Search

Cancer is one of the leading causes of morbidity and mortality in the global population. The effective management of cancer-associated pain and anesthesia are critical aspects of comprehensive cancer treatment. However, the role and mechanism of anesthesia and analgesia-related drugs in tumors remain controversial. In this study, the efficacy of 16 commonly used analgesics and anesthetics against non-small cell lung cancer (NSCLC) was evaluated. Among the 16 examined injections, butorphanol tartrate injection significantly inhibited the proliferation of NSCLC cells and increased the sensitivity of the EGFR-TKI-resistant H1975 cell line to gefitinib. Benzethonium chloride (BC) is the main active antitumor ingredient of butorphanol tartrate injection. BC may regulate the cell cycle, apoptosis and EMT signaling pathways by modulating the P53 signaling pathway. Our study reveals the therapeutic value of butorphanol tartrate injection and BC in the treatment of NSCLC and provides a theoretical basis for comprehensive therapies for NSCLC., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests. Ethical approval and consent to participate: All animal experiments were approved by the Animal Ethics Committee of the Zhejiang Academy of Traditional Chinese Medicine and were conducted according to the Guidelines for the Care and Use of Animals for Scientific Research. Consent for publication: The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

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 α 2 -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., (© 2024 EVJ Ltd.)

Chickens ( Gallus gallus domesticus ) are commonly used for research, food production, show, and companionship. Sedation is often necessary for sample collection, imaging, or treatment. Dexmedetomidine has been previously used to sedate birds, often with other sedatives. Butorphanol tartrate, a Schedule IV controlled substance, is commonly used but presents regulatory challenges. Nalbuphine hydrochloride, an opioid with similar receptor affinity to butorphanol, has potential as a noncontrolled alternative. Although information regarding nalbuphine use in birds is limited, its noncontrolled status makes it more accessible. The purpose of this study was to determine the effective dose to produce sedation in 50% (ED 50 ) of patients and to estimate the calculated effective dose of dexmedetomidine in combination with either butorphanol (DexBut) or nalbuphine (DexNal) in domestic hens to sedate 99% of patients (ED 99 ). Eighteen 33-week-old laying Buff Orpington hens were divided into 2 groups: one receiving DexBut (n = 9) and the second receiving DexNal (n = 9). Each hen was sedated with varying doses of intramuscular dexmedetomidine with a constant dose of either 2 mg/kg IM butorphanol or 12.5 mg/kg IM nalbuphine by an up-and-down design. Sedation was determined using a clinically applicable scoring system. The ED 50 values of dexmedetomidine with 2 mg/kg IM of butorphanol, calculated by both the up-and-down method and logistic regression, were 38 and 49 µg/kg, respectively, while the ED 50 values of dexmedetomidine in combination with 12.5 mg/kg IM of nalbuphine were 19 and 18 µg/kg, respectively. The estimated dexmedetomidine ED 99 values with butorphanol or nalbuphine were 51 and 19 µg/kg, respectively. Multiple chickens in both groups exhibited open-mouth breathing and comb pallor but no lasting morbidity or mortality occurred. Combinations of DexBut or DexNal should be considered for sedation of domestic chickens.

Chemical immobilization is commonly used to capture and handle free-ranging elk (Cervus canadensis). Butorphanol-azaperone-medetomidine (BAM) and nalbuphine-medetomidine-azaperone (NalMed-A) are compounded drug combinations that are lower-scheduled in the US than drugs historically used for elk immobilizations. We compared BAM and NalMed-A for immobilization of free-ranging elk using free-darting and Clover trapping. From January 2020 to April 2022, 196 female elk were immobilized in Pennsylvania, USA. We report vital rates, induction and recovery times, and the need for supplemental drugs. We built mixed-effects logistic regression models to describe differences between drug choice based on induction and recovery times, capture method, and individual variation. Several models were competing, including our null model, which suggests that BAM and NalMed-A are comparable based on the parameters we evaluated. Supplemental drug administration was more frequently needed in NalMed-A immobilizations (21.2%) than in BAM immobilizations (9.0%). Overall, we found minor differences between BAM and NalMed-A, both of which appear to be effective for immobilizing elk in both free-darting and Clover trapping scenarios when performing moderately invasive, minimally painful procedures on free-ranging elk., (© Wildlife Disease Association 2024.)

Objective: To evaluate if opioid-induced behavioral effects, such as sedation, can be detected using a shuttle box experimental apparatus and whether thermal preference following noxious stimulation using mustard oil is reversed by morphine administration in fish., Methods: 5 goldfish (Carassius auratus) underwent 2 randomized blinded experimental trials, with a crossover study design. First, opioid effects were tested in a shuttle box without painful stimulus. Fish were injected 5 days apart with butorphanol at 0.4 or 10 mg/kg, morphine at 5 or 10 mg/kg, or saline IM. After 30 minutes, each fish was placed in a shuttle box for 2 hours with a temperature gradient of 26 to 28 °C. Temperature preference, time spent immobile, and swimming velocity were assessed. The second trial consisted of cutaneous noxious stimulation using mustard oil immersion for 5 minutes followed by an assessment of thermal preference for 4 minutes in the shuttle box after either morphine at 10 mg/kg or saline IM injections. Linear mixed models were used to compare treatment groups., Results: Before noxious stimulation, a low dose of morphine caused sedation compared with control group and high-dose morphine and butorphanol treatments. Immersion in mustard oil caused fish to spend more time in the cold area in the control group. Morphine administration reversed this pattern., Conclusions: The sedative and analgesic effects of opioids were detected through this model., Clinical Relevance: The shuttle box model could be used to assess the analgesic effects of other opioids in goldfish while reducing biases associated with the sedative and stimulatory effects of these drugs.

Objective: This study evaluated the 50% effective dose (ED 50 ) and 95% effective dose (ED 95 ) of butorphanol tartrate in patients undergoing painless gastroscopy., Methods: Patients who underwent painless gastroscopy at Binzhou Medical University Hospital were divided into the youth, middle-aged, and older groups. The ED 50 and ED 95 required for successful sedation using butorphanol tartrate were measured using the Dixon up-and-down method in patients in the different age groups. Patients in each group were administered intravenous butorphanol 5 minutes before gastroscopy. Each patient was administered 2 mg/kg propofol. The ED 50 and ED 95 of butorphanol were calculated using probit analysis., Results: In total, 95 patients were included. The ED 50 s of butorphanol in the youth, middle-aged, and older groups were 7.384, 6.657, and 6.364 μg/kg, respectively. The ED 95 s of butorphanol doses in these groups were 9.108, 8.419, and 7.348 μg/kg, respectively., Conclusions: The ED 50 and ED 95 varied among the age groups, indicating that the effective dose decreases with age., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Administration of butorphanol, azaperone, and medetomidine (BAM) for immobilization of black howler monkeys ( Alouatta pigra ) has not been previously reported. In this observational study, 0.02 ml/kg of compounded BAM (butorphanol 27.3 mg/ml, azaperone 9.1 mg/ml, medetomidine 10.9 mg/ml) was administered IM in 10 captive black howler monkeys. Time to immobilization was recorded, an arterial blood gas performed, and at 5-min intervals, HR, RR, oscillometric arterial blood pressure, SPO 2, and rectal temperature were measured. Naltrexone and atipamezole were administered IM at procedure completion and recovery times were recorded. If invasive procedures such as surgery were necessary and additional drugs needed, further data from that individual was removed from data analysis. Final BAM dosages were 0.55 ± 0.12 mg/kg butorphanol, 0.19 ± 0.04 mg/kg azaperone, and 0.22 ± 0.05 mg/kg medetomidine. Nine of 10 monkeys achieved sedation allowing for physical exam, venipuncture, and tuberculin skin testing within 4 ± 2 min. No monkeys reached a plane of immobilization allowing for intubation. Physiologic variables were acceptable for this species. Hypoxemia (SPO 2 < 95%) was observed in three monkeys via pulse oximetry, and normoxemia was observed on arterial blood gas. Recovery was smooth and rapid. Therefore, BAM is a viable option for noninvasive procedures or as a premedication prior to induction of anesthesia in black howler monkeys.

Twenty lesser chevrotains ( Tragulus sp.), 10 males and 10 females, were anesthetized with a combination of butorphanol-midazolam-medetomidine (BMidM), to assess the efficacy of this protocol for short procedures in this genus. The animals received BMidM (0.32, 0.06, 0.15 mg/kg, respectively) intramuscularly via hand injection. Physiological variables were recorded once the animals reached a working depth of anesthesia that lasted 30 min (range 12-60 min). At the end of the procedure, medetomidine and butorphanol were antagonized with atipamezole (0.75 mg/kg) and naltrexone (0.3 mg/kg) intramuscularly, respectively. Induction and recovery were 9.4 ± 4.0 min and 10.2 ± 4.1 min, respectively. Supplementation with isoflurane via face mask was required in five animals to reach light anesthesia. Times to reach the various stages of anesthesia were compared between sexes. There was no difference between males and females reaching the different stages of anesthesia, except for the time required to reach the ambulatory stage, in which females took a significantly longer time (11.8 min vs 7.8 min for the males) to stand after the injection of the antagonists ( P = 0.02). Heart rate, respiratory rate, rectal temperature, and peripheral hemoglobin oxygen saturation were similar between sexes and stable throughout the procedure. At the dosage tested BMidM was a reliable and safe protocol for short, minimally invasive procedures in lesser chevrotains with a fast induction and smooth recovery without complications.

Objective: To compare the effects of intranasal (IN) and intramuscular (IM) midazolam-butorphanol-ketamine on intraocular pressure (IOP), tear production (TP) and sedation in rabbits., Study Design: Prospective, randomized, crossover experimental study., Animals: Fourteen male New Zealand White rabbits, aged 1-2 years, body mass 3.1 ± 0.8 kg (mean ± standard deviation)., Methods: Rabbits were administered midazolam (1 mg kg -1 ), butorphanol (1.5 mg kg -1 ) and ketamine (5 mg kg -1 ) via IN and IM routes. IOP, TP and sedation scores were assessed at 0 (before drug administration), 5, 15, 30, 45 and 60 minutes after drug administration. Heart rate (HR), respiratory rate (f R ), rectal temperature (RT), noninvasive mean arterial blood pressure (MAP) and peripheral hemoglobin oxygen saturation (SpO 2 ) were simultaneously recorded until 45 minutes after drug administration. The onset and duration of sedation and sedation scores were recorded., Results: Drug delivery route had no significant impact on mean IOP (p = 0.271) or TP (p = 0.062), and there were no significant changes over time for IOP (p = 0.711) or TP (p = 0.372). Similarly, delivery route had no significant impact on HR (p = 0.747), f R (p = 0.872), RT (p = 0.379), MAP (p = 0.217) and SpO 2 (p = 0.254). Sedation onset was faster with IN (3.0 ± 1.0 minutes) than with IM administration (4.9 ± 0.7 minutes) (p = 0.011), but sedation duration was significantly longer with IM (52.6 ± 7.2 minutes) than with IN delivery (30.7 ± 6.8 minutes) (p = 0.004). There was no significant difference in sedation scores between the two delivery routes at any of the recorded time points., Conclusions and Clinical Relevance: The combination of midazolam-butorphanol-ketamine had minimal impact on physiological and ocular variables regardless of the route of administration, whereas IN drug administration led to a shorter onset and duration of action than IM administration., (Copyright © 2024 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

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., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

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., (© 2024 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

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 (C max ) and time to maximum concentration (T max ) 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., (© 2024 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.)

Purpose: To evaluate the effect of post-surgical photobiomodulation therapy in dogs., Methods: Twenty dogs were selected for elective gastropexy and randomly divided into a control (CG, n = 10) and a PBMT group (PBMTG, n = 10). Pre‑medication consisted of medetomidine and butorphanol. Meloxicam was administered before the procedure. Induction was performed with propofol and maintained with sevoflurane. Local blocks with lidocaine were used. Incisional gastropexy was performed in all animals. PBMTG received PBMT immediately after surgery. The need for postoperative rescue analgesia, if the animal had eaten by the evaluation momen, and pain scores were collected using the Glasgow Composite Measure Pain Scale - Short Form (CMPS‑SF) at 1, 2, 4, 6, 8, 12, 16, 20, and 24 h post‑endotracheal extubation. CMPS‑SF scores were compared with the Mann-Whitney Test and proportions of animals that required rescue analgesia and had eaten with a χ 2 test. P was set at < 0.05., Results: No rescue analgesia was needed for any animal. Still, significant differences were observed in CMPS-SF scores between CG and PBMTG between 1 and 4 h post-extubation. PBMTG had a significantly higher proportion of animals eating up to the 8 h post-extubation evaluation moment., Conclusion: Adding post-surgical photobiomodulation to a standard anesthesia and analgesia protocol reduced CMPS-SF scores and increased the proportion of animals that resumed eating compared to the standard protocol alone., (© 2024. The Author(s).)

General anesthesia in calves is easier to perform under field conditions, total intravenous anesthesia (TIVA) than using inhalation anesthesia. In the present study, cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry were assessed during continuous infusion of a combination solution of 0.01% xylazine, 0.001% butorphanol, and 0.2% propofol (XBP) at doses of 6 (G6; 10 μg/kg/min xylazine, 1 μg/kg/min butorphanol, 200 μg/kg/min propofol) and 9 mL/kg/h (G9; 15 μg/kg/min xylazine, 1.5 μg/kg/min butorphanol 300 μg/kg/min propofol). For both groups, five castrated Holstein calves received intravenous injections of xylazine (0.2 mg/kg) and propofol (2 mg/kg), followed by a continuous infusion of XBP for 60 min to maintain anesthesia. Respiratory management consisted of tracheal intubation followed by spontaneous inhalation of pure oxygen. Cardiopulmonary, anesthesia, hematology, and blood biochemistry variables were assessed at rest (baseline) and every 5 or 15 min after the start of the XBP infusion. Quality of arousal was assessed based on the swallowing reflex recovery time from the stop of XBP infusion, and the sternal position time and standing time after atipamezole administration. XBP produced adequate sedation, analgesia, and muscle relaxation in all calves and maintained stable anesthesia for 60 min. As XBP infusion time passed, rectal temperature and heart rate became lower, and mean arterial blood pressure increased. In both groups, hematologic and blood biochemical effects were mild. The quality of arousal was not different, and all calves were standing. The results of the present study suggested that XBP is useful for TIVA in calves., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The decontamination process for plumage-contaminated wild birds, such as those affected by oil spills, is lengthy and involves manual restraint and manipulation of all body parts. Birds commonly react to this in ways that suggest they are extremely stressed (eg, struggling, vocalizing). We proposed to reduce stress during the wash process using sedation and hypothesized that the use of sedation would not negatively impact survival. Contaminated birds in need of washing were randomly selected to be either sedated (butorphanol 2 mg/kg IM + midazolam 1 mg/kg IM and flumazenil 0.1 mg/kg IM for reversal) or not sedated at 3 US rehabilitation centers over the course of 1 year. Response to sedation was rated on a scale of 0-4 with 0 as no effect to 4 as excessively sedate. Data such as cloacal temperatures at various time points, lengths of various portions of the wash process, preening behavior in the drying pen, and disposition were collected. No statistical differences were found between sedated and nonsedated birds for any of the data points collected, including survival. There was a significant association between birds with higher cloacal temperatures in the drying pen and with birds held longer in the drying pen with improved survival; however, these findings were unrelated to whether the birds were sedated. Our findings show that sedation with butorphanol 2 mg/ kg IM and midazolam 1 mg/kg IM reversed with flumazenil 0.1 mg/kg IM can be used during the wash process for wild birds without adverse effects. Careful attention must be given to heat support for all birds while drying to prevent hypothermia.

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.

Background: The intramuscular (IM) administration of 7.5-10 mg/kg of alfaxalone produces anesthetic effects that enable endotracheal intubation with mild cardiorespiratory depression in dogs. However, the effects of IM co-administration of medetomidine, butorphanol, and alfaxalone on cardiorespiratory function under inhalation anesthesia have not been studied., Aim: To assess the cardiorespiratory function following the IM co-administration of 5 μg/kg of medetomidine, 0.3 mg/kg of butorphanol, and 2.5 mg/kg of alfaxalone (MBA) in dogs anesthetized with sevoflurane., Methods: Seven intact healthy Beagles (three males and four females, aged 3-6 years old and weighing 10.0-18.1 kg) anesthetized with a predetermined minimum alveolar concentration (MAC) of sevoflurane were included in this study. The baseline cardiorespiratory variable values were recorded using the thermodilution method with a pulmonary artery catheter after stabilization for 15 minutes at 1.3 times their individual sevoflurane MAC. The cardiorespiratory variables were measured again following the IM administration of MBA. Data are expressed as median [interquartile range] and compared with the corresponding baseline values using the Friedman test and Sheff's method. A p < 0.05 was considered statistically significant., Results: The intramuscular administration of MBA transiently decreased the cardiac index [baseline: 3.46 (3.18-3.69), 5 minutes: 1.67 (1.57-1.75) l/minute/m 2 : p < 0.001], respiratory frequency, and arterial pH. In contrast, it increased the systemic vascular resistance index [baseline: 5,367 (3,589-6,617), 5 minutes:10,197 (9,955-15,005) dynes second/cm 5 /m 2 : p = 0.0092], mean pulmonary arterial pressure, and arterial partial pressure of carbon dioxide., Conclusion: The intramuscular administration of MBA in dogs anesthetized with sevoflurane transiently decreased cardiac output due to vasoconstriction. Although spontaneous breathing was maintained, MBA administration resulted in respiratory acidosis due to hypoventilation. Thus, it is important to administer MBA with caution to dogs with insufficient cardiovascular function. In addition, ventilatory support is recommended., Competing Interests: The authors declare that there is no conflict of interest.

Aim: The aim of this study was to investigate whether multimodal analgesia can decrease postoperative opioid usage in patients undergoing shoulder arthroscopy., Methods: Patients diagnosed with subacromial impingement syndrome who underwent acromioplasty at our institution between October 2022 and November 2023 were retrospectively analyzed. Patients were divided into an observation group and a control group based on postoperative pain management methods. The control group received intravenous self-controlled electronic analgesia (sufentanil injection 1 μg/kg + butorphanol injection 4 mg + 0.9% NaCl injection to 100 mL), while the observation group received multimodal analgesia (ropivacaine subacromial pump 3 mL/h, combined with oral celecoxib and acetaminophen). Visual Analog Scale (VAS) scores were recorded preoperatively and at various postoperative time points, and opioid usage, length of hospital stay, and analgesia-related complications within 1 week postoperatively were compared between groups. The 36-item Short Form Health Survey (SF-36) scores and the Constant-Murley score (CMS), were also assessed 1 day and 1 week after treatment., Results: One hundred thirty-two patients were included in the study, 66 in the observation group and 66 in the control group. In the control group, there were 46 males and 20 females, with a mean age of 55.47 ± 11.42 years and in the observation group 44 males and 22 females, with a mean age of 56.13 ± 12.19 years The observation group consistently reported significantly lower pain intensity compared to the control group at 8 h (T1), 24 (T2), and 48 h (T3) after surgery (p < 0.05). Additionally, the observation group exhibited significantly lower opioid usage and complication rates compared to the control group (p < 0.05). SF-36 scores and CMS scores were significantly higher in the observation group 1 week after treatment compared to the control group (p < 0.05)., Conclusions: Following shoulder arthroscopy, multimodal analgesia effectively reduces opioid consumption, lowers complication rates, and provides effective short-term pain relief. This approach carries significant implications for improving patient outcomes.

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)., (© 2023. The Author(s).)

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., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

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., (© 2021 American College of Veterinary Surgeons.)

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.

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), ETCO 2 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. SpO 2 (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.

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 (PaO 2 ) < 60 mm Hg. This elephant was also hypercapnic (PaCO 2 > 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).

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., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Liu et al.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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.

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., (© 2020 American College of Veterinary Ophthalmologists.)

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 SpO 2 was significantly greater in AMB compared to A and AK. Oxygen supplementation, anaesthetic monitors and atipamezole should be available especially when AMB is administered., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The efficacy, safety, physiologic effects, and reversibility of butorphanol-medetomidine-midazolam (BMM) immobilization were evaluated in black-footed cats ( Felis nigripes ) and compared between captive and wild animals. Nine captive and 14 wild black-footed cats were hand injected into an accessible hind limb muscle group with the BMM combination. The captive cats (captive group) received a lower dose of the combination (butorphanol, 0.25 ± 0.03 mg/kg; medetomidine, 0.06 ± 0.01 mg/kg; midazolam, 0.13 ± 0.02 mg/kg), whereas the wild cats received a higher dose (butorphanol, 0.53 ± 0.11 mg/kg, medetomidine, 0.13 ± 0.03 mg/kg, midazolam, 0.27 ± 0.05 mg/kg). Two capture methods were required to restrain the wild cats; previously collared cats were tracked and excavated out of their burrows during daylight hours (excavated group), whereas uncollared cats were randomly located using spotlights and pursued by a vehicle at night (pursued group). Inductions were rapid and no spontaneous arousals occurred. Mean arterial blood pressure in all cats was within normal limits for domestic cats. Initial rectal temperatures varied greatly among the groups, but decreased in all groups as the immobilization progressed. In the pursued animals, heart rates and respiratory rates were initially elevated. All cats had moderate hypoxemia, hypocapnia, and metabolic acidosis. Intramuscular administration of naltrexone, atipamezole, and flumazenil resulted in rapid, uncomplicated recoveries. BMM is thus a safe, effective immobilizing drug combination for both captive and wild black-footed cats, but higher doses are required in wild animals. The capture methods exerted a greater influence on the physiology of the immobilized animals than did the doses of the drugs used. Although this drug combination can be used safely to immobilize black-footed cats, supplemental oxygen should always be available for use, especially in pursued animals due to hypoxia.

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.

The tranquilizer combination of butorphanol, azaperone, and medetomidine (BAM) has shown good efficacy for immobilization of wildlife, including black bears (Ursus americanus). BAM is antagonized with a combination of naltrexone and atipamezole. We immobilized 19 adult captive wild caught black bears and, except for three bears that were euthanized immediately, bears were recovered with naltrexone and atipamezole. Tissue residues (≥0.01 ppm) for the tranquilizers butorphanol, azaperone, and medetomidine were detected in liver and muscle of all three bears euthanized on day 0 postinjection (PI). Azaperone was not detected after 1 d PI. Residue for medetomidine was detected in two bears: in the liver 3 d PI and in the kidney 6 d PI. Butorphanol was reported in three bears: in fat 5 d PI, in kidney 6 d PI, and, surprisingly, in kidney, muscle, and fat 7 d PI. No tissue residues were detected in the three bears euthanized at 8 d PI. Tissue residues for the antagonists, naltrexone and atipamezole, were detected in bears euthanized 2 and 6 d PI, but not in tissues from animals euthanized at 7 or 8 d PI., (© Wildlife Disease Association 2020.)

Objective: To investigate the impact of intramuscular (IM) co-administration of the peripheral α 2 -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., (Copyright © 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

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., (Copyright © 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

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.

Objectives: The aim of this study was to compare the effects of butorphanol and buprenorphine, as part of a multimodal analgesic protocol, on recovery and analgesia in cats undergoing orchiectomy., Methods: In a prospective, randomized, blind clinical trial, 47 adult male cats were randomly assigned to receive either butorphanol (0.3 mg/kg, n = 24) or buprenorphine (0.02 mg/kg, n = 23) in combination with dexmedetomidine (25 μg/kg) and alfaxalone (2 mg/kg) as a single intramuscular injection for the induction of general anesthesia. Isoflurane carried in oxygen was supplemented as needed during orchiectomy. All cats received lidocaine (2 mg/kg intratesticular), meloxicam (0.3 mg/kg SC) and atipamezole (125 μg/kg IM) postoperatively. Pain and sedation scales were applied at baseline, and 2, 4 and 6 h postoperatively. Time to achieve sternal recumbency and to begin eating were also recorded., Results: Pain scale scores were low and showed no difference between the treatment groups at all time points ( P ⩾0.99, all time points). Four cats exceeded the analgesia intervention threshold for rescue analgesia (butorphanol, n = 3; buprenorphine, n = 1). There was no difference in sedation scores between groups at any time point ( P >0.99, all time points). Significantly more cats in the buprenorphine group (n = 12) required isoflurane than in the butorphanol group (n = 2) ( P  = 0.0013; relative risk 6.3, 95% confidence interval [CI] 1.8-23.5). There was no significant difference in time to achieve sternal recumbency ( P  = 0.96, 95% CI -20 to 20) between groups or in return to eating ( P  = 0.48, 95% CI -92.0 to 113.5), with most cats eating within 1 h of surgery (butorphanol, 79%; buprenorphine, 83%)., Conclusions and Relevance: There were no significant differences in analgesia or recovery between butorphanol and buprenorphine treatment groups as part of a multimodal injectable anesthetic protocol. Butorphanol is associated with superior depth of anesthesia, facilitating injectable anesthesia.

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.

Background: Butorphanol, a synthetic opioid partial agonist analgesic, has been widely used to control perioperative pain. However, the ideal dose and availability of butorphanol for gastrointestinal (GI) endoscopy are not well known. The aim of this study was to evaluated the 95% effective dose (ED 95 ) of butorphanol and sufentanil in GI endoscopy and compared their clinical efficacy, especially regarding the recovery time., Methods: The study was divided into two parts. For the first part, voluntary patients who needed GI endoscopy anesthesia were recruited to measure the ED 95 of butorphanol and sufentanil needed to achieve successful sedation before GI endoscopy using the sequential method (the Dixon up-and-down method). The second part was a double-blind, randomized study. Two hundred cases of painless GI endoscopy patients were randomly divided into two groups (n = 100), including group B (butorphanol at the ED 95 dose) and group S (sufentanil at the ED 95 dose). Propofol was infused intravenously as the sedative in both groups. The recovery time, visual analogue scale (VAS) score, hand grip strength, fatigue severity scores, incidence of nausea and vomiting, and incidence of dizziness were recorded., Results: The ED 95 of butorphanol for painless GI endoscopy was 9.07 μg/kg (95% confidence interval: 7.81-19.66 μg/kg). The ED 95 of sufentanil was 0.1 μg/kg (95% CI, 0.079-0.422 μg/kg). Both butorphanol and sufentanil provided a good analgesic effect for GI endoscopy. However, the recovery time for butorphanol was significantly shorter than that for sufentanil (P < 0.05, group B vs. group S:21.26 ± 7.70 vs. 24.03 ± 7.80 min)., Conclusions: Butorphanol at 9.07 μg/kg was more effective than sufentanil for GI endoscopy sedation and notably reduced the recovery time., Trial Registration: Chinese Clinical Trail Registry (Registration number # ChiCTR1900022780; Date of Registration on April 25rd, 2019).

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.

Kawai et al. (2011) recently introduced a mixture of three anesthetic agents (here called MMB) that has an effect similar to ketamine/xylazine in mice, which might allow more effective reaction to changes in the animal condition, as an antagonist is available, and which can be used without license for handling narcotic drugs. Using Kawai's study as a baseline, we tested whether this anesthesia and its antagonist can also be used in avian studies. In the present study, we used two species, the zebra finch and the Bengalese finch, of the avian family Estrildidae. In zebra finches, anesthesia effects similar to the use of ketamine/xylazine and to those obtained in mice can be reached by the use of MMB if a higher dose is applied. MMB leads to more variable anesthesia, but has the advantage of a longer time window of deep anesthesia. An antagonist to one component of MMB reduced the awaking time, but was not as effective as in mice. For Bengalese finches, MMB cannot be generally recommended because of difficult handling and high mortality rate when used without antagonist, but could be used for perfusions instead of pentobarbital.

Twenty-one free-ranging warthogs ( Phacochoerus africanus ) in the Kruger National Park, South Africa, were immobilized with a combination of medetomidine (0.07 ± 0.01 mg/kg), butorphanol (0.26 ± 0.04 mg/kg), tiletamine-zolazepam (0.69 ± 0.15 mg/kg), and ketamine (1.43 ± 0.21 mg/kg) administered intramuscularly by dart. Induction, immobilization, and recovery characteristics were evaluated using a standardized scoring system. In the immobilized warthogs, physiological variables were measured every 5 min and arterial blood gases were analyzed at 15-min intervals. At 45 min after initial drug administration, atipamezole (0.34 ± 0.050 mg/kg) and naltrexone (0.53 ± 0.079 mg/kg) were administered intravenously. Overall, induction quality after darting was scored as excellent and the mean time to safe handling was 5.9 ± 2.0 min. Based on muscle relaxation, and loss of palpebral and pedal reflexes, most subjects (17 out of 21) reached a plane of surgical anesthesia by 10 and 15 min; 20 out of 21 warthogs were in this plane for the duration of the monitoring period. In the immobilized warthogs the overall mean heart rate was 65 ± 15.3 beats per minute, mean respiratory rate was 14.7 ± 5.6 breaths per minute, and the mean rectal temperature was 37.9 ± 1.4°C during the 40 min. Arterial blood gas results showed hypoxemia (mean PaO 2 62.1 ± 16.2 mmHg), hypercapnia (mean PaCO 2 47.1 ± 5.1 mmHg), and acidemia (mean pH = 7.36 ± 0.04). Values for PaO 2 and pH improved over the immobilization period. After antagonist administration, overall recovery quality from immobilization was scored as good, with animals standing at a mean time of 7.3 ± 4.9 min. The drug combination proved to be effective in the immobilization of free-ranging warthogs with rapid induction, good anesthesia, and limited cardiorespiratory changes. This anesthetic protocol produces effective, safe, and partially reversible immobilization in warthogs.

Effective pain relief in animals relies on the ability to discern pain and assess its severity. However, few objective measures exist to assess the presence and severity of pain in axolotls, and few resources are available regarding drugs and appropriate doses to provide pain relief in this species. This study evaluated behavioral tools for cageside pain assessment and validated a reproducible and reliable quantitative method to evaluate analgesic efficacy in axolotls. Animals were divided into control and treatment groups ( n = 6 per group); treatment groups received buprenorphine through injection (50 mg/kg every 24 h for 48 h intracelomically) or butorphanol immersion (0.50 or 0.75 mg/L every 24 h for 48 h). Qualitative behavioral tests, adapted from other amphibian studies, included tapping on the home tank, directing water jets or physically touching specific anatomic points on the animal, and placing a novel object in the home tank. Quantitative methods used to produce noxious stimuli were the acetic acid test and von Frey aesthesiometers. Animals that were treated with analgesics did not demonstrate a significant difference compared with controls during behavioral assessment at 1, 6, 12, 25, 30, and 48 h after analgesia administration. The acetic acid test revealed a reproducible, concentration-dependent pain response. However, a significant difference in the AAT response was not observed between control and treated groups with the tested analgesics and doses.

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., (© 2020 John Wiley & Sons Ltd.)

Recently, a mixture of medetomidine, midazolam and butorphanol (MMB) has been used as an injectable general anesthetic agent for laboratory animals. The purpose of this study was to establish data to encourage practical usage of MMB, and to clarify the effects of MMB on the respiratory function in rats. To compare the anesthetic efficacy between the injection routes, the anesthetic effects of MMB by subcutaneous (s.c.) or intraperitoneal (i.p.) injection were evaluated in rats. To assess the respiratory function, the blood gas parameters and electrolytes were assessed in serial venous blood samples collected from before s.c. injection of MMB to 270 min after the injection. Recovery from anesthesia and the respiratory changes after atipamezole injection at 30 min after MMB injection was also examined. Subcutaneous injection of MMB was associated with more rapid induction and a longer duration of anesthesia as compared to i.p. injection. The blood gas analysis findings showed MMB had effects on respiratory function, that is, elevations of the partial pressures of carbon dioxide and bicarbonate and reduction of the blood pH. Atipamezole injection resulted in recovery from the MMB-induced anesthetic effect as well as respiratory depression. In conclusion, MMB provides more effective anesthesia administered by s.c. injection compared to i.p. injection and induces respiratory change. These changes were counteracted by atipamezole. Therefore, we recommend MMB administered by s.c. injection for anesthesia, followed by injection of atipamezole after the operative procedure to allow recovery.

Seven anesthesia events were performed over 6 wk on a 1.5-yr-old female okapi ( Okapia johnstoni ) being managed for a fetlock injury. A combination of butorphanol (B) (median; range) (0.045; 0.031-0.046 mg/kg), medetomidine (M) (0.037; 0.031-0.037 mg/kg), ketamine (K) (0.553; 0.536-1.071 mg/kg), and thiafentanil (T) (0.0045; 0.0040-0.0046 mg/kg) was administered in a padded stall. One dart containing all drugs was used for the first two anesthesias. Subsequently, BM was administered 10 min prior to KT using two darts. Time (median; range) from initial injection to first effects (6; 3-7 min) and recumbency (14; 4-20 min) were recorded. Induction quality with the one-dart protocol was poor or fair and was good or excellent with the two-dart protocol. Following recumbency, the okapi was intubated and ventilated, and physiological parameters were recorded. Anesthesia was consistently achieved with BMKT, but induction was smoother with the staged two-dart approach. Neither resedation nor renarcotization was observed post-reversal.

Objective: To evaluate the sedative and cardiorespiratory effects of IM administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs., Animals: 6 young healthy mixed-breed hounds., Procedures: Dogs received each of 3 treatments (alfaxalone [2 mg/kg] and butorphanol [0.4 mg/kg] combined with acepromazine [0.02 mg/kg; AB-ace], midazolam [0.2 mg/kg; AB-mid], or dexmedetomidine [0.005 mg/kg; AB-dex], IM) in a blinded, randomized crossover-design study with a 1-week washout period between treatments. Sedation scores and cardiorespiratory variables were recorded at predetermined time points. Data were analyzed by use of mixed-model ANOVA and linear generalized estimating equations with post hoc adjustments., Results: All treatments resulted in moderate to deep sedation (median score, ≥ 15/21) ≤ 5 minutes after injection. Sedation scores did not differ among treatments until the 40-minute time point, when the score was higher for AB-dex than for other treatments. Administration of AB-dex resulted in median scores reflecting deep sedation until 130 minutes, versus 80 and 60 minutes for AB-ace and AB-mid, respectively, after injection. Heart rate, cardiac output, and oxygen delivery decreased significantly after AB-dex, but not AB-ace or AB-mid administration. Respiratory variables remained within clinically acceptable ranges after all treatments. Undesirable recovery characteristics were observed in 4 dogs after AB-mid treatment. Four dogs required atipamezole administration 180 minutes after AB-dex injection., Conclusions and Clinical Relevance: All protocols produced reliable sedation. The results indicated that in young, healthy dogs, AB-mid may produce undesirable recovery characteristics; AB-dex treatment caused cardiovascular depression and should be used with caution.

Objective: To determine the ability to evaluate laryngeal function under sedation with dexmedetomidine alone or in combination with opioids., Study Design: Randomized, crossover, blinded study., Animals: Eight adult research hounds weighing 8 to 22.5 kg., Methods: Dogs were sedated with propofol, dexmedetomidine, dexmedetomidine and butorphanol, or dexmedetomidine and hydromorphone. Digital images were collected with video laryngoscopy before and after doxapram administration. Maximal inspiratory normalized glottal gap (GGA n ) and laryngeal motion were compared between and within protocols before and after doxapram by using a difference of least squares mean., Results: Normal laryngeal function was confirmed in all dogs with all protocols except propofol, which resulted in two false positive results. No difference between protocols was detected for predoxapram GGA n . Postdoxapram GGA n was greater than predoxapram GGA n for all four sedation protocols (P ≤ .0030). Compared with propofol, postdoxapram GGA n was greater for all three dexmedetomidine protocols (P ≤ .0420)., Conclusion: Dexmedetomidine alone or in combination with opioids was an effective sedation protocol for laryngeal examination, producing sufficient immobilization to prevent jaw motion and without affecting arytenoid abduction., Clinical Significance: Dexmedetomidine sedation does not inhibit normal laryngeal motion. Laryngeal examination with propofol alone can produce false positive results., (© 2019 The American College of Veterinary Surgeons.)

Objective: To explore the influence of butorphanol on myocardial ischemia/reperfusion (I/R) injury in rats through the mitogen-activated protein kinase (MAPK) signaling pathway., Materials and Methods: The I/R model in Sprague-Dawley rats was established. The rats were randomly divided into normal group (n=20), myocardial I/R model group (model group, n=20), and butorphanol treatment group (treatment group, n=20). Next, the liver function indicators such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), and the myocardial function index creatine kinase (CK) in rats were detected. ELISA was carried out to measure the relative levels of tumor necrosis factor-gamma (TNF-γ), interleukin-6 (IL-6), and IL-1α in serum samples of rats. The cardiac function indexes were examined via magnetic resonance imaging (MRI) and echocardiography (ECG). Besides, the pathological changes of the myocardial tissues were detected through hematoxylin-eosin (HE) staining. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blotting were performed to measure the mRNA and protein expression levels of the relative genes in the MAPK signaling pathway in the rat myocardial tissues., Results: The serum levels of ALP, ALT, and CK in I/R model group were significantly higher than those in the normal group. In I/R model group, the relative levels of TNF-γ, IL-6, and IL-1α, as well as left ventricular end-diastolic diameter (LVEDd) and left ventricular end-systolic diameter (LVESd), were remarkably higher, while the fractional shortening (FS, %) and the ejection fraction (EF, %) were lower in comparison with those in the normal group. The HE staining results showed that the myocardial tissues in the I/R model group exhibited severe injury. The expression levels of Caspase3, MAPK, and c-Jun N-terminal kinase (JNK) were clearly higher in the I/R model group than those in the treatment group (p<0.05), while the expression level of extracellular regulated protein kinase 1 (ERK1) was remarkably lower (p<0.05). The protein level of MAPK in the treatment group was overtly reduced compared with that in the I/R model group (p<0.05)., Conclusions: Butorphanol can modulate the recovery of the myocardial injury in the rats after the myocardial I/R by inhibiting the MAPK signaling pathway.