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This report describes the use of an ultrapotent, opioid‐free anaesthesia with an infusion of butorphanol, ketamine and guaifenesin in two captive adult male greater one‐horned rhinoceros (Rhinoceros unicornis). Animals were premedicated intramuscularly with azaperone (0.05 mg/kg), butorphanol tartrate (0.05 and 0.02 mg/kg, respectively) and an α2‐agonist (detomidine 0.02 mg/kg and medetomidine 0.01 mg/kg, respectively). Once sternolaterally recumbent, rhinoceros were induced with intravenous ketamine (0.02 and 0.05 mg/kg, respectively) and midazolam (7.0 and 8.0 μg/kg, respectively). Intravenous infusions of guaifenesin (15.1 and 25 mg/kg/h, respectively) and of ketamine (22.5 and 29.1 μg/kg/h, respectively) and butorphanol (15.7 and 20.3 μg/kg/h, respectively), allowed stable anaesthesia maintenance for dental procedures to take place. Supplemental boluses of ketamine and α2‐agonist were required during noxious stimulation in both cases. Animals were reversed with intramuscular atipamezole (0.07–0.08 mg/kg) and naltrexone (0.06–0.08 mg/kg), with or without flumazenil (0.10 μg/kg), allowing smooth and quick recovery. [ABSTRACT FROM AUTHOR]

Background: Intravenous infusions of alpha‐2 adrenoceptor sedatives and opioids can potentially facilitate surgery in donkeys while standing. Literature on this subject matter is scant. Objectives: Evaluation of efficacy of sedation from α2‐adrenoceptors (dexmedetomidine or xylazine) and butorphanol during ovariectomy in standing donkeys. Study design: Randomised, masked in vivo experiment. Methods: Thirteen female donkeys were sedated with butorphanol (0.05 mg/kg bwt followed by 0.05 mg/kg bwt/h) IV. Concomitantly, 6 of the 13 jennies were sedated with dexmedetomidine 2.5 mcg/kg bwt followed by 2.5 mcg/kg bwt/h (Dex‐B group), while seven jennies were sedated with xylazine 0.5 mg/kg bwt followed by 0.5 mg/kg bwt/h (Xyl‐B group). A line block of the left flank and an infiltration block around uterine ligament were performed with lidocaine. While the jennies underwent ovariectomies standing, sedation scores and head height above ground were assessed at 2 and 10 min after sedative boluses and every 10 min thereafter. If sedation was too light or too deep, the dose of dexmedetomidine or xylazine was increased or decreased by 25% of the original infusion rate, while butorphanol infusion rate was constant. Physiological parameters were measured. Normally distributed data were compared using the two‐sample t test while repeatedly measured data were tested for differences between and within groups using repeated measures analysis of variance (ANOVA) by ranks followed by a Wilcoxon test with Tukey Honest Significant Difference for multiple testing. Statistical significance was set at p < 0.05. Results: Both Dex‐B and Xyl‐B caused moderate to marked sedation adequate for ovariectomy in donkeys. Evident sedation was absent by 60 min of termination of infusions. No adverse physiological effects were observed. Main limitations: Study on ovariectomy cases only, no pharmacokinetic profiling. Conclusions: Dexmedetomidine or xylazine and butorphanol sedation is feasible for ovariectomy in standing donkeys. [ABSTRACT FROM AUTHOR]

This study aimed to compare the effect of intranasal (IN) and intramuscular (IM) administration of butorphanol and zolazepam‐tiletamine (ZT) combination on intraocular pressure (IOP) and tear secretion (TS) in rabbits. Fourteen healthy male New Zealand White rabbits weighing 3.05 ± 0.72 kg, aged between 1 and 2 years old, were included in the study. Animals randomly received 0.5 mg/kg butorphanol and 15 mg/kg ZT combination either with IN or IM administration. IOP and TS were measured at baseline (T0), and followed by 5, 15, 30, 45, and 60 min after drug administration. The sedation variables, the time to onset of sedation, duration of sedation, and sedation scores were also recorded. The route of administration for the butorphanol and ZT combination had no significant effect on the mean IOP (p =.301) and TS (p =.445). Furthermore, there were no significant changes observed in the IOP (p =.472) and TS (p =.348) over time. The time to onset of sedation was earlier in the IN group (4.57 ± 0.79 min) than in the IM group (5.86 ± 0.9 min; p =.0004). The duration of sedation was significantly longer for IM (57.43 ± 3.41 min) compared with IN (45.0 ± 1.91 min; p <.0001). No significant difference in the sedation score was observed between groups at all time points. In conclusion, both IN and IM administration of the butorphanol and ZT combination in rabbits had similar effects on IOP and TS. [ABSTRACT FROM AUTHOR]

Background: Cough is a common clinical complaint in small animal practice with limited treatment options for chronic underlying conditions. Objectives: The present study aimed to evaluate the efficacy of three antitussive drugs in a novel, minimally invasive canine acute cough model. Methods: Five clinically healthy Beagles were used to create an acute cough model by administering sterile saline via a transtracheally placed central venous catheter. Single‐dose antitussive effects of butorphanol, maropitant and Danpron were assessed. Cough frequency was measured before and at hourly intervals up to 3 h post‐administration of each drug, with a linear mixed model used for statistical analysis. Results: Butorphanol (0.3 m/kg, IM) significantly reduced cough frequency at 1 and 3 h post‐administration. Danpron (0.1 mL/kg, IM) also significantly reduced cough frequency 1 h post‐administration; however, this effect was not sustained at 3 h. Maropitant (1 mg/kg, IM) did not significantly reduce cough frequency. The cough induction method was effective and minimally invasive, with no adverse effects. Conclusion: The present study demonstrated that butorphanol has a potent and prolonged antitussive effect in an acute canine cough model, whereas Danpron shows a transient effect. These findings provide valuable insights into the comparative efficacy of commonly used antitussive drugs in dogs. [ABSTRACT FROM AUTHOR]

Butorphanol is commonly administered, both by the intravenous and intramuscular routes, to racehorses to facilitate handling for diagnostic procedures. As the administration of butorphanol for therapeutic purposes is considered appropriate, in order to avoid inadvertent positive drug tests, a thorough understanding of the pharmacokinetics of this drug is necessary. In the current study, 12, exercised Thoroughbred horses were administered a single intramuscular dose of 0.1 mg/kg butorphanol, and serum and urine samples were collected at various times post drug administration for determination of butorphanol concentrations using a highly sensitive liquid chromatography tandem mass spectrometry method. Serum data were modeled using a nonlinear mixed effect population PK model. The maximum concentration (Cmax) and time to maximum concentration (Tmax) were 139.9 ± 72.8 ng/mL and 0.43 ± 0.44 h (mean ± SD), respectively. Although likely not clinically relevant, but important for drug testing purposes, a prolonged terminal phase was observed, yielding a terminal half‐life of 7.67 ± 1.86 h. Using the blood screening limits proposed by the Horseracing Integrity and Welfare Unit, the detection time for intramuscular administration of butorphanol was estimated to be 96 h. [ABSTRACT FROM AUTHOR]

Alfaxalone is a commonly employed veterinary anaesthetic induction and sedation agent. A 4% w/v preserved, aqueous formulation of alfaxalone 'RD0387' (A4%) has recently been developed. To evaluate the sedative effects of A4%, three doses, 5 mg kg−1 (A5); 7.5 mg kg−1 (A7.5) and 10 mg kg−1 (A10) were administered intramuscularly into the epaxial musculature of six healthy adult mixed‐breed dogs in an experimental, randomized, blinded, crossover study. Sedation time variables, quality of sedation (including onset of sedation and recovery), physiological variables, response to cephalic vein catheterization and frequency of undesirable events were recorded. Continuous variables were analysed between treatments (one‐way ANOVA or restricted maximum likelihood modelling) and within treatments compared with baseline (Tukey's test). Categorical data were analysed between treatments (Kruskal‐Wallis' test) and within treatments from baseline (Dunn's test). Significance was set at p <.05. All dogs became sedated (laterally recumbent) and sedation onset was significantly faster in groups A7.5 (9.8 ± 5.3 min) and A10 (9.1 ± 5.6 min) compared to A5 (25.6 ± 16.1 min) (p =.033, p =.027, respectively). Duration of sedation was significantly longer in A10 (168.5 ± 70.6 min) and A7.5 (143.8 ± 58 min) compared to A5 (63.8 ± 28.2 min) (p =.005 and p =.003, respectively). Dogs in A10 had a superior quality of onset of sedation compared to A5 (p =.028). Sedation scores and quality of recovery from sedation were not significantly different between doses. Two dogs (2/6) in A5 were insufficiently sedated for cephalic catheterization. Ataxia was the most frequently observed undesirable event with an overall frequency of 78% (14/18) and 89% (16/18) during sedation onset and recovery, respectively. Overall, A4% administered IM in dogs at 7.5 and 10 mg kg−1 resulted in sufficient sedation for IV catheterization in dogs. To improve the speed and quality of the sedation, it is recommended that future research focuses on combining A4% with other sedative or analgesic drugs. [ABSTRACT FROM AUTHOR]

Summary: Background: The use of combinations of α2‐adrenergic agonists and opioids has been published as providing superior sedation than either drug alone. Objectives: The present study aimed to compare the sedative and physiological effects of intravenous (IV) administration of dexmedetomidine alone and in combination with methadone, morphine, tramadol or pethidine in miniature donkeys. Study design: Experimental, crossover Latin square, randomised, blinded study. Methods: Twelve clinically healthy miniature donkeys with a mean age of 6 ± 2 (mean ± SD) years, weight of 94 ± 5 kg and height at withers of 0.80 ± 0.06 m were assigned to six IV treatments. They received either 0.9% saline, 5 μg/kg dexmedetomidine, 5 μg/kg dexmedetomidine and 0.2 mg/kg methadone, 5 μg/kg dexmedetomidine and 0.1 mg/kg morphine, 5 μg/kg dexmedetomidine and 2 mg/kg tramadol or 5 μg/kg dexmedetomidine and 1 mg/kg pethidine, with a washout period of 8 days. The degree of sedation was investigated using a numerical ranking scale of 0–3. Heart rate (HR), respiratory rate (RR), rectal temperature (RT) and intestinal motility were performed before and 5, 10, 15, 30, 45, 60, 75, 90 and 120 min after drug administration. Results: Animals in dexmedetomidine or dexmedetomidine/opioid treatments were sedated for 5–60 min. Sedation was significantly higher in dexmedetomidine/opioid treatments than in dexmedetomidine at 15–30 min (p < 0.05). In all treatments, HR and RR significantly decreased from baseline at 5–75 and 30–60 min, respectively (p < 0.05). Intestinal motility was decreased in dexmedetomidine and dexmedetomidine/opioid treatments at 5–60 and 5–90 min, respectively. Compared to dexmedetomidine, intestinal motility was significantly lower in dexmedetomidine/opioid treatments at 75–90 min. Main limitations: Assessment of only HR and RR are inadequate to describe the cardiorespiratory effects of dexmedetomidine/opioids. Conclusions: The use of combinations of dexmedetomidine/opioids would be considered for superior sedation for 15–30 min after administration in miniature donkeys. No significant differences were detected between opioids in combination with dexmedetomidine in miniature donkeys. [ABSTRACT FROM AUTHOR]

The purpose of this study was to assess antinociception and correlation of antinociception and hypothermic effects after intravenous opioids in dogs. Nine healthy male Beagles were enrolled in the study. They were acclimated to a thermal nociceptive device, then received three IV treatments (saline, butorphanol 0.4 mg/kg and methadone 0.5 mg/kg) in a randomized complete block design. Rectal temperature and thermal withdrawals were assessed prior to and 0.5–6 h after drug administration. One dog was excluded due to lack of withdrawal to thermal stimuli. Rectal temperatures were not significantly different between treatments at time 0, but significantly decreased from 0.5 to 5 h for both opioids compared to saline. Withdrawals were significantly decreased, compared to saline, from 0.5 to 4 h for butorphanol and 0.5–5 h for methadone. A significant (p =.0005) and moderate (R2 =.43) correlation between antinociception and hypothermia occurred. Based on these data, intravenous butorphanol (0.4 mg/kg) and methadone (0.5 mg/kg) provided 4 and 5 h of antinociception, respectively. Opioid hypothermia can serve as an easy, noninvasive and humane manner for preclinical assessment of opioid antinociception in dogs prior to evaluation in clinical trials. This is a major refinement in animal welfare for assessing novel opioids, opioid doses and dose intervals in dogs. [ABSTRACT FROM AUTHOR]

Coenurosis is a parasitic disease affecting the central nervous system of small ruminants. This case describes the anaesthetic management of a ewe undergoing craniotomy for associated‐brain cyst removal. As small ruminants are food‐producing animals, there is limited access to veterinary medicinal products, and choosing an appropriate anaesthetic protocol is challenging. After premedication with detomidine (0.03 mg/kg intramuscularly) and butorphanol (0.1 mg/kg intravenously), anaesthesia was induced with lidocaine (1 mg/kg) and ketamine (2 mg/kg intravenously), and maintained with isoflurane in oxygen, using controlled mechanical ventilation. The animal was placed in sternal recumbency, with the head slightly elevated. A lidocaine incisional infiltration was performed, and dexamethasone (0.06 mg/kg intravenously) was administered. Vital parameters remained stable throughout anaesthesia, but moderate agitation was noticed at recovery, treated with butorphanol (0.05 mg/kg intravenously). While the ewe showed clinical improvement initially, its neurological status deteriorated in the following days, leading to euthanasia. Postmortem examination revealed intracranial haematoma. [ABSTRACT FROM AUTHOR]

A 75 kg, 4‐year‐old, male, neutered, Saanen‐cross, pet‐owned, adult goat presented for left trochlear sulcoplasty for treatment of lateral patellar luxation. Premedication consisted of intravenous butorphanol (0.2 mg/kg), and midazolam (0.5 mg/kg, intravenous), followed by ketamine (2 mg/kg, intravenous) and propofol (2 mg/kg, intravenous) for induction of anaesthesia. Anaesthesia was maintained using isoflurane in oxygen (100%) and mechanical ventilation was started. An ultrasound‐guided saphenous and sciatic nerve block with 0.1 mL/kg of ropivacaine 0.75% and 0.25%, respectively, was performed. Anaesthesia was uneventful, except for a transient period of hypotension and a nociceptive reaction during skin suture. Recovery was uneventful. No motor block was observed using this combination of ropivacaine concentrations. Buprenorphine (0.01 mg/kg, intravenous) was initiated (twice daily first day; once daily second and third day) 6.5 hours after the nerve block due to discomfort. Meloxicam (0.5 mg/kg, intravenous) was administered once daily for 5 days, after which the patient was fully ambulatory. [ABSTRACT FROM AUTHOR]

This report describes the peri‐operative anaesthesia and analgesia management of a 5‐year‐old Kunekune pig undergoing surgical correction of an umbilical hernia. Premedication with azaperone (1 mg/kg), xylazine (0.5 mg/kg), butorphanol (0.2 mg/kg) and ketamine (5 mg/kg) intramuscularly preceded induction of anaesthesia with ketamine (2 mg/kg) intravenously. General anaesthesia was maintained with isoflurane in 100% oxygen. Analgesia was supported intraoperatively by a transversus abominis plane block with lidocaine (1.5 mg/kg), and a ketamine (10 μg/kg/min) infusion intravenously. Crystalloid fluid boluses and atropine intravenously were administered, and mechanical ventilation was stopped to aid correction of hypotension. Post‐operative analgesia was supported with a continuous infusion of ketamine (5 μg/kg/min) intravenously, butorphanol (0.2 mg/kg) intravenously every 6 hours, paracetamol (10 mg/kg) intravenously orally every 8 hours and meloxicam (0.4 mg/kg) intravenously orally every 24 hours. The pig made progressive clinical improvement and was discharged 7 days after the surgery. [ABSTRACT FROM AUTHOR]

Study Objective: To describe the impact of protocol‐driven dexmedetomidine (and clonidine) use on opioid exposure in post‐surgical neonates. Design: Retrospective chart review. Setting: A Level III, surgical NICU. Patients: Surgical neonates who received clonidine or dexmedetomidine concomitantly with an opioid for sedation and/or analgesia post‐operatively. Intervention: Implementation of a standardized sedation/analgesia weaning protocol. Measurements and Main Results: There were clinically, although not statistically, significant reductions in opioid wean duration (240 vs. 227 h, p = 0.82), total opioid duration (604 vs. 435 h, p = 0.23), and total opioid exposure (91 vs. 51 mg ME/kg, p = 0.13), and limited impact on NICU outcomes or pain/withdrawal scores with use of the protocol. Increases in use of medications in alignment with the protocol (e.g., scheduled acetaminophen and opioids weaned first) were noted. Conclusions: We have been unable to demonstrate a reduction in opioid exposure with use of alpha‐2 agonists alone; addition of a weaning protocol showed a reduction in opioid duration and exposure (although not statistically significant). At this point, dexmedetomidine and clonidine should not be introduced outside standardized protocols with scheduled acetaminophen post‐operatively. [ABSTRACT FROM AUTHOR]

Between 2012 and 2022, the Vancouver Aquarium Marine Mammal Rescue Centre sedated 110 harbor seal pups for physical examinations, diagnostic procedures, or treatment. A sedation protocol of butorphanol and midazolam (0.1–0.2 mg/kg each) was administered via a single i.v. injection in 171 procedures. Of these, 21 pups were anesthetized only with the injectables, while supplemental isoflurane inhalation anesthesia by mask was provided during 58 procedures; 92 other animals required intubation for respiratory support due to apnea or to achieve a deeper plane of anesthesia to facilitate more invasive procedures. Of the 171 sedations, five were euthanized due to poor prognosis and six failed to recover. Maximum sedation, sufficient for intended procedure or anesthesia induction, was achieved within a mean of 8.5 ± 5.8 min for i.v. injection (n = 133). Sedation duration (drug administration to full recovery) without supplemental inhalation anesthesia had a mean of 30.2 min and ranged from 14 to 52 min (n = 13). When used in stabilized young harbor seals, administration of injectable butorphanol and midazolam proved to be an effective protocol to obtain safe and reliable sedation for physical examination, minimally invasive diagnostic procedures, or as a premedication for general anesthesia. [ABSTRACT FROM AUTHOR]

Background. The optimal analgesic dose of S-ketamine after laparoscopic gastrointestinal malignancy surgery remains unclear. This study aimed to evaluate the effect of S-ketamine combined with sufentanil in patient-controlled intravenous analgesia (PCIA) on postoperative pain relief in elderly patients undergoing laparoscopic surgery for gastrointestinal tumors. Methods. Elderly patients undergoing laparoscopic radical resection of gastrointestinal cancer were randomly assigned to one of three postoperative analgesia groups: F group received 2 ug/kg sufentanil in PCIA, LSF group received 0.5 mg/kg S-ketamine and 1.5 ug/kg sufentanil, and SF group received 1 mg/kg S-ketamine and 1 ug/kg sufentanil. The PCIA also contained 0.15 mg/kg of butorphanol and 0.02 mg/kg of ramosetron. Study drugs were administered via PCIA for 48 hours postoperatively. The primary outcome was the accumulated parecoxib sodium requirements within 48 hours after surgery. Results. A total of 105 patients were randomized, and 95 completed the trial (F group: n = 32, LSF group: n = 32, and SF group: n = 31). The cumulative consumption of parecoxib sodium within 48 hours postoperatively was lower in the SF group compared to that in the F group (median difference: −40 mg; 95% confidence interval: −40 to 0; P = 0.0028). The number of PCIA compressions within 48 hours after surgery was smaller in the SF group compared to that in the F group. NRS pain scores at 6 h and 12 h postoperatively were reduced in the SF group compared to that in the F group, both at rest and during movement. Compared to the F group, the incidence of postoperative mild depression was lower, the time to first flatus and time to first defecation were shorter, and the incidence of postoperative vomiting was lower in the SF group. The mechanical pain threshold, hyperalgesia area, and sedation scores were similar between the SF and F groups. No differences were observed in the abovementioned parameters between the LSF group and the F group. Conclusion. This trial demonstrated that 1.0 mg/kg S-ketamine combined with 1 ug/kg sufentanil in PCA decreased cumulative parecoxib sodium consumption within 48 hours after laparoscopic radical resection of gastrointestinal cancer in elderly patients. [ABSTRACT FROM AUTHOR]

Impaired respiratory function reduces haemoglobin oxygen affinity in COVID-19 Keywords: COVID-19; haemoglobin-oxygen affinity; haemoglobin P50; oxyhaemoglobins; PaO2 to fraction of inspired oxygen ratio; SARS-CoV-2 EN COVID-19 haemoglobin-oxygen affinity haemoglobin P50 oxyhaemoglobins PaO2 to fraction of inspired oxygen ratio SARS-CoV-2 e44 e47 4 02/21/23 20230301 NES 230301 Using homology modelling and molecular docking algorithms, Liu and Li predicted the existence of interactions between SARS-Cov-2 and haemoglobin (Hb) and suggested that these interactions may change haemoglobin-oxygen (Hb-O SB 2 sb ) affinity.[1] Hb-O SB 2 sb affinity has been extensively studied in intensive care unit (ICU) patients with COVID-19 (usually intubated and mechanically ventilated) showing normal to increased affinity.[[2], [4]] Higher Hb-O SB 2 sb affinity facilitates Hb oxygenation in the lungs while reducing tissue O SB 2 sb unloading; a reduced Hb-O SB 2 sb affinity has the opposite effect. COVID-19, haemoglobin-oxygen affinity, haemoglobin P50, oxyhaemoglobins, PaO2 to fraction of inspired oxygen ratio, SARS-CoV-2. [Extracted from the article]

A 9‐year‐old, male, 0.69 kg, corn snake was referred for enucleation of its right eye. Pre‐anaesthetic medication consisted of butorphanol (1 mg/kg) and alfaxalone (10 mg/kg) intramuscularly. Orotracheal intubation was then performed. General anaesthesia was maintained with sevoflurane in 100% oxygen. During the general anaesthesia, the snake was manually ventilated. At the end of the surgery, the orbit was packed with a haemostatic sponge soaked in 0.75 mg/kg of 0.5% bupivacaine. Meloxicam (0.4 mg/kg) was administered subcutaneously as a part of the multimodal analgesic protocol. Total anaesthetic time was 90 minutes. Following 2 minutes of sevoflurane discontinuation, the snake started moving and the trachea was extubated. The snake displayed normal behaviour, although a short period of hypothermia was suspected in recovery. No other complications were encountered. The snake was discharged 4 hours after the end of surgery; meloxicam (0.2 mg/kg) was prescribed once daily, orally, for 14 days. [ABSTRACT FROM AUTHOR]

A 6‐month‐old, male peacock (Pavo cristatus) underwent right‐sided corrective tibiotarsal osteotomy under general anaesthesia. Butorphanol (1 mg/kg) and midazolam (1 mg/kg) were administered in the pectoral muscle as pre‐anaesthetic medications. Anaesthesia was induced with intravenous alfaxalone (2.5 mg/kg) and maintained with isoflurane in oxygen. Intermittent positive‐pressure ventilation was applied. A nerve stimulator‐guided femoral nerve block and a nerve stimulator‐ and ultrasound‐guided sciatic nerve block were performed before surgery with lidocaine. An intravenous bolus of ketamine (1 mg/kg), followed by infusion (20 µg/kg/min) was administered intraoperatively. No nociception was recorded during surgery. This case report describes a successful multimodal analgesic technique in a peacock anaesthetised for orthopaedic surgery. [ABSTRACT FROM AUTHOR]

Objective: To describe the effects of gabapentin on ocular and behavioral parameters following oral administration in healthy cats. Materials and methods: Masked, placebo‐controlled, randomized crossover‐design study. Ten young, healthy cats were scheduled for two veterinary visits 7 days apart and randomly assigned to receive a compounded capsule containing 100 mg of gabapentin or placebo (100 mg lactose powder) at the first visit and the opposite treatment at the second visit. Respiratory rate, heart rate, stress score, sedation score, compliance score, horizontal pupil diameter, intraocular pressure, and Schirmer tear test‐1 were measured prior to and 1.5, 3, and 6 h following capsule administration. Stress score, sedation score, and compliance score were assigned based on established behavioral scales. Results of the two treatments were statistically compared with a p‐value <0.05 considered significant. Results: Respiratory rate was significantly reduced at 1.5 (p = 0.049) and 3 (p = 0.03) hours following gabapentin administration. Stress score was significantly reduced at 1.5 (p = 0.01) hours following gabapentin administration. Sedation score was significantly increased at 1.5 (p = 0.015) and 3 (p = 0.03) hours following gabapentin administration. Gabapentin had no significant effect on heart rate, compliance score, or ocular values measured in this study. Conclusions: Gabapentin reduces stress and increases sedation at 1.5 h after treatment, with no significant effect on horizontal pupil diameter, intraocular pressure or Schirmer tear test‐1 results. [ABSTRACT FROM AUTHOR]

The purpose of this study was to improve butorphanol dosing in dogs. Twelve Beagles (6 males, 6 females) were enrolled. Six were randomly allocated to each butorphanol treatment: IV (0.4 mg/kg), IV loading dose (0.2 mg/kg) with IV CRI (0.2 mg/kg/h for 8 h), SC (0.4 mg/kg), SC (0.8 mg/kg) with an equal volume sodium bicarbonate (SC‐bicarbonate), and IV after CYP inhibitors. We hypothesized that the CRI would produce longer durations than IV bolus, and SC‐bicarbonate suspension would produce longer durations than SC. Hypothermia, an opioid effect paralleling antinociception in dogs, and sedation were evaluated. Pharmacokinetics and CYP inhibitor effects on butorphanol pharmacokinetics were determined. Rectal temperatures were significantly lower than baseline from 1.5–4 h (IV), 1–5 h (CRI), and 2–7 h (SC‐bicarbonate), but not after SC. Dogs in all treatments had sedation. Butorphanol's half‐life was ~1.5 h. SC‐bicarbonate had lower bioavailability (61%) relative to SC, with no sustained release, and the CRI mean steady‐state plasma concentration was 43.1 ng/ml. CYP inhibitors had minor pharmacokinetic effects on butorphanol. Butorphanol 0.4 mg/kg IV and 0.2 mg/kg loading dose with 0.2 mg/kg/h CRI decreased rectal temperature, but 0.4 mg/kg SC did not. Further studies are required to determine clinical analgesia of butorphanol. [ABSTRACT FROM AUTHOR]

Background. The objective of this study was to observe the effects of butorphanol as an adjuvant to ropivacaine for the adductor canal block (ACB) on postoperative analgesia in patients undergoing total knee arthroplasty (TKA). Methods. Seventy-four patients undergoing TKA were included and randomly divided into two groups: Group BR received 20 ml of 0.33% ropivacaine plus 1 mg butorphanol and Group R received 20 ml of 0.33% ropivacaine plus 1 ml normal saline for ultrasound-guided adductor canal blocks. The primary outcomes were the duration of the sensory block and the pain visual analogue scale (VAS), and secondary outcomes included the number of PCIA attempts (patient-controlled intravenous analgesia) and the time to first pressing and rescue analgesia. Other outcomes included knee active range of motion (ROM), quadriceps strength, the time to first mobilization, the duration of postoperative hospital stay, Knee Society Score (KSS), and postoperative complications. Results. Since two patients in each group rejected postoperative assessments, 35 patients were included in each group. Compared with Group R, Group BR had longer duration of sensory blocks (18.42 ± 3.46 vs. 15.36 ± 2.29 h, p < 0.01) and lower postoperative pain scores within 24 hours at rest and within 12 hours with activity (p < 0.01). The number of PCIA attempts decreased within 48 hours after surgery (4.5 ± 1.2 vs. 7.8 ± 1.5 times, p < 0.01), and the time to first pressing was later (20.31 ± 2.59 vs. 16.25 ± 2.31 h, p < 0.01). In addition, Group BR had bigger knee ROM at within 24 hours after the operation than Group R (68.37 ± 4.70°vs. 59.21 ± 6.41,85.67 ± 5.17 vs. 74.37 ± 4.68°, 97.62 ± 5.43 vs. 84.18 ± 4.49°, p < 0.01). There was no significant difference between the two groups (p > 0.05) in terms of rescue analgesia, quadriceps strength, the time to first mobilization, the duration of postoperative hospital stay, the KSS function scores, and postoperative complications. Conclusions. Butorphanol plus ropivacaine ultrasound-guided adductor canal block can prolong the duration of sensory block, relieve early postoperative pain, and improve the range of motion of the knee joint, without affecting the occurrence of postoperative complications. Name of the Registry. Chinese Clinical Trial Registry. Trial Registration Number. ChiCTR2100041859. URL of Trial Registry Record. http://www.chictr.org.cn/edit.aspx?pid=119731&htm=4. Date of Registration. 08/01/2021 0:00:00. [ABSTRACT FROM AUTHOR]

A 4‐month‐old, male winter white dwarf hamster and an adult, male winter white dwarf hamster of unknown age were presented for surgical procedures of the face. An injectable anaesthesia protocol with DKMH (dexmedetomidine 0.1 mg/kg, ketamine 20 mg/kg, midazolam 1 mg/kg and hydromorphone 0.4 or 0.8 mg/kg) was administered subcutaneously to anaesthetise each hamster. Anaesthesia was induced in less than 1 minute and a surgical plane of anaesthesia was maintained for the duration of the procedure for both hamsters. Postoperatively, flumazenil (0.1 mg/kg) and atipamezole (1 mg/kg) were administered subcutaneously and the hamsters recovered uneventfully without anaesthetic‐related complications. [ABSTRACT FROM AUTHOR]

A 5‐month‐old female cria with body mass of 30 kg was referred to the Langford Vet farm animal practice for management of a left tibial eminence avulsion fracture. Preanaesthetic medication consisted of xylazine 0.3 mg/kg and butorphanol 0.2 mg/kg intravenously, followed by induction of anaesthesia with ketamine 4 mg/kg intravenously. Anaesthesia was maintained with isoflurane vaporised in oxygen. A multimodal analgesic approach consisting of an ultrasound‐guided sciatic and saphenous nerve block using a combination of 2 mg/kg of lidocaine and 10 μg/kg of detomidine and a continuous infusion of ketamine 25 μg/kg/minute were used. Total anaesthetic time was 375 minutes. The cria received paracetamol 5 mg/kg and flunixin meglumine 2 mg/kg intravenously in the postoperative period. The cria was weight bearing on the operated hind limb 3 hours post‐extubation. Intravenous meloxicam (0.5 mg/kg/day) was administered 24 hours postoperatively for 4 days. Amoxicillin 15 mg/kg intramuscularly every 48 hours was continued until discharge. [ABSTRACT FROM AUTHOR]

A 17‐year‐old, domestic, entire, male, miniature donkey with a history of syncope because of sinus bradycardia, high‐grade second degree and occasional third degree atrioventricular block was referred for pacemaker implantation under general anaesthesia. After local anaesthesia with topical EMLA cream and subcutaneous mepivacaine infiltration and following tranquilisation with intravenous acepromazine, a temporary pacing catheter was inserted via introducer catheter through the left jugular vein into the right ventricle's apex. After initiation of internal pacing, medetomidine and butorphanol were administered intravenously, followed by ketamine and diazepam. Maintenance of anaesthesia was with isoflurane combined with medetomidine and lidocaine constant‐rate infusions. Intramuscular morphine and intravenous medetomidine were administered for recovery. The procedure was uneventful with no anaesthesia‐related complications, and manually assisted recovery was smooth. The present report describes the anaesthetic challenges and management of pacemaker implantation under general anaesthesia in a miniature donkey. [ABSTRACT FROM AUTHOR]

Chemical immobilization is an important tool for the capture, study, and management of wildlife. Increased regulation of traditional opioids has necessitated a search for alternative drugs in wildlife capture. Butorphanol–azaperone–medetomidine (BAM) is one promising alternative that has been used in a range of taxa, though often on medium‐size mammals using ground‐based methods. We tested the efficacy of BAM via remote delivery from a helicopter in a wild population of moose (Alces alces shirasi) in northwestern Wyoming. In March 2020 and 2021, we immobilized male (n = 15) and female (n = 26) moose with butorphanol (0.20 mg/kg), azaperone (0.066 mg/kg), and medetomidine (0.079 mg/kg), with antagonists atipamezole (0.495–0.527 mg/kg) and naltrexone (0.124–0.151 mg/kg) to reverse immobilizations. Mean induction (x̄ ± SE; 9.2 ± 0.6 min) and mean recovery times (7.2 ± 0.5 min) were longer but still comparable to published instances of moose captured using traditional chemical immobilizers (carfentanil, etorphine, thiafentanil). All animals survived >60 days post‐capture. Our findings add to a body of work demonstrating that BAM provides rapid inductions, reliable sedation, and quick reversals in a variety of taxa and by aerial remote delivery. [ABSTRACT FROM AUTHOR]

Background: The use of combinations of α2‐adrenergic agonists and opioids has been published as providing superior sedation than either drug alone. Introduction: The present study aims to compare the sedative and physiological effects of intravenous (IV) administration of medetomidine alone and in combination with methadone, morphine, tramadol, and pethidine in goats. Methods: Ten healthy goats aged 12 ± 3 months and weight of 22 ± 4 kg were used in an experimental, crossover (Latin square), randomized, and blinded study. The animals were assigned to five IV treatments with a minimum washout period of 8 days between treatments: medetomidine (20 μg kg−1), medetomidine/methadone (0.5 mg kg−1), medetomidine/morphine (0.5 mg kg−1), medetomidine/tramadol (5 mg kg−1), and medetomidine/pethidine (1 mg kg−1). Results: Clinical adverse effects such as tremors (facial and generalized), bruxism, nystagmus, mydriasis, and vocalization were presented in all the medetomidine/opioid treatments. Clinical adverse effects were observed at 10–90 minutes in medetomidine/opioid treatments. Animals in all treatments were sedated at 5–90 minutes. Sedation was significantly higher in medetomidine/opioid treatments than in medetomidine at 15–30 minutes after administration (P < 0.05). In all treatments, heart rate and respiratory rate significantly decreased from baseline at 5–105 and 30–60 minutes, respectively. There was no significant difference in heart and respiratory rates between different treatments at any time point. Ruminal motility was decreased in medetomidine and medetomidine/opioid treatments at 10–75 and 10–105 minutes, respectively. Compared with medetomidine, ruminal motility was significantly lower in medetomidine/opioid treatments at 75–105 minutes. Conclusion: The use of combinations of medetomidine/opioids would be considered for superior sedation at 15–30 minutes after administration in goats. No significant differences were detected among opioids in combination with medetomidine in goats. The use of combinations of medetomidine/opioids would be considered for superior sedation at 1530 minutes after administration in goats. No significant differences were detected among opioids in combination with medetomidine in goat. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore the value of computed tomography (CT) images based on electronic health (E-health) combined with painless gastrointestinal endoscopy (PGE) in the diagnosis of neurocognitive function in patients with combined anesthesia of propofol and butorphanol tartrate. 126 patients undergoing PGE were selected as the research objects, and all were performed with CT perfusion imaging before and after anesthesia to obtain the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). The Montreal Cognitive Assessment (MoCA) was adopted to evaluate the cognitive function of patients. The results showed that after anesthesia, the levels of CBF and CBV in the left and right thalami, frontal lobe, and temporal lobe of the patients were lower than those before anesthesia, while TTP and MTT were higher than those before anesthesia (P < 0.05). The MoCA score after anesthesia was lower than that before anesthesia (P < 0.05). After anesthesia, the CBF, CBV, TTP, and MTT values of the left and right frontal lobes and left and right temporal lobes were significantly positively correlated with MoCA (P < 0.05). In conclusion, the brain CT image parameters based on E-health can clearly display the blood perfusion in the lesion area of the patient, which was beneficial to the PGE-assisted judgment of cognitive dysfunction in patients with propofol tartrate and butorphanol tartrate anesthesia. Therefore, CT-assisted PGE examination based on E-health had a certain clinical value in evaluating the neurocognitive function of patients. [ABSTRACT FROM AUTHOR]

This report describes the perioperative anaesthesia and analgesia management of a 4‐month‐old lamb undergoing surgical decompression of a paraspinal abscess while adhering to the drug‐prescribing cascade. This is a legal requirement covered under UK prescribing regulations. Premedication with 2 μg/kg detomidine and 0.1 mg/kg butorphanol preceded induction, with 6 mg/kg ketamine administered to effect. General anaesthesia was maintained with isoflurane in 100% oxygen, 1 μg/kg/h detomidine and 10 μg/kg/min ketamine. Additional analgesia was provided with 10 mg/kg paracetamol, 0.5 mg/kg meloxicam and infiltration of 10 mg lidocaine. Postoperative analgesia was achieved with ketamine 5 μg/kg/min IV, butorphanol 0.1 mg/kg IV q6h, 0.5 mg/kg meloxicam IV q24h and 10 mg/kg paracetamol IV q8h. A withdrawal period of 28 days for meat/offal and 15 days for milk was recommended. Neurological improvement was observed, and the lamb was discharged at 7 days. [ABSTRACT FROM AUTHOR]

Ischemic heart disease is the leading cause of cardiovascular mortality, which is related to cardiac myocyte apoptosis. Butorphanol is an opioid receptor agonist with potential cardioprotective function. The purpose of this work is to explore the function and mechanism of butorphanol in oxygen and glucose deprivation/reperfusion (OGD/R)‐induced cardiomyocyte apoptosis. The overlapping targets of ischemic heart disease and butorphanol were analyzed according to GeneCards, ParmMapper, Cytoscape, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Human cardiomyocyte AC16 cells were incubated with butorphanol and then stimulated with OGD/R. Cell injury was investigated by Cell Counting Kit‐8, lactate dehydrogenase (LDH) assay kit, TUNEL staining, caspase‐3 activity assay kit, and Western blotting. The proteins in signaling pathways were measured using Western blotting. A total of 93 overlapping targets of ischemic heart disease and butorphanol were obtained. Pathway analysis exhibited that these targets might be involved in multiple signaling pathways. Butorphanol alone showed little cytotoxicity to cardiomyocytes, and it protected against OGD/R‐induced viability inhibition, LDH release, cell apoptosis, and increase of caspase‐3 activity and expression levels of cleaved caspase‐3 and Bim. Butorphanol promoted the activation of the phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt)/forkhead box O (FoxO) and hypoxia‐inducible factor‐1α (HIF‐1α)/vascular endothelial growth factor (VEGF) pathways and attenuated the activation of the mitogen‐activated protein kinase (MAPK) signaling in OGD/R‐treated cardiomyocytes. In conclusion, butorphanol prevents OGD/R‐induced cardiomyocyte apoptosis through activating the PI3K/Akt/FoxO and HIF‐1α/VEGF pathways and inactivating the MAPK pathway. The purpose of this work is to explore the function and mechanism of butorphanol in oxygen and glucose deprivation/reperfusion (OGD/R)‐induced cardiomyocyte apoptosis. A total of 93 overlapping targets of ischemic heart disease and butorphanol were obtained. Pathway analysis exhibited that these targets might be involved in multiple pathways. Butorphanol protected against OGD/R‐induced apoptosis. Butorphanol promoted the PI3K/Akt/FoxO and HIF‐1α/VEGF pathways and attenuated the MAPK signaling in OGD/R‐treated cardiomyocytes. In conclusion, butorphanol prevents OGD/R‐induced cardiomyocyte apoptosis through multiple pathways. [ABSTRACT FROM AUTHOR]

Background: Butorphanol–azaperone–medetomidine (BAM™) has not been evaluated in horses. Objectives: The objective of this study was to evaluate BAM™ for chemical restraint of feral horses. Study design: Retrospective and prospective descriptive studies. Methods: Data were collected retrospectively from medical records of 28 feral horses immobilised with BAM™ over a 6‐year period. Prospectively, 0.0125 mL/kg bwt of BAM™ (butorphanol 27.3 mg/mL, azaperone 9.1 mg/mL and medetomidine 10.9 mg/mL) intramuscularly (im) was administered to eight stallions via dart, and once recumbent, 1.0 mg/kg bwt ketamine was given intravenously (iv). Induction and recovery time and quality via a standardised rubric (1 = very poor; 5 = excellent) and visual analogue scale (VAS), need for additional darts, weight tape measurement and serial physiological parameters were recorded. Serial arterial blood gas analysis was performed during recumbency. Following castration, horses were given 0.1 mg/kg bwt atipamezole (25% iv and 75% im) and allowed to recover unaided. Results: Retrospectively, 28 horses were successfully immobilised with BAM™ without a major complication. Prospectively, eight horses were given a median (range) actual BAMTM dose of 0.0143 (0.0127‐0.0510) mL/kg bwt. Three of eight horses needed 1, 2 or 5 additional darts. Median (range) time to recumbency was 11 (2‐44) minutes. Median (range) induction (n = 4) and recovery (n = 6) scores via rubric and VAS were 5 (4‐5) and 5 (5‐5) and 92 (86‐93) and 98 (92‐99) cm, respectively. Four of seven horses were hypoxaemic at ≥1 time point with otherwise acceptable physiological parameters. Following atipamezole, median (range) time to sternal recumbency and standing was 12 (2‐18) and 17 (11‐52) minutes, respectively (n = 6). Main limitations: The sample size was small. Data could not be collected before darting or after recovery. Some data were missing from retrospective analysis. Conclusions: Intramuscular BAM™ with iv ketamine provided chemical restraint suitable for field castration of feral horses with no mortality. Hypoxaemia occurred in the majority of horses. [ABSTRACT FROM AUTHOR]

The combination of midazolam, medetomidine and azaperone (MMA) was compared with the combination of butorphanol, azaperone and medetomidine (BAM) for the sedation of southern ground hornbills when administered orally in a bait. The BAM combination (30 mg butorphanol, 12 mg azaperone and 12 mg medetomidine per ml of solution) at a dose of 0.14 ml/kg was the only combination that did not result in re‐sedation after reversal. However, induction of sedation was long, and sedation was only deep enough for capture, handling, and minor non‐invasive procedures. The MMA combination and higher doses of the BAM combination resulted in quicker inductions although individuals showed mild to severe signs of re‐sedation, starting at 4 hours after reversal and continuing for as long as 17 hours after reversal. Care should therefore be taken when administering these combinations orally to southern ground hornbills as it appears that absorption, metabolism and excretion are unpredictable in this species. [ABSTRACT FROM AUTHOR]

Butorphanol and buprenorphine are mixed opioid receptor agonist‐antagonist drugs widely used as analgesics in people and animals. There are few reports concerning the interaction of multiple opioids, and their antinociceptive effects, when combined with other opioids, remain unclear. Therefore, we report the preliminary findings of the antinociceptive effects of the combined use of butorphanol and buprenorphine in C57BL/6JJcl mice. Both drugs were administered either simultaneously or in different orders. Compared with the baseline values, the tail‐flick and hot‐plate test latencies increased regardless of the order of administration. Furthermore, enhanced latencies were observed on administration of butorphanol followed by buprenorphine. Combined use of these drugs may not attenuate analgesic efficacy. Besides, enhancement of these effects can be obtained by changing the order of the administration of these drugs. It is necessary to further investigate the molecular basis of the underlying mechanism in future definitive studies. [ABSTRACT FROM AUTHOR]

This study characterized the pharmacokinetics of butorphanol in cats anesthetized with isoflurane. Six young healthy male neutered cats were used. Cats were anesthetized with isoflurane in oxygen. Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for butorphanol and lactated Ringer's solution administration. Butorphanol tartrate (1 mg/kg over 5 min) was administered intravenously. Blood samples were collected prior to butorphanol administration and at various times up to 365 min following administration. Plasma butorphanol concentration was measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time‐concentration data using nonlinear mixed effect modeling. A three‐compartment model best fitted the data. Typical value (% interindividual variability) for the three volumes of distribution, the metabolic clearance, and the two distribution clearances were 230 (72), 1095 (not estimated), and 2596 (not estimated) ml/kg, and 18.4 (72), 169.6 (52), and 55.0 (43), respectively. Pharmacokinetic simulation suggested that a loading dose (µg/kg) calculated as 0.287 × target plasma concentration in ng/ml (CT) followed by intravenous infusions (µg/kg/min) of 0.098 × CT for 20 min, 0.049 × CT for 40 min, and 0.022 × CT thereafter would rapidly achieve and maintain CT ± 10% for up to 6.5 h. [ABSTRACT FROM AUTHOR]

Background: A great number of sedatives and anaesthetics have been used to perform surgeries or routine ophthalmologic examinations in animals and sometimes the combination of these medicines has more suitable effects than each one alone. Objectives: This paper aims to explore the main effects of Medetomidine + Acepromazine, Dexmedetomidine + Acepromazine on intraocular pressure, tear secretion and pupil diameter. Methods: To accomplish the aforementioned aim, 32 adult dogs (aged one‐to‐three‐years‐old) were clinically examined. Dogs were divided into four groups consisting of group DA, Dexmedetomidine (5 µg/kg) + Acepromazine (0.05 mg/kg); Group D, Dexmedetomidine (5 µg/kg); Group M, Medetomidine (10 µg/kg); Group MA, Medetomidine (10 µg/kg) + Acepromazine (0.05 mg/kg). The ocular factors including tear production, pupil diameter and intraocular pressure of both right and left eyes were first measured and then recorded in each dog at time T0 (−15 min). Afterwards, the drugs were administered intramuscularly, based on which the ocular factors were re‐measured at T1 (+5 min), T2 (+15 min) and T3 (+20 min). All four groups showed a reduction in intraocular pressure, which was significant in DA, D and M groups. Results: Furthermore, there was a fluctuation in the amount of tear secretion in DA and D groups (increase and then decrease), as well as a significant reduction in M and MA groups. Decreasing in pupil diameter also occurred in all four groups, but the reduction was significant only in DA and MA groups. Conclusion: According to the results obtained, as the changes caused by the systemic administration of the above drug compounds did not exceed the physiological range, it can be concluded that these combinations could be utilized as suitable sedatives or pre‐anaesthetic compounds in the eye surgeries. [ABSTRACT FROM AUTHOR]

The present prospective randomized experimental study aimed to assess the intraperitoneal (ip) administration of lidocaine or tramadol, alone or in combination, on postoperative pain management following ovariohysterectomy in dogs. Eighteen healthy female mixed‐breed dogs, aged 1–2 years, weighed 16.7 ± 3.8 kg, were used. Animals were sedated with acepromazine (0.1 mg/kg, intramuscular). Forty minutes later, anaesthesia was induced through intravenous titration with diazepam (0.5 mg/kg) and ketamine (10 mg/kg) and maintained with isoflurane 1.5%. Afterwards, ovariohysterectomy was performed, and prior to the closure of the linea alba, animals received lidocaine containing epinephrine (8.8 mg/kg, ip) in group L, tramadol (4 mg/kg, ip) in group T and lidocaine containing epinephrine (8.8 mg/kg, ip) plus tramadol (4 mg/kg, ip) in the LT group. Cortisol, vital signs and pain scoring systems were evaluated at different time points. Vital signs did not change among the groups. Cortisol level in the LT group significantly decreased compared to the L and T groups one, three and six hours after surgery. Pain scores also did not change among the groups based on Sammarco and Simple descriptive (SDS) scoring method. However, pain scores in the LT group were higher than the two other groups according to the University of Melbourne pain scale (UMPS) and the short form of Glasgow pain scale (CMPS‐SF). According to the obtained results, the combination of lidocaine and tramadol seemed to be able to provide better analgesia compared with their separate administration. Therefore, combined intraperitoneal administration of lidocaine (8.8 mg/kg) and tramadol (4 mg/kg) with a final volume of (0.2 ml/kg) following ovariohysterectomy is recommended. [ABSTRACT FROM AUTHOR]

The emergence of novel doping agents is a continuous issue for analysts who aim to maintain the integrity of horseracing together with the well‐being and safety of the animals and riders involved. Untargeted mass spectrometric analysis presents a potential improvement for antidoping as it enables the detection of compounds being indirectly affected by an administered drug. In this study, liquid chromatography–high‐resolution mass spectrometry was used to investigate a 12‐horse administration study of the synthetic opioid, butorphanol. A mass spectrometric workflow capable of detecting metabolic differences for an extended period of time was successfully developed. This proof‐of‐concept study demonstrates the potential of untargeted workflows to provide a list of biomarkers of exposure and effect that are indicative of drug administration which may be implemented into routine testing for improved doping control. [ABSTRACT FROM AUTHOR]

Objective: To compare effects of 2 IM sedation protocols, alfaxalone‐butorphanol (AB) versus dexmedetomidine‐butorphanol (DB), on echocardiographic (ECHO) variables in cats following sedation and blood donation. Design: Experimental randomized, blinded crossover study. Setting: University teaching hospital. Animals: Eleven client‐owned healthy cats. Interventions: Cats received a baseline ECHO without sedation prior to their first donation. Cats were sedated intramuscularly with AB (alfaxalone, 2 mg/kg, and butorphanol, 0.2 mg/kg) for 1 donation and DB (dexmedetomidine, 10 μg/kg, and butorphanol 0.2, mg/kg) for another, with a minimum 6 weeks between donations. A post‐sedation, post‐donation ECHO was performed after each blood donation. Measurements and main results: Eight cats completed the study. Compared to baseline, DB combined with blood donation decreased heart rate (−84/min; P < 0.0001), fractional shortening (−16.5%; P < 0.0001), ejection fraction (‐21.0%; P = 0.0002), and cardiac output (−292 mL/min, P = 0.0001); AB combined with blood donation increased heart rate (+45/min; P = 0.0003) and decreased left ventricular end diastolic volume (−1.57 mL; P < 0.0001). Compared to AB, DB decreased heart rate (−129/min; P < 0.0001) and fractional shortening (−21.6%; P < 0.0001) and increased left ventricular end‐systolic (+1.14 mL; P = 0.0004) and diastolic volumes (+1.93 mL; P < 0.0002). Cats administered DB had a significant increase in regurgitant flow across mitral, aortic, and pulmonic valves following blood donation (P < 0.05). One cat administered DB developed spontaneous echo contrast in the left ventricle following donation. Conclusions and clinical relevance: Compared to AB, DB had more pronounced effects on ECHO variables in cats following IM sedation and blood donation. Due to its minimal impact on ECHO variables, AB may be a more desirable sedation protocol in this population of cats. [ABSTRACT FROM AUTHOR]

Key points: This study demonstrates that both CO2‐induced respiratory and cardiovascular responses are augmented in spontaneously hypertensive rats (SHRs).Genetic ablation of the retrotrapezoid nucleus (RTN) neurons depresses enhanced hypercapnic ventilatory response and eliminates CO2‐stimulated increase in arterial pressure and heart rate in SHRs.SHRs have a high protein level of pH‐sensitive channels in the RTN, including the TASK‐2 channel, Kv12.1 channel and acid‐sensing ion channel 3.The inhibition of putative TASK‐2 channel activity by clofilium diminishes amplified hypercapnic ventilatory and cardiovascular responses, and reduces the number of CO2‐activated RTN neurons in SHRs.These results indicate that RTN neurons contribute to enhanced CO2‐stimulated respiratory and cardiovascular responses in SHRs. The respiratory regulation of cardiovascular activity is essential for maintaining an efficient ventilation and perfusion ratio. Activation of central respiratory chemoreceptors not only elicits a ventilatory response but also regulates sympathetic nerve activity and arterial blood pressure (ABP). The retrotrapezoid nucleus (RTN) is the most completely characterized cluster of central respiratory chemoreceptors. We hypothesize that RTN neurons contribute to augmented CO2‐stimulated respiratory and cardiovascular responses in adult spontaneously hypertensive rats (SHRs). Our findings indicate that SHRs exhibit more enhanced hypercapnic cardiorespiratory responses than age‐matched normotensive Wistar–Kyoto rats. Genetic ablation of RTN neurons notably depresses an enhanced hypercapnic ventilatory response (HCVR) and eliminates a CO2‐stimulated greater increase in ABP and heart rate in SHRs. In addition, SHRs have a higher protein level of pH‐sensitive channels in the RTN, including TASK‐2 channels, Kv12.1 channels and acid‐sensing ion channel 3. Administration of clofilium (i.p.), an unselective inhibitor of TASK‐2 channels, not only significantly reduces the enhanced HCVR but also inhibits CO2‐amplified increases in ABP and heart rate in SHRs. Moreover, clofilium significantly decreases the number of CO2‐activated RTN neurons in SHRs. Taken together, we suggest that RTN neurons play an important role in enhanced hypercapnic ventilatory and cardiovascular responses in SHRs and the putative mechanism involved is associated with TASK‐2 channel activity in the RTN. Key points: This study demonstrates that both CO2‐induced respiratory and cardiovascular responses are augmented in spontaneously hypertensive rats (SHRs).Genetic ablation of the retrotrapezoid nucleus (RTN) neurons depresses enhanced hypercapnic ventilatory response and eliminates CO2‐stimulated increase in arterial pressure and heart rate in SHRs.SHRs have a high protein level of pH‐sensitive channels in the RTN, including the TASK‐2 channel, Kv12.1 channel and acid‐sensing ion channel 3.The inhibition of putative TASK‐2 channel activity by clofilium diminishes amplified hypercapnic ventilatory and cardiovascular responses, and reduces the number of CO2‐activated RTN neurons in SHRs.These results indicate that RTN neurons contribute to enhanced CO2‐stimulated respiratory and cardiovascular responses in SHRs. [ABSTRACT FROM AUTHOR]

Background: Anaesthesia is often required in common marmosets undergoing various procedures. The aim of this study was to evaluate anaesthetic and cardiopulmonary effects of alfaxalone, alfaxalone‐ketamine and alfaxalone‐butorphanol‐medetomidine in common marmosets. Methods: The following treatments were repeatedly administered to seven female common marmosets: Treatment A, alfaxalone (12 mg kg‐1) alone; treatment AK, alfaxalone (1 mg animal−1) plus ketamine (2.5 mg animal−1); treatment AMB, alfaxalone (4 mg kg−1), medetomidine (50 µg kg−1) plus butorphanol (0.3 mg kg−1); and treatment AMB‐Ati, AMB with atipamezole at 45 minutes. Results and Conclusions: Marmosets became laterally recumbent and unresponsive for approximately 30 minutes in A and AK and for approximately 60 minutes in AMB. The animals showed rapid recovery following atipamezole injection in AMB‐Ati. The decrease in heart rate and SpO2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered. [ABSTRACT FROM AUTHOR]

Combinations of midazolam, allopregnanolone, and perampanel were assessed for antiseizure activity in a rat diisopropylfluorophosphate (DFP) status epilepticus model. Animals receiving DFP followed by atropine and pralidoxime exhibited continuous high‐amplitude rhythmical electroencephalography (EEG) spike activity and behavioral seizures for more than 5 hours. Treatments were administered intramuscularly 40 min after DFP. Seizures persisted following midazolam (1.8 mg/kg). The combination of midazolam with either allopregnanolone (6 mg/kg) or perampanel (2 mg/kg) terminated EEG and behavioral status epilepticus, but the onset of the perampanel effect was slow. The combination of midazolam, allopregnanolone, and perampanel caused rapid and complete suppression of EEG and behavioral seizures. In the absence of DFP, animals treated with the three‐drug combination were sedated but not anesthetized. Animals that received midazolam alone exhibited spontaneous recurrent EEG seizures, whereas those that received the three‐drug combination did not, demonstrating antiepileptogenic activity. All combination treatments reduced neurodegeneration as assessed with Fluoro‐Jade C staining to a greater extent than midazolam alone, and most reduced astrogliosis as assessed by GFAP immunoreactivity but had mixed effects on markers of microglial activation. We conclude that allopregnanolone, a positive modulator of the GABAA receptor, and perampanel, an AMPA receptor antagonist, are potential adjuncts to midazolam in the treatment of benzodiazepine‐refractory organophosphate nerve agent–induced status epilepticus. [ABSTRACT FROM AUTHOR]

Acute nerve agent exposure induces status epilepticus (SE), which can cause brain damage or death. Research aiming at developing effective therapies for controlling nerve agent–induced SE is commonly performed in adult rats. The characteristics of nerve agent–induced SE in young rats are less clear; relevant knowledge is necessary for developing effective pediatric therapies. Here, we have used electroencephalographic (EEG) recordings and analysis to study seizures in postnatal day 21 rats exposed to 1.2 × LD50 of soman, and compared the antiseizure efficacy of midazolam (MDZ)—currently considered by the Food and Drug Administration to replace diazepam for treating SE in victims of nerve agent exposure—with that of LY293558, an AMPA/GluK1 receptor antagonist, administered in combination with caramiphen, an antimuscarinic with N‐methyl‐d‐aspartate receptor antagonistic properties. Prolonged SE developed in 80% of the rats and was reflected in behavioral seizures/convulsions. Both MDZ and LY293558 + caramiphen stopped the SE induced by soman, but there was a significant recurrence of seizures within 24 h postexposure only in the MDZ‐treated group, as revealed in the raw EEG data and their representation in the frequency domain using a fast Fourier transform and in spectral analysis over 24 hours. In contrast to the high efficacy of LY293558 + caramiphen, MDZ is not an effective treatment for SE induced by soman in young animals. [ABSTRACT FROM AUTHOR]

This study was conducted to compare the efficacy of combinations of morphine, dexmedetomidine and maropitant in preventing the changes in electroencephalographic (EEG) indices of nociception in anaesthetized dogs subjected to a noxious electrical stimulus. In a crossover study, eight healthy adult dogs were randomly allocated to four groups: Mor: morphine 0.6 mg/kg; Dex + Mor: morphine 0.3 mg/kg + dexmedetomidine 5 μg/kg; Maro + Mor: morphine 0.3 mg/kg + maropitant 1 mg/kg; and Dex + Maro + Mor: morphine 0.2 mg/kg + dexmedetomidine 3 μg/kg + maropitant 0.7 mg/kg. Following intramuscular administration of test drugs in a minimal anaesthesia model, a supramaximal electrical stimulus (50 V at 50 Hz for 2 s) was applied and the EEG data were recorded. There were significant increases (p <.05) in the poststimulus median frequency (F50) only in groups Mor and Maro + Mor. Dex + Mor group had a significantly lower change in F50 and F95 compared to all other treatment groups. There was no correlation of the changes in EEG frequencies with blood plasma concentration of the drugs during and after noxious stimulation. Combination of dexmedetomidine and morphine was most effective in abolishing the changes in EEG indices in response to a noxious stimulus indicating a supra‐additive interaction between these two drugs. [ABSTRACT FROM AUTHOR]

Summary: Sedation facilitates the ocular examination in horses. Alpha2‐adrenoceptor agonists are commonly used in equine practice. If the eye is painful, the combination of an α2‐adrenoceptor agonist and butorphanol provides a greater analgesic effect. Unfortunately, little is known about the effects of α2‐adrenoceptor agonists on equine Schirmer tear test I (STT I) values. The aim of the study was to assess the effects of intravenous romifidine, detomidine, detomidine combined with butorphanol, and xylazine on the STT I values in horses. Forty healthy client‐owned Italian saddle horses were enrolled. Horses received 0.04 mg/kg bwt of romifidine or 15 μg/kg bwt of detomidine or 10 μg/kg bwt of detomidine combined with 10 μg/kg bwt of butorphanol or 0.7 mg/kg bwt of xylazine intravenously. The Schirmer tear test strip was inserted into the lateral third side of the inferior conjunctival fornix for 1 min in each eye. The STT I measurements were performed before sedation and at 5, 15, 30, 60, 120 and 180 min after the administration of sedation. The data were analysed by ANOVA. Romifidine did not affect the STT I values. Detomidine significantly reduced the STT I values at 15 min (18.17 ± 0.97 mm/min). The combination of detomidine and butorphanol significantly reduced the STT I values at 30 and 60 min (17.44 ± 0.99, 15.81 ± 0.99 mm/min). Xylazine significantly increased the STT I values at 5, 15 and 30 min (25.17 ± 0.99, 26.72 ± 0.99, 28.07 ± 0.99 mm/min). The STT I values at 180 min were similar to those before sedation. These results suggest that the administration of xylazine or detomidine alone or combined with butorphanol is associated with significant changes in aqueous tear production, whereas romifidine does not affect the STT I values. Romifidine is therefore suitable for chemical restraint to measure tear production in horses. [ABSTRACT FROM AUTHOR]

Background: This study evaluated and compared cardiorespiratory and blood gas parameters, as well as sedation, analgesia and recovery of two protocols: ketamine (10 mg/kg) or dexmedetomidine (10 μg/kg), with midazolam (0.5 mg/kg) and butorphanol (0.3 mg/kg), IM (KBM and DBM, respectively) in brown howler monkeys (Alouatta guariba clamitans). Material and methods: Twelve brown howler monkeys were selected in two groups and evaluated for cardiorespiratory parameters and sedation, from 5‐30 minutes after latency. Blood gas and arterial lactate were taken at 5 and 30 minutes. In the end, time and quality of recovery were evaluated. Results: The HR in DBM group was significantly lower at all times. The sedation score was higher in DBM. Recovery in DBM was faster. All animals had moderate hypoxaemia. Conclusion: Both protocols produce satisfactory anaesthesia and analgesia, but DBM provides deeper sedation with faster recovery. Oxygen supplementation is recommended in both due to hypoxaemia. [ABSTRACT FROM AUTHOR]

Objective: To describe the use of a ketamine‐dexmedetomidine combination and mild hypothermia for the treatment of status epilepticus in 3 dogs that did not respond to GABAergic medication. Case Series Summary: Three dogs, each with a diagnosis of idiopathic epilepsy, were presented to the emergency department in a state of status epilepticus. The dogs were treated unsuccessfully with benzodiazepine as a first‐line therapy that was followed by IV propofol anesthesia maintained for at least 12 hours. When general anesthesia was discontinued, seizures reoccurred. All 3 dogs then received a bolus of ketamine (1 mg/kg, IV) over a period of 5 minutes that was followed by a bolus of dexmedetomidine (3 μg/kg, IV) over the same time period and then followed by a continuous infusion for 12 hours of ketamine at a constant rate of 1 mg/kg/h and dexmedetomidine at a variable rate of 3–7 μg/kg/h. Body temperature was maintained between 36.7 and 37.7°C at a state of mild hypothermia throughout treatment. The dogs recovered uneventfully over 48 hours after treatment was discontinued with no evidence of seizures. No notable alterations in physiological parameters were observed during the drug infusions. All dogs were discharged following examinations that showed normal neurological function. New or Unique Information Provided: This case series highlights the potential benefits of a ketamine‐dexmedetomidine infusion combined with mild hypothermia for the treatment of status epilepticus refractory to GABAergic therapy in dogs suffering from idiopathic epilepsy. After the dogs were weaned from the ketamine‐dexmedetomidine infusion, all dogs experienced complete recovery. Thus, this case series introduces a novel approach to treat this intense condition. [ABSTRACT FROM AUTHOR]

In equine and racing practice, detomidine and butorphanol are commonly used in combination for their sedative properties. The aim of the study was to produce detection times to better inform European veterinary surgeons, so that both drugs can be used appropriately under regulatory rules. Three independent groups of 7, 8 and 6 horses, respectively, were given either a single intravenous administration of butorphanol (100 µg/kg), a single intravenous administration of detomidine (10 µg/kg) or a combination of both at 25 (butorphanol) and 10 (detomidine) µg/kg. Plasma and urine concentrations of butorphanol, detomidine and 3‐hydroxydetomidine at predetermined time points were measured by liquid chromatography–tandem mass spectrometry (LC‐MS/MS). The intravenous pharmacokinetics of butorphanol dosed individually compared with co‐administration with detomidine had approximately a twofold larger clearance (646 ± 137 vs. 380 ± 86 ml hr−1 kg−1) but similar terminal half‐life (5.21 ± 1.56 vs. 5.43 ± 0.44 hr). Pseudo‐steady‐state urine to plasma butorphanol concentration ratios were 730 and 560, respectively. The intravenous pharmacokinetics of detomidine dosed as a single administration compared with co‐administration with butorphanol had similar clearance (3,278 ± 1,412 vs. 2,519 ± 630 ml hr−1 kg−1) but a slightly shorter terminal half‐life (0.57 ± 0.06 vs. 0.70 ± 0.11 hr). Pseudo‐steady‐state urine to plasma detomidine concentration ratios are 4 and 8, respectively. The 3‐hydroxy metabolite of detomidine was detected for at least 35 hr in urine from both the single and co‐administrations. Detection times of 72 and 48 hr are recommended for the control of butorphanol and detomidine, respectively, in horseracing and equestrian competitions. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the pharmacokinetics of morphine in combination with dexmedetomidine and maropitant injected intramuscularly in dogs under general anaesthesia. Eight healthy dogs weighing 25.76 ± 3.16 kg and 3.87 ± 1.64 years of age were used in a crossover study. Dogs were randomly allocated to four groups: (1) morphine 0.6 mg/kg; (2) morphine 0.3 mg/kg + dexmedetomidine 5 μg/kg; (3) morphine 0.3 mg/kg + maropitant 1 mg/kg; (4) morphine 0.2 mg/kg + dexmedetomidine 3 μg/kg + maropitant 0.7 mg/kg. Blood samples were collected before, 15 and 30 min, and 1, 2, 3 4, 6 and 8 hr after injection of the test drugs. Plasma concentration of the drugs was determined by liquid chromatography‐mass spectrometry. The elimination half‐life (T1/2) of morphine was higher and the clearance rate (CL) was lower when combined with dexmedetomidine (T1/2 = 77.72 ± 20.27 min, CL = 119.41 ± 23.34 ml kg−1 min−1) compared to maropitant (T1/2 = 52.73 min ± 13.823 ml kg−1 min−1, CL = 178.57 ± 70.55) or morphine alone at higher doses (T1/2 = 50.53 ± 12.55 min, CL = 187.24 ± 34.45 ml kg−1 min−1). Combining morphine with dexmedetomidine may increase the dosing interval of morphine and may have a clinical advantage. [ABSTRACT FROM AUTHOR]