Individual Minimum Alveolar Concentration Research Articles

Effects of tasipimidine premedication with and without methadone and dexmedetomidine on cardiovascular variables during propofol-isoflurane anaesthesia in Beagle dogs

ObjectiveTo evaluate cardiovascular effects of oral tasipimidine on propofol-isoflurane anaesthesia with or without methadone and dexmedetomidine at equianaesthetic levels. Study designProspective, placebo-controlled, blinded, experimental trial. AnimalsA group of seven adult Beagle dogs weighing (mean ± standard deviation) 12.4 ± 2.6 kg and a mean age of 20.6 ± 1 months. MethodsThe dogs underwent four treatments 60 minutes before induction of anaesthesia with propofol. PP: placebo orally and placebo (NaCl 0.9%) intravenously (IV); TP: tasipimidine 30 μg kg–1 orally and placebo IV; TMP: tasipimidine 30 μg kg–1 orally and methadone 0.2 mg kg–1 IV; and TMPD: tasipimidine 30 μg kg–1 orally with methadone 0.2 mg kg–1 and dexmedetomidine 1 μg kg–1 IV followed by 1 μg kg–1 hour–1.Isoflurane in oxygen was maintained for 120 minutes at 1.2 individual minimum alveolar concentration preventing motor movement. Cardiac output (CO), tissue blood flow (tbf), tissue oxygen saturation (stO2) and relative haemoglobin content were determined. Arterial and mixed venous blood gases, arterial and pulmonary artery pressures and heart rate (HR) were measured at baseline; 60 minutes after oral premedication; 5 minutes after IV premedication; 15, 30, 60, 90 and 120 minutes after propofol injection; and 30 minutes after switching the vaporiser off. Data were analysed by two-way anova for repeated measures; p < 0.05. ResultsTasipimidine induced a significant 20–30% reduction in HR and CO with decreases in MAP (10–15%), tbf (40%) and stO2 (43%). Blood pressure and oxygenation variables were mainly influenced by propofol-isoflurane-oxygen anaesthesia, preceded by short-lived alterations related to IV methadone and dexmedetomidine. Conclusions and clinical relevanceTasipimidine induced mild to moderate cardiovascular depression. It can be incorporated into a common anaesthetic protocol without detrimental effects in healthy dogs, when anaesthetics are administered to effect and cardiorespiratory function is monitored.

Cardiorespiratory effects of intramuscular alfaxalone combined with low-dose medetomidine and butorphanol in dogs anesthetized with sevoflurane

Background: The intramuscular (IM) administration of 7.5–10 mg/kg of alfaxalone produces anesthetic effects that enabled endotracheal intubation with mild cardiorespiratory depression in dogs. However, the effects of IM co-administration of medetomidine, butorphanol, and alfaxalone on cardiorespiratory function under inhalation anesthesia have not been studied. Aim: To assess the cardiorespiratory function following the IM co-administration of 5 μg/kg of medetomidine, 0.3 mg/kg of butorphanol, and 2.5 mg/kg of alfaxalone (MBA) in dogs anesthetized with sevoflurane. Methods: Seven intact healthy Beagles (three males and four females, aged 3–6 years old and weighing 10.0–18.1 kg) anesthetized with a predetermined minimum alveolar concentration (MAC) of sevoflurane were included in this study. The baseline cardiorespiratory variable values were recorded using the thermodilution method with a pulmonary artery catheter after stabilization for 15 min at 1.3 times their individual sevoflurane MAC. The cardiorespiratory variables were measured again following the IM administration of MBA. Data are expressed as median [interquartile range] and compared with the corresponding baseline values using the Friedman test and Sheff’s method. A P &lt; 0.05 was considered statistically significant. Results: The intramuscular administration of MBA transiently decreased the cardiac index (baseline: 3.46 [3.18–3.69], 5 min: 1.67 [1.57–1.75] L/min/m2 : P &lt; 0.001), respiratory frequency, and arterial pH. In contrast, it increased the systemic vascular resistance index (baseline: 5,367 [3,589–6,617], 5 min:10,197 [9,955–15,005] dynes sec/cm5/m2 : P = 0.0092), mean pulmonary arterial pressure, and arterial partial pressure of carbon dioxide. Conclusion: The intramuscular administration of MBA in dogs anesthetized with sevoflurane transiently decreased cardiac output due to vasoconstriction. Although spontaneous breathing was maintained, MBA administration resulted in respiratory acidosis due to hypoventilation. Thus, it is important to administer MBA with caution to dogs with insufficient cardiovascular function. In addition, ventilatory support is recommended.

Local anesthesia in piglets undergoing castration-A comparative study to investigate the analgesic effects of four local anesthetics on the basis of acute physiological responses and limb movements.

Surgical castration of male piglets without analgesia is a painful procedure. This prospective, randomized and double-blinded study aimed to evaluate the analgesic effects of four different local anesthetics for piglet castration during the first week of life. In total, 54 piglets aged 3 to 7 days were distributed into 6 treatment groups: handling (H); castration without pain relief (sodium chloride, NaCl); and castration with a local anesthetic: 4% procaine (P), 2% lidocaine (L), 0.5% bupivacaine (B) or 20 mg/ml mepivacaine (M). By excluding stress and fear as disruptive factors via a minimum anesthesia model, all piglets received individual minimum alveolar concentration (MAC) isoflurane anesthesia. Twenty minutes before castration, all treatment groups except group H received one injection per testis. Then, 0.5 ml of a local anesthetic or NaCl was injected intratesticularly (i.t.), and 0.5 ml was administered subscrotally. Acute physiological responses to noxious stimuli at injection and castration were evaluated by measuring blood pressure (BP), heart rate (HR), cortisol, epinephrine, norepinephrine and chromogranin A (CgA); limb movements were quantified. The results confirm that castration without analgesia is highly painful. Surgical castration without pain relief revealed significant changes in mean arterial blood pressure (MAP) and HR. Local anesthetic administration significantly reduced changes in BP and HR associated with castration. Piglets receiving a preoperative local anesthetic exhibited the fewest limb movements during castration, while the NaCl group exhibited the most. Injection itself was not associated with significant changes in MAP or HR. However, many piglets exhibited limb movements during injection, indicating that the injection itself causes nociceptive pain. No significant differences were found between groups regarding parameters of plasma cortisol, catecholamines and CgA. In conclusion, all four local anesthetics administered are highly effective at reducing signs of nociception during castration under light isoflurane anesthesia. However, injection of a local anesthetic seems to be painful.

Influence of sevoflurane anesthesia with mechanical ventilation and fluid-therapy on distribution of subcutaneously administered robenacoxib in dogs.

Robenacoxib is a novel nonsteroidal anti-inflammatory drug approved for dogs. The present study aimed to evaluate influences of sevoflurane anesthesia on the distribution of robenacoxib in dogs. Ten healthy beagle dogs (1 to 11 years old, 9.3 to 14.3 kg body weight, 6 males and 4 females) were subcutaneously administered robenacoxib (2 mg/kg) under conscious condition or sevoflurane anesthesia inhaled a 1.3-fold predetermined individual minimum alveolar concentration of sevoflurane at a 28-day interval. The dogs under sevoflurane anesthesia were also mechanically ventilated and received fluid-therapy. On each occasion, serum samples were collected from the dogs before and at 5, 15, 30, 60, 120, 180, and 240 min after the robenacoxib administration. Serum robenacoxib concentration was measured by a liquid chromatography-tandem mass spectrometry. Maximum serum concentration of robenacoxib (Cmax) was 2.2 µg/ml [range: 1.2–4.6] (median [range: minimum-maximum]) and time of Cmax (Tmax) was 90 min [range: 60–120] in the conscious dogs. In the sevoflurane-anesthetized dogs, the Cmax significantly declined (1.3 µg/ml [range: 0.8–1.4], P=0.008) and Tmax was delayed (120 min [range: 120–240], P=0.018) compared with those in the conscious dogs. The serum robenacoxib concentration at 240 min (C240) decreased to 0.5 µg/ml [range: 0.2–0.9] in the conscious dogs, while it remained higher in the sevoflurane-anesthetized dogs (1.0 µg/ml [range: 0.3–1.4], P=0.011). In conclusion, the anesthetic procedure with sevoflurane, mechanically ventilated, and received fluid-therapy might affect the pharmacokinetics of subcutaneously administered robenacoxib in dogs.

Plethysmography variability index for prediction of fluid responsiveness during graded haemorrhage and transfusion in sevoflurane-anaesthetized mechanically ventilated dogs

ObjectiveTo examine the accuracy of plethysmography variability index (PVI) as a noninvasive indicator of fluid responsiveness in hypovolaemic dogs. Study designProspective experimental study. AnimalsSix adult healthy sevoflurane-anaesthetized Beagle dogs. MethodsDogs were anaesthetized with 1.3-fold their individual minimum alveolar concentration of sevoflurane. The lungs were mechanically ventilated after neuromuscular blockade with vecuronium bromide. Cardiopulmonary variables including mean arterial blood pressure (MAP), central venous pressure (CVP), transpulmonary thermodilution cardiac output (TPTDCO), stroke volume (SV), perfusion index (PI), pulse pressure variation (PPV), stroke volume variation (SVV) and PVI were determined during six stages of graded venous blood withdrawal (5 mL kg−1 increments) and six stages of graded blood infusion (5 mL kg−1 increments). The cardiopulmonary variables were analysed using paired t test or Wilcoxon signed rank test. Correlations between PPV and SVV or PVI were analysed by linear regression. The accuracy of PPV, SVV and PVI for predicting fluid responsiveness was examined by using receiver operating characteristic curve analysis. A value of p < 0.05 was considered statistically significant. ResultsBlood withdrawal resulted in significant increases in PPV and PVI and decreases in MAP, CVP, TPTDCO, SV and PI. Blood infusion resulted in significant increases in MAP, CVP, TPTDCO, SV and PI and decreases in PPV and PVI. PPV and PVI showed a relevant correlation (p < 0.001, r2 = 0.62) and threshold values of PPV ≥ 16% (sensitivity 71%, specificity 82%) and PVI ≥ 12% (sensitivity 78%, specificity 72%) for identifying fluid responsiveness. SVV did not change. Conclusions and clinical relevanceNoninvasive measurement of PVI predicted fluid responsiveness with moderate accuracy equal to PPV in sevoflurane-anaesthetized mechanically ventilated dogs. Provisional threshold values for identification of fluid responsiveness were PPV ≥ 16% and PVI ≥ 12%. Clinical trials are needed to confirm these threshold values in dogs.

Cardiopulmonary effects of reverse Trendelenburg position at 5° and 10° in sevoflurane-anesthetized steers

ObjectiveTo assess the cardiopulmonary effects caused by reverse Trendelenburg position (RTP) at 5° and 10° in sevoflurane-anesthetized yearling steers. Study designProspective, experimental study. AnimalsEight Holstein steers aged (mean ± standard deviation) 12 ± 2 months and weighing 145 ± 26 kg. MethodsIn the first phase of the study, the individual minimum alveolar concentration (MAC) of sevoflurane was determined using electrical stimulation. In the second phase, the effects of RTP were assessed. The animals were anesthetized on three separate events separated by ≥7 days in an incomplete crossover design: control treatment using a table without tilt (RTP0); treatment with the table at 5° RTP (RTP5) and table tilted 10° RTP (RTP10). Subjects were physically restrained in dorsal recumbency on the table, which was already tilted according to each treatment. Anesthesia was induced with sevoflurane at 8% in 5 L minute–1 oxygen via face mask followed by maintenance with sevoflurane at 1.3 MAC and spontaneous breathing. Cardiopulmonary variables were obtained immediately after instrumentation (T0) and then after 30, 60, 120 and 180 minutes (T30, T60, T120 and T180, respectively). ResultsThe mean sevoflurane MAC for the eight steers was 2.12 ± 0.31%. Cardiac output was lower at all time points and the systemic vascular resistance index was higher at T120 and T180 in RTP10 compared with RTP0. Oxygen consumption was lower at T0 and at T180 in RTP10 compared with RTP0 and at all time points except T30 compared with RTP5. Oxygen extraction was lower at T0 in RTP10 compared with RTP0 and RTP5, and at T60 and T180 compared with RTP5. Conclusions and clinical relevanceRTP 5° and 10° did not improve ventilatory and oxygenation variables in sevoflurane-anesthetized steers when compared with no tilt, however the cardiovascular variables were adversely affected in RTP10.

Effects of isoflurane with and without dexmedetomidine or remifentanil on heart rate variability before and after nociceptive stimulation at different multiples of minimum alveolar concentration in dogs

To evaluate the influence of 3 anesthetic protocols and multiples of minimum alveolar concentration (MAC) on heart rate variability (HRV) with and without nociceptive stimulation in dogs. 6 healthy adult Beagles. Each dog was anesthetized 3 times: with isoflurane alone, with isoflurane and a constant rate infusion of dexmedetomidine (IsoD; 3 μg/kg/h, IV), and with isoflurane and a constant rate infusion of remifentanil (IsoR; 18 μg/kg/h, IV). Individual MAC was determined via supramaximal electrical stimulation. Sinus rhythm-derived intervals between 2 adjacent R-R intervals were exported from ECG recordings. Selected HRV time and frequency domain variables were obtained (at 2-minute intervals) and analyzed offline with signed rank tests before and after stimulation at 0.75, 1.0, and 1. 5 MAC for each anesthetic session. The isoflurane session had the overall lowest prestimulation SDNN (SD of all R-R intervals) values. Prestimulation SDNN values decreased significantly with increasing MAC in all sessions. For the IsoD session, SDNN (milliseconds) or high-frequency power (milliseconds(2)) was inversely correlated with MAC (Spearman rank correlation coefficient for both variables, -0.77). In the isoflurane and IsoR sessions, heart rate increased significantly after stimulation. In the IsoD session, poststimulation SDNN was increased significantly, compared with prestimulation values, at 0.75 and 1.0 MAC. On the basis of SDNN and high-frequency power values, anesthetic levels between 0.75 and 1.5 MAC within the same anesthetic protocol could be differentiated, but with a large overlap among protocols. Usefulness of standard HRV variables for assessment of anesthetic depth and nociception in dogs is questionable.

Intracranial pressure and cardiopulmonary variables during isoflurane or sevoflurane anesthesia at various minimum alveolar concentration multiples in normocapnic dogs

To compare effects of isoflurane and sevoflurane on intracranial pressure and cardiovascular variables at 1.0, 1.5, and 2.0 times the minimum alveolar concentration (MAC) in mechanically ventilated normocapnic dogs. 6 healthy male Beagles. The individual MAC was determined for each agent with an electrical stimulus. After a minimum of 1 week, anesthetic induction by use of a mask with one of the inhalation anesthetics selected randomly was followed by mechanical ventilation and instrumentation for measurement of intracranial pressure and cardiovascular variables. Heart rate; systolic, mean, and diastolic arterial blood pressures; central venous pressure; mean pulmonary arterial pressure; pulmonary artery occlusion pressure; cardiac output; intracranial pressure (ICP); core body temperature; end-tidal inhalation anesthetic and carbon dioxide concentration; and arterial blood gas values were measured after attaining equilibrium at 1.0, 1.5, and 2.0 MAC of each inhalation anesthetic. Cardiac index, systemic vascular resistance, pulmonary vascular resistance, and cerebral perfusion pressure (CPP) were calculated. Mean ICP did not differ within and between anesthetics at any MAC. Compared with equipotent concentrations of isoflurane, the CPP and mean values for systolic, mean, and diastolic arterial blood pressures were increased at 2.0 MAC for sevoflurane, whereas mean values for mean and diastolic arterial blood pressures and systemic vascular resistance were increased at 1.5 MAC for sevoflurane. Although ICP was similar in healthy normocapnic dogs, CPP was better maintained during 2.0 MAC for sevoflurane, compared with isoflurane.

Concentration-dependent isoflurane effects on withdrawal reflexes in pigs and the role of the stimulation paradigm

In this prospective two-phase experimental trial, 10 pigs were anaesthetized twice with isoflurane only. In the first phase, the individual minimum alveolar concentration (MAC) was determined and in the second phase the effects on withdrawal reflexes of increasing end-tidal isoflurane concentrations (from 1.6% to 2.8%) were assessed. Single, 10 and 60 repeated electrical stimulations were used to evoke withdrawal reflexes which were recorded and quantified by electromyography. Recruitment curves for reflex amplitude for increasing stimulation intensities and isoflurane concentrations were constructed. Isoflurane MAC was 1.9 ± 0.3%. Reflexes evoked by repeated stimulation were suppressed at isoflurane concentrations significantly higher than those which suppressed complex movements during MAC determination (P=0.014 and P=0.006 for 10 and 60 repeated stimuli respectively). Isoflurane up to 2.8% was still not able to abolish reflex activity evoked by repeated stimulations in all pigs. Single stimulation reflexes were suppressed at significantly lower concentrations than repeated stimulation reflexes (P=0.008 and P=0.004 for 10 and 60 repeated stimuli, respectively). Reflex amplitude was significantly correlated with isoflurane concentration (P<0.001, r=-0.85) independent of the individual MAC. The findings indicate that the level at which isoflurane suppresses withdrawal reflexes is dependent on the stimulation paradigm (single vs. repeated electrical stimulation), and there is limited value in expressing reflex withdrawal suppression in terms of MAC as purposeful and reflex movements are independently affected by isoflurane in individual animals.

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.

Cardiovascular Effects of Tramadol in Dogs Anesthetized with Sevoflurane

Cardiovascular effects of tramadol were evaluated in dogs anesthetized with sevoflurane. Six beagle dogs were anesthetized twice at 7 days interval. The minimum alveolar concentration (MAC) of sevoflurane was earlier determined in each dog. The dogs were then anesthetized with sevoflurane at 1.3 times of predetermined individual MAC and cardiovascular parameters were evaluated before (baseline) and after an intravenous injection of tramadol (4 mg/kg). The administration of tramadol produced a transient and mild increase in arterial blood pressure (ABP) (P=0.004) with prolonged increase in systemic vascular resistance (SVR) (P<0.0001). Compared with baseline value, mean ABP increased significantly at 5 min (119% of baseline value, P=0.003), 10 min (113%, P=0.027), and 15 min (111%, P=0.022). SVR also increased significantly at 5 min (128%, P<0.0001), 10 min (121%, P=0.026), 30 min (114%, P=0.025), 45 min (113%, P=0.025) and 60 min (112%, P=0.048). Plasma concentrations of tramadol were weakly correlated with the percentage changes in mean ABP (r=0.642, P<0.0001) and SVR (r=0.646, P<0.0001). There was no significant change in heart rate, cardiac output, cardiac index, stroke volume, pulmonary arterial pressure, right atrial pressure and pulmonary capillary wedge pressure. In conclusion, the administration of tramadol produces a prolonged peripheral vascular constriction in dogs anesthetized with sevoflurane, which is accompanied with a transient and mild increase in arterial blood pressure. It also indicated that the degree of vasoconstriction might depend on the plasma concentration of tramadol.

Effects of isoflurane upon minimum alveolar concentration and cerebral cortex depression in pigs and goats: An interspecies comparison

This study compared the effects of isoflurane in pigs (n=10 Yorkshire-Landrace cross) and dairy goats (n=10) by evaluation of electroencephalographic (EEG) burst suppression thresholds (BST) in the cerebral cortex and minimum alveolar concentration (MAC) values in the spinal cord. The study also investigated whether individual MAC values can predict the effects of isoflurane on the cerebral cortex. MAC values and BST/MAC ratios were significantly different between species. Inhibition of movement by isoflurane may be less effective in pigs than in goats. No significant correlation was found between individual MAC and BST values, indicating that in single animals the individual MAC poorly reflects the cerebrocortical depressant effect of isoflurane in pigs and goats.

Effect of remifentanil hydrochloride administered via constant rate infusion on the minimum alveolar concentration of isoflurane in cats

To evaluate the effects of increasing doses of remifentanil hydrochloride administered via constant rate infusion (CRI) on the minimum alveolar concentration (MAC) of isoflurane in cats. 6 healthy adult cats. For each cat, 2 experiments were performed (2-week interval). On each study day, anesthesia was induced and maintained with isoflurane; a catheter was placed in a cephalic vein for the administration of lactated Ringer's solution or remifentanil CRIs, and a catheter was placed in the jugular vein for collection of blood samples for blood gas analyses. On the first study day, individual basal MAC (MAC(Basal)) was determined for each cat. On the second study day, 3 remifentanil CRIs (0.25, 0.5, and 1.0 microg/kg/min) were administered (in ascending order); for each infusion, at least 30 minutes elapsed before determination of MAC (designated as MAC(R0.25), MAC(R0.5), and MAC(R1.0), respectively). A 15-minute washout period was allowed between CRIs. A control MAC (MAC(Control)) was determined after the last remifentanil infusion. Mean +/- SD MAC(Basal) and MAC(Control) values at sea level did not differ significantly (1.66 +/- 0.08% and 1.52 +/- 0.21%, respectively). The MAC values determined for each remifentanil CRI did not differ significantly. However, MAC(R0.25), MAC(R0.5), and MAC(R1.0) were significantly decreased, compared with MAC(Basal), by 23.4 +/- 7.9%, 29.8 +/- 8.3%, and 26.0 +/- 9.4%, respectively. The 3 doses of remifentanil administered via CRI resulted in a similar degree of isoflurane MAC reduction in adult cats, indicating that a ceiling effect was achieved following administration of the lowest dose.

Relationship of bispectral index to hemodynamic variables and alveolar concentration multiples of sevoflurane in puppies

The relationships between bispectral index (BIS), cardiovascular variables and minimum alveolar concentration (MAC) multiples of sevoflurane in puppies were determined. Five puppies were anesthetized with sevoflurane on two occasions. First, the individual sevoflurane MAC values were determined for each puppy. Secondly, dogs were anesthetized with sevoflurane at each of 5 MAC multiples, 0.75, 1, 1.25, 1.5 and 1.75 MAC administered in random order. Hemodynamic parameters and BIS data were collected for 20 min. Somatic stimulus was then applied and the same parameters and data were collected for 6 min. Correlation between BIS and end tidal sevoflurane and between BIS and hemodynamic parameters were studied. We found positive significant correlation in both cases. BIS is lower in puppies that in adults at the same alveolar anesthetic concentrations and sevoflurane appears to be a safe anesthetic in puppies.

Comparison of variability in cardiorespiratory measurements following desflurane anesthesia at a multiple of the minimum alveolar concentration for each dog versus a multiple of a single predetermined minimum alveolar concentration for all dogs in a group

To determine whether the variability of cardiorespiratory measurements is smaller when administering desflurane at a multiple of the individual's minimum alveolar concentration (MAC) or at a predetermined, identical concentration in all subjects. 10 dogs. Desflurane was administered at 1.5 times the individual's MAC (iMAC) and 1.5 times the group's MAC (gMAC). The order of concentrations was randomly selected. Heart rate, respiratory rate, arterial blood pressure, central venous pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, arterial and mixed-venous blood gas tensions and pH, and cardiac output were measured. The desflurane concentration required to achieve a mean arterial pressure (MAP) of 60 mm Hg was then determined. Finally, the desflurane concentration required to achieve an end-tidal PCO(2) of 55 mm Hg was measured. Variances when administering 1.5 iMAC or 1.5 gMAC were not significantly different for any variable studied. Differences between the MAC multiples needed to reach an MAP of 60 mm Hg and the mean of the sample were significantly larger when gMAC was used, compared with iMAC, indicating that a multiple of iMAC better predicted the concentration resulting in a MAP of 60 mm Hg. Results suggest that, in a small group of dogs, variability in cardiorespiratory measurements among dogs is unlikely to differ whether an inhalant anesthetic is administered at a multiple of the iMAC in each dog or at an identical gMAC in all dogs.

Evaluation of administration of isoflurane at approximately the minimum alveolar concentration on depression of a nociceptive withdrawal reflex evoked by transcutaneous electrical stimulation in ponies

To investigate effects of isoflurane at approximately the minimum alveolar concentration (MAC) on the nociceptive withdrawal reflex (NWR) of the forelimb of ponies as a method for quantifying anesthetic potency. 7 healthy adult Shetland ponies. Individual MAC (iMAC) for isoflurane was determined for each pony. Then, effects of isoflurane administered at 0.85, 0.95, and 1.05 iMAC on the NWR were assessed. At each concentration, the NWR threshold was defined electromyographically for the common digital extensor and deltoid muscles by stimulating the digital nerve; additional electrical stimulations (3, 5, 10, 20, 30, and 40 mA) were delivered, and the evoked activity was recorded and analyzed. After the end of anesthesia, the NWR threshold was assessed in standing ponies. Mean +/- SD MAC of isoflurane was 1.0 +/- 0.2%. The NWR thresholds for both muscles increased significantly in a concentration-dependent manner during anesthesia, whereas they decreased in awake ponies. Significantly higher thresholds were found for the deltoid muscle, compared with thresholds for the common digital extensor muscle, in anesthetized ponies. At each iMAC tested, amplitudes of the reflex responses from both muscles increased as stimulus intensities increased from 3 to 40 mA. A concentration-dependent depression of evoked reflexes with reduction in slopes of the stimulus-response functions was detected. Anesthetic-induced changes in sensory-motor processing in ponies anesthetized with isoflurane at concentrations of approximately 1.0 MAC can be detected by assessment of NWR. This method will permit comparison of effects of inhaled anesthetics or anesthetic combinations on spinal processing in equids.

Pharmacokinetics of ketamine and its metabolite, norketamine, after intravenous administration of a bolus of ketamine to isoflurane-anesthetized dogs

To determine the pharmacokinetics of ketamine and norketamine in isoflurane-anesthetized dogs. Animals-6 dogs. The minimum alveolar concentration (MAC) of isoflurane was determined in each dog. Isoflurane concentration was then set at 0.75 times the individual's MAC, and ketamine (3 mg/kg) was administered IV. Blood samples were collected at various times following ketamine administration. Blood was immediately centrifuged, and the plasma separated and frozen until analyzed. Ketamine and norketamine concentrations were measured in the plasma samples by use of liquid chromatography-mass spectrometry. Ketamine concentration-time data were fitted to compartment models. Norketamine concentration-time data were examined by use of noncompartmental analysis. The MAC of isoflurane was 1.43 +/- 0.18% (mean +/- SD). A 2-compartment model best described the disposition of ketamine. The apparent volume of distribution of the central compartment, the apparent volume of distribution at steady state, and the clearance were 371.3 +/- 162 mL/kg, 4,060.3 +/- 2,405.7 mL/kg, and 58.2 +/- 17.3 mL/min/kg, respectively. Norketamine rapidly appeared in plasma following ketamine administration and had a terminal half-life of 63.6 +/- 23.9 minutes. A large variability in plasma concentrations, and therefore pharmacokinetic parameters, was observed among dogs for ketamine and norketamine. In isofluraneanesthetized dogs, a high variability in the disposition of ketamine appears to exist among individuals. The disposition of ketamine may be difficult to predict in clinical patients.

Cardiovascular and respiratory effects of ketamine infusions in isoflurane-anesthetized dogs before and during noxious stimulation

To characterize the effects of ketamine administration on the cardiovascular and respiratory systems and on acid-base balance and to record adverse effects of ketamine in isoflurane-anesthetized dogs. 6 healthy adult mongrel dogs. Dogs were anesthetized with isoflurane (1.25 times the individual minimum alveolar concentration) in oxygen, and ketamine was administered IV to target pseudo-steady-state plasma concentrations of 0, 0.5, 1, 2, 5, 8, and 11 microg/mL. Isoflurane concentration was reduced to an equipotent concentration. Cardiovascular, respiratory, and acid-base variables; body temperature; urine production; and adverse effects were recorded before and during noxious stimulation. Cardiac index, stroke index, rate-pressure product, systemic vascular resistance index, pulmonary vascular resistance index, left ventricular stroke work index, right ventricular stroke work index, arterial oxygen concentration, mixed-venous oxygen concentration, oxygen delivery, oxygen consumption, oxygen extraction ratio, alveolar-arterial oxygen partial pressure gradient, and venous admixture were calculated. Plasma ketamine and norketamine concentrations were measured. Overall, ketamine administration improved ventilation, oxygenation, hemodynamics, and oxygen delivery in isoflurane-anesthetized dogs in a dosedependent manner. With the addition of ketamine, core body temperature was maintained or increased and urine production was maintained at an acceptable amount. However, at the higher plasma ketamine concentrations, adverse effects such as spontaneous movement and profuse salivation were observed. Myoclonus and dysphoria were observed during recovery in most dogs. Infusion of ketamine appears to be a suitable technique for balanced anesthesia with isoflurane in dogs. Plasma ketamine concentrations between 2 to 3 microg/mL elicited the most benefits with minimal adverse effects.

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.

Assessment of the hemodynamic effects of lidocaine administered IV in isofluraneanesthetized cats

To determine the hemodynamic effects of lidocaine (administered IV to achieve 6 plasma concentrations) in isoflurane-anesthetized cats. 6 cats. Cats were anesthetized with isoflurane in oxygen (end-tidal isoflurane concentration set at 1.25 times the predetermined individual minimum alveolar concentration). Lidocaine was administered IV to each cat to achieve target pseudo-steady-state plasma concentrations of 0, 3, 5, 7 9, and 11 microg/mL, and isoflurane concentration was reduced to an equipotent concentration. At each plasma lidocaine concentration, cardiovascular and blood gas variables; PCV; and plasma total protein, lactate, lidocaine, and monoethylglycinexylidide concentrations were measured in cats before and during noxious stimulation. Derived variables were calculated. n isoflurane-anesthetized cats, heart rate, cardiac index, stroke index, right ventricular stroke work index, plasma 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, compared with values determined without lidocaine administration. Mean arterial pressure, central venous pressure, pulmonary artery pressure, systemic and pulmonary vascular resistance indices, PCV, arterial and mixed-venous hemoglobin concentrations, plasma lactate concentration, arterial oxygen concentration, and oxygen extraction ratio were significantly higher during administration of lidocaine, compared with values determined without lidocaine administration. Noxious stimulation did not significantly affect most variables. In isoflurane-anesthetized cats, although IV administration of lidocaine significantly decreased inhalant requirements, it appeared to be associated with greater cardiovascular depression than an equipotent dose of isoflurane alone. Administration of lidocaine to reduce isoflurane requirements is not recommended in cats.