Impact of butorphanol versus sufentanil on postoperative cognition and inflammation in elderly: a pilot study.

Background: This randomized controlled trial aimed to compare the effects of butorphanol and sufentanil on early post-operative cognitive dysfunction (POCD) and systemic inflammation in older surgical patients. Methods: Patients (aged 65 years or above) undergoing surgeries with general anesthesia were randomized to either the butorphanol group (40 µg/kg during anesthesia induction) or the sufentanil group (0.4 µg/kg). Cognitive function changes during the perioperative period were assessed using the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale up to 3 days after surgery. POCD was defined as a Z-score or composite Z-score greater than 1.96 for both MMSE and MoCA scores. Circulating inflammatory factors, including tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 10 (IL-10), were measured using enzyme-linked immunosorbent assay. Results: The study included 114 patients (median age: 71 years, 57.7% male). Compared to sufentanil, butorphanol significantly reduced the incidence of POCD on the first (11.5% versus 32.7%, p = 0.017) and third day (3.8% versus 15.4%, p = 0.046) after surgery. Additionally, patients receiving butorphanol had significantly lower circulating levels of TNF-α and IL-1ß at the time of discharge from the post-anesthesia care unit and on the first and third day after surgery (p < 0.05 for all comparisons). Furthermore, circulating IL-10 levels were significantly higher in patients receiving butorphanol (p < 0.05 for all comparisons). Conclusion: Administration of butorphanol during anesthesia induction, as opposed to sufentanil, was associated with a significant reduction in the early incidence of POCD in older surgical patients, possibly attributed to its impact on systemic inflammation.Clinical trial registration: The present study was registered in the China Clinical Trial Center (ChiCTR2300070805, 24/04/2023).

Cardiorespiratory effects of intramuscular alfaxalone combined with low-dose medetomidine and butorphanol in dogs anesthetized with sevoflurane.

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/m2 : 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/cm5/m2 : 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.

Effects of Medetomidine-Butorphanol and Medetomidine-Buprenorphine on Oxidative Stress and Vital Parameters in Dogs Undergoing Ovariohysterectomy.

Oxidative stress (OS) is caused by an imbalance between the production of oxygen-containing free radicals and their elimination. General anesthesia increases the production of reactive oxygen species (ROS) and therefore causes oxidative stress. Our objective was to determine the effects of medetomidine-butorphanol (MEDBUT) and medetomidine-buprenorphine (MEDBUP) on oxidative stress and cardiorespiratory parameters in dogs undergoing ovariohysterectomy (OHE). Ten healthy female dogs were randomly assigned to two groups: the MEDBUT group (n = 5) received medetomidine and butorphanol, while the MEDBUP group (n = 5) received medetomidine and buprenorphine. OS was evaluated by measuring total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) during five different time points (from the administration of anesthetic drugs to 2 h after surgery). The observed vital cardiorespiratory parameters included heart rate (HR), respiratory rate (fR), noninvasive systolic (SAP) and diastolic (DAP) arterial blood pressures, oxygen saturation (SpO2), end-tidal CO2 (EtCO2), and body temperature (BT). Cardiorespiratory parameters were altered at a significantly greater degree in animals sedated with MEDBUT (p < 0.05). The administration of medetomidine-butorphanol was more likely to increase OS parameters, while medetomidine-buprenorphine showed decreased levels of oxidative stress throughout the study.

Effect of Butorphanol-Medetomidine and Butorphanol-Dexmedetomidine on Echocardiographic Parameters during Propofol Anaesthesia in Dogs.

This study compared the effects of butorphanol-medetomidine and butorphanol-dexmedetomidine combinations on echocardiographic parameters during propofol anaesthesia in dogs. The dogs were randomly divided into two groups. In the butorphanol-medetomidine (BM) group, butorphanol (0.2 mg/kg) and medetomidine (15 µg/kg) were intravenously administered; in the butorphanol-dexmedetomidine (BD) group, butorphanol (0.2 mg/kg) and dexmedetomidine (7.5 µg/kg) was used. Anaesthesia was induced with propofol and maintained with a constant-rate infusion of propofol (0.2 mg/kg/min). The echocardiographic parameters were assessed in conscious dogs (T0). Echocardiography was conducted again at 10 min post premedication (T1), followed by assessments at 30 (T2), 60 (T3), and 90 (T4) mins. The dogs were subjected to diagnostic procedures (radiography, computed tomography) under anaesthesia. A significant reduction in heart rate and cardiac output was noted in both groups at T1. There was no significant difference in the stroke volume between the BM and BD groups. The application of butorphanol-dexmedetomidine caused a significant increase in the left ventricular internal diameter in diastole and the diameter of the left atrium compared to that caused by butorphanol-medetomidine. This study documented that butorphanol-medetomidine and butorphanol-dexmedetomidine combinations caused similar reductions in heart rate and cardiac output in both groups. 'New´ valvular regurgitation occurred following their administration.

Cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry during continuous intravenous infusion of a combination solution of xylazine, butorphanol, and propofol in calves.

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.

ED50 of remimazolam combined with different doses butorphanol for first trimester artificial abortion.

Introduction: Remimazolam (RMZ) is a novel intravenous sedative drug of ultra-short benzodiazepine. The optimal dose of RMZ plus butorphanol for sedation during first trimester artificial abortion is unknown. Therefore, the present study aimed to evaluate the median effective dose (ED50) of RMZ combined with different doses of butorphanol on the sedative effect for first-trimester artificial abortion. Methods: Sixty-one female patients were randomly assigned to Group B10 (31 patients) and Group B15 (30 patients). RMZ was administered 5 min after IV butorphanol at doses of 10 µg/kg (Group B10) and 15 µg/kg (Group B15). Cervical dilatation at the time of using a cervical dilating rod, if the patient has body movement and affects the gynecologist's operation, we define it as "Ineffective." Therefore, the dose of RMZ was increased in the next patient. Otherwise, it was defined as "Effective," and the dose of RMZ was reduced in the next patient. According to the pre-experiment, the first dose of RMZ in the first patient was 0.35 mg/kg, and the adjacent geometric dose ratio was 0.9. The centered isotonic regression was performed to determine the ED50 of RMZ. The total RMZ dose administered, recovery time, and anesthesia-related adverse events were all recorded. Results: The ED50 (90% CI) of RMZ was 0.263 (0.215-0.310) mg/kg in Group B10, and 0.224 (0.191-0.261) mg/kg in Group B15, respectively. The recovery time in Group B10 was significantly shorter than in Group B15 (9.8 ± 2.3 vs. 12.5 ± 3.6 min, p ≤ 0.001). There was no significant difference in the incidence rate of all anesthesia-related adverse events between the two groups (p > 0.05). Conclusion: The ED50 of RMZ combined with a 10 µg/kg or 15 µg/kg dose of butorphanol was 0.263 and 0.224 mg/kg during painless first trimester artificial abortion. However, RMZ combined with a 10 µg/kg dose of butorphanol seems to have a shorter recovery time. Clinical trial registration: https://www.chictr.org.cn/bin/project/edit?pid=166623.

Evaluating Sedation Strategies for Magnetic Resonance Imaging: A Comprehensive Review of Intravenous Fentanyl, Butorphanol, and Midazolam in Adult and Pediatric Populations.

Magnetic resonance imaging (MRI) is a critical diagnostic tool that often requires patient sedation to ensure optimal image quality and patient comfort, particularly in those with anxiety or an inability to remain still. This comprehensive review examines the efficacy, safety, and practical considerations of three commonly used intravenous sedatives, namely, fentanyl, butorphanol, and midazolam, in adult populations undergoing MRI procedures. This review highlights the pharmacological profiles, advantages, and limitations associated with each sedative agent through a detailed analysis of current literature, clinical guidelines, and practice-based evidence. Fentanyl is noted for its potent analgesic properties and rapid onset of action, making it suitable for painful procedures. Butorphanol, with its unique opioid agonist-antagonist activity, presents an alternative with a balance between analgesia and sedation, potentially offering a safer profile for certain patient populations. Midazolam, widely recognized for its anxiolytic and amnestic effects, remains a staple in managing procedure-related anxiety. The review further discusses patient selection criteria, dosing strategies, and the importance of individualized sedation planning to enhance patient experience and procedural outcomes. Future directions highlight the potential of emerging sedation agents and non-pharmacological approaches to improve patient comfort and compliance. The findings underscore the necessity for healthcare providers to adapt sedation practices to the specific needs of each patient, considering both the clinical context and the inherent characteristics of the sedative agents. This review aims to guide clinicians in selecting the most appropriate sedation strategy for adult patients undergoing MRI, optimizing patient care and diagnostic efficacy.

Safety and effectiveness of butorphanol in epidural labor analgesia: A protocol for a systematic review and meta-analysis.

BACKGROUND: Epidural analgesia is the most effective analgesic method during labor. Butorphanol administered epidurally has been shown to be a successful analgesic method during labor. However, no comprehensive study has examined the safety and efficacy of using butorphanol as an epidural analgesic during labor. AIM: To assess butorphanol's safety and efficacy for epidural labor analgesia. METHODS: The PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, and Google Scholar databases will be searched from inception. Other types of literature, such as conference abstracts and references to pertinent reviews, will also be reviewed. We will include randomized controlled trials comparing butorphanol with other opioids combined with local anesthetics for epidural analgesia during labor. There will be no language restrictions. The primary outcomes will include the visual analog scale score for the first stage of labor, fetal effects, and Apgar score. Two independent reviewers will evaluate the full texts, extract data, and assess the risk of bias. Publication bias will be evaluated using Egger's or Begg's tests as well as visual analysis of a funnel plot, and heterogeneity will be evaluated using the Cochran Q test, P values, and I2 values. Meta-analysis, subgroup analysis, and sensitivity analysis will be performed using RevMan software version 5.4. This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Protocols statement, and the PRISMA statement will be used for the systematic review. RESULTS: This study provides reliable information regarding the safety and efficacy of using butorphanol as an epidural analgesic during labor. CONCLUSION: To support clinical practice and development, this study provides evidence-based findings regarding the safety and efficacy of using butorphanol as an epidural analgesic during labor.

Population pharmacokinetics of butorphanol following intramuscular administration to exercised thoroughbred horses.

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

The impact of opioid administration on the incidence of postanaesthetic colic in horses.

Effective management of postoperative pain is essential to ensure patient welfare, reduce morbidity and optimize recovery. Opioids are effective in managing moderate to severe pain in horses but concerns over their adverse effects on gastrointestinal (GI) motility and associated increased colic risk limit their widespread use. Studies investigating the impact of systemic opioids on both GI motility and colic incidence in horses have yielded inconclusive outcomes. Therefore, this retrospective study aims to assess the influence of systemic administration of butorphanol, morphine, and methadone on post-anaesthetic colic (PAC) incidence. Horses undergoing general anaesthesia for non-gastrointestinal procedures that were hospitalized for at least 72 h post-anaesthesia were included in this study. Anaesthetised horses were stratified by procedure type into horses undergoing diagnostic imaging without surgical intervention, emergency or elective surgery. In addition, patients were grouped by opioid treatment regime into horses receiving no opioids, intraanaesthetic, short- (<24 h) or long-term (>24 h) postoperative opioids. Administered opioids encompassed butorphanol, morphine and methadone. The number of horses showing signs of colic in the 72 h after anaesthesia was assessed for each group. A total of 782 horses were included, comprising 659 undergoing surgical procedures and 123 undergoing diagnostic imaging. The overall PAC incidence was 15.1%. Notably, horses undergoing diagnostic imaging without surgery had a significantly lower PAC rate of 6.5% compared to those undergoing surgery (16.7%, p = 0.0146). Emergency surgeries had a significantly lower PAC rate of 5.8% compared to elective procedures (18%, p = 0.0113). Of the 782 horses, 740 received intraoperative opioids and 204 postoperative opioids, 102 of which long-term (≥24 h). Neither intraoperative (p = 0.4243) nor short-term postoperative opioids (p = 0.5744) increased PAC rates. Notably, only the long-term (≥24 h) administration of morphine significantly increased PAC incidence to 34% (p = 0.0038). In contrast, long-term butorphanol (5.3% PAC, p = 0.8482) and methadone (18.4% PAC, p = 0.6161) did not affect PAC rates. In summary, extended morphine administration was the only opioid treatment associated with a significantly increased risk of PAC.

Effectiveness of Butorphanol in alleviating intra- and post-operative visceral pain following microwave ablation for hepatic tumor: a dual-central, randomized, controlled trial.

Many patients who underwent hepatic percutaneous microwave ablation (MWA) reported experiencing pain during the procedure. This study utilized a well-designed multicentral, randomized, and placebo-controlled format to investigate the effects of Butorphanol. Patients who underwent MWA were randomly assigned to either Butorphanol or normal saline group. The primary outcomes of the study were assessed by measuring the patients' intraoperative pain levels using a 10-point visual analog scale (VAS). Secondary outcomes included measuring postoperative pain levels at the 6-h mark (VAS) and evaluating comprehensive pain assessment outcomes. A total of 300 patients were divided between the control group (n = 100) and the experimental group (n = 200). Butorphanol showed statistically significant reductions in intraoperative pain levels compared to the placebo during surgery (5.00 ± 1.46 vs. 3.54 ± 1.67, P < 0.001). Significant differences were observed in postoperative pain levels at the 6-h mark and in the overall assessment of pain (1.39 + 1.21 vs. 0.65 + 0.81, P < 0.001). Butorphanol had a significant impact on reducing the heart rate of patients. The empirical evidence supports the effectiveness of Butorphanol in reducing the occurrence of visceral postoperative pain in patients undergoing microwave ablation for hepatic tumor. Furthermore, the study found no noticeable impact on circulatory and respiratory dynamics.

Sedation with dexmedetomidine-butorphanol or xylazine-butorphanol continuous intravenous infusions during unilateral ovariectomy in standing donkeys.

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

Butorphanol inhibits androgen biosynthesis and metabolism in rat immature Leydig cells in vitro.

Butorphanol is a synthetic opioid analgesic medication that is primarily used for the management of pain. Butorphanol may have an inhibitory effect on androgen biosynthesis and metabolism in rat immature Leydig cells. The objective of this study was to investigate the influence of butorphanol on androgen secretion by rat Leydig cells isolated from the 35-day-old male rats. Rat Leydig cells were cultured with 0.5-50 µM butorphanol for 3 h in vitro. Butorphanol at 5 and 50 µM significantly inhibited androgen secretion in immature Leydig cells. At 50 µM, butorphanol also blocked the effects of luteinizing hormone (LH) and 8bromo-cAMP-stimulated androgen secretion and 22R-hydroxycholesterol- and pregnenolone-mediated androgen production. Further analysis of the results showed that butorphanol downregulated the expression of genes involved in androgen production, including Lhcgr (LH receptor), Cyp11a1 (cholesterol side-chain cleavage enzyme), Srd5a1 (5α-reductase 1), and Akr1c14 (3α-hydroxysteroid dehydrogenase). Additionally, butorphanol directly inhibited HSD3B1 (3ß-hydroxysteroid dehydrogenase 1) and SRD5A1 activity. In conclusion, butorphanol may have side effects of inhibiting androgen biosynthesis and metabolism in Leydig cells.

Effects of Butorphanol on Respiration in White Rhinoceros (Ceratotherium simum) Immobilized with Etorphine-Azaperone.

This article reports on respiratory function in white rhinoceros (Ceratotherium simum) immobilized with etorphine-azaperone and the changes induced by butorphanol administration as part of a multifaceted crossover study that also investigated the effects of etorphine or etorphine-butorphanol treatments. Six male white rhinoceros underwent two immobilizations by using 1) etorphine-azaperone and 2) etorphine-azaperone-butorphanol. Starting 10 min after recumbency, arterial blood gases, limb muscle tremors, expired minute ventilation, and respiratory rate were evaluated at 5-min intervals for 25 min. Alveolar to arterial oxygen gradient, expected respiratory minute volume, oxygen consumption, and carbon dioxide production were calculated. Etorphine-azaperone administration resulted in hypoxemia and hypercapnia, with increases in alveolar to arterial oxygen gradient, oxygen consumption, and carbon dioxide production, and a decrease in expired minute ventilation. Muscle tremors were also observed. Intravenous butorphanol administration in etorphine-azaperone-immobilized white rhinoceros resulted in less hypoxemia and hypercapnia; a decrease in oxygen consumption, carbon dioxide production, and expired minute ventilation; and no change in the alveolar to arterial oxygen gradient and rate of breathing. We show that the immobilization of white rhinoceros with etorphine-azaperone results in hypoxemia and hypercapnia and that the subsequent intravenous administration of butorphanol improves both arterial blood oxygen and carbon dioxide partial pressures.

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.

Butorphanol inhibits ferroptosis to attenuate PC12 cell injury by blocking JNK/p38 signaling.

Butorphanol is a synthetic selective opioid receptor antagonist that exhibits substantial analgesic effects. The present study aimed to explore the effects of butorphanol on a neurodegenerative disease cell model and to investigate its specific regulatory mechanism. Cell viability of PC12 cells was assessed using the Cell Counting Kit-8 assay. Oxidative stress levels were measured by the corresponding kits and western blotting of specific protein markers. Apoptosis was determined using the terminal-deoxynucleoitidyl transferase mediated nick end labeling assay and by western blotting. Western blotting was used to analyze the expression levels of c-Jun NH2-terminal kinase (JNK)/p38 signaling pathway-related proteins. Thiobarbituric acid-reactive substances and Fe+2 content were detected using the corresponding assay kits and the expression levels of ferroptosis-associated proteins were assessed by western blotting following the addition of the JNK activator anisomycin (ANI). Oxidative stress and apoptosis were examined with the aforementioned assays following the supplementation of ANI or the ferroptosis inducer erastin (ERA). It was revealed that butorphanol dose-dependently enhanced the viability and suppressed the oxidative stress and apoptosis of H2O2-treated PC12 cells. In addition, butorphanol blocked JNK/p38 signaling and hampered ferroptosis, while this effect was reversed by ANI. ANI or ERA reversed the effects of butorphanol on oxidative stress and apoptosis of H2O2-treated PC12 cells. In summary, butorphanol suppressed ferroptosis by blocking JNK/p38 signaling to impart inhibitory effects on oxidative stress and apoptosis in a neurodegenerative disease cell model.

Comparing the Efficacy of Two Immobilization Drug Combinations for the Chemical Restraint of Bobcats (Lynx rufus).

Chemical immobilization agents that provide rapid induction time, short duration of action, wide margin of safety, and postreversal recovery are important attributes to the handling process of immobilized animals. We evaluated differences in induction, recovery, and physiologic parameters in 23 (13 female, nine adults and four yearlings; 10 male, nine adults and one yearling) free-ranging bobcats (Lynx rufus) chemically immobilized with an intramuscular combination of ketamine (10 mg/kg) and xylazine (KX; 1.5 mg/kg; n=11) or a combination of butorphanol (0.8 mg/kg), azaperone (0.27 mg/kg), and medetomidine (BAM; 0.32 mg/kg; n=12). Induction parameters, time to first effect, hemoglobin oxygen saturation, and anesthesia between bobcats administered KX and BAM were similar. Pulse rate was significantly higher for KX than for BAM. Time to standing and full recovery after reversal were faster for bobcats administered BAM than KX. Six of 11 (55%) bobcats given KX were effectively immobilized with a single injection, and five required additional drugs to allow adequate time for processing. Of 12 bobcats given BAM, six (50%) were effectively immobilized with a single injection, three (25%) individuals were not completely immobilized and required additional doses to allow adequate time for processing, and three (25%) required additional doses after complete arousal during processing. We found that BAM provided reduced sedation and processing times (<30 min), whereas KX provided extended sedation and processing times beyond 30 min. We suggest that researchers increase initial BAM drug volumes for yearling and adult bobcats at time of processing and consider taking appropriate safety precautions when handling free-ranging bobcats.

Butorphanol-Azaperone-Medetomidine Is as Safe and Effective as Nalbuphine-Azaperone-Medetomidine for Immobilization of Juvenile American Black Bears (Ursus americanus).

Immobilization kits including butorphanol-azaperone-medetomidine (BAM) and nalbuphine-azaperone-medetomidine can provide effective, safe, and easy-to-use protocols in bears. Nalbuphine-azaperone-medetomidine is not commercially available but may be useful for wildlife agencies because it does not contain controlled substances. This study directly compared BAM to nalbuphine-azaperone-medetomidine immobilization in 10 juvenile healthy black bears (10 mo old; four females, six males) undergoing prerelease examinations after rehabilitation. Bears were immobilized via remote delivery of 1 mL of BAM (n=5) or nalbuphine-azaperone-medetomidine (n=5) intramuscularly in the shoulder during December (randomized, blinded trial). Bears were intubated, monitored with an electrocardiogram, pulse oximeter, capnograph, noninvasive blood pressure cuff, and rectal thermometer, and underwent physical examination, sample collection, morphometrics, and ear-tag placement. Induction, physiologic, and recovery parameters were recorded, including arterial blood gas analysis. The anesthetic agents were antagonized with atipamezole and naltrexone. There were no differences between protocols in induction or recovery times. There were no differences between protocols in heart rate, respiratory rate, temperature, oxygen saturation, end-tidal CO2, mean arterial pressure, or blood gas analysis or any differences between male and female bears in any parameters. Bears were hypertensive and normoxemic with low oxygen saturation via pulse oximeter, but all recovered smoothly and were released within 2 h of recovery. This study supports that nalbuphine-azaperone-medetomidine is clini-cally as safe and effective as BAM in American black bears.

Comparison of Ketamine-Xylazine, Butorphanol-Azaperone-Medetomidine, and Nalbuphine-Medetomidine-Azaperone for Raccoon (Procyon lotor) Immobilization.

Raccoons (Procyon lotor) are frequently handled using chemical immobilization in North America for management and research. In a controlled environment, we compared three drug combinations: ketamine-xylazine (KX), butorphanol-azaperone-medetomidine (BAM), and nalbuphine-medetomidine-azaperone (NalMed-A) for raccoon immobilization. In crossover comparisons, raccoons received a mean of the following: 8.66 mg/kg ketamine and 1.74 mg/kg xylazine (0.104 mL/kg KX); 0.464 mg/kg butorphanol, 0.155 mg/kg azaperone, and 0.185 mg/kg medetomidine (0.017 mL/kg BAM); and 0.800 mg/kg nalbuphine, 0.200 mg/kg azaperone, and 0.200 mg/kg medetomidine (0.020 mL/kg NalMed-A). Induction time was shortest with KX (mean±SE, 10.0±0.7 min) and longest with NalMed-A (13.0±1.3 min). A sampling procedure was completed on 89% (16/18), 72% (13/18), and 89% (16/18) of the raccoons administered KX, BAM, and NalMed-A, respectively. Reasons for incomplete sampling included inadequate immobilization (one KX and one NalMed-A), responsive behaviors (one each with KX, BAM, NalMed-A), or animal safety (four BAM). Mean recovery time for KX was 32.8±7.1 min without antagonizing and 28.6±5.2 min following delivery of an antagonist. Mean recovery time was 6.2±0.8 min for BAM and 5.1±0.5 min for NalMed-A after antagonizing. Only with KX were raccoons observed to recover without use of an antagonist. Supplemental oxygen was provided to 23% (3/13), 72% (13/18), and 71% (12/17) of raccoons immobilized with KX, BAM, and NalMed-A, respectively. Hypoxemia at <80% oxygen saturation occurred in 0% (0/17), 27% (4/15), and 6% (1/16) of the raccoons administered KX, BAM, and NalMed-A, respectively; all raccoons fully recovered from chemical immobilization. All combinations could be used for raccoon immobilization; however, the need for delivery of supplemental oxygen to a majority of raccoons immobilized with BAM and NalMed-A may limit broader use of these agents for certain field studies involving capture, sample, and release of free-ranging animals from a practical standpoint.

Midazolam and butorphanol combination for sedating beluga whales (Delphinapterus leucas).

Safe sedation doses for performing minor procedures such as bronchoscopy, endoscopy, and tooth extraction for beluga whales (Delphinapterus leucas) require elucidation. This study aimed to provide suggestions for determining appropriate midazolam and butorphanol doses to adequately sedate beluga whales to complete procedures and minimize the risk of side effects. We administered midazolam and butorphanol to six captive beluga whales (9-44 years old). Topical lidocaine anesthesia was administered during bronchoscopy. The sedation doses for the beluga whales varied from 0.020 to 0.122 mg/kg for midazolam and from 0.020 to 0.061 mg/kg for butorphanol. In beluga whales, optimal midazolam and butorphanol doses were lowest in old whales. These findings contribute to knowledge regarding appropriate sedation and prevention of overdose accidents during minor procedures in beluga whales.