Dexmedetomidine-induced fever and delirium: A case report.

WHAT IS KNOWN AND OBJECTIVE: Dexmedetomidine is a selective alpha-2 agonist used for sedation in the intensive care unit (ICU). CASE DESCRIPTION: A 41-year-old woman intubated in the ICU and being treated for acute respiratory distress syndrome (ARDS) received dexmedetomidine following successful extubation to treat increasing agitation thought to be secondary to a history of polysubstance abuse. Following initiation of the dexmedetomidine, the patient became febrile as well as increasingly more agitated and delirious. All potential fever or delirium causes were evaluated. Following discontinuation of dexmedetomidine, her fever, agitation and delirium ceased. WHAT IS NEW AND CONCLUSION: We depict the first known case of dexmedetomidine causing high fevers and delirium.

Measurement of intraocular pressure in healthy anesthetized horses during hoisting.

OBJECTIVE: To measure intraocular pressure (IOP) in horses during hoisting after induction of anesthesia. STUDY DESIGN: Prospective nonrandomized clinical study. ANIMALS: Eighteen healthy adult horses aged [mean±standard deviation (SD)] 10±4.2 years and weighing 491±110 kg anesthetized for elective procedures. METHODS: IOP was measured in the superior eye of each horse based on planned recumbency after induction of anesthesia. Measurements were taken directly after premedication with xylazine or detomidine with butorphanol, after induction with diazepam-ketamine, after intubation, when suspended by the hoist and on the operating table. During hoisting, the head was supported and the eye-heart height was measured to account for variations in head positioning among patients. IOPs were compared across time points using repeated-measures analysis of variance. Regression was used to compare IOP outcome with potential cofactors. RESULTS: Compared with measurements after premedication (17.5±2.5 mmHg) (mean±SD), hoisting significantly increased IOP (32.4±15.3 mmHg) (p<0.01). The highest recorded IOP in the hoist was 80.0 (range, 16.0-80.0) mmHg. The difference in IOP between premedication and hoisting was 15.0±16.2 (range, -1.0 to 68.0) mmHg. Body weight had a significant effect on absolute IOP and change in IOP in the hoist (p<0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Hoist IOP was significantly higher than post-premedication IOP with heavier horses having higher hoist IOPs and greater increases in IOP. The clinician should take this relationship into account when anesthetizing and hoisting larger horses where an increase in IOP could be detrimental.

THE EFFECT OF DEXMEDETOMIDINE ON RADIOGRAPHIC CARDIAC SILHOUETTE SIZE IN HEALTHY CATS.

Dexmedetomidine, an alpha2 -adrenergic agonist, may be used in companion animals for chemical restraint, including cardiac evaluation. Echocardiographic changes associated with alpha2 -adrenergic agonists have been described; however reports of radiographic changes in cats were not found at the time of this study. Aims of this observational, prospective, experimental study were to describe the effects of dexmedetomidine on the radiographic appearance of the cardiac silhouette in healthy, adult cats. Fourteen healthy adult cats received dexmedetomidine 40 mcg/kg IM. Right lateral, left lateral, ventrodorsal, and dorsoventral thoracic radiographs were obtained for each cat at three time points: presedation, intrasedation, and postsedation (≥ two hours after reversal with atipamezole). Radiographs were evaluated in a blinded, randomized fashion by two independent observers using the vertebral heart score on all four views, the number of intercostal spaces on lateral projections, and the percent width of thorax on ventrodorsal and dorsoventral projections. Median vertebral heart score on right lateral view was significantly increased intrasedation (median = 7.8; range = 7.25-8.25) compared to presedation (median = 7.5; range = 7-8 [P = 0.001]). Median percentage width was significantly higher intrasedation (70% on VD; range 65-80 [P = 0.001], and 75% on DV; range 65-80 [P = 0.006]) compared to presedation (65%; range 65-75 on both projections). Dexmedetomidine was associated with a small but significant increase in cardiac silhouette size on right lateral (vertebral heart score), ventrodorsal (percentage width), and dorsoventral (percentage width) radiographs in healthy adult cats. This effect should be taken into consideration for future interpretation of thoracic radiographs in dexmedetomidine-sedated cats.

The effect of dexmedetomidine on the firing properties of STN neurons in Parkinson's disease.

Dexmedetomidine (an alpha-2 adrenergic agonist) sedation is commonly used during subthalamic nucleus (STN) deep-brain stimulation (DBS). Its effects on the electrophysiological characteristics of human STN neurons are largely unknown. We hypothesised that dexmedetomidine modulates the firing rates and bursting of human STN neurons. We analysed microelectrode recording (MER) data from patients with Parkinson's disease who underwent STN DBS. A 'Dex bolus' group (dexmedetomidine bolus prior to MER; 27 cells from seven patients) was compared with a 'no sedation' group (29 cells from 11 patients). We also performed within-patient comparisons with varying dexmedetomidine states. Cells were classified as dorsal half or ventral half based on their relative location in the STN. Neuronal burst and oscillation characteristics were analysed using the Kaneoke-Vitek methodology and local field potential (LFP) oscillatory activity was also investigated. Dexmedetomidine was associated with a slight increase in firing rate (41.1 ± 9.9 vs. 34.5 ± 10.6 Hz, P = 0.02) but a significant decrease in burstiness (number of bursts, P = 0.02; burst index, P < 0.001; percentage of spikes in burst, P = 0.002) of dorsal but not ventral STN neurons. This was not associated with modulation of beta oscillations in the spike-oscillations analysis(beta peak, P = 0.4; signal-to-noise ratio in the beta range for spikes and bursts, P = 0.3 and P = 0.5, respectively) and LFP analysis (Beta power, P = 0.17). As bursting pattern is often used to identify STN and guide electrode placement, we recommend that high-dose dexmedetomidine should be avoided during DBS surgery.

Effects of three antagonists on selected pharmacodynamic effects of sublingually administered detomidine in the horse.

OBJECTIVE: To describe the effects of alpha2 -adrenergic receptor antagonists on the pharmacodynamics of sublingual (SL) detomidine in the horse. STUDY DESIGN: Randomized crossover design. ANIMALS: Nine healthy adult horses with an average age of 7.6 ± 6.5 years. METHODS: Four treatment groups were studied: 1) 0.04 mg kg(-1) detomidine SL; 2) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.075 mg kg(-1) yohimbine intravenously (IV); 3) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 4 mg kg(-1) tolazoline IV; and 4) 0.04 mg kg(-1) detomidine SL followed 1 hour later by 0.12 mg kg(-1) atipamezole IV. Each horse received all treatments with a minimum of 1 week between treatments. Blood samples were obtained and plasma analyzed for yohimbine, atipamezole and tolazoline concentrations by liquid chromatography-mass spectrometry. Behavioral effects, heart rate and rhythm, glucose, packed cell volume (PCV) and plasma proteins were monitored. RESULTS: Chin-to-ground distance increased following administration of the antagonists, however, this effect was transient, with a return to pre-reversal values as early as 1 hour. Detomidine induced bradycardia and increased incidence of atrioventricular blocks were either transiently or incompletely antagonized by all antagonists. PCV and glucose concentrations increased with tolazoline administration, and atipamezole subjectively increased urination frequency but not volume. CONCLUSIONS AND CLINICAL RELEVANCE: At the doses administered in this study, the alpha2 -adrenergic antagonistic effects of tolazoline, yohimbine and atipamezole on cardiac and behavioral effects elicited by SL administration of detomidine are transient and incomplete.

Effect of MK-467 on organ blood flow parameters detected by contrast-enhanced ultrasound in dogs treated with dexmedetomidine.

OBJECTIVE: To evaluate the dexmedetomidine-induced reduction in organ blood flow with quantitative contrast-enhanced ultrasound (CEUS) method and to observe the influence of MK-467 on such reduction. STUDY DESIGN: Randomized cross-over study. ANIMALS: Six adult purpose-bred laboratory beagle dogs (mean body weight 15.3 ± 1.9 kg). METHODS: Contrast-enhanced ultrasound was performed on six conscious healthy laboratory beagles. The animals on separate occasions underwent three treatments: awake without any medication (CTRL), dexmedetomidine 10 µg kg(-1) (DEX) and DEX + MK-467 500 µg kg(-1) (DMK) intravenously (IV). The kidney (10-15 minutes post-treatment), spleen (25-30 minutes post-treatment), small intestine (40-45 minutes post-treatment) and liver (50-55 minutes post-treatment) were examined with CEUS. A time curve was generated and the following perfusion parameters were analysed: arrival time (AT), time to peak from injection (TTPinj), peak intensity (PI) and wash-in rate (Wi). In addition to CEUS, renal glomerular filtration rate was indirectly estimated by the rate of iohexol elimination. RESULTS: AT and TTPinj were significantly higher for DEX than for CTRL in all studied organs. The same parameters were significantly higher for DEX than for DMK in the kidney, spleen and small intestine. PI was significantly lower for DEX than for CTRL or DMK in the kidney. Wi was significantly lower for DEX than for CTRL or DMK in the kidney and significantly lower than for CTRL only in the small intestine. Plasma concentration of iohexol was significantly higher after DEX than CTRL administration. CONCLUSIONS: Contrast-enhanced ultrasound was effective in detecting DEX-induced changes in blood flow. MK-467 attenuated these changes. CLINICAL RELEVANCE: Clinicians should consider the effects of the sedation protocol when performing CEUS. Addition of MK-467 might beneficially impact the haemodynamic function of sedation with alpha-2 adrenoceptor agonists.

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.

Tizanidine Toxicity From Ciprofloxacin: A Cautionary Tale.

Tizanidine is an alpha-2 adrenergic agonist used commonly by medical professionals to treat patients' chronic spasticity, muscle spasms, and neuralgia usually associated with myofascial components. This medication is also used very frequently in detoxification centers on patients treated for analgesic withdrawal, especially those who are suffering from rebound headaches due to the discontinuation of analgesics. Tizanidine is metabolized in the human body by the cytochrome P450 CYP1A2. On the other hand, ciprofloxacin is a common antibiotic belonging to the class of fluoroquinolones and is used to treat various infections. Ciprofloxacin inhibits the bacterial DNA-gyrase enzyme resulting in the destruction of the organism. Ciprofloxacin is also an inhibitor of the cytochrome P450 CYP1A2. Even though these two medications show obvious interaction still, however, both these medications are often prescribed together, and their interactions/contraindications are often overlooked by many physicians and other providers. We hereby describe the case report of the interaction between tizanidine and ciprofloxacin, along with the adverse outcome related to the concomitant use of these two drugs.

Comparison of Recovery Quality Following Medetomidine versus Xylazine Balanced Isoflurane Anaesthesia in Horses: A Retrospective Analysis.

Medetomidine partial intravenous anaesthesia (PIVA) has not been compared to xylazine PIVA regarding quality of recovery. This clinical retrospective study compared recoveries following isoflurane anaesthesia balanced with medetomidine or xylazine. The following standard protocol was used: sedation with 7 µg·kg-1 medetomidine or 1.1 mg·kg-1 xylazine, anaesthesia induction with ketamine/diazepam, maintenance with isoflurane and 3.5 µg·kg-1·h-1 medetomidine or 0.7 mg·kg-1·h-1 xylazine, and sedation after anaesthesia with 2 µg·kg-1 medetomidine or 0.3 mg·kg-1 xylazine. Recovery was timed and, using video recordings, numerically scored by two blinded observers. Influence of demographics, procedure, peri-anaesthetic drugs, and intraoperative complications (hypotension, hypoxemia, and tachycardia) on recovery were analysed using regression analysis (p < 0.05). A total of 470 recoveries (medetomidine 279, xylazine 191) were finally included. Following medetomidine, recoveries were significantly longer (median (interquartile range): 57 (43-71) min) than xylazine (43 (32-59) min) (p < 0.001). However, the number of attempts to stand was similar (medetomidine and xylazine: 2 (1-3)). Poorer scores were seen with increased pre-anaesthetic dose of xylazine, intraoperative tetrastarch, or salbutamol. However, use of medetomidine or xylazine did not influence recovery score, concluding that, following medetomidine-isoflurane PIVA, recovery is longer, but of similar quality compared to xylazine.

Analgesic and Cardiopulmonary Effects of Epidural Romifidine and Morphine Combination in Horses.

The study aim is to compare the effects of epidural administration of two different doses of romifidine combined with morphine in horses. A prospective crossover blinded experimental design was used. Five adult healthy horses two males and three females with a mean body weight of 380 ± 45 Kg (335-425 kg), were studied. Treatments consisted of romifidine 30 µg/kg (R30) or 60 µg/kg (R60) combined with morphine 0.1 mg/kg with a washout interval of 72 hours, administered through an epidural catheter placed at the first intercoccygeal space. Heart rate (HR) and respiratory rate (fR), pH, blood gases, arterial blood pressures (mmHg), and threshold for electrical noxious stimulation was evaluated for 120 minutes and after 240 minutes of epidural injection. Data were collected before injections and every 15 minutes for 120 minutes, and at 240 minutes of epidural administration. Significant sedation occurred in both treatments with no statistically significant difference between them. There were significant changes in fR and HR from baseline but no difference between treatments. Arterial blood pressures were significantly lower in R60 treatment from 75 up to 120 minutes post epidural injection. Analgesia was considered moderate for both treatments lasting longer with romifidine at 60 µg/kg. Epidurally administered romifidine and morphine combination in horses produces dose-dependent sedation, arterial hypotension, and antinociceptive effects.

Low-dose clonidine in veterans with Posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) symptoms of hyperarousal are mediated through sympathetic nervous system hyperactivity. PTSD symptoms, including distressing thoughts and memories, flashbacks, hyperarousal, and sleep disturbances, have been linked with elevated norepinephrine levels in the cerebrospinal fluid. Clonidine, an alpha2-adrenergic agonist, reduces the release of norepinephrine and has been suggested as a treatment for PTSD. However, literature for use of clonidine in PTSD is limited. The objective of this study was to evaluate clinical records of patients with PTSD treated with clonidine to assess reported efficacy and safety. A cohort of veterans with PTSD treated with clonidine at a midwestern VA hospital between July 2015 and January 2018 were studied retrospectively. Medical records of 79 patients with moderate to severe PTSD symptoms were reviewed by three independent clinicians using the Clinical Global Impressions (CGI) scale to quantify symptom severity (CGI-S) before starting clonidine and subjects' change in symptoms (CGI-I) after starting clonidine. Data on adverse events were also collected. Subgroup analyses were conducted on the impact of comorbid diagnoses, concurrent medications, and substance use. Mean CGI-S score at baseline was 4.8 (5 = markedly ill). After treatment with low-dose clonidine, 72% of patients experienced improvement, and 49% scored "much improved" or "very much improved." Adverse effects were reported by 18 out of 79 subjects. In this retrospective analysis of veterans prescribed clonidine for PTSD, CGI-I scores suggested improvement in PTSD symptoms, and minimal side effects were reported. In addition, some comorbid diagnoses and concurrent medications were correlated with variations in outcomes.

Efficacy of lofexidine for mitigating opioid withdrawal symptoms: results from two randomized, placebo-controlled trials.

Objectives: Fear of opioid withdrawal syndrome (OWS) often dissuades opioid discontinuation. Lofexidine is an FDA-approved, alpha2-adrenergic receptor agonist for treatment of OWS. Pivotal trial results from the per-protocol statistical analyses have been published. However, the FDA prescribing information presents these efficacy results using a different, standardized statistical approach that does not transform data or impute missing values. This analysis is easier to interpret and allows comparison across studies. This reanalysis is presented here. Methods: Studies were double-blind, placebo-controlled for 7 days in Study 1 and 5 days in Study 2. Opioid-dependent adults received placebo or lofexidine; efficacy was assessed using the Short Opioid Withdrawal Scale of Gossop (SOWS-G) daily. Results: Study 1 (N = 602) mean SOWS-G scores were 6.1 (SE: 0.35), 6.5 (SE: 0.34), and 8.8 (SE: 0.47) over Days 1-7 for lofexidine 2.88 mg/day, 2.16 mg/day, and placebo, respectively (for 2.88, p < .0001; for 2.16 mg, p < .0001). Study 2 (N = 264) mean SOWS-G scores were 7.0 (SE: 0.44) and 8.9 (SE: 0.48) over Days 1-5 for lofexidine 2.16 mg/day and placebo, respectively (p = .0037). Median time to treatment discontinuation was approximately 2 days later with lofexidine treatment than with placebo and significantly more lofexidine-treated subjects completed the studies. Hypotension and bradycardia were more common with lofexidine. More placebo subjects withdrew prematurely for lack of efficacy. Conclusion: This simplified analysis confirmed previous per-protocol results, that lofexidine better reduces OWS severity and increases retention compared with placebo in opioid-dependent adults. These results are robust and comparable across studies using various methods of analysis. ClinicalTrials.gov identifier: Study 1, NCT01863186; Study 2 NCT00235729. URL: https://clinicaltrials.gov/.

Topical Brimonidine or Intravitreal BDNF, CNTF, or bFGF Protect Cones Against Phototoxicity.

PURPOSE: To develop a focal photoreceptor degeneration model by blue light-emitting diode (LED)-induced phototoxicity (LIP) and investigate the protective effects of topical brimonidine (BMD) or intravitreal brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), or basic fibroblast growth factor (bFGF). METHODS: In anesthetized, dark-adapted, adult female Swiss mice, the left eye was dilated and exposed to blue light (10 seconds, 200 lux). After LIP, full-field electroretinograms (ERG) and spectral-domain optical coherence tomography (SD-OCT) were obtained longitudinally, and reactive-Iba-1+monocytic cells, TUNEL+ cells and S-opsin+ cone outer segments were examined up to 7 days. Left eyes were treated topically with BMD (1%) or vehicle, before or right after LIP, or intravitreally with BDNF (2.5 µg), CNTF (0.2 µg), bFGF (0.5 µg), or corresponding vehicle right after LIP. At 7 days, S-opsin+ cone outer segments were counted within predetermined fixed-size areas (PFA) centered on the lesion in both flattened retinas. RESULTS: SD-OCT showed a circular region in the superior-temporal left retina with progressive thinning (207.9 ± 5.6 µm to 160.7 ± 6.8 µm [7 days], n = 8), increasing TUNEL+ cells (peak at 3 days), decreasing S-opsin+ cone outer segments, and strong microglia activation. ERGs were normal by 3 days. Total S-opsin+ cones in the PFA for LIP-treated and fellow-retinas were 2330 ± 262 and 5601 ± 583 (n = 8), respectively. All neuroprotectants (n = 7-11), including topical BMD pre- or post-LIP, or intravitreal BDNF, CNTF, and bFGF, showed significantly greater S-opsin+ cone survival than their corresponding vehicle-treated groups. CONCLUSIONS: LIP is a reliable, quantifiable focal photoreceptor degeneration model. Topical BMD or intravitreal BDNF, CNTF, or bFGF protect against LIP-induced cone-photoreceptor loss. TRANSLATIONAL RELEVANCE: Topical BMD or intravitreal BDNF, CNTF, or bFGF protect cones against phototoxicity.

Pharmacokinetic and pharmacodynamics of xylazine administered to exercised thoroughbred horses.

There is limited data describing xylazine serum concentrations in the horse and no reports of concentrations beyond 24 hours. The primary goal of the study reported here was to update the pharmacokinetics of xylazine following intravenous (IV) administration in order to assess the applicability of current regulatory recommendations. Pharmacodynamic parameters were determined using PK-PD modeling. Sixteen exercised adult Thoroughbred horses received a single IV dose of 200 mg of xylazine. Blood and urine samples were collected at time 0 and at various times for up to 96 hours and analyzed using liquid chromatography tandem mass spectrometry. Xylazine serum concentrations were best fit by a 3-compartment model. Mean ± SEM systemic clearance, volume of distribution at steady state, beta half-life and gamma half-life were 12.7 ± 0.735 mL/min/kg, 0.660 ± 0.053 L/kg, 2.79 ± 0.105 hours and 26.0 ± 1.9, respectively. Immediately following administration, horses appeared sedate as noted by a decrease in chin-to-ground distance, decreased locomotion and decreased heart rate (HR). Sedation lasted approximately 45 minutes. Glucose concentrations were elevated for 1-hour post administration. The EC50 (IC50) was 636.1, 702.2, 314.1 and 325.7 ng/mL for HR, atrioventricular block, chin-to-ground distance and glucose concentrations, respectively. The Emax (Imax) was 27.3 beats per minute, 47.5%, 42.4 cm and 0.28 mg/dL for HR, atrioventricular block, chin-to-ground distance and glucose concentrations, respectively. Pharmacokinetic parameters differ from previous reports and a prolonged detection time suggests that an extended withdrawal time, beyond current regulatory recommendations, is warranted to avoid inadvertent positive regulatory findings in performance horses. Copyright © 2016 John Wiley & Sons, Ltd.

Successful use of guanfacine in a patient with chronic refractory cough: A case report.

Chronic idiopathic cough is a common and often frustrating complaint for patients as well as providers. When common etiologies of cough are ruled out and/or do not respond to usual treatments, neurogenic cough should be considered as a diagnosis of exclusion. Here, we report on a 58-year-old woman with an 8-year history of chronic, treatment-refractory cough of unknown etiology that we diagnosed as neurogenic cough and successfully treated with guanfacine monotherapy, with rapid and durable improvement in symptoms. This case was particularly challenging for a number of reasons, including a distant past smoking history and previous pneumonia, a significant psychiatric history, and a mildly deviated nasal septum and nasal osteophyte, all or some of which could have contributed to the etiology of the cough. This case illustrates that neurogenic cough should be a diagnostic consideration in patients presenting with chronic cough in whom other treatment modalities have failed, and also suggests that the therapeutic use of guanfacine in this clinical setting warrants future investigation.

Neuroprotection by alpha 2-adrenergic agonists in cerebral ischemia.

Ischemic brain injury is implicated in the pathophysiology of stroke and brain trauma, which are among the top killers worldwide, and intensive studies have been performed to reduce neural cell death after cerebral ischemia. Alpha 2-adrenergic agonists have been shown to improve the histomorphological and neurological outcome after cerebral ischemic injury when administered during ischemia, and recent studies have provided considerable evidence that alpha 2-adrenergic agonists can protect the brain from ischemia/reperfusion injury. Thus, alpha 2-adrenergic agonists are promising potential drugs in preventing cerebral ischemic injury, but the mechanisms by which alpha 2-adrenergic agonists exert their neuroprotective effect are unclear. Activation of both the alpha 2-adrenergic receptor and imidazoline receptor may be involved. This mini review examines the recent progress in alpha 2-adrenergic agonists - induced neuroprotection and its proposed mechanisms in cerebral ischemic injury.

Comparison of lidocaine, xylazine, and lidocaine-xylazine for caudal epidural analgesia in cattle.

OBJECTIVE: To directly compare the time to onset and duration of analgesia produced by a lidocaine/xylazine combination with that produced by lidocaine and xylazine administered alone in the caudal epidural space of dairy cattle. Design Prospective randomized experimental study. ANIMALS: Nine adult (> 4 years of age) dairy cows (520-613 kg). METHODS: Caudal epidural analgesia was produced in all cows with 2% lidocaine (0.22 mg kg-1; 5.5 mL 500 kg-1), 10% xylazine (0.05 mg kg-1 diluted to 5.5 mL 500 kg-1 with sterile water), and 2% lidocaine/10% xylazine (0.22 mg kg-1/0.05 mg kg-1; total volume of 5.7 mL 500 kg-1), at no earlier than weekly intervals in a Latin square design. Time to onset, duration and cranial spread of analgesia were recorded, as were degree of sedation, ataxia and ptyalism. RESULTS: No significant difference (p > 0.05) was noted for time (mean ± SEM) of onset of analgesia between lidocaine (4.8 ± 1.0 minutes) and the lidocaine/xylazine combination (5.1 ± 0.9 minutes) but onset of analgesia following xylazine was significantly longer (11.7 ± 1.0 minutes) than either of the other two treatments. Lidocaine/xylazine (302.8 ± 11.0 minutes) produced analgesia of significantly longer duration than that of xylazine (252.9 ± 18.9 minutes) and both the lidocaine/xylazine combination and xylazine alone produced analgesia of significantly longer duration than that produced by lidocaine (81.8 ± 11.8 minutes). In all cattle, xylazine, administered either alone or with lidocaine, induced mild to moderate sedation and ataxia and cutaneous analgesia from the coccyx to T13. Mild ataxia was also present in those cattle receiving lidocaine alone. CONCLUSION: The combination of xylazine and lidocaine produces analgesia of quicker onset and longer duration than xylazine administered alone and of longer duration than lidocaine administered alone. CLINICAL RELEVANCE: Utilizing this combination, long-duration obstetrical and surgical procedures could commence relatively soon after epidural injection and could be completed without re-administration of anesthetic agents.

Eszopiclone and dexmedetomidine depress ventilation in obese rats with features of metabolic syndrome.

STUDY OBJECTIVES: Obesity alters the therapeutic window of sedative/hypnotic drugs and increases the probability of respiratory complications. The current experiments used an established rodent model of obesity to test the hypothesis that the sedative/hypnotic drugs eszopiclone and dexmedetomidine alter ventilation differentially in obese rats compared with lean/fit rats. DESIGN: This study used a within-groups/between-groups experimental design. SETTING: University of Michigan. PARTICIPANTS: Experiments were conducted using lean/fit rats (n = 21) and obese rats (n = 21) that have features of metabolic syndrome. INTERVENTIONS: Breathing was measured with whole-body plethysmography after systemic administration of vehicle (control), the nonbenzodiazepine, benzodiazepine site agonist eszopiclone, or the alpha-2 adrenergic receptor agonist dexmedetomidine. MEASUREMENTS AND RESULTS: Data were analyzed using two-way analysis of variance and appropriate post hoc comparisons. At baseline, the obese/metabolic syndrome rats had increased respiratory rates (21.6%), lower tidal volumes/body weight (-24.1%), and no differences in minute ventilation compared to lean/fit rats. In the obese rats, respiratory rate was decreased by dexmedetomidine (-29%), but not eszopiclone. In the lean and the obese rats, eszopiclone decreased tidal volume (-12%). Both sedative/hypnotic drugs caused a greater decrease in minute ventilation in the obese (-26.3%) than lean (-18%) rats. Inspiratory flow rate (VT / TI) of the obese rats was decreased by dexmedetomidine (-10.6%) and eszopiclone (-18%). Duty cycle (TI / TTOT) in both rat lines was decreased by dexmedetomidine (-16.5%) but not by eszopiclone. CONCLUSIONS: Dexmedetomidine, in contrast to eszopiclone, decreased minute ventilation in the obese/metabolic syndrome rats by depressing both duty cycle and inspiratory flow rate. The results show for the first time that the obese phenotype differentially modulates the respiratory effects of eszopiclone and dexmedetomidine. These differences in breathing are consistent with previously documented differences in sleep between lean/fit and obese rats. These findings also encourage future studies of obese/metabolic syndrome rats that quantify the effect of sedative/hypnotic drugs on respiratory mechanics as well as hypoxic and hypercapnic ventilatory responses. Continued findings of favorable homology between obese humans and rodents will support the interpretation that these obese rats offer a unique animal model for mechanistic studies.

Dexmedetomidine in current anaesthesia practice- a review.

Dexmedetomidine is an alpha 2 adrenergic receptor agonist, even ten times more selective than clonidine. It is a very versatile drug in anaesthesia practice, finding place in increasing number of clinical scenarios and is no more limited to intensive care unit (ICU) sedation. It is analgesic, has anaesthetic sparing effect, sympatholytic property, useful in other procedural sedation and also has cardiovascular stabilizing property. It reduces delirium and preserves respiratory function which adds benefits to its uses. The aim of this review is to make awareness of its role in present anaesthesia and discuss its limitations at the same time.

A Case of Amitraz Insecticide Intoxication after Ingestion of Large Amount

Amitraz is used as farm-animal insecticide. Its side effects in humans are related to its pharmacological activity on alpha 2-adrenergic receptors. The case describes a previously healthy 46-year-old woman who intentionally ingested approximately 250mL of liquid amitraz. She presented with vomiting, altered mental status, miosis, dry mouth, hypopnea, metabolic and respiratory acidosis, hypotension, hypothermia, polyuria, metabolic acidosis, elevated serum aminotransferase and abdominal distension. Supportive treatments including mechanical ventilation, hydration, dopamine infusion, bicarbonate infusion and gastric decompression resulted in improvement. By hospital day 3, she recovered with resolution of abdominal distension. It is paramount to recognize amitraz poisoning when apesticide-intoxicated patient presets with signs and symptoms consistent with organophosphate intoxicated patients but with greater alpha 2-adrenergic related symptoms such as decreased bowel motility and xerostomia.