Painless Gastrointestinal Endoscopy Assisted with Computed Tomography Image Information Data Monitoring in Postoperative Neurocognitive Dysfunction in Patients with Combined Anesthesia of Propofol and Butorphanol Tartrate under Electronic Health.

The aim of this study was to explore the value of computed tomography (CT) images based on electronic health (E-health) combined with painless gastrointestinal endoscopy (PGE) in the diagnosis of neurocognitive function in patients with combined anesthesia of propofol and butorphanol tartrate. 126 patients undergoing PGE were selected as the research objects, and all were performed with CT perfusion imaging before and after anesthesia to obtain the cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and time to peak (TTP). The Montreal Cognitive Assessment (MoCA) was adopted to evaluate the cognitive function of patients. The results showed that after anesthesia, the levels of CBF and CBV in the left and right thalami, frontal lobe, and temporal lobe of the patients were lower than those before anesthesia, while TTP and MTT were higher than those before anesthesia (P < 0.05). The MoCA score after anesthesia was lower than that before anesthesia (P < 0.05). After anesthesia, the CBF, CBV, TTP, and MTT values of the left and right frontal lobes and left and right temporal lobes were significantly positively correlated with MoCA (P < 0.05). In conclusion, the brain CT image parameters based on E-health can clearly display the blood perfusion in the lesion area of the patient, which was beneficial to the PGE-assisted judgment of cognitive dysfunction in patients with propofol tartrate and butorphanol tartrate anesthesia. Therefore, CT-assisted PGE examination based on E-health had a certain clinical value in evaluating the neurocognitive function of patients.

Effect of a combination of butorphanol and detomidine on endoscopic assessment of laryngeal function in Thoroughbred yearlings.

BACKGROUND: To the authors' knowledge, the effect of a combination of butorphanol tartrate and detomidine hydrochloride on the laryngeal function and symmetry of the arytenoid cartilages in young Thoroughbred horses has not been examined. Therefore, this study aimed to examine the effects of administration of butorphanol and detomidine on left-to-right rima glottidis ratio (L:R RGR), cross-sectional area of the rima glottidis (CSARG) and grade of laryngeal function of Thoroughbred yearlings examined endoscopically at rest. METHODS: Forty-six Thoroughbred yearlings underwent laryngeal video endoscopy, at rest, before and after sedation with butorphanol and detomidine. Three clinicians assigned grades of laryngeal function after reviewing the video recordings. The L:R RGR and CSARG were measured at the point of arytenoid cartilages' maximal abduction. Student's t-test was used to compare the L:R RGR and CSARG. Cohen's kappa (κ) was used to compare the intra- and interobserver agreements. Spearman's rank order was used to assess agreement between CSARG and grade of laryngeal function. RESULTS: Sedation had no effect on L:R RGR and CSARG. Mean intraobserver agreement of grade of laryngeal function of unsedated yearlings was 93.1%, and that of sedated yearlings was 92.9%. Mean interobserver agreement of grade of laryngeal function of unsedated yearlings was 92.8%, and that of sedated yearlings was 92.7%. Correlation between CSARG and laryngeal function grade was significant for both groups (p < 0.001). CONCLUSION: Sedating Thoroughbred yearlings with detomidine and butorphanol, before endoscopically examining the larynx, did not significantly affect the grade of laryngeal function.

Retrospective and prospective assessment of butorphanol, azaperone and medetomidine (BAM™) for immobilisation of feral horses (Equus ferus caballus).

BACKGROUND: Butorphanol-azaperone-medetomidine (BAM™) has not been evaluated in horses. OBJECTIVES: The objective of this study was to evaluate BAM™ for chemical restraint of feral horses. STUDY DESIGN: Retrospective and prospective descriptive studies. METHODS: Data were collected retrospectively from medical records of 28 feral horses immobilised with BAM™ over a 6-year period. Prospectively, 0.0125 mL/kg bwt of BAM™ (butorphanol 27.3 mg/mL, azaperone 9.1 mg/mL and medetomidine 10.9 mg/mL) intramuscularly (im) was administered to eight stallions via dart, and once recumbent, 1.0 mg/kg bwt ketamine was given intravenously (iv). Induction and recovery time and quality via a standardised rubric (1 = very poor; 5 = excellent) and visual analogue scale (VAS), need for additional darts, weight tape measurement and serial physiological parameters were recorded. Serial arterial blood gas analysis was performed during recumbency. Following castration, horses were given 0.1 mg/kg bwt atipamezole (25% iv and 75% im) and allowed to recover unaided. RESULTS: Retrospectively, 28 horses were successfully immobilised with BAM™ without a major complication. Prospectively, eight horses were given a median (range) actual BAMTM dose of 0.0143 (0.0127-0.0510) mL/kg bwt. Three of eight horses needed 1, 2 or 5 additional darts. Median (range) time to recumbency was 11 (2-44) minutes. Median (range) induction (n = 4) and recovery (n = 6) scores via rubric and VAS were 5 (4-5) and 5 (5-5) and 92 (86-93) and 98 (92-99) cm, respectively. Four of seven horses were hypoxaemic at ≥1 time point with otherwise acceptable physiological parameters. Following atipamezole, median (range) time to sternal recumbency and standing was 12 (2-18) and 17 (11-52) minutes, respectively (n = 6). MAIN LIMITATIONS: The sample size was small. Data could not be collected before darting or after recovery. Some data were missing from retrospective analysis. CONCLUSIONS: Intramuscular BAM™ with iv ketamine provided chemical restraint suitable for field castration of feral horses with no mortality. Hypoxaemia occurred in the majority of horses.

Echocardiographic Assessment of Healthy Midazolam/Butorphanol or Midazolam/Morphine-Sedated Dogs.

The purpose of this study was to assess the effects of midazolam combined with morphine or butorphanol on echocardiographic variables of healthy dogs. Twenty-four dogs of various breeds aged 34.33 ± 23.41 months and weighing 8.1 ± 4.7 kg were enrolled in the study. Subjects were randomly allocated in one of two experimental groups of sedation with intramuscular midazolam (0.3 mg/kg) combined with butorphanol (0.2 mg/kg) (GB, n = 12) or morphine (0.3 mg/kg) (GM, n = 12). Transthoracic echocardiographic examinations comprised B-Mode, M-Mode, spectral Doppler and pulsed tissue Doppler assessment. Data were recorded before sedation (TB) and 20 minutes following intramuscular administration of either sedation protocol (TS). Data were analyzed using repeated measures ANOVA followed by Tukey's posthoc test. Shortening fraction, ejection fraction, left ventricular diameter and volume did not differ among groups and time points. The A and E' waves were decreased in GM at TS compared to TB. Isovolumic relaxation time, Ae/Ao ratio, aortic and pulmonary flows and S' wave did not differ among time points and groups. These sedation protocols did not cause clinically relevant changes in echocardiographic variables, therefore can be used for sedation of uncooperative dogs during echocardiographic evaluation.

Assessment of sedation after intranasal administration of midazolam and midazolam-butorphanol in cockatiels (Nymphicus hollandicus).

OBJECTIVE To compare sedation in cockatiels (Nymphicus hollandicus) after intranasal administration of midazolam and midazolam-butorphanol. ANIMALS 9 healthy adult cockatiels. PROCEDURES A randomized, controlled, blinded, complete crossover study was conducted. Birds were assigned to 3 treatment groups. Midazolam (3 mg/kg), midazolam-butorphanol (3 mg/kg for each drug), or sterile saline (0.9% NaCl) solution (control treatment) was administered intranasally. Sedation quality was assessed at 3 time points by use of eye and body position; response to visual, auditory, and tactile stimulation; and response during manual restraint on the basis of eye position and struggling intensity. To evaluate attenuation of the manual restraint-induced stress response, heart rate, respiratory rate, and cloacal temperature were measured over a 15-minute period. Treatments were repeated after a minimum washout period of 7 days. RESULTS Median onset of first sedation effects was 85 seconds (range, 60 to 120 seconds) for midazolam and 90 seconds (range, 45 to 180 seconds) for midazolam-butorphanol. Midazolam-butorphanol resulted in significantly less vigorous struggling during restraint than did midazolam or the control treatment. Heart rate did not differ significantly among treatments. The stress-induced increase in respiratory rate was significantly attenuated by midazolam and midazolam-butorphanol, whereas the increase in cloacal temperature was not attenuated by midazolam or midazolam-butorphanol. CONCLUSIONS AND CLINICAL RELEVANCE Intranasal administration of midazolam and midazolam-butorphanol resulted in a rapid onset of sedation in cockatiels. Midazolam-butorphanol resulted in deeper sedation in both restrained and unrestrained birds than did midazolam alone. Midazolam and midazolam-butorphanol both provided safe and effective sedation in cockatiels.

Assessment of butorphanol-azaperone-medetomidine combination as anesthesia for semen collection and evaluation of semen quality in white-tailed deer (Odocoileus virginianus).

The aim of this current study was to evaluate the level of anesthesia produced by a combination of butorphanol-azaperone-medetomidine (BAM) for semen collection by electroejaculation on captive white-tailed bucks (Odocoileus virginianus). Ten male white-tailed deer, weighing 68.2-115.9kg, ranging in age from one to four years were randomly selected from housing pens and anesthetized with the BAM drug combination at a dose volume of 2.0mL each. Semen was collected from each animal using a standard cervid electroejaculation protocol while under BAM anesthesia. Physiological data was recorded following induction of anesthesia and during semen collection. Collected ejaculates were prepared for analysis using a standard extender protocol for cryopreservation. Eleven sperm viability parameters were quantified for each sample using a Computerized Assisted Sperm Analysis system, including total seminal volume; sperm concentration and total sperm number. kinematic parameters of motile spermatozoa were also assessed. Results demonstrated that BAM provided an effective plane of anesthesia for successful collection of viable sperm. Measured physiological variables of heart rate, respiration and body temperature all remained within safe, normal limits. Data recorded on semen characteristics from all collected ejaculates correlated well with key traits determined to be important for successful fertilization through measurement of total semen volume; sperm concentration; total sperm number; and kinematic parameters of motile spermatozoa. There were no serious adverse events. This field study indicates that BAM anesthesia is suitable for semen collection in white-tailed deer.

Behavioral response and cost comparison of manual versus pharmacologic restraint protocols in healthy dogs.

Although sedatives are routinely administered to dogs for diagnostic and minimally invasive procedures, manual restraint is often used. The study compared intra-procedural behavioral response, scored on a 100-point, visual analog scale, and cost of restraint in healthy dogs given 1 of 5 treatments: manual restraint, dexmedetomidine at 125 µg/m(2) (Dex 125) or 375 µg/m(2) (Dex 375), Dex 125 plus butorphanol at 0.4 mg/kg (Dex 125 + Bu), or Dex 375 plus butorphanol at 0.4 mg/kg (Dex 375 + Bu). Mean behavioral response scores in dogs declined from baseline in the manual restraint group and improved in a linear fashion in the group order Dex 125, Dex 375, Dex 125 + Bu, and Dex 375 + Bu. Dexmedetomidine at 375 µg/m(2) or at 125 µg/m(2) or at 375 µg/m(2) in combination with butorphanol produced the best intra-procedural behavioral response. The cost of sedative drugs was offset by the opportunity cost of diverting personnel from revenue-generating activity to manual restraint.

Réaction comportementale et comparaison du coût des protocoles de contention manuelle par rapport aux protocoles de retenue pharmacologiques chez des chiens en santé. Même si des sédatifs sont régulièrement administrés aux chiens pour des procédures diagnostiques ou minimalement invasives, la contention manuelle est souvent utilisée. L'étude a comparé la réaction comportementale durant la procédure, évaluée sur une échelle analogue visuelle de 100 points, et le coût de la retenue chez des chiens en santé auxquels on a administré l'un de 5 traitements : la contetnion manuelle, la dexmédétomidine à 125 µg/m2 (Dex 125) ou à 375 µg/m2 (Dex 375), la Dex 125 et du butorphanol à 0,4 mg/kg (Dex 125 + Bu) ou la Dex 375 et du butorphanol à 0,4 mg/kg (Dex 375 + Bu). Les notes moyennes de réaction comportementale chez les chiens ont chuté de la valeur de base dans le groupe de contention manuelle et elles se sont améliorées de façon linéaire dans l'ordre des groupes Dex 125, Dex 375, Dex 125 + Bu et Dex 375 + Bu. La dexmédétomidine à 375 µg/m2 ou à 125 µg/m2 ou à 375 µg/m2 en combinaison avec du butorphanol a produit la meilleure réaction comportementale pendant la procédure. Le coût des sédatifs a été compensé par le coût découlant de l'affectation du personnel à des activités produisant des revenus au lieu de la contention manuelle.(Traduit par Isabelle Vallières).

Assessment of brachial plexus blockade in chickens by an axillary approach.

OBJECTIVE: To assess the brachial plexus block in chickens by an axillary approach and using a peripheral nerve stimulator. STUDY DESIGN: Prospective, randomized, double-blinded study. ANIMALS: Six, 84-week old, female chickens. METHODS: Midazolam (1 mg kg(-1)) and butorphanol (1 mg kg(-1)) were administered into the pectoralis muscle. Fifteen minutes later, the birds were positioned in lateral recumbency and following palpation of the anatomic landmarks, a catheter was inserted using an axillary approach to the brachial plexus. Lidocaine or bupivacaine (1 mL kg(-1)) was injected after plexus localization by the nerve stimulator. Sensory function was tested before and after blockade (carpus, radius/ulna, humerus and pectoralis muscle) in the blocked and unblocked wings. The latency to onset of motor and sensory block and the duration of sensory block were recorded. A Friedman nonparametric one-way repeated-measures ANOVA was used to compare scores from baseline values over time and to compare the differences between wings at each time point. RESULTS: A total of 18 blocks were performed with a success rate of 66.6% (12/18). The latency for motor block was 2.8 +/- 1.1 and 3.2 +/- 0.4 minutes for lidocaine and bupivacaine, respectively. The latencies for and durations of the sensory block were 6.0 +/- 2.5 and 64.0 +/- 18.0 and 7.8 +/- 5.8 and 91.6 +/- 61.7 minutes for lidocaine and bupivacaine, respectively. There was no statistical difference between these times for lidocaine or bupivacaine. Sensory function was not abolished in nonblocked wings. CONCLUSIONS AND CLINICAL RELEVANCE: The brachial plexus block was an easy technique to perform but had a high failure rate. It might be useful for providing anesthesia or postoperative analgesia of the wing in chickens and exotic avian species that have similar wing anatomy.

WHO Expert Committee on Drug Dependence.

This report presents the recommendations of a WHO Expert Committee responsible for reviewing information on dependence-producing drugs to assess the need for their international control. The first part of the report contains a summary of the Committee's evaluations of seven substances (dronabinol, oripavine, buprenorphine, butorphanol, ketamine, khat and zopiclone). The report also discusses the substances that were pre-reviewed (gamma-hydroxybutyric acid and tramadol) and recommended gamma-hydroxybutyric acid for critical review at a future meeting. Two substances (gamma-butyrolactone and 1,4-butanediol) were identified for future pre-review). The second part of the report discusses the guidelines for the WHO review of dependence-producing psychoactive substances for international control. It includes sections on amending the current guidelines, interpretation of specific aspects of the guidelines and access to information necessary for the evaluation of substances. The final section considers other matters including activities of the EMCCDA, the use of pharmacovigilance data, promotion of education and information on the appropriate use of psychoactive drugs and the impact of international control on medical availability of substances.

The use and assessment of ketamine-medetomidine-butorphanol combinations for field anaesthesia in wild European badgers (Meles meles).

OBJECTIVE: To evaluate the effectiveness of four ketamine-based anaesthetics in badgers using a quantitative anaesthesia assessment technique. STUDY DESIGN: Prospective randomized 'blinded' experimental trial. METHODS: The quality of induction, of anaesthesia (at 5-minute intervals) and of recovery were assessed in 93 badgers, given either one of three ketamine (K)-medetomidine (M)-butorphanol (B) combinations: group A - M K B at 20/40/80 microg kg(-1); group B - M K B at 20/40/60 microg kg(-1); and group C - M K B at 20/60/40 microg kg(-1), or ketamine (K) alone at 2 mg kg(-1) (group D). The assessor was ignorant of the combination administered. Physiological variables (heart and respiratory rates and rectal temperature) were measured at 5-minute intervals during anaesthesia. Gingival mucus membrane colour was also recorded. RESULTS: Induction to anaesthesia was most rapid with ketamine (2 mg kg(-1)) although induction quality did not differ between techniques. Ketamine used alone gave the poorest score for anaesthesia quality. Heart rate (HR) and scores for gingival mucus membrane colour were higher in animals anaesthetized with ketamine alone. Rectal temperature did not differ significantly between the techniques at any time during anaesthesia. Ketamine used alone produced the poorest quality of recovery. CONCLUSION AND CLINICAL RELEVANCE: The M-K-B combinations investigated overcame several side effects associated with ketamine anaesthesia, but at the expense of more variable induction times, lower HRs, and poorer mucus membrane coloration.

Standing oral extraction of cheek teeth in 100 horses (1998--2003).

REASONS FOR PERFORMING STUDY: Extraction of cheek teeth (CT) by the conventional repulsion technique requires general anaesthesia and carries a high rate of post operative complications. Consequently, an alternative method of extraction, i.e. orally in standing horses, was evaluated. HYPOTHESIS: The need for and risks of general anaesthesia could be avoided and post extraction sequelae reduced by performing extractions orally in standing horses. METHODS: One hundred mainly younger horses (median age 8, range 2-18 years) with firmly attached CT that required extraction because of apical infections, displacements, diastemata, idiopathic fractures and the presence of supernumerary CT had the affected teeth (n = 111) extracted orally under standing sedation. Follow-up information was obtained for all cases, a median of 16 months later. RESULTS: Oral extraction was successful in 89 horses and unsuccessful in 11 due to damage to the CT clinical crown (n = 9) during extraction, for behavioural reasons (n = 1) and because the apex of a partly extracted CT fell back into the alveolus following sectioning (n = 1). Predispositions to extraction-related CT fractures were present in 5 of the 9 cases, i.e. advanced dental caries (n = 2) and pre-existing 'idiopathic' fractures (n = 3). The iatrogenically fractured CT were later repulsed under standing sedation (n = 3) and under general anaesthesia (n = 6). Eighty-one of the remaining 89 horses had successful oral CT extraction with no or minimal intra- or post operative complications occurring. Post operative complications in the other 8 cases included post extraction alveolar sequestration (n = 3), alveolar sequestration and localised osteomyelitis (n = 1), localised osteomyelitis (n = 1), incorporation of alveolar packing material into alveolar granulation tissue (n = 1), and nasal discharge due to continued intranasal presence of purulent food material (n = 1) and to ongoing sinusitis (n = 1). The above sequelae were treated successfully in all cases, with general anaesthesia required in just one case. Following oral extraction, significantly (P<0.001) fewer post operative problems developed in 54 horses with apically infected CT in comparison with 71 previous cases that had repulsion of apically infected CT at our clinic. CONCLUSIONS AND POTENTIAL RELEVANCE: Oral extraction of cheek teeth is a successful technique in the majority of younger horses with firmly attached CT and greatly reduces the post operative sequelae, compared with CT repulsion. Additionally, the costs and risks of general anaesthesia are avoided. Further experience and refinement in the described protocol could potentially increase the success of this procedure and also reduce the incidence of post operative sequelae.

Identifying controlled substance patterns of utilization requiring evaluation using administrative claims data.

OBJECTIVES: To develop a systems approach to identify, for further evaluation, patients with potential controlled substance misuse or mismanagement using software queries applied to administrative health claims data. STUDY DESIGN: Retrospective validation of the system using insurance claims. PATIENTS AND METHODS: Data from administrative health claims databases representing nearly 7 million individuals younger than 65 years were used by multidisciplinary expert panels to develop and validate controlled substance patterns of utilization requiring evaluation (CS-PURE) criteria. RESULTS: Thirty-four CS-PURE queries were developed in SAS and applied to administrative claims records to identify patients with potential controlled substance misuse or mismanagement. From these, we identified 10 CS-PURE with the highest expert agreement that intervention was warranted. Expert panel agree, ment that CS-PURE correctly identified cases ranged from 48% to 100%, with at least 50% agreement in 9 of 10 CS-PURE. The prevalence rates for CS-PURE ranged from 0.001% to 0.252%. This translates to identifying between 5 and 1116 patients for individual CS-PURE in a 500 000-member health plan. CONCLUSIONS: We developed and empirically validated a group of queries using CS-PURE to identify patients with potential controlled substance misuse or mismanagement that would warrant further evaluation by the treating physician, a quality assurance function, or the medical director. Claims-based CS-PURE identification is generalizable to most health insurers with access to medical and pharmaceutical claims records. Although CS-PURE are not direct measures of misuse, they can direct attention to potential problems to determine if intervention is needed.

Physicians and the pharmaceutical industry: a dysfunctional relationship.

The pharmaceutical industry is one of the largest and most profitable industries in the world, and in the United States, the industry has a particularly privileged economic position. Yet the cost of drugs in the United States is higher than anywhere else, due largely to the fact that the industry is focusing increasingly on marketing rather than on the development of meaningful new medications: available evidence does not support claims of great expense for the development of new drugs. Because of its vast resources, the pharmaceutical industry has assumed an increasing influence in medicine, which, given the differences in values and priorities between medicine and the drug companies, is a cause for concern. The pharmaceutical industry has acted to maximize its profits in ways that frequently conflict with medicine's need for truth and full disclosure. Indeed, the industry has arguably worked to compromise physicians' judgments, as well as academic standards. As a result, despite government regulation there have been unnecessary adverse effects from drugs. The experience with butorphanol (Stadol) exemplifies problems in the current system and the harm that can result. Changes are suggested to make the pharmaceutical industry more responsive to the needs of patients and physicians.

Cardiopulmonary assessment of medetomidine, ketamine, and butorphanol anesthesia in captive Thomson's gazelles (Gazella thomsoni).

This investigation evaluated the cardiopulmonary effects of medetomidine, ketamine, and butorphanol anesthesia in captive juvenile Thomson's gazelles (Gazella thomsoni). Butorphanol was incorporated to reduce the dose of medetomidine necessary for immobilization and minimize medetomidine-induced adverse cardiovascular side effects. Medetomidine 40.1 +/- 3.6 microg/kg, ketamine 4.9 +/- 0.6 mg/kg, and butorphanol 0.40 +/- 0.04 mg/kg were administered intramuscularly by hand injection to nine gazelles. Times to initial effect and recumbency were within 8 min postinjection. Cardiopulmonary status was monitored every 5 min by measuring heart rate, respiratory rate, indirect blood pressure, end-tidal CO2, and indirect oxygen-hemoglobin saturation by pulse oximetry. Venous blood gases were collected every 15 min postinjection. Oxygen saturations less than 90% in three gazelles suggested hypoxemia. Subsequent immobilized gazelles were supplemented with intranasal oxygen throughout the anesthetic period. Sustained bradycardia (<60 beats per minute, as compared with anesthetized domestic calves, sheep, and goats) was noted in eight of nine gazelles. Heart and respiratory rates and rectal temperatures decreased slightly, whereas systolic, mean, and diastolic blood pressure values were consistent over the anesthetic period. Mild elevations in end tidal CO2 and PCO2 suggested hypoventilation. Local lidocaine blocks were necessary to perform castrations in all seven of the gazelles undergoing the procedure. Return to sternal recumbency occurred within 7 min and return to standing occurred within 12 min after reversal with atipamezole (0.2 +/- 0.03 mg/kg) and naloxone (0.02 +/- 0.001 mg/kg). Medetomidine, ketamine, and butorphanol can be used to safely anesthetize Thomson's gazelles for routine, noninvasive procedures. More invasive procedures, such as castration, can be readily performed with the additional use of local anesthetics.

Evaluation of transdermal fentanyl patches for analgesia in cats undergoing onychectomy.

OBJECTIVE: To evaluate efficacy and safety of using transdermal fentanyl patches (TFP) for analgesia in cats undergoing onychectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 45 client-owned cats weighing > or = 2.7 kg (5.9 lb) undergoing onychectomy, onychectomy and ovariohysterectomy, or onychectomy and castration. PROCEDURE: Cats were randomly assigned to be treated with a TFP (25 micrograms/h) or butorphanol; TFP were applied a minimum of 4 hours before surgery (approx 8 hours prior to extubation). Rectal temperature, heart rate, respiratory rate, force applied by the forelimbs, and serum fentanyl concentration were measured, and temperament, recovery, degree of sedation, severity of pain, severity of lameness, and appetite were scored before and periodically for up to 40 hours after surgery. RESULTS: Cats treated with a TFP had better recovery scores at 2 of 4 evaluation times, lower sedation scores at 2 of 8 evaluation times, and lower pain scores at 6 of 8 evaluation times, compared with cats treated with butorphanol. Use of a pressure-sensitive mat to evaluate force applied by the forelimbs did not reveal any differences between groups but did reveal a significant difference between preoperative and postoperative values. Mean +/- SD serum fentanyl concentrations were 1.56 +/- 1.08, 4.85 +/- 2.38, 4.87 +/- 1.56, and 4.35 +/- 2.97 ng/ml approximately 8, 24, 32, and 48 hours, respectively, after TFP placement. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of a TFP (25 micrograms/h) for postoperative analgesia in cats undergoing onychectomy with or without surgical sterilization is safe and effective.

Assessment of opioid partial agonist activity with a three-choice hydromorphone dose-discrimination procedure.

The discriminative stimulus and subjective effects of opioid mixed agonist-antagonists were assessed in volunteer nondependent heroin users trained in a three-choice drug discrimination procedure to discriminate among the effects of i.m. administration of 2 ml of saline, 1 mg of hydromorphone, and 4 mg of hydromorphone (a morphine-like mu agonist). Other subjective, behavioral, and physiological measures were concurrently collected. The discrimination was readily learned by six of the eight subjects. After training, generalization curves were determined for the following i.m. drug conditions: hydromorphone (0.375-4.0 mg), pentazocine (7.5-60 mg), butorphanol (0.75-6 mg), nalbuphine (3-24 mg), and buprenorphine (0.075-0.6 mg). All five of the test drugs were discriminated significantly or showed trends toward being discriminated as hydromorphone 1 mg-like at one or more dose levels. Hydromorphone showed an inverted U-shaped dose-effect function on the hydromorphone 1 mg-like discrimination. Subjective effect measures produced clearer differentiation among the test drugs than did drug discrimination performance. The present results differ from those of a previous study that observed a close relationship between the results of the discrimination measure and subjective effect measures. The previous study used similar methods and test drugs but different training drugs (e.g., 3 mg of hydromorphone versus 6 mg of butorphanol versus saline). It appears that both the sensitivity of drug discrimination performance to between-drug differences and the relationship between discriminative and subjective effects depends upon the specific discrimination that is trained (e.g., two-choice or three-choice). The present high dose-low dose-saline discrimination procedure appears useful for assessing partial agonist activity. The present data are consistent with partial agonist activity for pentazocine, butorphanol, nalbuphine, and buprenorphine.

[Assessment of central hemodynamics during long microsurgical interventions using beforal in children]. / Otsenka tsentral'noi gemodinamiki pri dlitel'nykh mikrokhirurgicheskikh operatsiiakh u detei s primeneniem beforala.

Beforal was used for anesthesia in 21 children aged 4 to 14 years and weighing 15 to 65 kg. Surgical interventions lasted for 2.5 to 9 hours. The basic dose of beforal was 0.5 to 1 mg/kg. Anesthesia was maintained with half or third of the basic dose in combination with inhalations of nitrogen oxide and relanium (diazepam) in a dose of 0.3 to 0.4 mg/kg. Beforal as the only analgesic component of anesthesia effectively protected the organism of a child from surgical shock and its use was associated with stability of the studied hemodynamic parameters.

Pharmacokinetic/dynamic assessment in drug development: application to the investigational opioid mirfentanil.

The safety, pharmacokinetics, and pharmacodynamics of the investigational partial opioid agonist, mirfentanil, were determined in a dose-escalating, Phase 1 study in healthy male volunteers. Hemodynamic, central nervous system, and respiratory monitoring were used for safety assessment. The electroencephalogram (EEG) was evaluated as a surrogate measure of drug effect. Butorphanol was chosen as the control drug. In the mirfentanil group (n = 8) the dose was increased in sequential subjects from 25 micrograms.kg-1.min-1 for 30 min to 450 micrograms.kg-1.min-1 for 15 min, and in the butorphanol group (n = 10) from 2 micrograms.kg-1.min-1 for 30 min to 25 micrograms.kg-1.min-1 for 15 min. In the mirfentanil group, serious side effects were observed at plasma concentrations more than 2000 ng/mL: heart rates exceeded 130 bpm (n = 2), epileptiform EEG potentials (n = 2), and a convulsion (n = 1). The clearance of mirfentanil was high (5.8-7.2 L/min), and the volume of distribution large (247-348 L). The EEG of the subjects receiving mirfentanil showed no changes typical for opioids. Butorphanol however, caused intermittent slowing in the delta and theta ranges. The results of our study define the upper limit of safe plasma concentrations in future mirfentanil studies.

Drug discrimination assessment of agonist-antagonist opioids in humans: a three-choice saline-hydromorphone-butorphanol procedure.

To assess the discriminative stimulus properties of mixed agonist-antagonist opioids in humans, postaddict volunteers were trained in a three-choice drug discrimination procedure to discriminate among the effects of saline (4 ml i.m.), hydromorphone (3 mg i.m.) and butorphanol (6 mg i.m.). Subjects earned monetary reinforcement by correctly identifying the training drugs by letter code. Other subjective, behavioral and physiological measures were concurrently collected. After training, generalization curves for hydromorphone, butorphanol, pentazocine, nalbuphine and buprenorphine were determined. In generalization testing, both hydromorphone and butorphanol produced dose-related increases in hydromorphone-appropriate and butorphanol-appropriate responses, respectively, and other characteristic subjective effect measures. Nalbuphine produced dose-related increases in discrimination as butorphanol and in those subjective effect measures increased by butorphanol. Buprenorphine produced dose-related increases in discrimination as hydromorphone and in those subjective effect measures increased by hydromorphone. Pentazocine was not consistently discriminated as either butorphanol or hydromorphone. These results differ from those of previous discrimination studies using similar methods but different training drugs. Compared to a previous study in which pentazocine served as the kappa-like training drug, the use as a training drug of the more pharmacologically specific kappa-like drug butorphanol permitted greater differentiation among test drugs and yielded discrimination results more consistent with other pharmacological evidence (buprenorphine being mu-like and nalbuphine being kappa-like). There was a close relationship between results of the discrimination measures and the subjective effect measures.