazine in healthy cats. Fourteen male cats aged 0.9 ± 0.5 years and weighing 3.7 ± 0.7 kg were randomly assigned to one of two experimental groups: GD, dexmedetomidine 5 µg/kg; and GDA, dexmedetomidine 5 µg/kg with acepromazine 0.03 mg/kg, all intramuscularly. Measurements were recorded at baseline, at 20 minutes and then at 10-minute intervals following sedation and included heart rate (HR), respiratory rate (FR), systolic arterial pressure (SAP), rectal temperature (RT), number of episodes of emesis and sedation score (0-4). Data were compared using ANOVA for repeated measures followed by Sídák and Dunnet test. Sedation scores were compared between groups at T20 using Mann-Whitney test. Significance was considered when P <0.05. At T20, HR was significantly lower in GDA (99 ± 14 beats/min) compared with GD (133 ± 19 beats/min) and SAP was significantly lower in both groups compared with baseline (126 ± 14 vs. 148 ± 26 and 111 ± 13 vs. 144 ± 17 mmHg in GD and GDA, respectively). Duration of sedation was similar between groups, although sedation scores differed significantly at T20, with 1 (0-4) in GD and 4 (4-4) in GDA. More episodes of emesis were recorded in GD compared with GDA. The combination of dexmedetomidine and acepromazine produced more profound sedation with faster onset and lower incidence of emesis compared with dexmedetomidine alone in healthy cats.

Alpha Alert: Utilization of Transdermal Clonidine for Refractory Agitation.

Alpha-2 agonists are under-recognized for their class effects yet offer potential benefit in specialty palliative care via decreasing sympathetic output, inducing sedation, and modulating pain. Especially in clinical contexts where agitation predominates and patients are intolerant of oral medication route, transdermal medication delivery is advantageous. We report a case of agitated behaviors in setting of mixed Alzheimer/vascular-type dementia limiting hospital discharge to nursing facility that were ameliorated with transdermal clonidine. We suggest palliative clinicians routinely conceptualize the seemingly disparate alpha-2 agonists as a class for effective symptom palliation especially as new clinical evidence becomes available.

Evaluation of the use of intranasal atipamezole to reverse the sedative effects of xylazine in dogs.

OBJECTIVE: To assess the ability of intranasal atipamezole to reverse sedative effects of xylazine in dogs. DESIGN: Prospective proof-of-concept study. SETTING: University research laboratory. ANIMAL: Six healthy, staff-owned dogs. INTERVENTIONS: Dogs were sedated with 1.1 mg/kg of xylazine intravenously. The sedation score of each dog was recorded every 5 minutes until they achieved a sedation score of >13/21 for 3 readings. Once achieved, 0.3 mg/kg of atipamezole was administered intranasally using a mucosal atomization device. Sedation scores continued to be recorded every 5 minutes until successful reversal was achieved (<4/21). MEASUREMENTS AND MAIN RESULTS: Average times to standing and normal wakefulness after administration of intranasal atipamezole were 6 minutes, 30 seconds and 7 minutes, 20 seconds, respectively. CONCLUSIONS: Intranasal atipamezole successfully reversed the sedation effects of xylazine. The findings of this study provide justification for future controlled prospective studies into the potential use of intranasal atipamezole in a variety of settings including exposure to xylazine in operational canines as well as bioavailability studies for optimal dosing.

Dexmedetomidine as an Adjunct in a Fluoroscopically Guided Stellate Ganglion Block for Complex Regional Pain Syndrome.

Complex regional pain syndrome (CRPS) is a chronic pain disorder characterized by pain that is disproportionate to the inciting event. Autonomic and inflammatory responses predominate, and treatment plans that explicitly target these responses reduce symptoms for longer periods of time, are typically better tolerated, and have more favorable outcomes. Our patient was a young male who presented with a four-month history of a road traffic accident (RTA) that resulted in a fractured left distal radius and scaphoid. His main complaint was pain and discomfort, even after surgical forearm stabilization, as well as hyperesthesia, restricted range of motion, and new-onset tremors. The patient was provisionally diagnosed with complex regional pain syndrome (CRPS) and booked for a fluoroscopically guided stellate ganglion block when the oral medication regime provided minimal relief. A stellate ganglion block was administered using a combination of ropivacaine, methylprednisolone, and dexmedetomidine under fluoroscopic guidance. During our routine outpatient follow-ups, our patient's pain score on the visual analog scale (VAS) fell to zero, the burning, vasomotor, and temperature abnormalities subsided, and he gradually regained the use of his left forearm and hand. The etiology of complex regional pain syndrome is multifaceted. Early identification and therapy typically halt the progression. Long-term outcomes are improved by treatment strategies that target inflammatory and autonomic responses. Dexmedetomidine has a mild anti-nociceptive action when used as an adjuvant in peripheral nerve blocks and ganglion blocks, blocking pain transmission in Aδ and C fibers. We feel that by combining dexmedetomidine and a stellate ganglion block, we could provide immediate and long-term relief to our patient. More research is needed to monitor and analyze the efficacy of dexmedetomidine as a treatment for chronic pain syndromes such as CRPS.

The Role of Alpha-2 Agonists for Attention Deficit Hyperactivity Disorder in Children: A Review.

INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can affect academic, social, and personal functioning in children and adolescents. This review summarizes clinical trials demonstrating the effectiveness of Alpha-2 agonists in reducing symptoms of inattention, hyperactivity, and impulsivity in children with ADHD. Studies were identified through a systematic search of PubMed and Cochrane databases. However, these medications' long-term safety and efficacy remain uncertain, with a lack of data on their effects on growth, cardiovascular function, and other adverse events. Further studies are required to determine these medications' optimal dose and treatment duration. METHODS: Medications that target the noradrenergic system, such as Alpha-2 agonists, have been increasingly used as a treatment option for ADHD, with guanfacine and clonidine being two of the most commonly used medications. They function by selectively targeting Alpha-2 adrenergic receptors in the brain leading to improved attention and reduced hyperactivity and impulsivity symptoms in children with ADHD. RESULTS: Clinical trials have demonstrated the effectiveness of Alpha-2 agonists in treating ADHD in children by reducing symptoms of inattention, hyperactivity, and impulsivity. However, these medications' long-term safety and efficacy still need to be completely understood. Due to a lack of information on the effects of Alpha-2 agonists on growth, cardiovascular function, and other long-term adverse events, more studies must investigate the optimal dose and treatment duration for these medications. CONCLUSIONS: Despite these concerns, Alpha-2 agonists remain a valuable treatment option for ADHD in children, especially those unable to tolerate stimulant medications or who have coexisting conditions such as tic disorders. Future research should continue to explore the safety and efficacy of Alpha-2 agonists in the long term. In conclusion, Alpha-2 agonists show promise as a treatment for ADHD in children; however, the safety and efficacy of these drugs in the long term are not yet completely understood. Additional studies are required to investigate the optimal dose and treatment duration for these medications in their use as a treatment for this debilitating disease.

A Retrospective Analysis of Guanfacine for the Pharmacological Management of Delirium.

Background Delirium is a syndrome of acute brain failure that represents a change from an individual's baseline cognitive functioning characterized by deficits in attention and multiple aspects of cognition that fluctuate in severity over time. The symptomatic management of delirium's behavioral manifestations remains difficult. The alpha-2 agonists, dexmedetomidine and clonidine, are efficacious, but their potential cardiovascular adverse effects limit their utilization. Guanfacine is an oral alpha-2 agonist with a lower potential for such adverse outcomes; however, its use in delirium has not been studied. Methods A retrospective descriptive analysis of guanfacine for managing hyperactive or mixed delirium at Tampa General Hospital from January 2020 to October 2020 was conducted. The primary outcome was the time reduction in acute sedative administration. Secondary outcomes included renewed participation in physical therapy or occupational therapy (PT/OT), decreased opioid use, and an incidence of cardiovascular adverse effects. Results One hundred forty-nine patients were identified as having received guanfacine for managing delirium during the study period. All experienced a reduction in acute sedative use after the initiation of guanfacine. In 93 patients receiving PT/OT and no longer participating due to behavioral agitation, 74% had a documented renewal of services within four days. Of 112 patients on opioids, 70% experienced a 25% reduction in opioid administration within four days. No patients experienced consecutive episodes of hypotension that required a change in their clinical care. Two patients experienced a single episode of consecutive bradycardia that led to the discontinuation of guanfacine.  Conclusions Based on our retrospective study, guanfacine is a well-tolerated medication for the management of delirium. Even in medically and critically ill patients, cardiovascular adverse events were rare with guanfacine. Patients treated with guanfacine experienced decreased acute sedative use for behavioral agitation. Additionally, patients treated with guanfacine received fewer opioids and were better able to participate in PT/OT. Future studies with prospective, randomized, placebo-controlled designs are warranted to evaluate this promising intervention for delirium further.

Autonomic and hemodynamic effects of pre-anesthetic use of clonidine in healthy dogs.

The aim of this study was to evaluate the effects of pre-anesthetic use of clonidine on time-domain heart rate variability (HRV) and arterial blood pressure in healthy anesthetized dogs. Six healthy adult mixed-breed dogs were administered a clonidine (clonidine group, CLG) and 30 days later, a placebo (control group, CG) preanesthetic protocol, in addition to propofol, isoflurane, and an bolus of tramadol and the continuous infusion thereafter. The total time mean values of HRV meanNN, SDNN, SDANN, SDNNI, and rMSSD were higher in the CL group, as observed in some HRV variables on tramadol bolus time (T4), tramadol continuous infusion (T8), and tracheal extubation time (T10). No significant differences in arterial blood pressure were observed, however, two dogs had a second-degree atrioventricular block (Mobitz II) at the tramadol bolus time (T4). These results led us to conclude that the clonidine anesthetic protocol resulted in sympathetic outflow block and an increase in parasympathetic tone, without significant effects on blood pressure. Notably, cardiac electrical disturbance in two dogs in the CL group. Although the pre-anesthetic use of clonidine in dogs with fear-based behavioral problems should be considered, its association with tramadol should be avoided or carried out with caution owing to the existing cardiovascular risk.

Neste estudo objetivou-se avaliar os efeitos da administração pré-anestésica de clonidina na variabilidade da frequência cardíaca no domínio do tempo (VFC) e pressão arterial sanguínea de cães saudáveis anestesiados. Seis cães adultos hígidos, sem raça definida, foram submetidos a ambos protocolos anestésicos, com clonidina (grupo clonidina - GCL) e placebo (grupo controle - GC), associado ao propofol, isoflurano, bolus e infusão contínua de tramadol. Considerando o do tempo total de análise, os valores médios das variáveis de VFC NNmédio (GC=584.5±62.77, GCL=680.5±75.01), SDNN (GC=97.83±28.94, GCL=163.8±49.81), SDANN (GC=63.83±21.55, GCL=102.3±32.89), SDNNI (GC=60.83±28.53, GCL= 110.2±42.92) e rMSSD (GC=75.83±38.91, GCL=158.0±81.20) foram maiores no protocolo anestésico com clonidina, assim como também observado em algumas variáveis de VFC durante o tempo de administração do bolus (T4) (NNmédio: GC=643,70±123,10, GCL= 819,80±78,77) e infusão contínua (T8) (NNmédio: CG=599,20±35,66, CLG=785,00±52,13) de tramadol, assim como no tempo de extubação orotraqueal (T10) (NNmédio: GC=598,70±84,75, GCL=852,50±188,60; SDNN: GC=49,83±33,49, GCL=193,80±143,40; rMSSD: GC=43,50±33,86, GCL=314,20±294,60). Nenhuma diferença significativa na pressão arterial sanguínea foi observada, porém, dois cães apresentaram bloqueio atrioventricular de segundo grau (Mobitz II) no momento de aplicação do bolus de tramadol (T4). Assim, o protocolo anestésico com uso de clonidina resultou em bloqueio eferente simpático e aumento do tônus simpático, sem efeitos significativos sobre a pressão arterial, mas com ocorrência de distúrbio elétrico de condução cardíaco em dois cães. Embora o uso pré-anestésico de clonidina em cães com problemas comportamentais baseados no medo deva ser considerado, sua associação com tramadol deve ser evitada ou realizada com cautela devido ao risco cardiovascular existente.

Immobilization of Captive Kulans (Equus hemionus kulan) Without Using Ultrapotent Opioids.

Etorphine is widely used in zoological medicine for the immobilization of large herbivores. All reported immobilization protocols for kulans use etorphine as the primary immobilizing agent. However, etorphine can trigger severe side effects and is highly toxic for humans, its availability is occasionally limited for use in wildlife medicine. Therefore, two different alpha-2 agonist-based protocols for the general anesthesia of kulans were investigated and compared with the standard etorphine immobilization. In total, 21 immobilizations were performed within the scope of routine husbandry management at the Serengeti-Park Hodenhagen. Kulans were darted using a ketamine-medetomidine-midazolam-butorphanol (KMMB) protocol (n = 8, treatment group (TG) 1), a tiletamine-zolazepam-medetomidine-butorphanol (TZMB) protocol (n = 7, treatment group (TG) 2), or an etorphine-acepromazine-detomidine-butorphanol (EADB) protocol (n = 6, control group). Vital parameters included heart rate, respiratory rate, arterial blood pressure (invasive), end tidal CO2 (etCO2), electromyography and core body temperature, which were all assessed every 10 min. For blood gas analysis, arterial samples were collected 15, 30, 45 and 60 min after induction. Subjective measures of quality and efficacy included quality of induction, immobilization, and recovery. Time to recumbency was longer for TG 1 (9.00 ± 1.67 min) and TG 2 (10.43 ± 1.79 min) compared to the induction times in the control group (5.33 ± 1.93 min). Treatment group protocols resulted in excellent muscle relaxation, normoxemia and normocapnia. Lower pulse rates combined with systolic arterial hypertension were detected in the alpha-2 agonist-based protocols. However, only in TZMB-immobilized kulans, sustained severe systolic arterial hypertension was observed, with significantly higher values than in the TG 1 and the normotensive control group. At 60 min following induction, medetomidine and detomidine were antagonized with atipamezole IM (5 mg/mg medetomidine or 2 mg/mg detomidine), etorphine and butorphanol with naltrexone IV (2 mg/mg butorphanol or 50 mg/mg etorphine), and midazolam and zolazepam with flumazenil IV (0.3 mg per animal). All three combinations provided smooth and rapid recoveries. To conclude, the investigated treatment protocols (KMMB and TZMB) provided a safe and efficient general anesthesia in kulans with significantly better muscle relaxation, higher respiration rates and improved arterial oxygenation compared with the immobilizations of the control group. However, the control group (EADB) showed faster recoveries. Therefore, EADB is recommended for ultra-short immobilizations (e.g., microchipping and collaring), especially with free-ranging kulans where individual recovery is uncertain, whereas the investigated treatment protocols are recommended for prolonged medical procedures on captive kulans.

A Comprehensive Review of the Use of Alpha 2 Agonists in Spinal Anesthetics.

BACKGROUND: Spinal Anesthesia was the first regional anesthetic technique to be performed. It was performed by Dr. August Bier, known for the Bier block, and his colleagues on August 16, 1898. Dr. Bier opted for, what he referred to at the time as "cocainization of the spinal cord" by introducing 15 mg of cocaine intrathecally prior to the operation. The surgery was largely uneventful and painless. The patient only experienced some vomiting and a headache postoperatively. Dr. Bier's use of neuraxial anesthesia aimed to directly inject local anesthetics in and around the central nervous system (CNS) for more direct control of pain and anesthesia. Local anesthetics were an important discovery in anesthesiology. However, since the advent of local anesthetics and spinal anesthesia as an alternative technique to general anesthesia, much has been learned about both the benefits and adverse effects of local anesthetics. It was quickly learned that use of local anesthetics would be limited by their potential for life-threatening toxic effects. For this reason, there was a push towards development of novel local anesthetics that had a larger therapeutic window with less likelihood of serious side effects. In addition to developing newer local anesthetics, the idea of adding adjuvants provided an opportunity to potentially limit the life-threatening events. These adjuvants would include medications such as epinephrine and alpha-2 agonists, such as clonidine and dexmedetomidine. Other adjuvants include opioids, glucocorticoids, and mineralocorticoids. OBJECTIVES: In this review, we will delve further into the indications, contraindications, uses, mechanisms, and future of spinal anesthesia and its adjuvants. STUDY DESIGN: A literature review of recent publications in the field of alpha 2 agonists used in spinal anesthetics was carried out from 2015 to present day. Consensus opinions were formulated in various areas. SETTING: This literature review was carried out at various medical universities throughout the nation and Europe. LIMITATIONS: As research has only just begun in this field data is limited at this time. CONCLUSIONS: The use of spinal anesthesia provides a reliable dermatome blockade to facilitate many different surgical procedures. The combination of local anesthetics with opioid medications within the subarachnoid space has been the standard of care. Adjuvant medications like alpha 2 agonists may play a significant role in prolonging spinal blockade as well as limiting cardiovascular complications such as hypotension and bradycardia. The use of alpha 2 agonists instead of opioid medications intrathecally decreases pruritus and delayed respiratory depression. Animal models have demonstrated the synergistic effects of utilizing alpha 2 agonists with opioids in the subarachnoid space. The addition of clonidine to fentanyl and local anesthetic demonstrated a shorter time to neural blockade, but no significant change in duration of the spinal. Interestingly alpha 2 agonists with local anesthetics showed increase block duration compared to opioid with local anesthetics. Further human trials need to be undertaken to analyze the effectiveness of alpha 2 agonists in the intrathecal space, but preliminary data does indicate it is an exemplary alternative to opioids.

A Comparative Study of Intrathecal Hyperbaric Bupivacaine 0.5% with Morphine and Dexmedetomidine in Lower Limb Orthopedic Surgeries: A Double-Blind Randomized Clinical Trial.

Background: Pain and its alleviation have been a challenge for humans for centuries. Sub arachnoid block is most commonly practiced method for anaesthesia for lower limb surgeries. Adjuvants like opioids and alpha 2 agonists have proven benefits in augmentation of effects of local anaesthetics for spinal anesthesia. The aim of this study was to compare the effects of morphine and dexmedetomidine for sub arachnoid block in lower limb orthopaedic surgeries. Material and Methods: This is a prospective randomised controlled trial done in 120 patients who were posted for lower limb orthopaedic surgery. Along with bupivacaine, Group A received intrathecal dexmedetomidine while group B received intrathecal morphine. Results: the demographic profile was comparable in both the groups. The mean duration of motor block in Group A was 359.33 ± 34.4 and in Group B was 265.71 ± 28.47. The duration of rescue analgesia was almost double in Group A as compared to Group B with P < 0.0001 (CL 95%). Conclusion: Intrathecal dexmedetomidine and morphine both provided good postoperative analgesia. Dexmedetomidine provided a longer duration of analgesia than morphine, thereby increasing the time for first rescue analgesia, but at the cost of greater side effects.

Incidence of Fever Associated With Dexmedetomidine in the Adult Intensive Care Unit.

BACKGROUND: Published literature has described the temporal relationship of dexmedetomidine with elevated temperatures, but there is limited data to quantify the incidence of fever in ICU patients receiving dexmedetomidine. OBJECTIVE: The primary objective of this study was to estimate the incidence of temperature greater than or equal to 38.5°C in ICU patients receiving dexmedetomidine. METHODS: This was a retrospective cohort study of ICU patients who received dexmedetomidine with a propensity-matched subgroup analysis comparing dexmedetomidine fever patients to non-fever patients. Patients 18 years of age and older admitted between November 2017 and August 2018 who received continuous dexmedetomidine for 6 or more hours were eligible for inclusion. Included patients with a temperature of great than or equal to 38.5°C while receiving dexmedetomidine were established as having dexmedetomidine-related fever. RESULTS: Of 882 eligible ICU patients, 404 dexmedetomidine patients were included in the study. Sixty-one patients (15.1%) met the definition for the primary endpoint. Forty-two patients who received dexmedetomidine but experienced no fever were matched for multivariate analysis. The fever group received a higher mean maximum infusion rate (0.98 µg/kg/h ± 0.43 vs. 0.68 µg/kg/h ± 0.42, P < 0.001) and a longer median duration of dexmedetomidine (43.0 hours [range 7-711] vs. 24.3 hours [6-148], P = 0.001) compared to the non-fever group. CONCLUSION: Fever greater than 38.5°C was observed in 15.1% of ICU patients while receiving dexmedetomidine. Prospective studies are warranted to validate these findings.

Is the Sympathetic System Detrimental in the Setting of Septic Shock, with Antihypertensive Agents as a Counterintuitive Approach? A Clinical Proposition.

Mortality in the setting of septic shock varies between 20% and 100%. Refractory septic shock leads to early circulatory failure and carries the worst prognosis. The pathophysiology is poorly understood despite studies of the microcirculatory defects and the immuno-paralysis. The acute circulatory distress is treated with volume expansion, administration of vasopressors (usually noradrenaline: NA), and inotropes. Ventilation and anti-infectious strategy shall not be discussed here. When circulation is considered, the literature is segregated between interventions directed to the systemic circulation vs. interventions directed to the micro-circulation. Our thesis is that, after stabilization of the acute cardioventilatory distress, the prolonged sympathetic hyperactivity is detrimental in the setting of septic shock. Our hypothesis is that the sympathetic hyperactivity observed in septic shock being normalized towards baseline activity will improve the microcirculation by recoupling the capillaries and the systemic circulation. Therefore, counterintuitively, antihypertensive agents such as beta-blockers or alpha-2 adrenergic agonists (clonidine, dexmedetomidine) are useful. They would reduce the noradrenaline requirements. Adjuncts (vitamins, steroids, NO donors/inhibitors, etc.) proposed to normalize the sepsis-evoked vasodilation are not reviewed. This itemized approach (systemic vs. microcirculation) requires physiological and epidemiological studies to look for reduced mortality.

Cardiorespiratory, Sedative and Antinociceptive Effects of a Medetomidine Constant Rate Infusion with Morphine, Ketamine or Both.

Standing surgery under sedation reduces anesthetic-related mortality in horses. Medetomidine, alone and combined with morphine in a constant rate infusion (CRI), has been described for standing surgery but their cardiorespiratory, sedative and antinociceptive effects have never been compared. The addition of ketamine could improve analgesia in these procedures with minimal cardiorespiratory consequences. The objectives were to compare the cardiorespiratory effects, quality of sedation, antinociception and ataxia produced by administration of a medetomidine-based CRI with morphine, ketamine or both, in standing horses. A prospective, blind, randomized crossover, experimental design with six healthy adult horses was performed, in which four treatments were administered to all horses with at least two weeks of washout period: medetomidine (M); medetomidine and ketamine (MK); medetomidine and morphine (MMo); and medetomidine, morphine and ketamine (MMoK). Dosages were the same in all treatment groups: medetomidine at 5 µg/kg bwt followed by 5 µg/kg bwt/h, ketamine at 0.4 mg/kg/h and morphine at 50 µg/kg bwt, followed by morphine 30 µg/kg bwt/h. Drug infusions were maintained for 120 min. Cardiorespiratory variables, sedation degree and antinociceptive effects were evaluated during the procedure. All combinations produced similar sedation and antinociceptive effects and no clinically relevant alterations in cardiorespiratory variables occurred. Medetomidine CRI combined with morphine, ketamine or both are suitable and safe protocols for standing sedation in horses and the addition of morphine and/or ketamine did not cause any negative effect but no improving effect on sedation and antinociception was detected.

Pharmacological treatment for Tourette syndrome in children and adults: What is the quality of the evidence? A systematic review.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterised by involuntary muscle movements manifesting as motor and vocal tics. In the majority, tics are manageable without medication. Where tics cause discomfort or impair function, behavioural or pharmaceutical treatments may be considered. AIMS: To provide a meticulous examination of the quality of evidence for the current pharmacological treatments for TS. METHODS: PubMed and Google Scholar were searched to identify randomised, placebo-controlled trials (RCTs) of aripiprazole, risperidone, clonidine, guanfacine, haloperidol, pimozide, tiapride and sulpiride for the treatment of tics in children and adults with TS. Quality of reporting and risk of bias were assessed against the CONSORT checklist and Cochrane risk of bias criteria, respectively. RESULTS: Seventeen RCTs were identified. Response rates reached 88.6% for aripiprazole, 68.9% for clonidine, 62.5% for risperidone and 19% for guanfacine. Statistically significant improvements were reported for all medications compared to placebo in at least one study and for at least one measure of tic severity. Most studies predated the CONSORT and Cochrane criteria and did not score highly when assessed on these measures. CONCLUSIONS: There are relatively few placebo-controlled trials of commonly prescribed medications. Studies are often of poor quality and short duration. There is evidence for the efficacy of each medication, but no drug is clearly superior. Clonidine and guanfacine are better tolerated than antipsychotics, but less effective. There is too little evidence to determine whether adults respond differently from children.

Evaluation of intramuscular sodium nitroprusside injection to improve oxygenation in white-tailed deer (Odocoileus virginianus) anesthetized with medetomidine-alfaxalone-azaperone.

OBJECTIVE: In ungulates, α2-adrenergic agonists can decrease oxygenation possibly through alteration of pulmonary perfusion. Sodium nitroprusside can decrease pulmonary vascular resistance (PVR) and increase cardiac output (Q˙t) through vasodilation. The objective was to determine if sodium nitroprusside would improve pulmonary perfusion and attenuate the increased alveolar-arterial (a-a) gradient resulting from medetomidine-azaperone-alfaxalone (MAA) administration. STUDY DESIGN: Prospective, randomized, crossover study with a 2 week rest period. ANIMALS: A group of eight adult female captive white-tailed deer (Odocoileus virginianus). METHODS: Deer were administered MAA intramuscularly (IM), and auricular artery and pulmonary artery balloon catheters were placed. Deer spontaneously breathed air. Saline or sodium nitroprusside (0.07 mg kg-1) were administered IM 40 minutes after MAA injection. Heart rate (HR), mean arterial pressure (MAP), mean pulmonary arterial pressure (MPAP), pulmonary artery occlusion pressure (PAOP), right atrial pressure (RAP), Q˙t, arterial pH, PaCO2 and PaO2 were obtained immediately before nitroprusside injection (baseline) and 5, 10 and 15 minutes afterwards. Mixed venous blood samples were obtained at baseline and at 5 minutes. Systemic vascular resistance (SVR), PVR, intrapulmonary shunt fraction (Q˙s/Q˙t), a-a gradient, oxygen delivery (D˙O2) and oxygen extraction ratio (O2ER) were calculated. Statistical analysis was performed with repeated measures analysis of variance with correction factors. A p value < 0.05 was considered significant. RESULTS: With nitroprusside, MAP, MPAP, PAOP, RAP, SVR and O2ER significantly decreased and HR, Q˙t and D˙O2 increased compared with baseline and between treatments. There was a significant decrease in PVR and a-a gradient and increase in PaO2 compared with baseline and saline treatment. Changes were not sustained. CONCLUSIONS AND CLINICAL RELEVANCE: Nitroprusside temporarily changed hemodynamic variables, increased PaO2 and decreased a-a gradient. Nitroprusside possibly led to better pulmonary perfusion of ventilated alveoli. However, IM nitroprusside at this dose is not recommended because of severe systemic hypotension and short action.

Use of Detomidine Oromucosal Gel for Alleviation of Acute Anxiety and Fear in Horses: A Pilot Study.

The aim of this randomized, double-blind, placebo-controlled, parallel group clinical field study was to evaluate the effect of detomidine oromucosal gel in alleviating anxiety and fear in horses. Sixteen horses with a history of acute anxiety and fear associated with firework-related noise entered the study. On New Year's Eve, eight horses were treated with 30 µg/kg detomidine gel and eight horses with placebo gel. When fireworks were present, 75% (6/8) of the detomidine-treated horses were scored by their owners as having a good or excellent treatment effect on anxiety and fear, while 50% (3/6) of horses receiving placebo were scored to have a good effect. Horses' behavior was video-recorded and assessed with a focal animal continuous method by a treatment-blind expert observer. Results showed that when fireworks were present, walking behavior decreased significantly (p < 0.05) after treatment with detomidine and that horses of the placebo group, overall, showed more restlessness, vocalization, and signs of colic (Wilcoxon matched-pairs test on the first PC, p = 0.007). This study indicates that detomidine oromucosal gel can be used to alleviate acute noise-related anxiety and fear in horses, but larger treatment groups are needed to confirm the results.

Dexmedetomidine in cancer surgeries: Present status and consequences with its use.

Dexmedetomidine is a centrally acting α2 adrenoreceptor agonist used in perioperative medicine due to its sedative, analgesic and sympatholytic properties. Recently animal data has pointed towards potential role of dexmedetomidine in promoting cancer recurrence and metastasis when used perioperatively especially after breast surgeries. This is because of presence of α2 adrenoreceptors in breast cancer tissue. We reviewed existing literature in which dexmedetomidine was used in cancer surgeries and investigated its role in recurrence and metastasis.

Pharmacokinetics, sedation and hemodynamic changes following the administration of oral transmucosal detomidine gel in cats.

OBJECTIVES: The aim of this study was to describe the pharmacokinetics of oral transmucosal (OTM) detomidine gel in healthy cats and assess its effects on sedation and hemodynamic variables. METHODS: Eight adult cats weighing 4.12 kg ± 0.72 received 4 mg/m2 detomidine gel onto the buccal mucosa. Level of sedation, heart rate (HR), blood pressure (BP) and respiratory rate (f R) were assessed at predetermined intervals following administration. Blood samples for plasma detomidine concentrations and venous blood gas variables were collected from a medial saphenous catheter. Plasma detomidine concentrations were analyzed using ultra-high-pressure liquid chromatography with mass spectrometry detection, and pharmacokinetic estimates were obtained with compartmental methods. Data were analyzed using ANOVA and paired t-test or appropriate non-parametric tests. RESULTS: Sedation occurred in all cats, and was increased from baseline at 30 mins (P <0.001). Decreases in HR occurred from 15-60 mins, ranging from 140 to 165 beats per min (P <0.001). Blood glucose increased from 101 ± 12 mg/dl to 168 ± 27.3 mg/dl at 60 mins (P = 0.004). Systolic blood pressure decreased from baseline (139 ± 14.8 mmHg) to 103 ± 23.0 mmHg at 60 mins (P = 0.023). All changes abated by 120 mins. Emesis occurred in 7/7 cats within 2 mins of gel administration. Geometric mean (coefficient of variation) for clearance was 220.7 ml/min/kg (35.3 ml/min/kg), volume of distribution was 14.9 l/kg (39.9 l/kg) (both a function of bioavailability) and elimination half-life was 46.9 mins (16.0 mins). Maximum plasma concentrations of 10.5 ng/ml (35.5 ng/ml) detomidine occurred at 36.9 mins (21.5 mins). CONCLUSIONS AND RELEVANCE: OTM detomidine gel produced moderate sedation with minimal undesirable side effects in healthy cats, although emesis occurred in all cats. The pharmacokinetic profile supports short-term, minimally invasive sedation in this species. Further studies are warranted to assess its safety and feasibility for use in debilitated cats, or prior to general anesthesia.