Validation of the anesthetic effect of a mixture of remimazolam, medetomidine, and butorphanol in three mouse strains.

Proper administration of anesthesia is indispensable for the ethical treatment of lab animals in biomedical research. Therefore, selecting an effective anesthesia protocol is pivotal for the design and success of experiments. Hence, continuous development and refinement of anesthetic agents are imperative to improve research outcomes and elevate animal welfare. "Balanced anesthesia" involves using multiple drugs to optimize efficacy while minimizing side effects. The medetomidine, midazolam, and butorphanol, called MMB, and medetomidine, alfaxalone, and butorphanol, called MAB, are popular in Japan. However, the drawbacks of midazolam, including its extended recovery time, and the narrow safety margin of MAB, have prompted research for suitable alternatives. This study replaced midazolam in the MMB combination with remimazolam (RMZ), which is noted for its ultra-short half-life. The resulting combination, called MRB, was effective in providing a wider safety margin compared to MAB while maintaining an anesthesia depth equivalent level to that of MMB in mice. Notably, MRB consistently exhibited better recovery scores after antagonist administration in contrast to MMB. Furthermore, the re-sedation phenomenon observed with MMB was not observed with MRB. The rapid metabolism of RMZ enables reliable anesthesia induction, circumventing the complications linked to MAB. Overall, MRB excelled in providing extended surgical anesthesia and swift post-antagonist recovery. These results highlight the potential of RMZ for broader animal research applications.

Effect of butorphanol on visceral pain in patients undergoing gastrointestinal endoscopy: a randomized controlled trial.

BACKGROUND: Butorphanol slightly influences the respiratory and circulatory systems, has a better effect on relieving the discomfort caused by mechanical traction, and has a low incidence of postoperative nausea and vomiting (PONV). Combined butorphanol and propofol may suppress postoperative visceral pain, which is avoidable in gastrointestinal endoscopy. Thus, we hypothesized that butorphanol could decrease the incidence of postoperative visceral pain in patients undergoing gastroscopy and colonoscopy. METHODS: This was a randomized, placebo-controlled, and double-blinded trial. Patients undergoing gastrointestinal endoscopy were randomized to intravenously receive either butorphanol (Group I) or normal saline (Group II). The primary outcome was visceral pain after the procedure 10 min after recovery. The secondary outcomes included the rate of safety outcomes and adverse events. Postoperative visceral pain was defined as a visual analog scale (VAS) score ≥ 1. RESULTS: A total of 206 patients were enrolled in the trial. Ultimately, 203 patients were randomly assigned to Group I (n = 102) or Group II (n = 101). In total, 194 patients were included in the analysis: 95 in Group I and 99 in Group II. The incidence of visceral pain at 10 min after recovery was found to be statistically lower with butorphanol than with the placebo (31.5% vs. 68.5%, respectively; RR: 2.738, 95% CI [1.409-5.319], P = 0.002), and the notable difference was in pain level or distribution of visceral pain (P = 0.006). CONCLUSIONS: The trial indicated that adding butorphanol to propofol results in a lower incidence of visceral pain after surgery without noticeable fluctuations in circulatory and respiratory functions for gastrointestinal endoscopy patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT04477733 (PI: Ruquan Han; date of registration: 20/07/2020).

Cardiopulmonary effects and recovery characteristics associated with 2 sedative protocols for assisted ventilation in healthy neonatal foals.

Neonatal foals may require prolonged sedation to permit ventilatory support in the first few days of life. The objective of this study was to evaluate and compare the cardiopulmonary effects and clinical recovery characteristics of 2 sedative/analgesia protocols in healthy foals receiving assisted ventilation. Foals were randomized to receive dexmedetomidine, butorphanol, and propofol (DBP) or midazolam, butorphanol, and propofol (MBP) during a 24-hour period. Infusion rates of dexmedetomidine, midazolam, and propofol were adjusted and propofol boluses administered according to set protocols to maintain optimal sedation and muscle relaxation. Ventilatory support variables were adjusted to preset targets. Physiologic variables were recorded, cardiac output (CO) measured (thermodilution), and arterial and mixed venous blood collected for gas analysis at intervals up to 24 hours. Foals in group DBP received dexmedetomidine [2.4 ± 0.5 µg/kg body weight (BW) per hour], butorphanol (13 µg/kg BW per hour), and propofol (6.97 ± 0.86 mg/kg BW per hour), whereas foals in group MBP received midazolam (0.14 ± 0.04 mg/kg BW per hour), butorphanol (13 µg/kg BW per hour), and propofol (5.98 ± 1.33 mg/kg BW per hour). Foals in the DBP group received significantly more propofol boluses (9.0 ± 3.0) than those in the MBP group (4.0 ± 2.0). Although physiologic variables remained within acceptable limits, heart rate (HR), mean arterial pressure (MAP), and cardiac index (CI) were lower in foals in the DBP group than in the MBP group. Times to sternal recumbency, standing, and nursing were significantly shorter in the DBP than MBP group. We found that MBP and DBP protocols are suitable to assist ventilatory support in neonatal foals, although MBP results in a prolonged recovery compared to DBP.

Les poulains nouveau-nés peuvent nécessiter une sédation prolongée pour permettre une assistance ventilatoire au cours des premiers jours de vie. L'objectif de cette étude était d'évaluer et de comparer les effets cardio-pulmonaires et les caractéristiques de récupération clinique de deux protocoles sédatifs/analgésiques chez des poulains sains recevant une ventilation assistée. Les poulains ont été randomisés pour recevoir de la dexmédétomidine, du butorphanol et du propofol (DBP) ou du midazolam, du butorphanol et du propofol (MBP) pendant une période de 24 heures. Les débits de perfusion de dexmédétomidine, de midazolam et de propofol ont été ajustés et des bolus de propofol ont été administrés selon des protocoles définis pour maintenir une sédation et une relaxation musculaire optimales. Les variables d'assistance ventilatoire ont été ajustées à des cibles prédéfinies. Les variables physiologiques ont été enregistrées, le débit cardiaque (CO) mesuré (thermodilution) et le sang artériel et veineux mixte prélevé pour analyse des gaz à des intervalles allant jusqu'à 24 h. Les poulains du groupe DBP ont reçu de la dexmédétomidine [2,4 ± 0,5 µg/kg de poids corporel (PC) par heure], du butorphanol (13 µg/kg de PC par heure) et du propofol (6,97 ± 0,86 mg/kg de PC par heure), tandis que les poulains du groupe MBP ont reçu du midazolam (0,14 ± 0,04 mg/kg de PC par heure), du butorphanol (13 µg/kg de PC par heure) et du propofol (5,98 ± 1,33 mg/kg de PC par heure). Les poulains du groupe DBP ont reçu significativement plus de bolus de propofol (9,0 ± 3,0) que ceux du groupe MBP (4,0 ± 2,0). Bien que les variables physiologiques soient restées dans des limites acceptables, la fréquence cardiaque (FC), la pression artérielle moyenne (MAP) et l'index cardiaque (IC) étaient plus faibles chez les poulains du groupe DBP que dans le groupe MBP. Les temps de décubitus sternal, de station debout et d'allaitement étaient significativement plus courts dans le groupe DBP que dans le groupe MBP. Nous avons constaté que les protocoles MBP et DBP sont adaptés pour assister l'assistance ventilatoire chez les poulains nouveau-nés, bien que le MBP entraîne une récupération prolongée par rapport au DBP.(Traduit par Docteur Serge Messier).

BUTORPHANOL, AZAPERONE, AND MEDETOMIDINE ANESTHESIA IN FREE-RANGING EASTERN MOOSE (ALCES AMERICANUS).

Fifty-three free-ranging moose (Alces americanus) cows were darted from a helicopter with 3-4 ml of a premix combination of butorphanol (27.3 mg/ml), azaperone (9.1 mg/ml), and medetomidine (10.9 mg/ml; BAM), equivalent to estimated dosages of: butorphanol 0.26 ± 0.08 (mean ± SD) mg/kg, azaperone 0.09 ± 0.03 mg/kg, and medetomidine 0.11 ± 0.03 mg/kg. After a mean chase time (from sighting to darting) of 6.1 ± 5.5 min, the mean induction time (from darting to recumbency) was 8.3 ± 2.6 min. This combination provided a safe and reliable sedation for minor procedures that lasted 30-60 min. Heart rate (50.4 ± 7.0 beats/min), respiratory rate (21.3 ± 11.1 breaths/minute), ETCO2 via nasal canula (43.2 ± 7.0 mmHg), and rectal temperature (38.5°C ± 0.7°C) mostly remained at expected values for wild cervid and bovid species anesthetized with this drug combination. SpO2 (90.0% ± 3.7%) was suggestive of moderate hypoxemia despite intranasal oxygen supplementation (1 L per 100 kg/min). The recovery time to standing was 6.7 ± 3.8 min after reversal with IM naltrexone (3 mg/mg butorphanol) and atipamezole (5 mg/mg medetomidine). Despite a larger volume to inject, this protocol offers an alternative to highly potent opioids, and should be considered for practical or staff safety reasons. On the basis of the results of this study, the use of 4 ml of BAM is considered a safe and effective protocol for immobilization of cow moose under comparable settings.

Effect of Packaging Materials and the Leached Iron on the Stability of Butorphanol Tartrate Injection.

The aim of this study was to investigate the effect of various parameters on the stability of butorphanol tartrate injection and to screen the optimal packaging material. The effect of the headspace oxygen levels, ampoule color, manufacturer, and size on the stability of butorphanol tartrate formulation were evaluated. The headspace oxygen levels controlled by nitrogen purging were found to be particularly effective in improving stability of the butorphanol formulation, especially below 2%. Although it is a photolabile drug, butorphanol tartrate was getting degraded at much higher extent in amber color ampoules in comparison to clear ampoules. The degradation by oxidation was found to be a free radical-mediated process catalyzed by the presence of iron ions leached from the amber ampoules. The ampoule manufacturers also had a significant effect on the stability of butorphanol. Two-milliliter ampoules provided a better stability of the butorphanol tartrate injection than 1mL ampoules as 2-mL ampoules had the lower headspace oxygen level at the same level of oxygen content. The oxidation mechanism of the butorphanol tartrate injection was investigated under various conditions, which include iron powder spiking, removal of excipients, exposure to oxygen/nitrogen, exposure to stainless steel and at different pH. Iron powder spiking, presence of citric acid, exposure to oxygen, exposure to stainless steel, and high pH accelerated the oxidative degradation. The effect of oxygen, iron ion and citric acid is in agreement with a metal-catalyzed oxidation mechanism called Udenfriend reaction. Based on the formulation test results, limiting headspace oxygen level, ampoule color, manufacturer, size, controlling iron ion contamination, and pH are recommended for formulation development. In conclusion, it can be suggested that this study can lead to a better understanding of the degradation mechanism of butorphanol tartrate; hence, it would contribute to the development of butorphanol tartrate injection with improved stability. Virous packaging materials have different effects on the stability of butorphanol tartrate injection, and the leached iron of packaging ampoules and stainless steel can trigger Udenfriend reaction with butorphanol tartrate and citric acid (CA), which lead to the oxydative degradation of butorphanol tartrate injection.

EVALUATING THE USE OF A BUTORPHANOL-AZAPERONE-MEDETOMIDINE FIXED-DOSE COMBINATION FOR STANDING SEDATION IN AFRICAN ELEPHANTS (LOXODONTA AFRICANA).

This study investigated the use of a fixed-dose combination of 30 mg/ml butorphanol, 12 mg/ml azaperone, and 12 mg/ml medetomidine for the standing sedation of captive African elephants (Loxodonta africana). In total, seven females (mean age 19.6 yr; range 6-31 yr) and six males (mean age 33.5 yr; range 9-35 yr) were sedated. The estimated dose was 0.0005 ± 0.0001 ml/kg and 0.006 ± 0.001 ml/cm shoulder height, which resulted in a dose of 0.016 ± 0.002 mg/kg or 0.19 ± 0.04 mg/cm shoulder height butorphanol, 0.006 ± 0.0008 mg/ kg or 0.076 ± 0.015 mg/cm shoulder height azaperone, and 0.006 ± 0.0008 mg/kg or 0.076 ± 0.015 mg/cm medetomidine. First signs of sedation were observed within 3-10 min (mean 6 ± 2 min) after darting, and monitoring of the animals started on average at 24 ± 9 min after darting. No bradycardia was observed in any of the elephants (mean heart rate 40.0 ± 6.55 beats/min), although all the animals were mildly hypotensive (mean blood pressure 118.5/86 [94.5]). Rectal temperatures fell within acceptable ranges, and respiratory parameters were stable in all the animals throughout sedation and fell within the standard ranges reported for conscious, standing elephants. Only one elephant had clinically significant hypoxemia characterized by a partial pressure of oxygen (PaO2) < 60 mm Hg. This elephant was also hypercapnic (PaCO2 > 50 mm Hg), although pH and peripheral capillary oxygen saturation fell within acceptable ranges. None of the elephants reacted to moderately painful stimuli while sedated. The combination was reversed with intramuscular injections of naltrexone (1 mg for every 1 mg butorphanol) and atipamezole (5 mg for every 1 mg medetomidine). Recovery was smooth and calm in all the animals. Time from injection of the reversals until the first signs of recovery was 4.6 ± 2.01 min (range 1-8 min).

Comparison of sedation quality and safety of detomidine and romifidine as a continuous rate infusion for standing elective laparoscopic ovariectomy in mares.

OBJECTIVE: To compare efficacy and safety of a continuous rate infusion of detomidine hydrochloride and romifidine hydrochloride for standing elective bilateral laparoscopic ovariectomy in mares. STUDY DESIGN: Blinded, randomized prospective clinical study. ANIMALS: Eighteen healthy mares presenting for elective bilateral ovariectomy METHODS: Mares were randomly assigned to one of two sedation protocols. Prior to surgery, baseline head height, heart rate, respiratory rate, and postural sway were recorded. An IV loading dose of α2-agonist (46 µg/kg romifidine or 13.9 µg/kg detomidine) was administered. Standing sedation was maintained with a continuous rate infusion of the respective α2-agonist (126 µg/kg/h romifidine or 37.8 µg/kg/h detomidine). Intraoperative measurements included respiratory rate, heart rate, head height, postural sway, and response to surgical stimulus. Postoperatively, fecal output was recorded, and pain scoring was performed using composite pain score and visual analog scales. RESULTS: Three of 18 horses required additional α-2 agonists: one detomidine and two romifidine and butorphanol. Head height during surgery was lower (p < .001) in mares receiving detomidine. Postural sway around the vertical axis was greater in mares sedated with detomidine rather than romifidine (p = .013). No differences were detected in intraoperative heart rate, postoperative pain scores or postoperative fecal output between sedation techniques. CONCLUSION: Comparable scores for surgical stimulation and sedation were measured in both sedation groups. No differences in postoperative analgesia or manure production were identified. CLINICAL SIGNIFICANCE: Romifidine appears suitable as an alternative to detomidine and may limit ataxia and head drop in sedated horses.

The Effectiveness and Safety of Intravenous Dexmedetomidine of Different Concentrations Combined with Butorphanol for Post-Caesarean Section Analgesia: A Randomized Controlled Trial.

PURPOSE: The present study aimed to determine the effectiveness of intravenous dexmedetomidine of different concentrations and to evaluate its maternal and neonatal safety when combined with butorphanol in parturients undergoing cesarean section. PATIENTS AND METHODS: A total of 114 parturients between 24 and 43 years of age, with singleton pregnancy who underwent elective cesarean section under epidural anesthesia, were randomly allocated to four groups: group C received 0.9% sodium chloride after delivery, followed by butorphanol (3 µg·kg-1·h-1); patients in groups D1, D2, and D3 received 0.5 µg·kg-1·h-1 dexmedetomidine after delivery, followed by butorphanol (3 µg·kg-1·h-1) combined with dexmedetomidine 0.03, 0.05, and 0.08 µg·kg-1·h-1, respectively. The primary outcome was the visual analogue scale (VAS) score at 6 h after delivery when patients were at rest. Secondary outcome measures included VAS after delivery when patients were on movement and uterine cramping, Ramsay sedation scale (RSS), relative infant dose (RID) of dexmedetomidine, satisfaction with analgesia after surgery and symptoms of CNS depression in neonates. RESULTS: There were no significant differences in patient characteristics among the groups (P > 0.05). The VAS at all timepoints after delivery in groups D2 and D3 were significantly lower than in groups C and D1 (P < 0.001). RSS scores were clearly higher in group D3 than in the other three groups at 6 h and 12 h (P < 0.0001). RID in groups D1, D2, and D3 was 0.171%, 0.197%, and 0.370%, respectively. Compared with group D1, RID was higher in group D3 (P = 0.0079). Degree of satisfaction with analgesia was higher in groups D2 and D3 (P < 0.005). CONCLUSION: Continuous intravenous infusion of 0.05 µg·kg-1·h-1 dexmedetomidine combined with 3 µg·kg-1·h-1 butorphanol could be safely applied in healthy parturients with satisfactory analgesia after cesarean section without changes in sedation.

DEXMEDETOMIDINE, BUTORPHANOL, AND MIDAZOLAM AS A REVERSIBLE INDUCTION PROTOCOL IN NORTH AMERICAN RIVER OTTERS (LONTRA CANADENSIS).

Captured free-ranging North American river otters (Lontra canadensis) were immobilized for the placement of intra-abdominal radio transmitters in cooperation with the Iowa Department of Natural Resources. Twenty-four otters were induced with dexmedetomidine (0.03 mg/kg, IM), butorphanol (0.2 mg/kg, IM), and midazolam (0.15 mg/kg, IM) combined in one syringe. The otters were maintained on isoflurane during the surgical procedure. Heart rate and rhythm, respiratory rate, rectal temperature, and peripheral capillary oxygen saturation were recorded every 5 min for the duration of the procedures. The otters were reversed with atipamezole (0.3-2 mg/kg, IM), naltrexone (0.6 mg/kg, IM), and flumazenil (0.05 mg/kg, IM). Rapid and smooth induction was seen, with lateral recumbency reached within 6.2 ± 5.6 min. Episodes of resedation were seen in four otters that received 0.3 mg/kg atipamezole so the dose was increased to 1 mg/kg, and no further resedation events were noted. Two fatal complications occurred secondary to suspected respiratory arrest during recovery. This drug protocol provided a smooth and rapid induction in free-ranging river otters, but further research is required to determine the safety of this protocol for river otters in both zoo and free-ranging situations.

SEDATIVE AND CARDIORESPIRATORY EFFECTS OF INTRAMUSCULAR ALFAXALONE AND BUTORPHANOL AT TWO DOSAGES IN FERRETS (MUSTELA PUTORIUS FURO).

Veterinary care of ferrets often requires chemical restraint. This study hypothesized that IM alfaxalone and butorphanol would result in clinically useful sedation without clinically relevant cardiorespiratory effects. Twelve healthy 15-mo-old ferrets of equal sexes weighing 0.75 to 1.66 kg were enrolled. Using a prospective, blinded design, ferrets randomly received either IM alfaxalone 2.5 mg/kg and butorphanol 0.2 mg/kg (low dose [LD]) or IM alfaxalone 5 mg/kg and butorphanol 0.2 mg/kg (high dose [HD]) (n = 6/group). Sedation times and induction and recovery scores were recorded by a blinded observer. Anesthetic monitor placement was attempted in all recumbent ferrets, and physiologic parameters and reflexes were recorded every 5 min until return of spontaneous movement. Data were assessed for normality using a Shapiro-Wilk normality test and analyzed by two-sample t test or Mann-Whitney U test; one ferret in HD was excluded. Ferrets in LD and HD exhibited moderate and marked sedation, with one of six and four of five ferrets tolerating monitor placement, respectively. Mean ± SD time to first effects, recumbency, and recovery in LD and HD was 2.30 ± 1.13 and 2.054 ± 1.12 (P = 0.7240), 2.87 ± 1.25 and 2.72 ± 1.41 (P = 0.8529), and 65.43 ± 32.43 and 52.30 ± 13.19 (P = 0.4212), respectively. Median (range) duration of recumbency in LD and HD was 31.12 (25.58-115.72) and 35.47 (28.27-44.42) min (P = 0.3290), respectively. Among monitored ferrets, transient mild hypotension and hypoxemia were observed. Intramuscular alfaxalone 5 mg/kg with butorphanol 0.2 mg/kg provided clinically useful sedation in ferrets with mild transient cardiorespiratory derangements.

Plasma prolactin, thyroid-stimulating hormone, melanocyte-stimulating hormone, and adrenocorticotropin responses to thyrotropin-releasing hormone in mares treated with detomidine and butorphanol.

Stress or excitement is a concern when performing endocrine tests on fractious horses. Sedation may be a solution; however, perturbation of test results may preclude useful information. Thyrotropin-releasing hormone (TRH) is a known stimulator of prolactin, thyroid-stimulating hormone (TSH), melanocyte-stimulating hormone (MSH), and ACTH. Thyrotropin-releasing hormone-induced ACTH is a diagnostic tool for the assessment of endocrinopathies such as pituitary pars intermedia dysfunction. It is unknown if drugs commonly used for sedation alter endocrine responses. The objective of this study was to assess the effects of detomidine (DET) and butorphanol on endocrine responses to TRH. Nine light horse mares were used in a replicated 3 × 3 Latin square with the following treatments: saline, DET, and detomidine + butorphanol (DET/BUT), all administered intravenously at 0.01 mg/kg BW. A 1-wk washout period was allowed between phases, all of which were performed in December. Blood samples were collected at -10 and 0 min before treatment and 5 and 10 min post-treatment. Administration of 1 mg TRH occurred 10 min post-treatment, and blood sampling continued 5, 10, 20, and 30 min post-TRH. Data were analyzed by ANOVA as a replicated Latin square with repeated sampling. Plasma prolactin increased (P < 0.0001) after TRH in all groups, rapidly peaking at 5 min in drug-treated mares and 40 min in saline-treated mares. The peak prolactin response to TRH was 2-fold higher (P < 0.0001) in saline-treated mares compared with those drug-treated. A peak rise in plasma TSH was observed in DET/BUT-treated mares 10 min after TSH and was greater (P ≤ 0.007) compared with DET- and saline-treated mares. Plasma MSH was stimulated (P = 0.001) by DET and DET/BUT before TRH, and the peak MSH response to TRH was greater (P < 0.0001) in drug-treated mares, although not hastened as observed with prolactin and TSH. A peak rise in ACTH was observed in drug-treated mares 5 min after administration of TRH, whereas a peak rise was observed in control mares 10 min post-TRH and was almost 2-fold lower (P = 0.05) than the peak observed in DET and DET/BUT-treated mares. Basal ACTH concentrations were not affected by DET or DET/BUT, indicating that sedation with these compounds may be achieved when needing to measure basal plasma ACTH. Treatment with DET and DET/BUT did alter the prolactin, TSH, MSH, and ACTH responses to TRH; therefore, the use of these drugs may not be advisable when assessing endocrine responses to TRH stimulation.

A modified silent substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs.

OBJECTIVE: A previously published study successfully isolated photoreceptor responses from canine rods, long/medium-wavelength (L/M) cones, and short-wavelength (S) cones using silent substitution electroretinography (ERG) performed under general anesthesia. We hypothesized that responses would be similar in dogs under sedation and that a curtailed protocol suitable for use in clinical patients could effectively isolate responses from all three photoreceptor subtypes. ANIMALS STUDIED: Three normal adult purpose-bred beagles (2 females and 1 male). METHODS: Dogs were dark-adapted for 1 hour. Sine wave color stimuli were delivered using LEDs in a Ganzfeld dome. The ERG protocol under anesthesia was performed as previously published; sedated ERG protocols were performed after a 3-day washout period. Intravenous sedation (dexmedetomidine 1.25 mcg/kg, butorphanol 0.1 mg/kg) was administered for sedation. Statistical analysis was performed using two-way repeated-measures ANOVA and linear regression. RESULTS: In both anesthetized and sedated animals, rod-derived responses peaked at low frequency (4-12 Hz), L/M-cone responses peaked at high frequency (32-38 Hz), and S-cone responses peaked at low frequency (4-12 Hz). The frequencies eliciting maximal responses were similar in sedated and anesthetized protocols, although rod amplitudes were significantly higher in the sedated protocols compared with anesthetized (P < .001). CONCLUSION: We present a clinically applicable method to consistently isolate rod and cone subclass function in sedated dogs. This may allow detailed evaluation of photoreceptor function in clinical patients with rod or cone subclass deficits without the need for general anesthesia or protracted adaptation times.

Cats undergoing spay with medetomidine, ketamine and butorphanol develop arterial oxygen desaturation independent of surgical positioning and increased intraocular pressure in Trendelenburg position.

INTRODUCTION: This study observed the effects of three different surgical positions on arterial blood oxygenation measured noninvasively by pulse oximetry (SpO2) and on intraocular pressure (IOP) in anaesthetised cats undergoing spay. A total of 222 female feral cats were anaesthetised for a large-scale trap-neuter-return program with an intramuscular combination of medetomidine (0.03 - 0.05 mg/kg), ketamine (7 - 10 mg/kg) and butorphanol (0.4 mg/kg). Cats were randomly allocated to undergo spay in either Trendelenburg (70° downward head tilt), lateral or dorsal recumbency. SpO2 and pulse rate were measured at baseline, prior to surgical positioning, after one minute in surgical position and in one-minute intervals after surgical incision. Intraocular pressure was measured before positioning and at the end of surgery. At the end of surgery, all cats were placed into left lateral recumbency and all parameters were revaluated after five minutes. No significant differences between the three positions were found regarding SpO2, but an increase over time was observed. In total, 52 ± 10% (mean ± SD) of cats were hypoxaemic (SpO2 < 90%) at baseline. SpO2 improved over time, but 27 ± 3% (mean ± SD) of the cats remained hypoxaemic at the end of surgery. Trendelenburg position increased IOP during surgery (mean 31 ± 6 mmHg, individual max. 48 mmHg, versus 17 ± 4 mmHg in dorsal/lateral recumbency) but normalised after 5 mins in lateral recumbence. All cats recovered well from surgery and were released within 24 hours post-anaesthesia. Surgical position was shown to have no notable influence on SpO2 during anaesthesia in cats not receiving oxygen supplementation, whereas Trendelenburg position led to increased IOP. Oxygen supplementation is recommended with this anaesthetic protocol, as hypoxaemia is frequently observed.

INTRODUCTION: Dans cette étude, on a observé les effets de trois positions chirurgicales différentes sur l'oxygénation du sang artériel mesurée de manière non invasive par oxymétrie de pouls (SpO2) et sur la pression intraoculaire (PIO) chez des chattes anesthésiées subissant une stérilisation. Un total de 222 chattes sauvages ont été, dans le cadre d'un large programme de piégeage-castration-libération, anesthésiées avec une combinaison de médétomidine (0,03 à 0,05 mg/kg), de kétamine (7 à 10 mg/kg) et de butorphanol (0,4 mg/kg) par voie intramusculaire. Les chattes ont été réparties au hasard pour subir une stérilisation en Trendelenburg (inclinaison de la tête à 70 ° vers le bas), en décubitus latéral ou dorsal. La SpO2 et la fréquence du pouls ont été mesurées au départ, avant le positionnement chirurgical, après une minute en position chirurgicale et à des intervalles d'une minute après l'incision chirurgicale. La pression intraoculaire a été mesurée avant le positionnement et à la fin de la chirurgie. À la fin de la chirurgie, toutes les chattes ont été placées en décubitus latéral gauche et tous les paramètres ont été réévalués après cinq minutes. Aucune différence significative entre les trois positions n'a été constatée concernant la SpO2, mais une augmentation au fil du temps a été observée. Au total, 52 ± 10% (moyenne ± SD) des chattes étaient hypoxémiques (SpO2.

Clinical effects of two doses of butorphanol with detomidine for intravenous premedication of healthy warmblood horses.

OBJECTIVE: To compare the effects of two different doses of butorphanol combined with detomidine administered intravenously (IV) on quality of sedation, degree of ataxia and anaesthetic induction in horses. STUDY DESIGN: Randomized, blinded, clinical study. ANIMALS: A total of 40 client-owned healthy warmblood horses scheduled for elective surgery under general anaesthesia. METHODS: Horses were randomly allocated to be administered 8 µg kg-1 detomidine IV plus either 20 or 50 µg kg-1 butorphanol IV, with the principal investigator blinded to group allocation. Head height was measured before drug injection and 2 minutes thereafter. Data were compared using unpaired t test. Horses were filmed and scored using Simple Descriptive Scales for sedation (2 and 15 minutes after IV injection), ataxia (at walk, immediately after the 2 minute time point) and quality of swing-door induction following diazepam and ketamine administration. Data are shown as median (and range where appropriate). Scores were compared using chi-square tests (p < 0.05). RESULTS: There were 14 and 17 horses in high-dose (HD) and low-dose (LD) groups respectively. Data from nine horses were excluded. Mean head height reduction did not differ between groups (p = 0.86), nor did sedation scores at 2 minutes (median = 3 in both groups; p = 0.09) or 15 minutes (median = 2 in both groups; p = 0.63). There was no significant difference in the requirement for additional detomidine (p = 0.73) or in induction quality between groups (p = 0.99), but initial ataxia was significantly greater in the HD group 2 (1-3) versus 2.5 (1-3) in the LD group (p = 0.017). CONCLUSIONS AND CLINICAL RELEVANCE: In healthy warmblood horses, simultaneous administration of 50 rather than 20 µg kg-1 butorphanol with 8 µg kg-1 detomidine does not provide greater sedation or affect induction, but it causes more pronounced ataxia shortly after IV injection.

Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol, on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs.

OBJECTIVE: To investigate the impact of intramuscular (IM) co-administration of the peripheral α2-adrenoceptor agonist vatinoxan (MK-467) with medetomidine and butorphanol prior to intravenous (IV) ketamine on the cardiopulmonary and anaesthetic effects in dogs, followed by atipamezole reversal. STUDY DESIGN: Randomized, masked crossover study. ANIMALS: A total of eight purpose-bred Beagle dogs aged 3 years. METHODS: Each dog was instrumented and administered two treatments 2 weeks apart: medetomidine (20 µg kg-1) and butorphanol (100 µg kg-1) premedication with vatinoxan (500 µg kg-1; treatment MVB) or without vatinoxan (treatment MB) IM 20 minutes before IV ketamine (4 mg kg-1). Atipamezole (100 µg kg-1) was administered IM 60 minutes after ketamine. Heart rate (HR), mean arterial (MAP) and central venous (CVP) pressures and cardiac output (CO) were measured; cardiac (CI) and systemic vascular resistance (SVRI) indices were calculated before and 10 minutes after MVB or MB, and 10, 25, 40, 55, 70 and 100 minutes after ketamine. Data were analysed with repeated measures analysis of covariance models. A p-value <0.05 was considered statistically significant. Sedation, induction, intubation and recovery scores were assessed. RESULTS: At most time points, HR and CI were significantly higher, and SVRI and CVP significantly lower with MVB than with MB. With both treatments, SVRI and MAP decreased after ketamine, whereas HR and CI increased. MAP was significantly lower with MVB than with MB; mild hypotension (57-59 mmHg) was recorded in two dogs with MVB prior to atipamezole administration. Sedation, induction, intubation and recovery scores were not different between treatments, but intolerance to the endotracheal tube was observed earlier with MVB. CONCLUSIONS AND CLINICAL RELEVANCE: Haemodynamic performance was improved by vatinoxan co-administration with medetomidine-butorphanol, before and after ketamine administration. However, vatinoxan was associated with mild hypotension after ketamine with the dose used in this study. Vatinoxan shortened the duration of anaesthesia.

Evaluation of anaesthetic and cardiorespiratory effects after intramuscular administration of alfaxalone alone, alfaxalone-ketamine and alfaxalone-butorphanol-medetomidine in common marmosets (Callithrix jacchus).

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.

Improvement of a twice collection method of mouse oocytes by surgical operation.

Mouse oocytes are generally collected after euthanasia. However, if oocytes were collected without euthanasia, then mice could be used to collect oocytes again after recovery. This condition is especially useful for mice that are genotypically rare. In this study, we examined the reusability of mice after collecting oocytes via a surgical operation. When oocytes were collected using medetomidine/midazolam/butorphanol combination anesthesia and examined for the quality of oocytes after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), they could develop to full term at the same rate as controls. When oocytes were collected from those mice a second time, the average number of oocytes was reduced by nearly 1/3. However, the blastocyst and offspring rates of those oocytes after IVF or ICSI were the same as those of the control regardless of the recovery day period. Although germinal vesicle (GV) oocytes can be collected from all reused mice, the final number of offspring did not increase. Interestingly, when oocytes were collected from the front position of the ampulla, 76% of the oviducts possessed oocytes after reuse, and the average number of oocytes significantly increased to a level comparable to that of the control. Finally, we examined whether reused mice can be used as recipient females, and then healthy offspring were obtained similarly as the control recipients. In conclusion, we provide a new method to collect a sufficient number of oocytes from reused mice without concern.

EVALUATION OF TWO ANESTHETIC COMBINATIONS IN LOWLAND NYALA (TRAGELAPHUS ANGASII).

Fourteen lowland nyala (Tragelaphus angasii) in managed care were successfully anesthetized for a total of 17 anesthetic events using either a combination of butorphanol (0.75 ± 0.15 mg/kg), azaperone (0.25 ± 0.05 mg/kg), and medetomidine (0.30 ± 0.06 mg/kg) (BAM) or medetomidine (0.17 ± 0.01 mg/kg), azaperone (0.22 ± 0.02 mg/kg), and alfaxalone (0.52 ± 0.08 mg/kg) (MAA) delivered intramuscularly via dart. Mean time to initial effect, sternal recumbency, lateral recumbency, handling, and intubation were recorded. The nyala were maintained in sternal recumbency with supplemental oxygenation until 60 min after initial injection. Cardiopulmonary effects were recorded every 5 min after handling until reversal. Arterial blood samples were collected every 15 min for analysis. Level of sedation and quality of recovery were scored. Anesthesia was antagonized with atipamezole (at 5 mg per mg of medetomidine) for both protocols and naltrexone (at 2 mg per mg of butorphanol) for the BAM protocol delivered intramuscularly via hand injection. Mean time to extubation, head control, and standing post reversal were recorded. No hyperthermia, acidemia, apnea, or tachycardia occurred; however, animals did display hypoxemia. Two animals in the BAM cohort required supplementation to facilitate handling. These drug combinations provided satisfactory levels of sedation in most cases for safe handling and minor procedures in lowland nyala under managed care.

Anesthetic efficacy of propofol combined butorphanol in laparoscopic surgery for ectopic pregnancy: A protocol of systematic review and meta-analysis.

BACKGROUND: Recent studies have suggested that propofol combined butorphanol (PB) has anesthetic effect in laparoscopic surgery (LS) for ectopic pregnancy (EP). But investigations of its potential effects are inconsistent. We will explore the current literature examining PB in LS for EP. METHODS: We will perform a comprehensive search from MEDLINE, Embase, Cochrane Library, PsycINFO, Global Health, Web of Science, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure from inception to the present. Other literatures, such as conference abstracts, references to the relevant reviews will also be checked. Two authors will check the titles, abstracts, and full texts independently. They will also independently carry out data collection and study quality assessment. We will conduct statistical analysis using RevMan 5.3 software. RESULTS: This study will provide accurate results on the anesthetic effect and safety of PB in LS for EP. CONCLUSION: This study will establish high-quality evidence of the anesthetic effect and safety of PB in LS for EP to facilitate the clinical practice and guideline development. STUDY REGISTRATION NUMBER: INPLASY202040044.