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.

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.

Comparison of two sedation protocols for long electroretinography in horses using the Koijman electrode.

BACKGROUND: In modern times, horses are utilized not only for labour and transportation purposes but also for recreational activities such as competition and pleasure riding. In these various pursuits, the role of vision plays a crucial role. Electroretinography is the most used test to diagnose diseases of the retinal outer segment. There is a wide variety of devices to perform the electroretinography differing one from each other in the corneal electrode and the light stimulation. The Koijman electrode has been tested in dogs but not in horses. The main purpose of this study was to compare electroretinography parameters from horses sedated with detomidine alone or in combination with butorphanol, during a standardized protocol using the Koijman electrode and RETI-port® system. Seven mares were allocated to the detomidine and detomidine plus butorphanol group in a randomised, controlled, crossover study. Friedman and Willcoxon-signed ranked tests were used to compare the electroretinogram parameters. A Student's t-test was used to compare differences in the number of artefacts to valid values ratio obtained under both sedation protocols. RESULTS: Dark adaptation peaked after 16 min under scotopic conditions in both groups. No significant differences in electroretinogram parameters between groups were observed. During the mixed rod and cone response evaluation under scotopic conditions, all mares made a movement of the head resulting in a high number of artefacts. The detomidine plus butorphanol group showed a non-significant tendency to have fewer artefacts and a longer duration of sedation compared to the detomidine group. CONCLUSIONS: Detomidine alone or combined with butorphanol may be suitable to use Koijman electrode and the RETI-port® to perform a standardized long protocol in horses with some adaptations.

Epidural lidocaine, butorphanol, and butorphanol - lidocaine combination in dromedary camels.

BACKGROUND: The use of general anesthesia in dromedary camels is constrained by risks related to decubitus. Caudal epidural analgesia is an alternative convenient technique providing loco-regional analgesia for numerous invasive and noninvasive painful conditions. Lidocaine is probably the most commonly used local anesthetic in clinical practice, but has a relatively short duration and may not provide significant long term analgesic benefits. Epidural administration of an opioid-local anesthetic mixture would improve the quality and length of analgesia and minimizes the adverse motor effects provoked by local anesthetics. Butorphanol (potent agonist-antagonist opioid) has been used to improve the duration of epidural analgesia in some animal species, but not in camels. Therefore, our purpose was to investigate the onset and duration of analgesia as well as the clinical and hemato-biochemical effects produced by the epidural administration of butorphanol (0.04 mg/kg), lidocaine (0.22 mg/ kg), and butorphanol-lidocaine (0.04 mg/kg-0.22 mg/ kg) mixture in nine adult dromedary camels in a crossover experimental study. RESULTS: The onset of analgesia was not statistically different between lidocaine (6.5 ± 2.3 min) and butorphanol-lidocaine (7.3 ± 1.5 min) combination. Delayed onset of analgesia was reported after butorphanol administration (14.7 ± 3.5 min). Butorphanol-lidocaine combination produced marked longer duration (175 ± 8.7 min) than lidocaine (55 ± 6.8 min) and butorphanol (158 ± 5.3 min). Mild ataxia was observed in the butorphanol-lidocaine and lidocaine treated animals and slight sedation was reported after butorphanol and butorphanol-lidocaine administration. A transient significant increase in the glucose levels was recorded after all treatments. CONCLUSIONS: Epidural administration of butorphanol augments the analgesic effects and duration of lidocaine with minimal adverse effects.

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).

Sedative effects and changes in cardiac rhythm with intravenous premedication of medetomidine, butorphanol and ketamine in dogs.

OBJECTIVE: To determine the sedative effects and characteristics of cardiac rhythm with intravenous (IV) premedication of medetomidine, butorphanol and ketamine in dogs. STUDY DESIGN: Prospective, blinded, randomized clinical trial. ANIMALS: A total of 116 client-owned healthy dogs undergoing elective surgery. METHODS: Dogs were randomly allocated one of four groups: group M, medetomidine 5 µg kg-1; group B, butorphanol 0.2 mg kg-1; group MB, medetomidine 5 µg kg-1 and butorphanol 0.2 mg kg-1; or group MBK, medetomidine 5 µg kg-1, butorphanol 0.2 mg kg-1 and ketamine 1 mg kg-1 IV. Sedation was assessed using a numerical descriptive scale. Heart rate (HR) and rhythm were monitored; propofol dose (mg kg-1 IV) to allow orotracheal intubation was documented. Data were analysed using anova, accounting for multiple testing with the Tukey honest significant difference test. RESULTS: Sedation scores varied significantly between all groups at all time points, except between groups MB and MBK at four time points. HR decreased in all groups: most in groups M and MB, least in group B. HR was initially higher in group MBK than in groups M and MB. Arrhythmias occurred in all groups: group B showed second-degree atrioventricular blocks occasionally, all other groups showed additionally ventricular escape complexes and bundle branch blocks. Dose of propofol required for orotracheal intubation was significantly higher in group B (5.0 ± 2.0 mg kg-1) than in group M (2.6 ± 0.6 mg kg-1). Although no difference could be demonstrated between groups MB (1.4 ± 0.6 mg kg-1) and MBK (0.9 ± 0.8 mg kg-1), both groups required significantly less propofol than group M. CONCLUSION AND CLINICAL RELEVANCE: Medetomidine-based premedication protocols led to various bradyarrhythmias. Addition of subanaesthetic doses of ketamine to medetomidine-based protocols resulted in higher HRs, fewer bradyarrhythmias and fewer animals that required propofol for intubation without causing side effects in healthy dogs.

Comparison of the effect of sedation and general anesthesia on pattern and flash visual evoked potentials in normal dogs.

BACKGROUND: Visual evoked potentials (VEPs) can provide objective functional assessment of the post-retinal visual pathway. This study compared the effects of sedation (butorphanol and dexmedetomidine) and general anesthesia (propofol and sevoflurane) on pattern and flash VEPs. Dogs (n = 13) underwent sedation or anesthesia and VEPs were obtained from 3 subcutaneous recording electrodes placed on the head (O1, Oz, O2). RESULTS: Pattern VEPs could only be recorded under sedation and a maximum of 3 peaks were identified (N75, P100, N135). Flash VEPs could be recorded under both sedation and anesthesia and a maximum of 5 peaks were identified (N1, P1, N2, P2, N3). The latency of the N1 peak and the baseline-N1 amplitude were significantly longer under general anesthesia. CONCLUSION: Visual evoked potentials should be preferentially recorded in dogs sedated with dexmedetomidine and butorphanol, regardless of the stimulus.

Analgesic outcomes of tramadol alone and in combination with Butorphanol or Flurbiprofen Axetil after cesarean section: a retrospective study with propensity score matching analysis.

BACKGROUND: The Society for Obstetric Anesthesia and Perinatology recommends a multimodal analgesia regimen for cesarean delivery analgesia. This study aimed to compare the analgesic effects of tramadol alone and combined with butorphanol or flurbiprofen axetil after a cesarean section. METHODS: We performed a retrospective analysis based on the electronic medical records of a teaching hospital in China from January 2018 to January 2020. We collected data on demographic characteristics, anesthesia, analgesia strategy, and pain intensity postoperatively during the first 48 hours. Inadequate postoperative analgesia during this period was defined as an NRS score ≥ 4. We also collected data regarding off-bed activity and intestinal function recovery. Participants were classified into three groups according to analgesia regimens. Groups T, TF, and TB received tramadol, a mixture of tramadol and flurbiprofen axetil, and a combination of tramadol and butorphanol, respectively. Analgesic outcomes were compared using propensity score matching analysis. RESULTS: Data from 2323 cases of caesarean section were included in the analysis, and 521 pairs were matched in each group according to their propensity score. Compared with group T, The inadequate analgesia on pain at rest and pain at movement was lower in group TF (RR: 0.42, 95% CI: 0.36-0.49, P = 0.001 and RR: 0.58, 95% CI: 0.48-0.69, P < 0.001, respectively),and the incidence of inadequate control of pain at movement was higher in group TB (RR: 1.38, 95% CI: 1.22-1.55, P < 0.001). Additionally, the percentage of off-bed activity at 2 days postoperatively was higher in group TB than in groups TF and T (78.7% vs. 68.5 and 78.7% vs. 64.9%, respectively, P < 0.001). The incidence of intestinal function recovery 2 days after cesarean delivery in group TB was higher than that in group TF (73.3% vs. 66.2%, P = 0.013). CONCLUSIONS: Combining tramadol and flurbiprofen axetil could enhance the analgesic effect and be safely used for analgesia after a cesarean section. However, combining tramadol and butorphanol may produce an antagonistic effect.

Multiple pathways are responsible to the inhibitory effect of butorphanol on OGD/R-induced apoptosis in AC16 cardiomyocytes.

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

Dosing protocols to increase the efficacy of butorphanol in dogs.

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

Effect of intravenous butorphanol infusion on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To determine the effect of butorphanol, administered by intravenous (IV) infusion, on the minimum alveolar concentration of isoflurane (MACISO) in cats and to examine the dosage dependence of this effect. STUDY DESIGN: Randomized, placebo-controlled, crossover experimental study. ANIMALS: A group of six healthy adult male neutered cats. METHODS: Cats were anesthetized with isoflurane in oxygen. A venous catheter was placed for fluid and drug administration, and an arterial catheter was placed for measurement of arterial pressure and blood sampling. Four treatments were administered at random with at least 2 week interval between treatments: saline (control), butorphanol low dosage (treatment LD; 0.25 mg kg-1 IV bolus followed by 85 µg kg-1 minute-1 for 20 minutes, then 43 µg kg-1 minute-1 for 40 minutes, then 19 µg kg-1 minute-1), medium dosage (treatment MD, double the dosages in LD) and high dosage (treatment HD, quadruple the dosages in LD). MACISO was determined in duplicate using the bracketing technique and tail clamping. Pulse rate, arterial pressure, hemoglobin oxygen saturation, end-tidal partial pressure of carbon dioxide and arterial blood gas and pH were measured. RESULTS: Butorphanol reduced MACISO in a dosage-dependent manner, by 23 ± 8%, 37 ± 12% and 68 ± 10% (mean ± standard deviation) in treatments LD, MD and HD, respectively. The main cardiopulmonary effect observed was a decrease in pulse rate, significant in treatment HD compared with control. CONCLUSIONS AND CLINICAL RELEVANCE: Butorphanol caused a dosage-dependent MACISO reduction in cats. IV infusion of butorphanol may be of interest for partial IV anesthesia in cats.

Effects of vatinoxan in dogs premedicated with medetomidine and butorphanol followed by sevoflurane anaesthesia: a randomized clinical study.

OBJECTIVE: To investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration. STUDY DESIGN: A randomized, controlled, blinded, clinical trial. ANIMALS: A total of 28 client-owned dogs. METHODS: Dogs were premedicated with medetomidine (0.125 mg m-2) and butorphanol (0.2 mg kg-1) (group MB; n = 14), or medetomidine (0.25 mg m-2), butorphanol (0.2 mg kg-1) and vatinoxan (5 mg m-2) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg-1) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg-1) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (fR), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (Fe'Sevo) and carbon dioxide (Pe'CO2) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations. RESULTS: At the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute-1 (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in fR, Pe'CO2, Fe'Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups. CONCLUSIONS AND CLINICAL RELEVANCE: In group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups.

Comparison of hydromorphone and butorphanol for management of pain in equine patients undergoing elective arthroscopy: a randomized clinical trial.

OBJECTIVE: To compare the effects of hydromorphone and butorphanol in horses undergoing arthroscopy and describe the pharmacokinetics of hydromorphone in anesthetized horses. STUDY DESIGN: Randomized controlled clinical trial. ANIMALS: A total of 40 adult horses admitted for elective arthroscopy. METHODS: Horses were randomly assigned to be administered intravenous hydromorphone (0.04 mg kg-1; group TxH; n = 19) or butorphanol (0.02 mg kg-1; group TxB; n = 21) prior to surgery as part of a standardized anesthetic protocol. Pain was scored by two observers unaware of group assignment using the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) and a composite pain scale (CPS) prior to surgery (baseline), 2 hours (P2) and 4 hours (P4) following recovery from anesthesia. Blood samples were collected at various time points for determination of plasma hydromorphone concentration using liquid chromatography-tandem mass spectrometry. Data were analyzed with a mixed-effect model. RESULTS: Median (range) baseline EQUUS-FAP was 1.2 (0.0-4.0) with no effect of group, time points or interaction. Baseline CPS was similar between groups. Group TxH baseline CPS was 2.5 (0.0-10.0), increased at P2 [4.5 (0-10.0); p = 0.046] and returned to baseline values at P4 [3.0 (0.0-11.0)]. Group TxB baseline CPS was 2.0 (0.0-8.0), increased at P2 [3.5 (0.0-11.0); p = 0.009] and P4 [5.0 (0.0-11.0); p < 0.001]. Pharmacokinetic terminal half-life was 774 ± 82.3 minutes, area under the curve was 1362 ± 314 ng minutes mL-1, clearance was 30.7 ± 7.23 mL minute-1 kg-1 and volume of distribution at steady state was 884 ± 740 mL kg-1. CONCLUSIONS: Hydromorphone, but not butorphanol, decreased CPS back to baseline at P4 after recovery. CLINICAL RELEVANCE: Hydromorphone may provide superior postoperative analgesia compared with butorphanol in horses undergoing arthroscopy.

Effects of intravenous acepromazine and butorphanol on propofol dosage for induction of anesthesia in healthy Beagle dogs.

OBJECTIVE: To determine the effects of intravenous (IV) premedication with acepromazine, butorphanol or their combination, on the propofol anesthetic induction dosage in dogs. STUDY DESIGN: Prospective, blinded, Latin square design. ANIMALS: A total of three male and three female, healthy Beagle dogs, aged 3.79 ± 0.02 years, weighing 10.6 ± 1.1 kg, mean ± standard deviation. METHODS: Each dog was assigned to one of six IV treatments weekly: 0.9% saline (treatment SAL), low-dose acepromazine (0.02 mg kg-1; treatment LDA), high-dose acepromazine (0.04 mg kg-1; treatment HDA), low-dose butorphanol (0.2 mg kg-1; treatment LDB), high-dose butorphanol (0.4 mg kg-1; treatment HDB); and a combination of acepromazine (0.02 mg kg-1) with butorphanol (0.2 mg kg-1; treatment ABC). Physiologic variables and sedation scores were collected at baseline and 10 minutes after premedication. Then propofol was administered at 1 mg kg-1 IV over 15 seconds, followed by boluses (0.5 mg kg-1 over 5 seconds) every 15 seconds until intubation. Propofol dose, physiologic variables, recovery time, recovery score and adverse effects were monitored and recorded. Data were analyzed using mixed-effects anova (p < 0.05). RESULTS: Propofol dosage was lower in all treatments than in treatment SAL (4.4 ± 0.5 mg kg-1); the largest decrease was recorded in treatment ABC (1.7 ± 0.3 mg kg-1). Post induction mean arterial pressures (MAPs) were lower than baseline values of treatments LDA, HDA and ABC. Apnea and hypotension (MAP < 60 mmHg) developed in some dogs in all treatments with the greatest incidence of hypotension in treatment ABC (4/6 dogs). CONCLUSIONS AND CLINICAL RELEVANCE: Although the largest decrease in propofol dosage required for intubation was after IV premedication with acepromazine and butorphanol, hypotension and apnea still occurred.

Effects of Intramuscular Alfaxalone and Midazolam Compared With Midazolam and Butorphanol in Rhode Island Red Hens (Gallus gallus domesticus).

Chickens (Gallus gallus domesticus) often undergo veterinary procedures requiring sedation; however, there is little published research evaluating the efficacy of sedation protocols in this species. The objective of this study was to assess the effects of intramuscular alfaxalone and midazolam compared with intramuscular butorphanol and midazolam in chickens. In a complete crossover study, 11 healthy adult hens were randomly administered midazolam 2.5 mg/kg IM combined with either alfaxalone 15 mg/kg IM (AM, n = 11) or butorphanol 3 mg/kg IM (BM, n = 11), with a 35-day washout period between groups. Time to first effects, recumbency, standing, and recovery were recorded. Physiologic parameters and sedation scores were recorded every 5 minutes by 2 blinded investigators. Fifteen minutes after injection, positioning for sham whole body radiographs was attempted. At 30 minutes, flumazenil 0.05 mg/kg IM was administered to all hens. Peak total sedation score was significantly higher for AM compared with BM (P < 0.001). Mean ± SD or median (range) time to initial effects, recumbency, standing, and recovery in AM and BM were 1.9 ± 0.6 and 2.6 ± 0.9 (P = 0.02), 3.5 (1.6-7.6) and 4.8 (2.2-13.0) (P = 0.10), 40.3 (28.0-77.8) and 33.2 (5.2-41.3) (P = 0.15), and 71.2 (45.7-202.3) and 39.9 (35.9-45.9) minutes (P = 0.05), respectively. Radiographic positioning was successful in 6 of 11 (54.5%) and 0 of 11 (0%) birds in the AM and BM groups at 15 minutes, respectively. Heart and respiratory rates remained within acceptable clinical limits for all birds. Intramuscular AM resulted in significantly faster onset of sedative effects, significantly longer duration of recumbency, significantly higher peak sedation, and improved success of radiographic positioning compared with intramuscular BM. Intramuscular AM produces clinically effective sedation in chickens without clinically significant cardiorespiratory effects.

Comparison of intrathecal bupivacaine-fentanyl and bupivacaine-butorphanol combinations for joint replacement surgeries.

Background and Aims: The objective of the study was to compare duration of analgesia of fentanyl versus butorphanol as adjuvants to bupivacaine in spinal anesthesia. Material and Methods: A prospective, randomized, double-blinded study conducted in 80 patients of 18-75 years age group and American Society of Anesthesiologists Grades I and II undergoing joint replacement surgeries. A total of 40 patients in each Group A and Group B received 0.5% bupivacaine 3 ml with 25 mcg fentanyl and 25 mcg butorphanol respectively, in a total volume of 3.5 ml made with saline. Duration of analgesia, number of rescue analgesia, sensory, and motor block characteristics were compared between the two groups. Statistical analysis was done using t test and Chi-square test with SPSS 19.0 software. Results: Mean duration of analgesia was found more in Group B in comparison to Group A (P < 0.05). A number of doses of analgesic required postoperatively were more in Group A compared to Group B (P < 0.001). Time required for onset of sensory and motor block was comparable in both the groups. However, two segment regression of sensory block was slower in Group B compared to Group A (P < 0.05). Conclusion: We conclude that addition of butorphanol 25 µg as an adjuvant to 0.5% hyperbaric bupivacaine provided prolonged duration of analgesia compared to 25 mg fentanyl.

Use of Butorphanol as Treatment for Cholestatic Itch.

BACKGROUND: Pruritus is a debilitating symptom of cholestatic diseases such as primary biliary cholangitis and primary sclerosing cholangitis and often results in major reduction in quality of life for afflicted patients. Classic treatment options for the treatment of cholestatic pruritus include antihistamines, bile acid resins, serotonin reuptake inhibitors, and mu-opioid antagonists. Unfortunately, these drugs are not always successful in treating pruritus of cholestasis and may be associated with adverse effects. Recent advances in our understanding of itch pathophysiology have led to the use of butorphanol, a kappa-opioid agonist and mu-opioid antagonist, for the treatment of various forms of pruritus. Reports of butorphanol to treat cholestatic itch specifically are rare. AIMS: To better understand the role of butorphanol in the treatment of cholestatic pruritus, including characterization of its side effect profile. METHODS: We present a case series of eight adult patients with cholestatic disease who were treated with butorphanol in hopes of alleviating intractable pruritus. Patients were identified through a clinical data request form serviced by University of Miami Information Technology. RESULTS: Five out of eight patients (62.5%) reported successful reductions in itch severity after treatment with butorphanol, two patients reported no (or transient) change in itch severity, and one patient reported a paradoxical increase in itching. Side effects included somnolence, sedation, nausea, vomiting, and dizziness. CONCLUSIONS: Butorphanol was safe and leads to clinically significant symptomatic improvement. Clinicians should be aware of butorphanol as an off-label treatment option for pruritus of cholestasis. Further studies are needed to better characterize the effect of butorphanol on cholestatic itch.

Effects of isoflurane and sevoflurane alone and in combination with butorphanol or medetomidine on the bispectral index in chickens.

BACKGROUND: The bispectral index (BIS) is an anaesthesia monitoring technique able to assess the level of central nervous system depression in humans and various animal species. In birds, it has been validated in chickens undergoing isoflurane anaesthesia. The aim of this study was to evaluate in an avian species the influence of isoflurane and sevoflurane on BIS, each at different minimum anaesthetic concentrations (MAC) multiples, alone or combined with butorphanol or medetomidine. Ten chickens (5 males and 5 females) underwent general anaesthesia with isoflurane or sevoflurane alone, and combined with either intramuscular administration of butorphanol (1 mg/kg) or medetomidine (0.1 mg/kg), in a prospective and cross-over study (i.e., 6 treatments per animal). BIS measurements were compared to heart rate (HR), non-invasive blood pressure (NIBP) and to a visual analogue scale (VAS) of anaesthesia depth. RESULTS: HR was significantly increased, and both NIBP and VAS were significantly reduced, with higher gas concentrations. NIBP (but not HR or VAS) was additionally affected by the type of gas, being lower at higher concentrations of sevoflurane. Butorphanol had no additional effect, but medetomidine led to differences in HR, NIBP, and in particular a reduction in VAS. With respect to deeper level of hypnosis at higher concentrations and the absence of difference between gases, BIS measurements correlated with all other measures (except with HR, where no significant relationship was found) The difference in BIS before (BISpre) and after stimulation (BISpost) did not remain constant, but increased with increasing MAC multiples, indicating that the BISpost is not suppressed proportionately to the suppression of the BISpre values due to gas concentration. Furthermore, neither butorphanol nor medetomidine affected the BIS. CONCLUSIONS: The difference of degree of central nervous system depression monitored by BIS compared with neuromuscular reflexes monitored by VAS, indicate that BIS records a level of anaesthetic depth different from the one deducted from VAS monitoring alone. BIS provided complementary information such as that medetomidine suppressed spinal reflexes without deepening the hypnotic state. As a consequence, it is concluded that BIS improves the assessment of the level of hypnosis in chickens, improving anaesthesia monitoring and anaesthesia quality in this species.

Anesthetic effect of different doses of butorphanol in patients undergoing gastroscopy and colonoscopy.

BACKGROUND: This study aimed to investigate the anesthetic effect of butorphanol with different doses in patients undergoing gastroscopy and colonoscopy. METHODS: 480 patients undergoing gastroscopy and colonoscopy were recruited and randomly divided into four groups to receive different doses of butorphanol (Group A = 2.5 µg/kg, Group B = 5 µg/kg, Group C = 7.5 µg/kg and Group D = 10 µg/kg). Butorphanol was administered 5 min before propofol infusion. The primary outcome was the incidence of body movement. Secondary outcomes were postoperative recovery time, length of stay in the Post-Anesthesia Care Unit (PACU), the total dose of propofol, and the incidence of intraoperative hypoxemia, propofol injection pain, cough, postoperative nausea and vomiting, drowsiness, and dizziness. RESULTS: The incidence of body movement and the dose of propofol in Group C and D were lower than those in Group A and B (P < 0.05). The incidence and intensity of propofol injection pain and the incidence of cough in Group B, C, and D were lower than those in Group A (P < 0.05). The length of stay in PACU and the incidence of postoperative drowsiness and dizziness were higher in Group D than in Group A, B, and C (P < 0.05). CONCLUSION: Intravenous pre-injection of 7.5 µg/kg butorphanol with propofol can be the optimal dosage for patients undergoing gastroscopy and colonoscopy. TRIAL REGISTRATION: Trial registration: Chinese Clinical Trial Registry, ChiCTR2000031506. Registered 3 April 2020-Retrospectively registered, http://www.medresman.org.cn .

Pharmacokinetics of butorphanol in male neutered cats anesthetized with isoflurane.

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