The effective dose of butorphanol tartrate in patients of different ages undergoing painless gastroscopy.

OBJECTIVE: This study evaluated the 50% effective dose (ED50) and 95% effective dose (ED95) 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 ED50 and ED95 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 ED50 and ED95 of butorphanol were calculated using probit analysis. RESULTS: In total, 95 patients were included. The ED50s of butorphanol in the youth, middle-aged, and older groups were 7.384, 6.657, and 6.364 µg/kg, respectively. The ED95s of butorphanol doses in these groups were 9.108, 8.419, and 7.348 µg/kg, respectively. CONCLUSIONS: The ED50 and ED95 varied among the age groups, indicating that the effective dose decreases with age.

EVALUATION OF A BUTORPHANOL-MIDAZOLAM-MEDETOMIDINE PROTOCOL FOR SHORT PROCEDURES IN LESSER CHEVROTAINS (TRAGULUS SP.).

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.

IMMOBILIZATION OF BLACK HOWLER MONKEYS (ALOUATTA PIGRA) USING BUTORPHANOL, AZAPERONE, MEDETOMIDINE IS SAFE AND EFFECTIVE FOR NONINVASIVE PROCEDURES.

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, SPO2, 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 (SPO2 < 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.

Post-surgical photobiomodulation therapy improves outcomes following elective gastropexy in dogs.

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). Pre­medication 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 (CMPS­SF) at 1, 2, 4, 6, 8, 12, 16, 20, and 24 h post­endotracheal extubation. CMPS­SF scores were compared with the Mann-Whitney Test and proportions of animals that required rescue analgesia and had eaten with a χ2 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.

Comparative study of the effects of antitussive drugs in a canine acute cough model.

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.

Comparison of the effects of intranasal and intramuscular midazolam-butorphanol-ketamine on intraocular pressure, tear production and sedation in New Zealand White rabbits.

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 (fR), rectal temperature (RT), noninvasive mean arterial blood pressure (MAP) and peripheral hemoglobin oxygen saturation (SpO2) 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), fR (p = 0.872), RT (p = 0.379), MAP (p = 0.217) and SpO2 (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.

Comparison of Manual Restraint With and Without Sedation on Outcomes for Wild Birds Undergoing Decontamination.

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.

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.

Can Multimodal Analgesia Reduce Postoperative Opioid Consumption in Patients Undergoing Shoulder Arthroscopy? A Retrospective Study.

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.

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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