Effects of constant rate infusion of lidocaine and ketamine, with or without morphine, on isoflurane MAC in horses

REASONS FOR PERFORMING STUDY: Lidocaine and ketamine are administered to horses as a constant rate infusion (CRI) during inhalation anaesthesia to reduce anaesthetic requirements. Morphine decreases the minimum alveolar concentration (MAC) in some domestic animals; when administered as a CRI in horses, morphine does not promote haemodynamic and ventilatory changes and exerts a positive effect on recovery. Isoflurane-sparing effect of lidocaine, ketamine and morphine coadministration has been evaluated in small animals but not in horses. OBJECTIVES: To determine the reduction in isoflurane MAC produced by a CRI of lidocaine and ketamine, with or without morphine. HYPOTHESIS: Addition of morphine to a lidocaine-ketamine infusion reduces isoflurane requirement and morphine does not impair the anaesthetic recovery of horses. METHODS: Six healthy adult horses were anaesthetised 3 times with xylazine (1.1 mg/kg bwt i.v.), ketamine (3 mg/kg bwt i.v.) and isoflurane and received a CRI of lidocaine-ketamine (LK), morphine-lidocaine-ketamine (MLK) or saline (CTL). The loading doses of morphine and lidocaine were 0.15 mg/kg bwt i.v and 2 mg/kg bwt i.v. followed by a CRI at 0.1 mg/kg bwt/h and 3 mg/kg bwt/h, respectively. Ketamine was given as a CRI at 3 mg/kg bwt/h. Changes in MAC characterised the anaesthetic-sparing effect of the drug infusions under study and quality of recovery was assessed using a scoring system. Results: Mean isoflurane MAC (mean ± s.d.) in the CTL, LK and MLK groups was 1.25 ± 0.14%, 0.64 ± 0.20% and 0.59 ± 0.14%, respectively, with MAC reduction in the LK and MLK groups being 49 and 53% (P<0.001), respectively. No significant differences were observed between groups in recovery from anaesthesia. Conclusions and clinical relevance: Administration of lidocaine and ketamine via CRI decreases isoflurane requirements. Coadministration of morphine does not provide further reduction in anaesthetic requirements and does not impair recovery.     

Effects of morphine,butorphanol, buprenorphine,and U50488H on the minimum alveolar concentration of isoflurane in cats

OBJECTIVE: To determine whether opioids with varying interactions at receptors induce a reduction in minimum alveolar concentration (MAC) of isoflurane in cats. ANIMALS: 12 healthy, female, spayed cats. PROCEDURE: Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Each drug was studied separately, and for each drug cats were randomly allocated to receive 2 doses. The drugs studied were morphine (0.1 or 1.0 mg/kg), butorphanol (0.08 or 0.8 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg). All drugs were diluted in 5 ml of saline (0.9% NaCl) solution and infused IV for 5 minutes. The MAC of isoflurane was determined in triplicate, the drug administered, and the MAC of isoflurane redetermined for a period of 3 hours. RESULTS: All drugs had a significant effect on MAC over time. With morphine only, the effect on MAC over time was different between doses. The greatest mean (+/- SD) reductions in MAC of isoflurane in response to morphine, butorphanol, buprenorphine, and U50488H administration were 28 +/- 9, 19 +/- 3, 14 +/- 7, and 11 +/- 7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine (1.0 mg/kg) and butorphanol (0.08 and 0.8 mg/kg) induced significant reductions in MAC of isoflurane that were considered clinically important. Although significant, reductions in MAC of isoflurane induced by morphine (0.1 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg) were not considered clinically relevant because they fell within the error of the measurement technique. Administration of morphine or butorphanol decreases the need for potent inhalant anesthetics in cats and could potentially be beneficial in combination with inhalants.     

Effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats

OBJECTIVE: To determine effects of epidural administration of morphine and buprenorphine on the minimum alveolar concentration of isoflurane in cats. Animals-6 healthy adult domestic shorthair cats. PROCEDURES: Cats were anesthetized with isoflurane in oxygen. Morphine (100 microg/kg diluted with saline [0.9% NaCl] solution to a volume of 0.3 mL/kg), buprenorphine (12.5 microg/kg diluted with saline solution to a volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. The minimum alveolar concentration (MAC) of isoflurane was measured in triplicate by use of the tail clamp technique. At least 1 week was allowed between successive experiments. RESULTS: The MAC of isoflurane was 2.00 +/- 0.18%, 2.13 +/- 0.11%, and 2.03 +/- 0.09% in the morphine, buprenorphine, and saline solution groups, respectively. No significant difference in MAC was detected among treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: A significant effect of epidural administration of morphine or buprenorphine on the MAC of isoflurane in cats could not be detected. Further studies are needed to establish whether epidural opioid administration has other benefits when administered as a component of general anesthesia in cats.     

Effect of transdermally administered fentanyl on the minimum alveolar concentration of isoflurane in cats

OBJECTIVE: To determine the effect of two doses of fentanyl, administered transdermally, on the minimum alveolar concentration (MAC) of isoflurane in cats. STUDY DESIGN: Prospective, randomized study. ANIMALS: Five healthy, spayed, female cats. METHODS: Each cat was studied thrice with at least 2 weeks between each study. In study 1, the baseline isoflurane MAC was determined in triplicate for each cat. In studies 2 and 3, isoflurane MAC was determined 24 hours after placement of either a 25 or 50 microg hour(-1) fentanyl patch. In each MAC study, cats were instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Twenty-four hours prior to studies 2 and 3, a catheter was placed and secured in the jugular vein and either a 25 or 50 microg hour(-1) fentanyl patch was placed in random order on the left thorax. Blood samples for plasma fentanyl determination were collected prior to patch placement and at regular intervals up to 144 hours. After determination of MAC in studies 2 and 3, naloxone was administered as a bolus dose (0.1 mg kg(-1)) followed by an infusion (1 mg kg(-1) hour(-1)) and MAC redetermined. RESULTS: The baseline isoflurane MAC was 1.51 +/- 0.21% (mean +/- SD). Fentanyl (25 and 50 micro g hour(-1)) administered transdermally significantly reduced MAC to 1.25 +/- 0.26 and 1.22 +/- 0.16%, respectively. These MAC reductions were not significantly different from each other. Isoflurane MAC determined during administration of fentanyl 25 micro g hour(-1) and naloxone (1.44 +/- 0.16%) and fentanyl 50 micro g hour(-1) and naloxone (1.51 +/- 0.19%) was not significantly different from baseline MAC (1.51 +/- 0.21%). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl patches are placed to provide long-lasting analgesia. In order to be effective postoperatively, fentanyl patches must be placed prior to surgery. Plasma fentanyl concentrations achieved intraoperatively decrease the need for potent inhalant anesthetics in cats.     

Effects of epidurally administered morphine or buprenorphine on the thermal threshold in cats

Objective: To determine the antinociceptive effects of epidural administration of morphine or buprenorphine in cats by use of a thermal threshold model. ANIMALS: 6 healthy adult cats. PROCEDURES: Baseline thermal threshold was determined in duplicate. Cats were anesthetized with isoflurane in oxygen. Morphine (100 microg/kg diluted with saline [0.9% NaCl] solution to a total volume of 0.3 mL/kg), buprenorphine (12.5 microg/kg diluted with saline solution to a total volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. Thermal threshold was determined at various times up to 24 hours after epidural injection. RESULTS: Epidural administration of saline solution did not affect thermal threshold. Thermal threshold was significantly higher after epidural administration of morphine and buprenorphine, compared with the effect of saline solution, from 1 to 16 hours and 1 to 10 hours, respectively. Maximum (cutout) temperature was reached without the cat reacting in 0, 74, and 11 occasions in the saline solution, morphine, and buprenorphine groups, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of morphine and buprenorphine induced thermal antinociception in cats. At the doses used in this study, the effect of morphine lasted longer and was more intense than that of buprenorphine.     

Effects of intravenous lidocaine on the minimum alveolar concentration of isoflurane in cats

Lidocaine has been reported to decrease the minimum alveolar concentration (MAC) of inhalation anesthetics in several species and has been used clinically to reduce the requirements for other anesthetic drugs. This study examined the effects of intravenous lidocaine on isoflurane MAC in cats. Six cats were studied. In experiment 1, the MAC of isoflurane was determined. An intravenous bolus of lidocaine 2 mg kg^–1 was then administrated and venous plasma lidocaine concentrations measured to determine pharmacokinetic values. In experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 μg mL^–1 and the MAC of isoflurane was determined in triplicate at each lidocaine plasma concentration, using the tail‐clamp method. End‐tidal isoflurane concentration was determined using a calibrated infrared analyzer. Systolic blood pressure (Doppler), SpO2 and end‐tidal PCO2 (calibrated Raman spectrometer) were measured prior to each MAC determination. Body temperature was maintained between 38.5 and 39.5 °C by supplying external heat as needed. MAC values at the different lidocaine plasma concentrations were analyzed by a repeated measures ANOVA , using the Huynh–Feldt correction. The MAC of isoflurane in these cats was 2.21 ± 0.17. For the target concentrations of 1, 3, 5, 7, 9, and 11 μg mL^–1, the actual lidocaine plasma concentrations was 1.06 ± 0.12, 2.83 ±0.39, 4.93 ± 0.64, 6.86 ± 0.97, 8.86 ± 2.10, and 9.84 ± 1.34 μg mL^–1, respectively. At these target concentrations, the MAC of isoflurane was 2.14 ± 0.14, 1.88 ± 0.18, 1.66 ± 0.16, 1.47 ±0.13, 1.33 ± 0.23, and 1.06 ± 0.19%, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 μg mL^–1, linearly decreased isoflurane MAC by –6 to 6, 7 to 28, 19 to 35, 28 to 45, 29 to 53, and 44 to 59%, respectively. Lidocaine significantly dose‐dependently and linearly decreases the requirements for isoflurane in cats. No ceiling effect was observed within the range of plasma concentrations studied.     

Comparison of the effects of epidural or intravenous methadone on the minimum alveolar concentration of isoflurane in dogs

The effects of epidural and intravenous (IV) methadone (0.5mg/kg) on the minimum alveolar concentration of isoflurane (ISO(MAC)) were compared in dogs. Six dogs (16.5 ± 2.5 kg bodyweight) received three treatments in random order during isoflurane anaesthesia, with a 7 day washout interval between each study. Methadone was injected via a lumbosacral epidural catheter introduced 10 cm cranially into the epidural canal and the electrical stimulation for ISO(MAC) determination was applied either to the thoracic (EP(T) treatment) or to the pelvic limb (EP(P) treatment) during separate study days. In the IV treatment, ISO(MAC) was determined via electrical stimulation of the pelvic limb. Variables were recorded before (baseline), 2.5 and 5h after drug injection. The ISO(MAC) decreased significantly (P<0.05) from baseline at 2.5 and 5h after methadone in all treatments. At 2.5h, the magnitude of ISO(MAC) reduction did not differ between treatments (mean decreases from baseline: 30-33%). The ISO(MAC) reduction lasted longer following epidural methadone in the thoracic limb (decreases from baseline: 30% at 5h in the EP(T) treatment vs. 19% and 16% in the EP(P) and IV treatments, respectively). Although the isoflurane sparing effect provided by epidural methadone was not significantly greater than IV methadone during the initial stage (2.5h), it was more prolonged than the IV route in specific dermatomes (5h in the thoracic limb) with the epidural technique employed. Methadone may therefore provide a greater isoflurane sparing effect when administered epidurally, compared to IV, when noxious stimulation occurs in specific dermatomes.     

Naltrexone does not affect isoflurane minimum alveolar concentration in cats

ObjectiveTo test whether naltrexone, an opioid receptor antagonist, affects the minimum alveolar concentration (MAC) of isoflurane in cats, a species that is relatively resistant to the general anesthetic sparing effects of most opioids.Study designRandomized, crossover, placebo-controlled, blinded experimental design.AnimalsSix healthy adult cats weighing 4.9 ± 0.7 kg.MethodsThe cats were studied twice. In the first study, baseline isoflurane MAC was measured in duplicate. The drug (saline control or 0.6 mg kg^?1 naltrexone) was administered IV every 40–60 minutes, and isoflurane MAC was re-measured. In the second study, cats received the second drug treatment using identical methods 2 weeks later.ResultsIsoflurane MAC was 2.03 ± 0.12% and was unchanged from baseline following saline or naltrexone administration.Conclusion and clinical relevanceMinimum alveolar concentration was unaffected by naltrexone. Because MAC in cats is unaffected by at least some mu-opioid agonists and antagonists, spinal neurons that are directly modulated by mu-opioid receptors in this species cannot be the neuroanatomic sites responsible for immobility from inhaled anesthetics.     

A systematic review of sevoflurane and isoflurane minimum alveolar concentration in domestic cats

ObjectiveThe purpose of this systematic review is to summarize the results of studies which have determined the minimum alveolar concentration (MAC) of isoflurane and sevoflurane in domestic cats.Study DesignSystematic review.AnimalsCats.Methods usedA comprehensive search of research literature was performed without language restriction. The search utilized the Pubmed, Google Scholar, and CAB Abstracts electronic databases using a combination of free text terms ‘Minimum alveolar concentration’, ‘sevoflurane’, ‘isoflurane’, ‘anesthetic’, ‘cat’, ‘cats’ or ‘feline’. The search was conducted from November 2010 to June 2012.ResultsThe MAC for isoflurane ranged from 1.20 ± 0.13% to 2.22 ± 0.35% and the MAC for sevoflurane ranged from 2.5 ± 0.2% to 3.95 ± 0.33%. The average MAC for isoflurane was 1.71 ± 0.07% and for sevoflurane was 3.08 ± 0.4%.Conclusions &; Clinical RelevanceThe average MAC for isoflurane was 1.71 ± 0.07% and for sevoflurane was 3.08 ± 0.4%. Methodology differed among studies, and particular attention should be paid in the future to appropriate reporting of methods to allow sound conclusions to be made from the results.     

Inhalant anesthetic requirement in cats is animal-dependent

Minimum alveolar concentration (MAC) of an inhalant is an indicator of its anesthetic potency. Individuals vary in their sensitivity to anesthetic agents as demonstrated by different individual MAC values. We hypothesized that individual animal sensitivity would be maintained with different inhalant anesthetics. As part of separate studies, six female DSH cats, aged 24 ± 2.5 (mean ± SD) months and weighing 3.5 ± 0.3 kg, were studied similarly on three separate occasions over a 12‐month period to determine the MAC of isoflurane (ISO), sevoflurane (SEVO), and desflurane (DES), respectively. In each study, chamber induction was followed by orotracheal intubation, and anesthesia was maintained via a nonrebreathing circuit. ECG, pulse oximetry, Doppler systolic blood pressure, end‐tidal gases, and esophageal temperature were monitored. End‐tidal gases were hand‐sampled from a catheter whose tip lay level with the distal end of the ET tube. Gases were analyzed by Raman spectrometry and, for each agent, the analyzer was calibrated with at least three gas standards. MAC was determined in triplicate using standard tail‐clamp technique. Data were analyzed by two‐way anova followed by Tukey's test and significant differences were found. Average MACs (%) for ISO, SEVO, and DES were 1.90 ± 0.18, 3.41 ± 0.65, and 10.27 ± 1.06, respectively. Body temperatures, Doppler systolic blood pressure, and SpO₂ were recorded at the time of MAC determinations for ISO, SEVO, and DES were 38.3 ± 0.3, 38.6 ± 0.1, 38.3 ± 0.35 °C; 71 ± 8, 75 ± 16, 88 ± 12 mm Hg; 99 ± 1, 99 ± 1, 99 ± 1%, respectively. Both the anesthetic agent and the individual cat had significant effects on MAC (p = 0.0001 and 0.0185, respectively). MAC varied between individuals and cats were consistent in their order of sensitivity to inhalant anesthetics across the three agents. Within this group of cats, the relationship of individual MAC to the group MAC for each of the three inhalant agents was maintained. This suggests that any individual may be consistently more or less sensitive to a variety of inhalant agents.     

Isoflurane sparing action of epidurally administered xylazine hydrochloride in anesthetized dogs

OBJECTIVE: To evaluate the influence of epidural administration of xylazine hydrochloride on the minimum alveolar concentration of isoflurane (MAC(ISAO)) and cardiopulmonary system in anesthetized dogs. ANIMALS: 6 clinically normal dogs. PROCEDURE: Dogs were anesthetized with isoflurane in oxygen after randomly being assigned to receive 1 of the following 4 treatments: epidural administration of saline (0.9% NaCl) solution or xylazine at a dose of 0.1, 0.2, or 0.4 mg x kg(-1). Experiments were performed on 5 occasions with at least a 1-week interval between experiments; each dog received all 4 treatments. Following instrumentation, the concentration of isoflurane was maintained constant for 15 minutes at the MAC(ISO) that had been determined for each dog, and data on heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and arterial pH were collected. The epidural treatment was administered, and 30 minutes later, data were again collected. From this point on, determination of the MAC(ISO) following epidural treatment (ie, MAC(ISO+EPI)) was initiated. Cardiopulmonary data were collected before each electrical supramaximal stimulus during MAC(ISO+EPI) determinations. RESULTS: The mean (+/-SD) MAC(ISO) was 1.29 +/- 0.04%. The epidural administration of xylazine at doses of 0.1, 0.2, and 0.4 mg x kg(-1) decreased the MAC(ISO), respectively, by 8.4 +/- 2.4%, 21.7 +/- 4.9%, and 33.4 +/- 2.64%. Cardiopulmonary effects were limited. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of xylazine decreases the MAC(ISO) in a dose-dependent manner and is associated with few cardiopulmonary effects in anesthetized dogs.     

Effects of morphine,lidocaine, ketamine,and morphine-lidocaine-ketamine drug combination on minimum alveolar concentration in dogs anesthetized with isoflurane

OBJECTIVE: To determine the effects of constant rate infusion of morphine, lidocaine, ketamine, and morphine-lidocaine-ketamine (MLK) combination on end-tidal isoflurane concentration (ET-Iso) and minimum alveolar concentration (MAC) in dogs anesthetized with isoflurane and monitor depth of anesthesia by use of the bispectral index (BIS). ANIMALS: 6 adult dogs. PROCEDURE: Each dog was anesthetized with isoflurane on 5 occasions, separated by a minimum of 7 to 10 days. Individual isoflurane MAC values were determined for each dog. Reduction in isoflurane MAC, induced by administration of morphine (3.3 microg/kg/min), lidocaine (50 microg/kg/min), ketamine (10 microg/kg/min), and MLK, was determined. Heart rate, mean arterial blood pressure, oxygen saturation as measured by pulse oximetry (Spo2), core body temperature, and BIS were monitored. RESULTS: Mean +/- SD isoflurane MAC was 1.38 +/- 0.08%. Morphine, lidocaine, ketamine, and MLK significantly lowered isoflurane MAC by 48, 29, 25, and 45%, respectively. The percentage reductions in isoflurane MAC for morphine and MLK were not significantly different but were significantly greater than for lidocaine and ketamine. The Spo2, mean arterial pressure, and core body temperature were not different among groups. Heart rate was significantly decreased at isoflurane MAC during infusion of morphine and MLK. The BIS was inversely related to the ET-Iso and was significantly increased at isoflurane MAC during infusions of morphine and ketamine, compared with isoflurane alone. CONCLUSIONS AND CLINICAL RELEVANCE: Low infusion doses of morphine, lidocaine, ketamine, and MLK decreased isoflurane MAC in dogs and were not associated with adverse hemodynamic effects. The BIS can be used to monitor depth of anesthesia.     

Hemodynamic Effects of Epidural Ketamine in Isoflurane-Anesthetized Dogs

Objective —The purpose of this study was to determine the hemodynamic effects of epidural ketamine administered during isoflurane anesthesia in dogs. Study Design —Prospective, single-dose trial. Animals —Six healthy dogs (five males, one female) weighing 25.3 ± 3.88 kg. Methods —Once anesthesia was induced, dogs were maintained at 1.5 times the predetermined, individual minimum alveolar concentration (MAC) of isoflurane. Dogs were instrumented and allowed to stabilize for 30 minutes before baseline measurements were recorded. Injection of 2 mg/kg of ketamine in 1 mL saline/4.5 kg body weight was then performed at the lumbosacral epidural space. Hemodynamic data were recorded at 5, 10, 15, 20, 30, 45, 60, and 75 minutes after epidural ketamine injection. Statistical analysis included an analysis of variance (ANOVA) for repeated measures over time. All data were compared with baseline values. A P < .05 was considered significant. Results —Baseline values ±standard error of the mean (X ± SEM) for heart rate, mean arterial pressure, mean pulmonary artery pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, stroke index, systemic vascular resistance, pulmonary vascular resistance, and rate-pressure product were 108 ± 6 beats/min, 85 ± 10 mm Hg, 10 ± 2 mm Hg, 3 ± 1 mm Hg, 5 ± 2 mm Hg, 2.3 ± 0.3 L/min/m², 21.4 ± 1.9 mL/beat/m², 3386 ± 350 dynes/sec/cm⁵, 240 ± 37 dynes/sec/cm⁵, and 12376 ± 1988 beats/min±mm Hg. No significant differences were detected from baseline values at any time after ketamine injection. Conclusions —The epidural injection of 2 mg/kg of ketamine is associated with minimal hemodynamic effects during isoflurane anesthesia. Clinical Relevance —These results suggest that if epidural ketamine is used for analgesia in dogs, it will induce minimal changes in cardiovascular function.     

Evaluation of a lithium dilution cardiac output technique as a method for measurement of cardiac output in anesthetized cats

OBJECTIVE: To evaluate the use of a lithium dilution cardiac output (LiDCO) technique for measurement of CO and determine the agreement between LiDCO and thermodilution CO (TDCO) values in anesthetized cats. ANIMALS: 6 mature cats. PROCEDURE: Cardiac output in isoflurane-anesthetized cats was measured via each technique. To induce different rates of CO in each cat, anesthesia was maintained at > 1.5X end-tidal minimum alveolar concentration (MAC) of isoflurane and at 1.3X end-tidal isoflurane MAC with or without administration of dobutamine (1 to 3 microg/kg/min, i.v.). At least 2 comparisons between LiDCO and TDCO values were made at each CO rate. The TDCO indicator was 1.5 mL of 5% dextrose at room temperature; with the LiDCO technique, each cat received 0.005 mmol of lithium/kg (concentration, 0.015 mmol/mL). Serum lithium concentrations were measured prior to the first and following the last CO determination. RESULTS: 35 of 47 recorded comparisons were analyzed; via linear regression analysis (LiDCO vs TDCO values), the coefficient of determination was 0.91. The mean bias (TDCO-LiDCO) was -4 mL/kg/min (limits of agreement, -35.8 to + 27.2 mL/kg/min). The concordance coefficient was 0.94. After the last CO determination, serum lithium concentration was < 0.1 mmol/L in each cat. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated a strong relationship and good agreement between LiDCO and TDCO values; the LiDCO method appears to be a practical, relatively noninvasive method for measurement of CO in anesthetized cats.     

Evaluation of perfusion index as a noninvasive tool to determine epidural anesthesia effectiveness in dogs

ObjectiveTo evaluate perfusion index (PI) as a noninvasive tool to determine effectiveness and onset of epidural anesthesia in dogs.Study designProspective clinical trial.AnimalsA total of 21 adult dogs, aged 6.5 ± 3 years and weighing 34.9 ± 6.4 kg, undergoing a tibial plateau leveling osteotomy.MethodsDogs were premedicated intramuscularly with acepromazine (0.03 mg kg^–1) and hydromorphone (0.1 mg kg^–1) and anesthetized with intravenous propofol (to effect) and isoflurane in oxygen. A surface transflectance probe was secured to the tail base to monitor PI and a dorsal pedal artery catheter was placed for invasive blood pressure monitoring. A lumbosacral epidural was performed with the dog in sternal recumbency. Dogs were randomly assigned for inclusion of epidural morphine (0.1 mg kg^–1) or morphine (0.1 mg kg^–1) and lidocaine (4 mg kg^–1). PI was recorded following instrumentation of each dog just prior to the epidural (baseline), at 10 minute intervals for 30 minutes, before and after the surgical skin incision and before and after completion of the osteotomy. Physiological variables and end-tidal isoflurane were recorded at the same time points.ResultsThere was no significant difference in PI between the groups at any time point. There was a significant change in end-tidal isoflurane before and after the skin incision in the epidural morphine and epidural morphine–lidocaine groups (p = 0.04, p = 0.05, respectively) and before and after the osteotomy in each group for heart rate (p = 0.001, p = 0.04), diastolic (p = 0.01, p = 0.01) and mean arterial blood pressure (p = 0.03, p = 0.05).Conclusions and clinical relevancePI did not provide an objective means for determining the onset or effectiveness of epidural anesthesia in anesthetized dogs and alternate methods of noninvasive assessment should be investigated.     

Effects of a constant‐rate infusion of dexmedetomidine on the minimal alveolar concentration of sevoflurane in ponies

Reasons for performing study: Dexmedetomidine has been administered in the equine as a constant‐rate infusion (CRI) during inhalation anaesthesia, preserving optimal cardiopulmonary function with calm and coordinated recoveries. Inhalant anaesthetic sparing effects have been demonstrated in other species, but not in horses. Objectives: To determine the effects of a CRI of dexmedetomidine on the minimal alveolar concentration (MAC) of sevoflurane in ponies. Methods: Six healthy adult ponies were involved in this prospective, randomised, crossover, blinded, experimental study. Each pony was anaesthetised twice (3 weeks washout period). After induction with sevoflurane in oxygen (via nasotracheal tube), the ponies were positioned on a surgical table (T0), and anaesthesia was maintained with sevoflurane (expired sevoflurane fraction 2.5%) in 55% oxygen. The ponies were randomly allocated to treatment D (dexmedetomidine 3.5 µg/kg bwt i.v. [T10–T15] followed by a CRI of dexmedetomidine at 1.75 µg/kg bwt/h) or treatment S (bolus and CRI of saline at the same volume and rate as treatment D). After T60, MAC determination, using a classic bracketing technique, was initiated. Stimuli consisted of constant‐current electrical stimuli at the skin of the lateral pastern region. Triplicate MAC estimations were obtained and averaged in each pony. Monitoring included pulse oximetry, electrocardiography, anaesthetic gas monitoring, arterial blood pressure measurement and arterial blood gases. Normocapnia was maintained by mechanical ventilation. Analysis of variance (treatment and period as fixed factors) was used to detect differences between treatments (α= 0.05). Results: An intravenous (i.v.) dexmedetomidine CRI decreased mean ± s.d. sevoflurane MAC from 2.42 ± 0.55 to 1.07 ± 0.21% (mean MAC reduction 53 ± 15%). Conclusions and potential relevance: A dexmedetomidine CRI at the reported dose significantly reduces the MAC of sevoflurane.     

Combined use of detomidine with opiates in the horse

The effects of administration of one of four opiates (pethidine 1 mg/kg bodyweight (bwt), morphine 0.1 mg/kg bwt, methadone 0.1 mg/kg bwt, and butorphanol 0.05 mg/kg bwt) given intravenously to horses and ponies already sedated with detomidine (10 micrograms/kg bwt) were investigated. Behavioural, cardiovascular and respiratory effects of the combinations were compared with those occurring with detomidine alone. Addition of the opiate increased the apparent sedation and decreased the response of the animal to external stimuli. At doses used, butorphanol produced the most reliable response. Side effects seen were increased ataxia (greatest following methadone and butorphanol) and excitement (usually muzzle tremors and muscle twitching). Following pethidine, generalised excitement was sometimes seen. Marked cardiovascular changes occurred in the first few minutes after morphine or pethidine injection, but within 5 mins cardiovascular changes were minimal. Following morphine or pethidine there was a significant increase in arterial carbon dioxide tension. Fourteen clinical cases were successfully sedated using detomidine/butorphanol combinations.     

Detomidine reduces isoflurane anesthetic requirement (MAC) in horses

Objective To quantitate the dose‐ and time‐related magnitude of the anesthetic sparing effect of, and selected physiological responses to detomidine during isoflurane anesthesia in horses. Study design Randomized cross‐over study. Animals Three, healthy, young adult horses weighing 485 ± 14 kg. Methods Horses were anesthetized on two occasions to determine the minimum alveolar concentration (MAC) of isoflurane in O₂ and then to measure the anesthetic sparing effect (time‐related MAC reduction) following IV detomidine (0.03 and 0.06 mg kg^?1). Selected common measures of cardiopulmonary function, blood glucose and urinary output were also recorded. Results Isoflurane MAC was 1.44 ± 0.07% (mean ± SEM). This was reduced by 42.8 ± 5.4% and 44.8 ± 3.0% at 83 ± 23 and 125 ± 36 minutes, respectively, following 0.03 and 0.06 mg kg^?1, detomidine. The MAC reduction was detomidine dose‐ and time‐dependent. There was a tendency for mild cardiovascular and respiratory depression, especially following the higher detomidine dose. Detomidine increased both blood glucose and urine flow; the magnitude of these changes was time‐ and dose‐dependent Conclusions Detomidine reduces anesthetic requirement for isoflurane and increases blood glucose concentration and urine flow in horses. These changes were dose‐ and time‐related. Clinical relevance The results imply potent anesthetic sparing actions by detomidine. The detomidine‐related increased urine flow should be considered in designing anesthetic protocols for individual horses.     

Pharmacokinetics of lidocaine and its active metabolite, monoethylglycinexylidide, after intravenous administration of lidocaine to awake and isoflurane-anesthetized cats

OBJECTIVE: To describe the pharmacokinetics of lidocaine and its active metabolite, monoethylglycinexylidide (MEGX), after i.v. administration of a single bolus of lidocaine in cats that were awake in phase 1 and anesthetized with isoflurane in phase 2 of the study. ANIMALS: 8 healthy adult cats. PROCEDURE: During phase 1, cats were administered lidocaine (2 mg/kg, i.v.) as a bolus injection (time 0). During phase 2, cats were anesthetized with isoflurane and maintained at 0.75 times the minimum alveolar concentration of isoflurane for each specific cat. After a 15-minute equilibration period, lidocaine (2 mg/kg, i.v.) was administered as a bolus injection to each cat (time 0). In both phases, plasma concentrations of lidocaine and MEGX were measured at various time points by use of liquid chromatography-mass spectrometry. RESULTS: Anesthesia with isoflurane significantly decreased the volume of the central compartment, clearance, and elimination half-life of lidocaine and significantly increased the extrapolated plasma drug concentration at time 0, compared with values for awake cats. Pharmacokinetics of MEGX were also changed by isoflurane-induced anesthesia because the maximum observed plasma concentration (C(max)), area under the concentration-time curve extrapolated to infinity, and time to C(max) were significantly higher in anesthetized cats, compared with values for awake cats. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetics of lidocaine and MEGX were substantially altered in cats anesthetized by use of isoflurane. When pharmacokinetic variables are used to determine loading and infusion doses in awake or anesthetized cats, they should be measured in cats that are awake or anesthetized, respectively.     

Effects of opioids and anesthetic drugs on body temperature in cats

ObjectiveTo determine which class of opioid alone or in conjunction with other anesthetic drugs causes post-anesthetic hyperthermia in cats.Study designProspective, randomized, crossover study.AnimalsEight adult, healthy, cats (four spayed females and four castrated males weighing 3.8 ± 0.6 kg).MethodsEach cat was instrumented with a wireless thermistor in the abdominal cavity. Temperature in all phases was recorded every 5 minutes for 5 hours. Population body temperature (PBT) was recorded for ～8 days. Baseline body temperature is the final 24 hours of the PBT. All injectable drugs were given intramuscularly. The cats were administered drugs in four phases: 1) hydromorphone (H) 0.05, 0.1, or 0.2 mg kg^?1; 2) morphine (M) (0.5 mg kg^?1), buprenorphine (BUP) (0.02 mg kg^?1), or butorphanol (BUT) (0.2 mg kg^?1); 3) ketamine (K) (5 mg kg^?1) or ketamine (5 mg kg^?1) plus hydromorphone (0.1 mg kg^?1) (KH); 4) isoflurane in oxygen for 1 hour. Fifteen minutes prior to inhalant anesthetic, cats received either no premed (I), hydromorphone (0.1 mg kg^?1) (IH), or hydromorphone (0.1 mg kg^?1) plus ketamine (5 mg kg^?1) (IHK).ResultsMean PBT for all unmedicated cats was 38.9 ± 0.6 °C (102.0 ± 1 °F). The temperature of cats administered all doses of hydromorphone increased from baseline (p < 0.03) All four opioids (H, M, BUP and BUT) studied increased body temperature compared with baseline (p < 0.005). A significant difference was observed between baseline temperature values and those in treatment KH (p < 0.03). Following recovery from anesthesia, temperature in treatments IH and IHK was different from baseline (p < 0.002).Conclusions and clinical relevanceAll of the opioids tested, alone or in combination with ketamine or isoflurane, caused an increase in body temperature. The increase seen was mild to moderate (<40.1 °C (104.2 °F) and self limiting.