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.     

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.     

Determination of the sevoflurane sparing effect of methadone in cats

ObjectiveTo determine the magnitude and duration of sevoflurane minimum alveolar concentration (MAC) reduction following a single intravenous (IV) dose of methadone in cats.Study designProspective experimental study.AnimalsEight (four females and four males) healthy mixed-breed adult (1–2 years) cats weighing 5.82 ± 0.42 kg.MethodsAnesthesia was induced and maintained with sevoflurane. Intravenous catheters facilitated administration of methadone and lactated Ringer’s solution. After baseline MAC determination in triplicate using a tail clamp technique, 0.3 mg kg^?1 of methadone was administered IV. End-tidal sevoflurane concentration (e′SEVO) was reduced and MAC was redetermined. In an effort to determine the duration of MAC reduction, measurements were repeated in a stepwise manner until MAC values returned to baseline. After the last stimulation, the e′SEVO was increased to 1.2 individual MAC for 15 minutes, then sevoflurane was discontinued and cats were allowed to recover from anesthesia.ResultsBaseline sevoflurane MAC was 3.18 ± 0.06%. When compared with baseline the sevoflurane MAC after methadone administration was significantly reduced by 25, 15 and 7% at 26, 76 and 122 minutes, respectively. The final MAC value (3.09 ± 0.07%) determined 156 minutes after methadone administration was not significantly different from baseline.Conclusions and clinical relevanceIntravenous methadone (0.3 mg kg^?1) significantly decreased MAC of sevoflurane in cats but the effect was short-lived.     

Effect of epidural and intravenous use of the neurokinin-1 (NK-1) receptor antagonist maropitant on the sevoflurane minimum alveolar concentration (MAC) in dogs

ObjectiveTo determine the effect of maropitant, an NK-1 receptor antagonist on the minimum alveolar concentration (MAC) of sevoflurane after intravenous and epidural administration to dogs.Study designProspective experimental study.AnimalsSeven, adult, spayed-female dogs (24.8 ± 1.9 kg).MethodsEach dog was anesthetized twice with sevoflurane in oxygen, with at least 10 days separating the anesthetic events. The minimum alveolar concentration (MAC) of sevoflurane was determined using the tail-clamp technique. During the first anesthetic event, the MAC of sevoflurane was determined initially and again after intravenous administration of maropitant (5 mg kg^?1) and an infusion (150 μg kg^?1 hour^?1). During the second anesthetic event, an epidural catheter was advanced to the 4th lumbar vertebra and MAC was determined after administration of saline and maropitant (1 mg kg^?1) epidurally. All MAC determinations were done in duplicate. The MAC values were adjusted to sea level and compared using student's t-test.ResultsThe baseline MAC for sevoflurane was 2.08 ± 0.25%. Intravenous maropitant decreased (p < 0.05) MAC by 16% (1.74 ± 0.17%). In contrast, epidural administration of either saline or maropitant did not change (p > 0.05) the MAC (2.17 ± 0.34% and 1.92 ± 0.12%, respectively).Conclusion and clinical relevanceMaropitant decreased the MAC of sevoflurane when administered intravenously to dogs but not after epidural administration.     

Effect of fentanyl target-controlled infusions on isoflurane minimum anaesthetic concentration and cardiovascular function in red-tailed hawks (Buteo jamaicensis)

ObjectiveTo determine the impact of three different target plasma concentrations of fentanyl on the minimum anaesthetic concentration (MAC) for isoflurane in the red-tailed hawk and the effects on the haemodynamic profile.Study designExperimental study.Animal populationSix healthy adult red-tailed hawks (Buteo jamaicensis) of unknown sex with body weights (mean ± SD) of 1.21 ± 0.15 kg.MethodsThis study was undertaken in two phases. In the first phase anaesthesia was induced with isoflurane in oxygen via facemask and maintained with isoflurane delivered in oxygen via a Bain circuit. Following instrumentation baseline determination of the MAC for isoflurane was made for each animal using the bracketing method and a supramaximal electrical stimulus. End-tidal isoflurane concentration (E′Iso) was then set at 0.75 × MAC and after an appropriate equilibration period a bolus of fentanyl (20 μg kg^?1) was administered intravenously (IV) in order to determine the pharmacokinetics of fentanyl in the isoflurane-anaesthetized red-tailed hawk. During the second phase anaesthesia was induced in a similar manner and E′Iso was set at 0.75 × MAC for each individual. Fentanyl was infused IV to achieve target plasma concentrations between 8 and 32 ng mL^?1. At each fentanyl plasma concentration, the MAC for isoflurane and cardiovascular variables were determined. Data were analyzed by use of repeated-measures anova.ResultsMean ± SD fentanyl plasma concentrations and isoflurane MACs were 0 ± 0, 8.51 ± 4, 14.85 ± 4.82 and 29.25 ± 11.52 ng mL^?1, and 2.05 ± 0.45%, 1.42 ± 0.53%, 1.14 ± 0.31% and 0.93 ± 0.32% for the target concentrations of 0, 8, 16 and 32 ng mL^?1, respectively. At these concentrations fentanyl significantly (p = 0.0016) decreased isoflurane MAC by 31%, 44% and 55%, respectively. Dose had no significant effect on heart rate, systolic, diastolic or mean arterial blood pressure.Conclusions and clinical relevanceFentanyl produced a dose-related decrease of isoflurane MAC with minimal effects on measured cardiovascular parameters in red-tailed hawks.     

Effect of maropitant,a neurokinin‐1 receptor antagonist,on the minimum alveolar concentration of sevoflurane during stimulation of the ovarian ligament in cats

ObjectiveDetermine if maropitant decreases the minimum alveolar concentration (MAC) of sevoflurane during stimulation of the ovarian ligament in cats.Study designProspective study.AnimalsFifteen, female cats weighing 2.5 ± 0.6kg (mean ± SD).MethodsAnesthesia was induced and maintained with sevoflurane. The right ovary was accessed via laparoscopy. A suture around the ovary and ovarian ligament was exteriorized through the abdominal wall for stimulation. A stimulus–response curve was created to identify the optimal force for MAC comparisons. In 10 cats, MAC was determined with only sevoflurane (baseline) then after 1 and 5 mg kg^?1 intravenous maropitant administration. The stimulation tension force used was 4.9 N. Repeated measures anova was used to compare the groups. MAC was defined as the average of the cross‐over concentrations and reported MAC is adjusted to sea‐level and depicted as mean ± SD.ResultsThe stimulus‐response curve was hyperbolic and plateaued at 4.3 ± 3 N. The optimal tension force chosen to compare MAC was 4.9 N. The baseline sevoflurane MAC was 2.96 ± 0.3%. Maropitant, 1 mg kg^?1, decreased the MAC to 2.51 ± 0.3% (15%, p < 0.01). The higher maropitant dose of 5 mg kg^?1 did not change MAC further when compared to the low dose (2.46 ± 0.4%, p = 0.33).Conclusion and clinical relevanceThe ovarian ligament stimulation model is suitable to determine MAC during visceral stimulation in cats. Maropitant decreased the anesthetic requirements during visceral ovarian and ovarian ligament stimulation in cats. Maropitant (1 mg kg^?1) decreases MAC by 15%; a higher dose had no additional effect.     

Effects of dopamine,norepinephrine or phenylephrine on the prevention of hypotension in isoflurane-anesthetized cats administered vatinoxan or vatinoxan and dexmedetomidine

ObjectiveTo determine the dose of phenylephrine, norepinephrine and dopamine necessary to maintain mean arterial pressure (MAP) within 70–80 mmHg during administration of isoflurane, isoflurane and vatinoxan and isoflurane, vatinoxan and dexmedetomidine at three plasma concentrations.Study designRandomized crossover experimental study.AnimalsA group of five adult healthy neutered male cats.MethodsInstrumentation occurred during anesthesia with isoflurane in oxygen. Isoflurane end-tidal concentration was set to 1.25 × minimum alveolar concentration (MAC). Phenylephrine, norepinephrine or dopamine was administered to maintain MAP 70–80 mmHg. A target-controlled infusion system was used to administer vatinoxan at a target plasma concentration of 1 μg mL^–1 and three dexmedetomidine concentrations (5, 10 and 20 ng mL^–1). Isoflurane concentration was altered to maintain an equivalent 1.25 MAC. Heart rate, arterial blood pressure, central venous pressure, pulmonary artery pressure, pulmonary artery occlusion pressure, body temperature, arterial and mixed venous blood gas, cardiac output and drug concentrations were measured at baseline (isoflurane alone), during vatinoxan administration, and during administration of vatinoxan and dexmedetomidine at the three target concentrations.ResultsMAP < 70 mmHg was observed with vatinoxan alone and in the dopamine treatment with dexmedetomidine concentrations ≤ 10 ng mL^–1. Norepinephrine and phenylephrine maintained MAP 70–80 mmHg during vatinoxan and dexmedetomidine ≤ 10 ng mL^–1. As the target dexmedetomidine concentration increased, the dose of norepinephrine and phenylephrine needed to maintain MAP 70–80 mmHg decreased; no treatment was necessary to maintain MAP > 70 mmHg at the 20 ng mL^–1 target dexmedetomidine concentration in most cats.Conclusions and clinical relevanceNorepinephrine and phenylephrine, but not dopamine, are effective to prevent hypotension in isoflurane-anesthetized cats administered dexmedetomidine and vatinoxan.     

The effect of experimentally induced hypothyroidism on the isoflurane minimum alveolar concentration in dogs

ObjectiveTo determine the effect of experimentally induced hypothyroidism on isoflurane (ISO) minimum alveolar concentration (MAC) in dogs.Study designProspective experimental study.AnimalsEighteen adult female mongrel dogs, age 2–4 years and weighing 8.2–13.1 kg.MethodsHypothyroidism was induced in nine dogs by the intravenous administration of 1 mCi kg⁻¹ of ¹³¹Iodine. The remaining nine dogs served as controls. Dogs were studied 9–12 months after the induction of hypothyroidism. Anesthesia was induced with ISO in oxygen via a mask. The trachea was intubated, and anesthesia was maintained using ISO in oxygen using a semi-closed rebreathing circle system. The dogs were mechanically ventilated to maintain an end-tidal carbon dioxide concentration between 35 and 45 mmHg. End-tidal ISO concentrations were measured with an infrared gas analyzer. The MAC was determined in duplicate using a tail clamp technique. The mean values for the groups were compared using a two sample t-test.ResultsThe mean ± SD MAC of isoflurane in the hypothyroid and euthyroid dogs was 0.98 ± 0.31% and 1.11 ± 0.26%, respectively. The mean MAC of isoflurane in hypothyroid dogs was not significantly different from the mean MAC of isoflurane in the control dogs (p=0.3553).Conclusion and clinical relevanceThe MAC of ISO in dogs was not significantly affected by experimentally induced hypothyroidism. The dose of ISO in dogs with hypothyroidism does not need to be altered.     

GABA(A) receptor antagonism increases NMDA receptor inhibition by isoflurane at a minimum alveolar concentration

ObjectiveAt the minimum alveolar concentration (MAC), isoflurane potentiates GABA_A receptor currents and inhibits NMDA receptor currents, and these actions may be important for producing anesthesia. However, isoflurane modulates GABA_A receptors more potently than NMDA receptors. The objective of this study was to test whether isoflurane would function as a more potent NMDA receptor antagonist if its efficacy at GABA_A receptors was decreased.Study designProspective experimental study.AnimalsFourteen 10-week-old male Sprague–Dawley rats weighing 269 ± 12 g.MethodsIndwelling lumbar subarachnoid catheters were surgically placed in isoflurane-anesthetized rats. Two days later, the rats were anesthetized with isoflurane, and artificial CSF containing either 0 or 1 mg kg^?1 picrotoxin, a GABA_A receptor antagonist, was infused intrathecally at 1 μL minute^?1. The baseline isoflurane MAC was then determined using a standard tail clamp technique. MK801 (dizocilpine), an NMDA receptor antagonist, was then administered intravenously at 0.5 mg kg^?1. Isoflurane MAC was re-measured.ResultsPicrotoxin increased isoflurane MAC by 16% compared to controls. MK801 significantly decreased isoflurane MAC by 0.72% of an atmosphere in controls versus 0.47% of an atmosphere in rats receiving intrathecal picrotoxin.Conclusions and clinical relevanceA smaller MK801 MAC-sparing effect in the picrotoxin group is consistent with greater NMDA antagonism by isoflurane in these animals, since it suggests that fewer NMDA receptors are available upon which MK801 could act to decrease isoflurane MAC. Decreasing isoflurane GABA_A potentiation increases isoflurane NMDA antagonism at MAC. Hence, the magnitude of an anesthetic effect on a given channel or receptor at MAC may depend upon effects at other receptors.     

Phenylpiperidine opioid effects on isoflurane minimum alveolar concentration in cats

Different structurally related phenylpiperidine opioids exhibit different isoflurane-sparing effects in cats. Because minimum alveolar concentration (MAC) in cats is affected only by very high plasma concentrations of some phenylpiperidine opioids, we hypothesized these effects are caused by actions on nonopioid receptors. Using a prospective, randomized, crossover design, six cats were anesthetized with isoflurane, intubated, ventilated, and instrumented. Isoflurane MAC was measured in triplicate using a tail-clamp and bracketing technique. A computer-controlled intravenous infusion using prior pharmacokinetic models targeted plasma concentrations of 60 ng/ml fentanyl, 10 ng/ml sufentanil, or 500 ng/ml alfentanil, and isoflurane MAC was measured in duplicate. Next, naltrexone 0.6 mg/kg was administered to cats hourly during the opioid infusion, and isoflurane MAC was measured in duplicate. Blood was collected during MAC determinations to measure opioid concentrations. Responses were analyzed using repeated measures ANOVA with significance at p < .05. Alfentanil and sufentanil decreased isoflurane MAC by 16.4% and 6.4%, respectively, and these effects were completely reversed by naltrexone. Fentanyl had no significant effect on isoflurane MAC. Alfentanil and sufentanil modestly reduce isoflurane MAC via agonist effects on opioid receptors. However, these effects are too small to justify clinical use of phenylpiperidine opioids as single agents to reduce MAC in cats.     

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

ObjectiveTo determine the effect of butorphanol, administered by intravenous (IV) infusion, on the minimum alveolar concentration of isoflurane (MAC_ISO) in cats and to examine the dosage dependence of this effect.Study designRandomized, placebo-controlled, crossover experimental study.AnimalsA group of six healthy adult male neutered cats.MethodsCats 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). MAC_ISO 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.ResultsButorphanol reduced MAC_ISO 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 relevanceButorphanol caused a dosage-dependent MAC_ISO reduction in cats. IV infusion of butorphanol may be of interest for partial IV anesthesia in cats.     

The effect of epidural morphine on the minimum alveolar concentration of isoflurane in cats

This study was undertaken to evaluate the effect of 3 different doses of epidurally administered morphine sulphate on the minimum alveolar concentration (MAC) of isoflurane in healthy cats. Five 4-year-old, spayed female cats weighing 4.7 ± 0.8 kg were allocated randomly to receive one of 3 doses of morphine on each study day. The 3 doses of morphine were 0.05, 0.1 and 0.2 mg/kg bwt and each cat was studied 3 times so that each cat received all doses. On each study day, cats were anaesthetised with isoflurane and instrumented. The MAC of isoflurane was determined in triplicate and morphine sulphate was administered via an epidural catheter chronically implanted prior to the study. Maximum MAC reduction was determined over the following 2 h. At the end of the study cats were allowed to recover. There was a significant reduction in MAC of isoflurane, with all doses of epidural morphine (P<0.05). The maximum reduction in MAC of isoflurane after 0.05 mg/kg bwt, 0.10 mg/kg bwt and 0.20 mg/kg bwt morphine was 21.4 ± 9.796, 30.8 ± 9.696, and 30.2 ± 6.8%, respectively, with no significant difference between doses. Systolic, mean and diastolic blood pressure, heart rate, respiratory rate and arterial pH decreased significantly whereas arterial carbon dioxide tension increased significantly after morphine administration (P<0.05). The means for all variables returned to pre-morphine values when the end-tidal isoflurane concentration was reduced to the new MAC point. In conclusion, epidural morphine decreased the concentration of isoflurane required to prevent movement in response to noxious mechanical stimulation to the tail base. A similar effect may be seen clinically allowing lower doses of isoflurane to be used to provide surgical anaesthesia for procedures involving the hind limbs, pelvis and tail.     

Effects of two continuous infusion doses of lidocaine on isoflurane minimum anesthetic concentration in chickens

ObjectiveTo assess the effect of two intravenous (IV) doses of lidocaine on the minimum anesthetic concentration (MAC) of isoflurane in chickens.Study designBlinded, prospective, randomized, experimental crossover study.AnimalsA total of six adult female chickens weighing 1.90 ± 0.15 kg.MethodsChickens were anesthetized with isoflurane and mechanically ventilated. Isoflurane MAC values were determined (T0) in duplicate using an electrical noxious stimulus and the bracketing method. After MAC determination, a low dose (LD; 3 mg kg^–1 followed by 3 mg kg^–1 hour^–1) or high dose (HD; 6 mg kg^?1 followed by 6 mg kg^?1 hour^–1) of lidocaine was administered IV. MAC determination was repeated at 1.5 (T1.5) and 3 (T3) hours of lidocaine administration and blood was collected for analysis of plasma lidocaine and monoethylglycinexylidide (MEGX) concentrations. Pulse rate, peripheral hemoglobin oxygen saturation, noninvasive systolic arterial pressure and cloacal temperature were recorded at T0, T1.5 and T3. Treatments were separated by 1 week. Data were analyzed using mixed-effects model for repeated measures.ResultsMAC of isoflurane (mean ± standard deviation) at T0 was 1.47 ± 0.18%. MAC at T1.5 and T3 was 1.32 ± 0.27% and 1.26 ± 0.09% (treatment LD); and 1.28 ± 0.06% and 1.30 ± 0.06% (treatment HD). There were no significant differences between treatments or times. Maximum plasma lidocaine concentrations at T3 were 496 ± 98 and 1200 ± 286 ng mL^–1 for treatments LD and HD, respectively, and were not significantly different from T1.5. With treatment HD, plasma concentration of MEGX was significantly higher at T3 than at T1.5. Physiological variables were not significantly different among times with either treatment.Conclusions and clinical relevanceAdministration of lidocaine did not significantly change isoflurane MAC in chickens. Within treatments, plasma lidocaine concentrations were not significantly different at 1.5 and 3 hours.     

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.     

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.     

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.     

Effect of intravenous lidocaine on isoflurane MAC in dogs

Lidocaine decreases minimum alveolar concentration (MAC) of inhalational anesthetics. This study determined the influence of a low dose, 50 µg kg^?1 minute^?1 (LDI) and high dose, 200 µg kg^?1 minute^?1 (HDI) constant rate infusion of lidocaine on the MAC of isoflurane (I) in dogs. Ten mongrel dogs were anesthetized with I in oxygen and mechanically ventilated. End‐tidal anesthetic (Fe ′A) and CO₂ (Pe ′CO₂) concentrations were monitored at the endotracheal tube adaptor with an infrared gas analyzer calibrated before each experiment with a standardized calibration gas mixture designed for the analyzer. Pe ′CO₂ and body temperature were maintained within normal limits. Noxious stimuli included clamping the hindlimb paw (HC) and electrical current (50 V at 50 cycles second^?1 for 10 milliseconds pulse^?1) applied subcutaneously to the forelimb (FE) at the level of the ulna. After an initial equilibration period of at least 40 minutes at an Fe ′A of 1.7%, the Fe ′A was decreased to a value close to the estimated MAC for dogs. MAC was defined as the Fe ′A mid‐way between the value permitting and preventing purposeful movement. Following baseline MAC, a loading dose of 2 mg kg^?1 of lidocaine IV was administered over 3 minutes followed by the LDI, and MAC determinations for the combination started after 30 minutes of infusion. Once determined, the lidocaine infusion was stopped for 30 minutes and the dog maintained at the ETC that prevented movement without the lidocaine. Following this period, a second loading dose of lidocaine was given (2 mg kg^?1) over 3 minutes followed by the HDI, and the MAC determination procedure repeated after 30 minutes of infusion. Data were analyzed using an anova for repeated measures. MAC of I was 1.34 ± 0.035% (mean ± SEM) for both the FE and HC stimuli. The LDI significantly decreased MAC to 1.09 ± 0.043% (18.7% reduction) and HDI to 0.76 ± 0.030% (43.3% reduction). In conclusion, lidocaine infusions decreased the MAC of isoflurane in a dose‐dependent manner.     

Hemodynamic effects of intravenous lidocaine in isoflurane anesthetized cats

Lidocaine dose‐dependently decreases the minimum alveolar concentration (MAC) of isoflurane in cats. The purpose of this study was to determine the hemodynamic effects of six lidocaine plasma concentrations in isoflurane anesthetized cats. Six cats were studied. After instrumentation, end‐tidal isoflurane concentration was set at 1.25 times the individual minimum alveolar concentration (MAC), which was determined in a previous study. Lidocaine was administered intravenously to target pseudo‐steady state plasma concentrations of 0, 3, 5, 7, 9, and 11 μg ml^–1, and isoflurane concentration was reduced to an equipotent concentration, determined in a previous study. Cardiovascular variables; blood gases; PCV; total protein and lactate concentrations; and lidocaine and monoethylglycinexylidide concentrations were measured at each lidocaine target concentration, before and during noxious stimulation. Derived variables were calculated. Data were analyzed using a repeated measures anova , followed by a Tukey test for pairwise comparisons where appropriate. One cat was excluded from analysis because the study was aborted at 7 μg ml^–1 due to severe cardiorespiratory depression. Heart rate, cardiac index, stroke index, right ventricular stroke work index, total protein concentration, mixed‐venous PO₂ and hemoglobin oxygen saturation, arterial and mixed‐venous bicarbonate concentrations, and oxygen delivery were significantly lower during lidocaine administration than when no lidocaine was administered. Mean arterial pressure, central venous pressure, pulmonary artery pressure, systemic and pulmonary vascular resistance indices, PCV, arterial and mixed‐venous hemoglobin concentrations, lactate concentration, arterial oxygen concentration, and oxygen extraction ratio were significantly higher during administration of lidocaine than when no lidocaine was administered. Most changes were significant at lidocaine target plasma concentrations of 7 μg ml^–1 and above. Noxious stimulation did not significantly affect most variables. Despite significantly decreasing in inhalant requirements, when combined with isoflurane, lidocaine produces greater cardiovascular depression than an equipotent dose of isoflurane alone. The use of lidocaine to reduce isoflurane requirements is not recommended in cats.     

Effect of non-steroidal anti-inflammatory drugs on glomerular filtration rate and urinary N-acetyl-β-D-glucosaminidase activity in cats after dental surgery

ObjectiveTo compare the effects of meloxicam or carprofen on glomerular filtration rate (GFR), and to evaluate the effect of meloxicam on urinary N-acetyl-β-D-glucosaminidase (NAG) activity, of cats after dental surgery.Study designRandomized, blinded, controlled trial.AnimalsA total of 24 mixed breed cats.MethodsCats were randomly assigned to one of three groups (n = 8 per group): meloxicam (0.2 mg kg^–1); carprofen (4 mg kg^–1); or saline (2 mL). Acepromazine (0.04 mg kg^–1) and buprenorphine (0.02 mg kg^–1) were administered intramuscularly as preanaesthetic medication. Test drugs were injected subcutaneously at the time of preanaesthetic medication. Anaesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. Mean arterial blood pressure (MAP), respiratory rate (f_R), heart rate (HR) and haemoglobin oxygen saturation values (SpO₂) were recorded. All cats underwent ultrasonic dental scaling with polishing. Teeth extraction involved mucosal flap creation, removal of alveolar bone and flap closure. Plasma iohexol clearance (ICL), a measure of GFR, was estimated before and 24 hours after anaesthesia induction in all cats. Urinary NAG index was estimated in saline and meloxicam groups at the same time points as GFR. Between-group and -time point differences in GFR and NAG index were compared using mixed model analyses. Data are presented as mean ± standard deviation (p < 0.05).ResultsThere was no significant difference in plasma ICL rate (range: from 1.22 ± 0.05 to 1.27 ± 0.04 mL kg minute^–1) between groups or between time points. Urinary NAG index (range: from 1.0 ± 0.19 to 1.36 ± 0.29 Units gram^–1) was not significantly different between meloxicam and saline groups. MAP, HR, f_R and SpO₂ did not differ significantly between groups.Conclusions and clinical relevanceMeloxicam and carprofen appeared to produce nonsignificant effects on GFR, and meloxicam did not affect the urinary NAG activity, of cats after dental surgery.     

Use of naltrexone to antagonize high doses of remifentanil in cats: a dose-finding study

ObjectiveTo determine the dose of naltrexone necessary to fully antagonize a high dose of remifentanil in cats.Study designProspective experimental study.AnimalsSix healthy adult cats weighing 4.9 ± 0.7 kg.MethodsIn a first phase, remifentanil (200 μg kg^?1 followed by 60 μg kg^?1 minute^?1) was administered intravenously to two cats, causing an increase in locomotor activity. Naltrexone (100 μg kg^?1) was then administered intravenously every minute until the increase in locomotor activity had been reversed. In a second phase, six cats were used. Baseline thermal threshold was determined, naltrexone (600 μg kg^?1) was administered intravenously and 30 minutes later thermal threshold determination repeated. Remifentanil (200 μg kg^?1 followed by 60 μg kg^?1 minute^?1) was administered intravenously and thermal threshold determination repeated at 60, 120, 180, and/or 240 minutes after naltrexone administration. Thermal threshold determinations were started shortly after the start of the continuous rate infusion (CRI) of remifentanil and this CRI was discontinued immediately after thermal threshold determination. If an increase in thermal threshold was found, naltrexone administration was repeated at decreasing intervals in the next experiment (all cats were not used for all dosing intervals). Experiments were repeated until a naltrexone dosing interval was found that prevented increases in thermal threshold for 4 hours in all six cats.ResultsIn the first phase, both cats became severely dysphoric following remifentanil administration. A cumulative naltrexone dose of 300 μg kg^?1 was necessary to restore normal behavior in both cats. In the second phase, hourly administration of naltrexone (600 μg kg^?1) prevented increases in thermal threshold associated with hourly administration of remifentanil for 4 hours. Less frequent administration did not prevent increases in thermal threshold consistently.ConclusionsHourly administration of naltrexone (600 μg kg^?1) antagonizes the behavioral and antinociceptive effects of a high dose of remifentanil in cats.Clinical relevanceNaltrexone may be useful for the treatment of opioid overdose in cats.