Phillip Lerche

The cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in cats.

OBJECTIVE To determine the cardiorespiratory and anesthetic effects of 0, 5, 15, and 50 mg kg(-1) intravenous (IV) alfaxalone in hydroxypropyl beta cyclodextrin (Alfaxan; Jurox Pty Ltd, Rutherford, NSW, Australia) in cats. STUDY DESIGN Four treatments of alfaxalone were administered in sequential order. ANIMALS Eight healthy adult cats (four male; four female) weighing between 3.71 and 5.91 kg. METHODS Cats were instrumented for hemodynamic measurements. Four (0, 5, 15, and 50 mg kg(-1)) IV doses of alfaxalone were administered over one minute, with a 3-hour washout period between doses 0, 5, and 15 mg kg(-1) on Day 0. The 50 mg kg(-1) treatment was administered 24 hours later. Measurements of heart rate, aortic systolic, mean, and diastolic blood pressures, pulmonary arterial and right atrial mean pressures, cardiac output, respiratory rate, tidal and minute volumes, and arterial blood pH and blood gases (PaO(2), PaCO(2)) were performed at pre-determined intervals. Systemic vascular resistance and rate pressure product were calculated. The quality of induction, maintenance, and recovery from anesthesia and the response to noxious stimulation were categorically scored. RESULTS Alfaxalone administration resulted in dose-dependent cardiorespiratory depression. Decreases in arterial blood pressure and increases in heart rate occurred at higher doses. Most variables returned to baseline by 15-30 minutes. Respiratory rate, minute volume, and PaO(2) decreased. Apnea was the most common side effect. Induction and maintenance quality were judged to be good to excellent at all doses and quality of recovery good to excellent at all but the 50 mg kg(-1) dose. The duration of anesthesia and unresponsiveness to noxious stimulation increased with dose. The administration of the 50 mg kg(-1) dose produced marked cardiorespiratory depression and apnea. CONCLUSIONS AND CLINICAL RELEVANCE Alfaxalone produced dose-dependent anesthesia, cardiorespiratory depression and unresponsiveness to noxious stimulation in unpremedicated cats. Hypoventilation and apnea were the most common side effects.

Effect of intravenous administration of lactated Ringer's solution or hetastarch for the treatment of isoflurane-induced hypotension in dogs

OBJECTIVE To determine the effect of IV administration of crystalloid (lactated Ringers solution [LRS]) or colloid (hetastarch) fluid on isoflurane-induced hypotension in dogs. ANIMALS 6 healthy Beagles. PROCEDURES On 3 occasions, each dog was anesthetized with propofol and isoflurane and instrumented with a thermodilution catheter (pulmonary artery). Following baseline assessments of hemodynamic variables, end-tidal isoflurane concentration was increased to achieve systolic arterial blood pressure (SABP) of 80 mm Hg. At that time (0 minutes), 1 of 3 IV treatments (no fluid, LRS [80 mL/kg/h], or hetastarch [80 mL/kg/h]) was initiated. Fluid administration continued until SABP was within 10% of baseline or to a maximum volume of 80 mL/kg (LRS) or 40 mL/kg (hetastarch). Hemodynamic variables were measured at intervals (0 through 120 minutes and additionally at 150 and 180 minutes in LRS- or hetastarch-treated dogs). Several clinicopathologic variables including total protein concentration, PCV, colloid osmotic pressure, and viscosity of blood were assessed at baseline and intervals thereafter (0 through 120 minutes). RESULTS Administration of 80 mL of LRS/kg did not increase SABP in any dog, whereas administration of <or= 40 mL of hetastarch/kg increased SABP in 4 of 6 dogs. Fluid administration increased cardiac index and decreased systemic vascular resistance. Compared with hetastarch treatment, administration of LRS decreased blood viscosity. Treatment with LRS decreased PCV and total protein concentration, whereas treatment with hetastarch increased colloid osmotic pressure. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that IV administration of hetastarch rather than LRS is recommended for the treatment of isoflurane-induced hypotension in dogs.

Effect of 50% and maximal inspired oxygen concentrations on respiratory variables in isoflurane-anesthetized horses

BackgroundThe purpose of this study was to compare the effects of 0.5 fraction of inspired oxygen (FiO2) and >0.95 FiO2 on pulmonary gas exchange, shunt fraction and oxygen delivery (DO2) in dorsally recumbent horses during inhalant anesthesia. The use of 0.5 FiO2 has the potential to reduce absorption atelectasis (compared to maximal FiO2) and augment alveolar oxygen (O2) tensions (compared to ambient air) thereby improving gas exchange and DO2. Our hypothesis was that 0.5 FiO2 would reduce ventilation-perfusion mismatching and increase the fraction of pulmonary blood flow that is oxygenated, thus improving arterial oxygen content and DO2.ResultsArterial partial pressures of O2 were significantly higher than preanesthetic levels at all times during anesthesia in the >0.95 FiO2 group. Arterial partial pressures of O2 did not change from preanesthetic levels in the 0.5 FiO2 group but were significantly lower than in the >0.95 FiO2 group from 15 to 90 min of anesthesia. Alveolar to arterial O2 tension difference was increased significantly in both groups during anesthesia compared to preanesthetic values. The alveolar to arterial O2 tension difference was significantly higher at all times in the >0.95 FiO2 group compared to the 0.5 FiO2 group. Oxygen delivery did not change from preanesthetic values in either group during anesthesia but was significantly lower than preanesthetic values 10 min after anesthesia in the 0.5 FiO2 group. Shunt fraction increased in both groups during anesthesia attaining statistical significance at varying times. Shunt fraction was significantly increased in both groups 10 min after anesthesia but was not different between groups. Alveolar dead space ventilation increased after 3 hr of anesthesia in both groups.ConclusionsReducing FiO2 did not change alveolar dead space ventilation or shunt fraction in dorsally recumbent, mechanically ventilated horses during 3 hr of isoflurane anesthesia. Reducing FiO2 in dorsally recumbent isoflurane anesthetized horses does not improve oxygenation or oxygen delivery.

Effects of intravenous administration of perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVE-To determine the effects of IV administration of perzinfotel and a perzinfotel-fentanyl combination on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS-6 healthy sexually intact Beagles (3 males and 3 females). PROCEDURES-All dogs were instrumented with a telemetry device for continuous monitoring of heart rate, arterial blood pressure, and core body temperature (at a femoral artery). Dogs were anesthetized with propofol (6 mg/kg, IV) and isoflurane. Isoflurane MAC values were determined in 3 experiments in each dog, separated by at least 7 days, before (baseline) and after the following treatments: no treatment (anesthetic only), perzinfotel (20 mg/kg, IV), fentanyl (5 microg/kg bolus, IV, followed by a continuous IV infusion at 0.15 microg/kg/min), and a fentanyl-perzinfotel combination (20 mg of perzinfotel/kg, IV, plus the fentanyl infusion). Bispectral index and oxygen saturation as measured by pulse oximetry were also monitored throughout anesthesia. RESULTS-Without treatment, the mean +/- SD isoflurane MAC for all 6 dogs was 1.41 +/- 0.10%. Baseline MAC was 1.42 +/- 0.08%. Intravenous administration of perzinfotel, fentanyl, and the perzinfotel-fentanyl combination significantly decreased the MAC by 39%, 35%, and 66%, respectively. Perzinfotel and perzinfotel-fentanyl administration yielded significant increases in the bispectral index. Mean, systolic, and diastolic arterial blood pressures significantly increased from baseline values when perzinfotel was administered. Systolic arterial blood pressure significantly increased from the baseline value when perzinfotel-fentanyl was administered. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of perzinfotel, fentanyl, or a perzinfotel-fentanyl combination reduced isoflurane MAC in dogs and increased arterial blood pressure.

Retrospective evaluation of the effectiveness of epsilon aminocaproic acid for the prevention of postamputation bleeding in retired racing Greyhounds with appendicular bone tumors: 46 cases (2003–2008)

OBJECTIVES To determine the frequency of delayed postoperative bleeding in retired racing Greyhounds with appendicular bone tumors undergoing limb amputations. To identify if administration of epsilon-aminocaproic acid (EACA) was effective on the prevention of postoperative bleeding. DESIGN Retrospective study from December 2003 to December 2008. SETTING Veterinary university teaching hospital. ANIMALS Forty-six retired racing Greyhounds (RRGs) diagnosed with primary appendicular bone tumors that underwent limb amputation were included in the study. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Thirteen of 46 RRGs (28%) included in the study had delayed postoperative bleeding starting 48-72 h after surgery. Bleeding episodes included cutaneous, subcutaneous, and external bleeding that extended from the area of the surgical site that became widespread within hours, and that required administration of blood components. A paired t-test suggests that there was a significant decrease in PCV postoperatively for both dogs that bled and dogs that did not bleed (P < 0.0001). Forty of 46 RRGs (86%) received either fresh frozen plasma (FFP) or EACA or both, for the prevention of postoperative bleeding. A logistic regression model determined that dogs that did not receive EACA were 5.7 times more likely to bleed than dogs that did receive EACA, when controlling for whether or not they received FFP (95% CI: 1.02-32.15, P = 0.047). CONCLUSION This retrospective study suggests that preemptive postoperative administration of EACA appears to be efficacious in decreasing the frequency of bleeding in RRGs undergoing limb amputation; however, a prospective study is warranted to corroborate its effectiveness.

Pharmacokinetics of midazolam after intravenous administration to horses

REASONS FOR PERFORMING THE STUDY Midazolam is used to control seizures in horses and to enhance muscle relaxation, but its pharmacokinetics are unknown. OBJECTIVE To determine the pharmacokinetics and sedative effects of midazolam in horses. STUDY DESIGN Blinded, randomised, crossover design. METHODS Midazolam was administered i.v. at either 0.05 or 0.1 mg/kg bwt to 6 horses on 2 occasions at least 7 days apart using a crossover design. Blood samples were collected before and at predetermined times through 24 h after administration. Serum midazolam concentrations were determined by a liquid chromatography tandem-mass spectrometry method. Heart and respiratory rates and indices of sedation, ataxia, and sensitivity to stimuli were recorded before and at predetermined times after midazolam administration. RESULTS Pharmacokinetic analysis was performed on samples from 5 horses in each group. Median total clearance was 10.6 ml/min/kg (range 6.1-15.2 ml/min/kg) and 10.4 ml/min/kg (range 8.4-17.6 ml/min/kg), and median volume of distribution at steady state was 2094 ml/kg (range 2076-2413 ml/kg) and 2822 ml/kg (range 2270-7064 ml/kg) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Median distribution half-life was 24 min (range 6-42 min) and 39 min (range 33.6-72 min) and median terminal half-life was 216 min (range 120-248 min) and 408 min (range 192-924 min) after the 0.05 mg/kg and 0.1 mg/kg bwt doses, respectively. Cardiorespiratory parameters and sedation scores did not change. Midazolam caused agitation, postural sway, weakness, and one horse became recumbent after the 0.1 mg/kg bwt dose. CONCLUSIONS Midazolam produces ataxia and postural sway of short duration after i.v. administration to horses. Sedation was not evident after midazolam administration. Drug redistribution is likely the primary mechanism for the termination of effect. POTENTIAL RELEVANCE Midazolam produces muscle relaxation but not sedation in adult horses.

Effect of dexmedetomidine, morphine-lidocaine-ketamine, and dexmedetomidine-morphine-lidocaine-ketamine constant rate infusions on the minimum alveolar concentration of isoflurane and bispectral index in dogs

OBJECTIVE To determine the effect of dexmedetomidine, morphine-lidocaine-ketamine (MLK), and dexmedetomidine-morphine-lidocaine-ketamine (DMLK) constant rate infusions on the minimum alveolar concentration (MAC) of isoflurane and bispectral index (BIS) in dogs. ANIMALS 6 healthy adult dogs. PROCEDURES Each dog was anesthetized 4 times with a 7-day washout period between anesthetic episodes. During the first anesthetic episode, the MAC of isoflurane (baseline) was established. During the 3 subsequent anesthetic episodes, the MAC of isoflurane was determined following constant rate infusion of dexmedetomidine (0.5 μg/kg/h), MLK (morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine, 0.6 mg/kg/h), or DMLK (dexmedetomidine, 0.5 μg/kg/h; morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine 0.6 mg/kg/h). Among treatments, MAC of isoflurane was compared by means of a Friedman test with Conover posttest comparisons, and heart rate, direct arterial pressures, cardiac output, body temperature, inspired and expired gas concentrations, arterial blood gas values, and BIS were compared with repeated-measures ANOVA and a Dunn test for multiple comparisons. RESULTS Infusion of dexmedetomidine, MLK, and DMLK decreased the MAC of isoflurane from baseline by 30%, 55%, and 90%, respectively. Mean heart rates during dexmedetomidine and DMLK treatments was lower than that during MLK treatment. Compared with baseline values, mean heart rate decreased for all treatments, arterial pressure increased for the DMLK treatment, cardiac output decreased for the dexmedetomidine treatment, and BIS increased for the MLK and DMLK treatments. Time to extubation and sternal recumbency did not differ among treatments. CONCLUSIONS AND CLINICAL RELEVANCE Infusion of dexmedetomidine, MLK, or DMLK reduced the MAC of isoflurane in dogs.

Comparison of invasive and oscillometric blood pressure measurement techniques in anesthetized sheep, goats, and cattle

OBJECTIVE To determine the level of agreement between an oscillometric (O-NIBP) and an invasive method (IBP) of monitoring arterial blood pressure (ABP) in anesthetized sheep, goats, and cattle. STUDY DESIGN Prospective clinical study. ANIMALS Twenty sheep and goats, 20 cattle weighing < 150 kg body weight, and 20 cattle weighing 150 kg body weight. METHODS Animals were anesthetized and systolic ABP (SABP), mean ABP (MABP), and diastolic ABP (DABP) were measured using IBP and O-NIBP. Differences between IBP and O-NIBP, and 95% limits of agreement (LOA) between SABP, MABP, and DABP values were assessed by the Bland-Altman method. RESULTS Mean difference ± standard deviation (range) between SABP, DABP, and MABP measurements in sheep and goats was 0 ± 16 (-57 to 38) mmHg, 13 ± 16 (-37 to 70) mmHg, and 8 ± 13 (-34 to 54) mmHg, respectively. Mean difference between SABP, DABP, and MABP measurements in small cattle was 0 ± 19 (-37 to 37) mmHg, 6 ± 18 (-77 to 48) mmHg, and 4 ± 16 (-73 to 48) mmHg, respectively. Mean difference between SABP, DABP, and MABP measurements in large cattle was -18 ± 32 (-107 to 71) mmHg, 7 ± 29 (-112 to 63) mmHg, and -5 ± 28 (-110 to 60) mmHg, respectively. The 95% LOAs for SABP, DABP, and MABP were -31 to +31, -19 to +44, and -19 to +34 mmHg, respectively in sheep and goats; were -37 to +37, -19 to +44, and -19 to +34 mmHg, respectively in small cattle; and were -81 to +45, -50 to +63, and -59 to +50 mmHg, respectively in large cattle. CONCLUSIONS Agreement was poor between O-NIBP and IBP monitoring techniques. CLINICAL RELEVANCE Arterial BP should be monitored in anesthetized sheep, goats, and cattle using IBP.

Evaluation of a midazolam-ketamine-xylazine infusion for total intravenous anesthesia in horses.

OBJECTIVE To evaluate the use of midazolam, ketamine, and xylazine for total IV anesthesia (TIVA) in horses. ANIMALS 6 healthy Thoroughbred mares. PROCEDURES Horses were sedated with xylazine (1.0 mg/kg, IV). Anesthesia was induced with midazolam (0.1 mg/kg, IV) followed by ketamine (2.2 mg/kg, IV) and was maintained with an IV infusion of midazolam (0.002 mg/kg/min), ketamine (0.03 mg/kg/min), and xylazine (0.016 mg/kg/min). Horses underwent surgical manipulation and injection of the palmar digital nerves; duration of the infusion was 60 minutes. Additional ketamine (0.2 to 0.4 mg/kg, IV) was administered if a horse moved its head or limbs during procedures. Cardiopulmonary and arterial blood variables were measured prior to anesthesia; at 10, 20, 30, 45, and 60 minutes during infusion; and 10 minutes after horses stood during recovery. Recovery quality was assessed by use of a numeric (1 to 10) scale with 1 as an optimal score. RESULTS Anesthesia was produced for 70 minutes after induction; supplemental ketamine administration was required in 4 horses. Heart rate, respiratory rate, arterial blood pressures, and cardiac output remained similar to preanesthetic values throughout TIVA. Arterial partial pressure of oxygen and oxygen saturation of arterial hemoglobin were significantly decreased from preanesthetic values throughout anesthesia; oxygen delivery was significantly decreased at 10- to 30-minute time points. Each horse stood on its first attempt, and median recovery score was 2. CONCLUSIONS AND CLINICAL RELEVANCE Midazolam, ketamine, and xylazine in combination produced TIVA in horses. Further studies to investigate various dosages for midazolam and ketamine or the substitution of other α(2)-adrenoceptor for xylazine are warranted.

Total Intravenous Anesthesia in Horses

Total intravenous anesthesia (TIVA) is the mainstay of short-term (up to 60 minutes) and field anesthesia in horses. This article discusses the pros and cons of TIVA, commonly used TIVA protocols, and their use, monitoring during, and recovery from, TIVA.