Elizabeth A. Martinez

Pharmacokinetics and pharmacodynamics of butorphanol in llamas following intravenous and intramuscular administration

Our purposes were to evaluate the disposition of butorphanol (BUT) in llamas after intravenous (IV) and intramuscular (IM) administration, to evaluate the effect of BUT on certain physiologic variables, and to evaluate BUTs analgesic efficacy after IM administration. n n n nSix healthy neutered male llamas (4.5xa0±xa01.6xa0years) weighing 102.9xa0±xa016.4xa0kg were given BUT (0.1xa0mgxa0kg−1, IV or IM) using a nonrandomized crossover design; each llama received each treatment at a 1-month interval. The dose chosen for evaluation was that which is currently used to treat pain in llamas. Blood samples were withdrawn from the venous catheter, after flushing with heparinized saline and collecting a waste sample. A volume of 6xa0mL of blood were collected and placed in heparinized tubes at 0, 2, 5, 10, 15, and 30xa0minutes and 1, 2, 3, 4, 6, 8, 16, and 24xa0hour for the IV study and at 0, 15, 30, and 45xa0minutes and 1, 1.5, 2, 3, 4, 6, 8, 16, and 24xa0hour for the IM study. Drug in plasma was detected by high performance liquid chromatography and subjected to standard pharmacokinetic analysis using linear regression. Twoxa0months later, BUT was administered IM; physiologic variables (heart rate, respiratory rate, rectal temperature, indirect blood pressure) and analgesia were assessed at 15-min intervals for 2xa0hours. Analgesia was assessed using a modified hoof-tester fitted with an electronic force transducer to measure applied isometric force to the withers, mid-neck region, and metacarpus. Elimination between the two routes was compared using an unpaired two-tailed t-test; continuous variables after IM BUT were subjected to repeated measures anova; the p-valuesxa0<xa00.05 were considered statistically significant. n n n nThe C0 after IV BUT was 94.8xa0±xa053.1xa0ngxa0mL−1; Cmax after IM BUT was 34.3xa0±xa011.6xa0ngxa0mL−1. The Vss after IV BUT was 0.822xa0±xa00.329xa0Lxa0kg−1 and systemic clearance was 0.050xa0±xa00.014xa0Lxa0kg−1xa0minute−1. The slope of the elimination phase and the elimination half-life were significantly shorter after IV (15.9xa0±xa09.1xa0minutes) versus IM (66.8xa0±xa013.5xa0minutes) BUT. Bioavailability was 110xa0±xa049%. Heart rate decreased (30–105xa0minutes) and rectal temperature increased (30–60xa0min). Somatic analgesia increased at 30xa0minutes (plasma BUTxa0=xa023.8xa0ngxa0mL−1) in the withers compression model and did not return to baseline; in the mid-neck compression model, somatic analgesia increased at 45xa0minutes (21.0xa0ngxa0mL−1) and returned to baseline by 120xa0minutes (9.2xa0ngxa0mL−1). Two llamas were transiently sedated and two were transiently excited after IM BUT. The relationship among plasma BUT concentration, time, and analgesia differed with the area of compression. n n n nClinical trials in llamas could better define the plasma BUT concentrations associated with somatic and visceral analgesia. The longer half-life of IM BUT is more likely to be clinically convenient compared to IV BUT.

Assessment of cardiac troponin I and C‐reactive protein concentrations associated with anesthetic protocols using sevoflurane or a combination of fentanyl, midazolam, and sevoflurane in dogs

OBJECTIVEnTo report serum cardiac troponin I (cTnI) and C-reactive protein (CRP) concentrations in dogs anesthetized for elective surgery using two anesthetic protocols.nnnSTUDY DESIGNnProspective, randomized clinical study.nnnANIMALSnTwenty client-owned dogs presenting for elective ovariohysterectomy or castration.nnnMETHODSnThe dogs were randomized into two groups. All dogs were premedicated with glycopyrrolate (0.011 mg kg(-1)) and hydromorphone (0.1 mg kg(-1)) i.m. approximately 30 minutes prior to induction of anesthesia. Anesthesia in dogs in group 1 was induced with propofol (6 mg kg(-1)) i.v. to effect and in dogs in group 2 with diazepam (0.2 mg kg(-1)) i.v. followed by etomidate (2 mg kg(-1)) i.v. to effect. For maintenance of anesthesia, group 1 received sevoflurane (adjustable vaporizer setting 0.5-4%) and group 2 received a combination of fentanyl (0.8 microg kg(-1) minute(-1)) and midazolam (8.0 microg kg(-1) minute(-1)) i.v. plus sevoflurane (adjustable vaporizer setting 0.5-4%) to maintain anesthesia. Serum cTnI and CRP concentrations were measured at baseline and 6, 18, and 24 hours post-anesthetic induction. Biochemical analysis was performed at baseline. Lactate was obtained at baseline and 6 hours post-anesthetic induction. Heart rate and mean arterial blood pressure were measured intra-operatively.nnnRESULTSnBaseline serum cTnI and CRP concentrations were comparable between groups. A significant difference in serum cTnI or CRP concentrations was not detected post-operatively between groups at any time point. Serum CRP concentrations were significantly increased post-anesthetic induction in both groups, which was attributed to surgical trauma.nnnCONCLUSIONS AND CLINICAL RELEVANCEnThere was no significant difference in serum cTnI and CRP concentrations between anesthetic protocols. Further investigation in a larger number of dogs is necessary to confirm the current findings.

Complications common to ventricular assist device support are rare with 90 days of DeBakey VAD® support in calves

The DeBakey VAD® is a miniaturized, electromagnetically driven axial flow pump intended for long-term ventricular assist. Safety and performance data from six calves implanted with the complete DeBakey VAD® system are reported elsewhere; here we describe complications and necropsy findings for these same six animals, all of which survived 90 days. The study was conducted according to a uniform protocol, which included anticoagulation and antibiotic prophylaxis. Clinical complications tracked included bleeding, cardiovascular abnormalities (e.g., arrhythmias, tachycardia unrelated to pain, bradycardia), hemolysis, hepatic dysfunction, renal dysfunction, thromboembolism (neurologic or peripheral), or infection. Each adverse event was retrospectively categorized with regard to severity (mild, moderate, severe) and relationship to device. Clinical findings were confirmed by necropsy. There was no evidence of systemic infection, thromboembolism, hemolysis, or renal or hepatic dysfunction in these six animals during the study period. A single adverse event was noted in each of two of the calves. Both events were considered mild according to the predefined criteria. Bleeding related to the surgical implantation procedure and requiring reoperation occurred in one animal. The other animal had evidence of a superficial infection at the exit site of the cables on the left lateral thoracic wall; the infection did not extend into the thoracic cavity. Chronic, healed small renal infarct scars were present in several animals. Mild valvular endocardiosis was observed in two calves and mild fibroelastosis was present in the endocardium at the site of the inflow cannula in three calves; however, these lesions were not considered clinically significant. No other gross or histologic abnormalities were noted at necropsy. In conclusion, calves implanted with the complete DeBakey VAD® for 90 days demonstrated few complications and had no significant necropsy findings. Complications common to ventricular assist device (VAD) support (i.e., hemolysis, infection, bleeding, thromboembolism) were rare during long-term support (90 days) with the DeBakey VAD.

Newer neuromuscular blockers. Is the practitioner ready for muscle relaxants

Current research on the development of new neuromuscular blocking agents is directed towards producing agents that have a rapid onset of action and predictable duration of action and recovery times, with minimal hemodynamic effects. For the veterinary practitioner, these newer agents should be considered when muscle relaxation is required for certain surgical procedures. Care must be taken to monitor paralyzed patients appropriately to ensure adequate ventilation and anesthetic depth. Vigilant monitoring should exist during the recovery period for the development of muscle weakness from residual blockade and the ability to reverse the effects of neuromuscular blockade. The use of neuromuscular blocking agents in veterinary patients should continue to increase as newer drugs and better monitoring techniques are developed.

Neuromuscular blocking agents

In summary, with proper vigilance, neuromuscular blocking agents can be used safely in anesthetized equine patients to optimize conditions for certain surgical procedures. By appropriate use of neuromuscular monitoring techniques and reversal agents, residual blockade and muscle weakness should be avoided, allowing the horse to recover to standing without difficulty. Research is ongoing to develop the ideal muscle relaxant, one that has a rapid onset, predictable duration and recovery times, and negligible hemodynamic effects. As newer agents become available, they should be evaluated for their suitability for use in equine patients.

Repeated injectable anesthesia in six horses for cobalt therapy

Little information exists about repeated injectable anesthesia in horses, therefore our purpose is to report the anesthetic method we used to facilitate clinical treatment. Between 1992 and 1999, we anesthetized 6 horses 12 times each at 2^3 day intervals, to allow cobalt therapy (CO) of their tumors. One horse received an additional 10 treatments (T). The ¢ve mares and one gelding (3 QH, 1 Paint, 1TB, 1grade) had a mean age of 927 years (mean 2 SD) and mean weight of 505254 kg. Horses were anesthetized with xylazine (X, 1.020.08mg kgÿ1) and tiletamine-zolazepam (TZ, 1.020.08mg kgÿ1) given IV. Butorphanol (B, 0.02620.01) was given with X, 12 times in one horse and11 times in two horses. A portable multifunction monitor was used to provide ECG, hemoglobin saturation and NIBP. Additional drugs (X, B or ketamine) were required to maintain immobility during transport from the CO room or when horses were repositioned for bilateralT (¢ve horses). No horse required additional drugs after the fourth T. Heart rates were always within normal range (30^45 beats minÿ1) and mean arterial blood pressures were elevated (85^140mmHg). Mean maintenance time (T plus transport time) was 3026minutes, while recovery time (when placed in recovery stall to standing) was 46216 minutes. Oxygen was nasally insu¥ated at 15 Lminÿ1 during T and in recovery. Recoveries were generally good and improved over the course of T. All horses lost weight duringT; meanweight loss was 27222 kg. Horses appeared to acclimatize to transport and treatment, as judged by the fact that lower X doses (10% decrease) or no additional drugs were required during treatment or transport after the ¢rst 3^4 treatments. In conclusion, all horses tolerated repeated anesthesia with injectable agents without apparent adverse side e¡ects.

The effects of multiple anaesthetic episodes on equine recovery quality

BACKGROUNDnAlthough rare, 70% of equine fatalities during recovery from general anaesthesia (GA) are due to catastrophic fractures from poor recovery quality.nnnOBJECTIVEnTo determine the effect of repeated GA recovery on GA recovery quality.nnnSTUDY DESIGNnExperimental blinded trial.nnnMETHODSnEight adult horses underwent six GA events on sevoflurane for distal limb MRI examination over a 14-week period. Prior to GA recovery, xylazine was administered. Randomly ordered video-recorded GA recoveries were scored by three blinded board certified veterinary anaesthesiologists, unaware of patient identity or GA event number, for nine parameters using a 100 mm visual analogue scale (VAS) where 0 = worst and 100 = best. The number of attempts to stand, duration of lateral and sternal recumbency, total recovery duration and physiologic parameters during each GA event were recorded. Repeated measures ANOVA were used to detect differences. Agreement between observer VAS scores was determined via inter-rater reliability using an intraclass correlation.nnnRESULTSnWith GA recovery experience, VAS scores for balance and coordination, knuckling, and overall quality of recovery were improved and the duration of lateral recumbency was increased. There were no differences in total recovery duration, number of attempts to stand, physiologic parameters other than heart rate during GA, or VAS scores for activity in lateral recumbency, move to sternal, move to stand, or strength.nnnMAIN LIMITATIONSnEach GA event was relatively short and there was no surgical stimulation. The same results may not occur if there was surgical stimulation and pain during each GA event.nnnCONCLUSIONnRecovery from GA improves with multiple anaesthetic episodes in horses. Clinicians can advise clients that horses are likely to have better GA recovery on repeated GA recovery due to improved balance and coordination and reduced knuckling. Additionally, there is no change in anaesthetic morbidity with six repeated GA events over a 14-week period.

The effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and analgesia in goats

Six 3-year-old goats (three males and three females) weighing 60.0xa0±xa018xa0kg (meanxa0±xa0SD) were used to investigate the effect of medetomidine (MED; 20xa0µgxa0kg−1 IV) and its antagonism with atipamezole (ATI; 100xa0µgxa0kg−1 IV) on physiologic responses (heart rate (HR; beatsxa0minute−1), respiratory rate (RR; breathsxa0minute−1), electrocardiogram (ECG), rectal temperature (T; °C), blood pressure (oscillometric; mmxa0Hg), sedation (SED), posture (REC), analgesia (ALG), and stress-related hormonal and metabolic responses (epinephrine and norepinephrine (high performance liquid chromatography with electrochemical detection), cortisol (COR; µgxa0dL−1; radioimmunoassay), glucose (GLU; mgxa0mL−1; enzymatic colorimetric assay), and free fatty acids (modified enzymatic colorimetric assay)); each goat received ATI or SAL in random order separated by 1xa0week. Jugular catheters were placed for drug administration and blood sampling (10–12xa0mLxa0sample−1) using a lidocaine skin block (20xa0mg) 2xa0hours prior to beginning of each trial; during this trial, goats breathed room air. Physiologic parameters were measured, SED, REC, and ALG were scored, and blood samples were collected from jugular catheters at baseline (timexa0=xa0−30xa0minutes), 5xa0minutes post-MED administration (timexa0=xa0−25xa0minutes), 25xa0minute post-MED administration and immediately prior to antagonism (timexa0=xa00xa0minute), and at 5, 30, 60, and 120xa0minutes after administering ATI or SAL. ALG was tested by clamping the withers and metacarpus with hoof testers fitted with a force transducer to measure applied isometric force (lb) (a technique used previously in goats to evaluate analgesia). Continuous variables were analyzed by Repeated Measures analysis of variance (anova); categorical data were analyzed using a Friedman Repeated Measures anova on ranks. A p-value of <0.05 was considered significant. If a significant difference was found, a Dunnetts pair-wise comparison of means was conducted. Differences between ATI and SAL were examined at 5, 30, 60, and 120xa0minutes using a paired t-test with a Bonferroni correction. n n n nAdministration of MED resulted in a decrease in T (38.7xa0±xa00.3 to 34.5xa0±xa00.4xa0°C), HR (78xa0±xa019 to 55xa0±xa09), and RR (31xa0±xa012 to 14xa0±xa05) over time; an increase in mean arterial blood pressure (90xa0±xa019 to 132xa0±xa023), COR (0.254xa0±xa00.125 to 4.327xa0±xa01.233), and GLU (82.0xa0±xa013.2 to 255.9xa0±xa038.9); and changes in SED (alert to marked sedation), REC (standing to recumbent), and ALG (metacarpusxa0=xa05xa0±xa02 to 14xa0±xa00; withersxa0=xa03xa0±xa02 to 14xa0±xa00). GLU was 62–70% higher at 60 and 120xa0minutes and COR was 336% higher after SAL than after ATI at 120xa0minutes; at 30, 60, and 120xa0minutes, T was 4–10% higher after ATI than SAL. There were no other significant differences. n n n nREC, SED, and ALG were antagonized after ATI. ATI did not antagonize the effect of MED on HR, RR, or MAP, but stabilized T and antagonized the increase in GLU and COR.