Predictive factors and the effect of phenoxybenzamine on outcome in dogs undergoing adrenalectomy for pheochromocytoma.

BACKGROUND: Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. HYPOTHESIS: Dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs. ANIMALS: Forty-eight dogs that underwent adrenalectomy for pheochromocytoma. METHODS: A retrospective medical record review for dogs that underwent adrenalectomy for pheochromocytoma at a veterinary medical teaching hospital over the period from January 1986 through December 2005. RESULTS: Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly (P = .014) decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age (P = .028), lack of intraoperative arrhythmias (P = .0075), and decreased surgical time (P = .0089). CONCLUSIONS AND CLINICAL IMPORTANCE: Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs.

Changes in cell-mediated immune responses after experimentally-induced anaphylaxis in dogs.

Experimentally-induced type 1 hypersensitivities were induced in normal dogs to either ovalbumin or Ascaris antigen. In vitro and in vivo cell-mediated immune responses were measured before sensitization and again at 1 and 6 days after induction of anaphylaxis by intravenous challenge with antigen. Histamine-modulated lymphocyte functions, such as histamine-induced suppression, histamine co-mitogen induced blastogenesis and the in vivo cutaneous responses to intradermally injected mitogens decreased post anaphylaxis. Spontaneous suppression of the autologous mixed-lymphocyte reaction increased post anaphylaxis. Lymphocyte blastogenic response to Concanavalin A (Con A) decreased at 6 (but not at 1) days post anaphylaxis probably due to a mediator other than histamine. Blastogenesis of 24 h preincubated cells by suboptimal concentration of Con A, declined post anaphylaxis, but Con A-induced suppression was not significantly altered. Dogs with atopic dermatitis have some altered cell-mediated immune responses. Altered histamine-induced and spontaneous suppression, histamine suppression of mitogenesis and decreased contact sensitivity observed in this experimental type 1 hypersensitivity mimicked that of atopic dogs. Increased cutaneous response to mitogens observed in atopic dogs was not reproduced in the type 1 hypersensitive dogs. These findings suggest some of the altered cell-mediated immune functions observed in dogs with atopic dermatitis result from type 1 hypersensitivity. The other abnormalities may be intrinsic to the atopic state.

A computer-derived protocol to aid in selecting medical versus surgical treatment of horses with abdominal pain.

In order to determine which variables are useful in identifying horses with abdominal pain requiring surgery, data were analysed from 219 horses presented at one veterinary teaching hospital. Using multiple stepwise discriminant analysis with a recursive partitioning algorithm, we obtained a decision tree that identifies surgical and non-surgical patients. The prevalence of surgical patients was 79 per cent in this population. The sensitivity, specificity, and positive and negative predictive values of this decision tree were 99 per cent, 55 per cent, 90 per cent and 99 per cent respectively. Compared to the clinical decision, this decision tree yielded more false positives (11 per cent) but almost eliminated false negatives (1 per cent). This decision tree was validated by the jack-knife method and also by evaluation using a new sample in a second veterinary teaching hospital in which the prevalence of surgical patients was 55 per cent. This led to sensitivity, specificity and positive and negative predictive values of 93 per cent, 73 per cent, 81 per cent and 89 per cent respectively.

Clinical applications of quantitative acid-base chemistry.

Stewart used physicochemical principles of aqueous solutions to develop an understanding of variables that control hydrogen ion concentration (H+) in body fluids. He proposed that H+ concentration in body fluids was determined by PCO2, strong ion difference (SID = sum of strong positive ion concentrations minus the sum of the strong anion concentrations) and the total concentration of nonvolatile weak acid (Atot) under normal circumstances. Albumin is the major weak acid in plasma and represents the majority of Atot. These 3 variables were defined as independent variables, which determined the values of all other relevant variables (dependent) in plasma, including H+. The major strong ions in plasma are sodium and chloride. The difference between Na+ and Cl- may be used as an estimation of SID. A decrease in SID below normal results in acidosis (increase in H+) and an increase in SID above normal results in alkalosis (decrease in H+). Unidentified strong anions such as lactate will decrease the SID, if present. Equations developed by Fencl allow Stewart's work to be easily applied clinically for evaluating the metabolic (nonrespiratory) contribution to acid-base balance. This approach separates the net metabolic abnormality into components, and allows one to easily detect mixed metabolic acid-base abnormalities. The Fencl approach provides insight into the nature and severity of the disturbances that exist in the patient. Sodium, chloride, protein, and unidentified anion derangements may contribute to the observed metabolic acid-base imbalance.

The noxious effects of electroimmobilization in adult Holstein cows: a pilot study.

Ten adult Holstein cows were used in an experiment to determine whether the induction of electroimmobilization was a noxious event. The cows were halter trained and accustomed to being led into a set of stocks. The time taken for the cattle to walk the last ten metres into the stocks was recorded. The heart rate of the cow was recorded for a three minute period prior to a ten second exposure to a high pitched sound (the conditioning stimulus). Measurements were collected for three repetitions and then the cows were assigned to two groups of five. One group was immobilized for 30 seconds using a commercial electroimmobilizer, the other group was not treated. This procedure was repeated ten times over a period of eight days. The cows were then exposed to the conditioning stimulus and their response observed. The treated group took significantly (P less than 0.05) longer to get into the stocks and the regression slopes for heart rate were significantly different from the control group. The treated cows responded to the conditioning stimulus at five and nine months after the end of the conditioning period. Adult Holstein cows regarded electroimmobilization as a noxious event and were very strongly conditioned to this stimulus.

Evaluation of the interaction of mu and kappa opioid agonists on locomotor behavior in the horse.

This study was designed to determine the interactive effects of mu and kappa opioid agonists on locomotor behavior in the horse. Three doses of a mu agonist, fentanyl (5, 10, 20 micrograms/kg) and a kappa agonist U50,488H (30, 60, 120 micrograms/kg) were administered in a random order to six horses. Locomotor activity was measured using a two minute footstep count. Each dose of U50,488H was then combined with 20 micrograms/kg of fentanyl to determine the interactive effects of the drugs on locomotor activity. A significant increase in locomotor activity was seen with 20 micrograms/kg of fentanyl and all the drug combinations. The combination of U50,488H with fentanyl resulted in an earlier onset of locomotor activity. At the highest doses of the combination (U50,488H 120 micrograms/kg, fentanyl 20 micrograms/kg), the duration of locomotor activity was significantly increased when compared to the other doses. We conclude that locomotor activity is maintained or enhanced in horses when a receptor specific kappa agonist is combined with a mu receptor agonist.

Evaluation of acepromazine/meperidine/atropine premedication followed by thiopental anesthesia in the cat.

Cardiopulmonary function was assessed in healthy cats premedicated with intramuscular acepromazine, meperidine, atropine combination (premix), followed by induction and maintenance with intravenous thiopental for 30 min. Cardiac output by thermodilution, heart rate, blood pressure and blood gas analysis were evaluated over 120 min. A minor degree of respiratory depression was noted in the cats. Cardiac index (cardiac output/kg) was significantly depressed following thiopental induction and for the entire 120 min studied. Stroke volume was significantly reduced after premix administration and for 90 min posthiopental induction. No significant change in heart rate, systemic vascular resistance or blood pressure was observed. Significant cardiovascular depression was produced by the premedicant, and this persisted following thiopental anesthesia.

Cardiopulmonary effects of xylazine and yohimbine in laterally recumbent sheep.

The effects of yohimbine (0.125 mg/kg) on cardiopulmonary parameters in six adult, xylazine treated (0.15 mg/kg), laterally recumbent sheep were studied. Following collection of baseline data, xylazine was administered intravenously and data were collected five and fifteen minutes later. At twenty minutes post-xylazine either yohimbine (0.125 mg/kg) or saline was given and further collection of data occurred at 25, 30, 40 and 50 minutes. Xylazine administration resulted in significant (P less than 0.05) respiratory depression, as reflected by a decrease in arterial oxygen partial pressure (PaO2). No significant changes in haemodynamic variables were observed. Yohimbine produced a significant improvement in PaO2 at the 50 minute period and abolished the paradoxical respiratory pattern when present. The results indicated that yohimbine can be used as an antagonist to control the duration of xylazine induced respiratory depression, although the degree of reversal was less than is clinically desirable.

Evaluation of a xylazine-ketamine hydrochloride combination in the cat.

Cardiopulmonary function was assessed in healthy cats given a xylazine-ketamine hydrochloride combination intramuscularly. Cardiac output, heart rate, stroke volume and cardiac index were significantly decreased. Systolic, diastolic and mean arterial blood pressure were also significantly decreased. Systemic vascular resistance and central venous pressure were significantly increased. Blood gas values remained stable. In conclusion, significant cardiovascular depression was noted in normal cats given the xylazine-ketamine combination at the dosages listed.

Antagonism of xylazine induced sedation by idazoxan in calves.

Idazoxan was studied at three dose rates to assess its potential as an antagonist to xylazine. Calves in the study group were initially given xylazine at a dose rate of 0.2 mg/kg intravenously followed 12 minutes later by idazoxan at a dose rate of either 0.05, 0.075 or 0.10 mg/kg intravenously. A control group received a saline injection instead of idazoxan. All three dose levels of idazoxan successfully reversed the xylazine induced central nervous depression and all animals stood within two minutes of injection. No residual signs of sedation were noticed and relapse did not occur. In addition idazoxan was successful in reversing respiratory and cardiovascular depression produced by xylazine. The results indicated that idazoxan may be used for rapid reversal of xylazine induced sedation in calves.

Cardiopulmonary effects of a halothane/oxygen combination in healthy cats.

The effects of a halothane/oxygen combination on the cardiopulmonary function of 11 healthy cats were studied. Test parameters included cardiac output, measured via thermo-dilution, heart rate, respiratory rate, arterial blood pressure (systolic, diastolic and mean) and blood gas analysis. Values for systemic vascular resistance, cardiac index and stroke volume were calculated from these data. Cardiac output, cardiac index, heart rate, stroke volume, arterial blood pressure (systolic, diastolic and mean) and arterial blood pH were significantly decreased (p less than 0.001). Respiratory rate was also significantly decreased (p less than 0.007) with arterial CO2 tension being significantly increased (p less than 0.001). Statistically significant changes, where seen, persisted for the duration of the anesthetic period. Arterial O2 tension and systemic vascular resistance remained unchanged. All parameters returned to near pretest values within 30 minutes following cessation of halothane anesthesia.

Cardiopulmonary effects of a ketamine hydrochloride/acepromazine combination in healthy cats.

The effect of a ketamine hydrochloride/acepromazine combination on the cardiopulmonary function of 11 healthy cats was studied. Test parameters included cardiac output, measured by thermodilution, heart rate, respiratory rate, arterial blood pressure (systolic, diastolic and mean) and arterial blood gas analysis. Values for systemic vascular resistance, cardiac index and stroke volume were calculated. The cardiac output, cardiac index, stroke volume, arterial blood pressure and arterial blood pH decreased significantly (p less than 0.006). The arterial CO2 increased significantly (p less than 0.006). All changes occurred during the five to 45 minute postinduction time period. The heart rate, respiratory rate, arterial O2 and systemic vascular resistance were not significantly altered. The anesthetic regime maintained an adequate plane of surgical anesthesia for 30-45 minutes.

Effects of saffan on cardiopulmonary function in healthy cats.

The effects of saffan on cardiopulmonary function were evaluated in eight healthy adult cats. Measured values were cardiac output by thermodilution, heart rate by electrocardiogram, arterial blood gases, respiratory rate and systolic, diastolic and mean arterial blood pressures by arterial catheterization. Calculated values included cardiac index, stroke volume and systemic vascular resistance. Statistical analysis employed paired t-tests comparing pre saffan anesthetic induction and post saffan anesthetic parameters over a 120 minute time sequence. Thirty min after saffan induction, significant depression in cardiac output was evident while stroke volume was significantly depressed at 45 and 60 min, systolic blood pressure at 15 min and respiratory rate at 5, 10 and 15 min. No significant changes occurred in cardiac index, heart rate, arterial blood gases, diastolic and mean arterial blood pressure or systemic vascular resistance. It was concluded that saffan causes significant depression of cardiopulmonary function in normal adult cats.

The cardiovascular sparing effect of fentanyl and atropine, administered to enflurane anesthetized dogs.

Cardiovascular effects of high dose opioid together with low dose inhalant were compared with inhalant alone to determine whether opioid/inhalant techniques were less depressant on the cardiovascular system. The effects of positive pressure ventilation and increasing heart rate to a more physiological level were also studied. Cardiovascular measurements recorded during administration of enflurane at 1.3 minimum alveolar concentration (MAC; 2.89 +/- 0.02%) to spontaneously breathing dogs (time 1) and during controlled ventilation [arterial carbon dioxide tension at 40 +/- 3 mmHg (time 2)] were similar. At time 2, mixed venous oxygen tension and arterial and mixed venous carbon dioxide tensions were significantly decreased, while arterial and mixed venous pH were significantly increased compared to measurements at time 1. After administration of fentanyl to achieve plasma fentanyl concentration of 71.7 +/- 14.4 ng/mL and reduction of enflurane concentration to yield 1.3 MAC multiple (0.99 +/- 0.01%), heart rate significantly decreased, while mean arterial pressure, central venous pressure, stroke index, and systemic vascular resistance index increased compared to measurements taken at times 1 and 2. Pulmonary arterial occlusion pressure was significantly increased compared to measurements taken at time 2. After administration of atropine until heart rate was 93 +/- 5 beats/min (plasma fentanyl concentration 64.5 +/- 13.5 ng/mL) heart rate, mean arterial pressure, cardiac index, oxygen delivery index, and venous admixture increased significantly compared to values obtained at all other times.(ABSTRACT TRUNCATED AT 250 WORDS)

A computer-derived protocol using recursive partitioning to aid in estimating prognosis of horses with abdominal pain in referral hospitals.

In order to determine which variables are useful and accurate in estimating prognosis in horses with abdominal pain, data were analyzed from 231 horses presented at a veterinary teaching hospital. Using multiple stepwise discriminant analysis in a recursive partition model, we obtained a decision protocol that identified survivors and nonsurvivors. The prevalence of survivors was 61% in this population. The sensitivity, specificity, and positive and negative predictive values of this model were 71, 83, 87 and 65%, respectively. This decision protocol was validated by Jackknife classification and also by evaluation with a referral population of 100 horses in which the prevalence of survivors was 83%. This led to sensitivity, specificity, and positive and negative predictive values of 83, 78, 94 and 50%, respectively.

Systemic effects of topical and subconjunctival ophthalmic atropine in the horse.

OBJECTIVE: To identify any systemic effects of topical and subconjunctival administration of atropine sulfate in the horse. Animals studied Six mature grade horses were treated hourly in one eye with topical ophthalmic atropine drops for 24 h. Five horses were treated subconjunctivally in one eye with 3 mg of atropine sulfate. Procedures Pupillary light reflexes, pupil size, electrocardiographic parameters, girth measurements, intestinal motility, and clinical signs of abdominal pain were monitored. RESULTS: Alteration in auscultated gut motility and clinical signs of abdominal pain were the most sensitive indicators of the systemic manifestations of the topically applied atropine. Gut motility was absent in all horses for periods of 2-18 h in all four abdominal quadrants in horses given topically administered atropine. Signs of abdominal pain were observed in four of six horses that received topical atropine. In the subconjunctival test study, gut motility was absent in three horses for periods of 3-7 h. Uniocular subconjunctival injection of 3 mg atropine sulfate produced signs of abdominal pain in one of six horses. Conclusion The ophthalmic administration of atropine can affect gut motility and induce signs of colic in selected horses.

Humaneness of an electroimmobilization unit for cattle.

Application of an electroimmobilization unit was evaluated in adult Holstein cows. Twenty cows were acclimated to being led from their stanchion, down a corridor, and into a set of stocks. After the first 7 sessions when the cows were exposed to a conditioning stimulus, cows were assigned to 4 groups of 5. One group served as a control group, 2 groups were given a high or low stimulus with the electroimmobilizer immediately after the conditioning stimulus, and 1 group was given saline solution IM. These stimulus treatments were repeated 10 times, followed by an extinction trial of 10 sessions when stimulus treatments were stopped. The time taken to enter the stocks, the heart rate before and after treatment was given, and an assessment of the physical reaction were used as measurements of the response of each cow. At the end of the stimulus treatment phase, cows in high- or low-stimulus groups had significantly greater (P less than 0.05) reluctance to enter the stocks and had higher heart rates during the period before they were given the stimulus. These cows also had significantly greater (P less than 0.05) physical reaction than did cows in the control group and the group given the IM injection. Cows given the IM injection demonstrated significantly (P less than 0.05) greater physical reaction than did cows in the control group. Seemingly, electroimmobilization was a noxious event and was more noxious than a simple IM injection.

Influence of preinduction methoxamine, lactated Ringer solution, or hypertonic saline solution infusion or postinduction dobutamine infusion on anesthetic-induced hypotension in horses.

A controlled study of the cardiovascular responses in horses anesthetized with acepromazine (0.05 mg/kg of body weight, IV), guaifenesin (100 mg/kg, IV), thiamylal (5.0 mg/kg, IV), and halothane in O2 (1.2 to 1.4% end-expired concentration) was performed to determine whether hypotension could be prevented by use of various treatments. Six horses were given 5 treatments in a randomized sequence: no treatment (control), methoxamine (0.04 mg/kg, IV), lactated Ringer solution (20.0 ml/kg, IV), 7.5% hypertonic saline solution (4.0 ml/kg, IV), or constant infusion of dobutamine (5.0 mg/kg/min, IV) during anesthesia. Heart rate, ECG, blood pressure, central venous pressure, cardiac output, blood gas analysis, PVC, and plasma total protein concentration were measured during the study. Compared with the control value, an increase in blood pressure during halothane administration was observed after administration of lactated Ringer solution, hypertonic saline solution, or dobutamine (P less than 0.05). The improved blood pressure response to hypertonic saline solution and dobutamine was related to an increase in cardiac output, which was statistically significant (P less than 0.05). Other statistically significant differences in cardiopulmonary responses among treatments were not observed during anesthesia. The PCV was increased in response to dobutamine infusion, and plasma total protein concentration was reduced in response to administration of hypertonic saline or lactated Ringer solution.

Cardiovascular effects of equipotent isoflurane and alfentanil/isoflurane minimum alveolar concentration multiple in cats.

OBJECTIVE: To determine whether administration of opioids to anesthetized cats induced less cardiovascular depression than that induced by an equivalent amount of anesthetic alone, and to measure endocrine responses to a noxious stimulus. ANIMALS: 6 healthy female cats. PROCEDURE: Anesthesia was induced with isoflurane and was maintained for 60 minutes at 1.3 isoflurane MAC. Blood gas tensions, pH, and plasma alfentanil and hormone concentrations, blood pressures, and cardiac output were measured. A noxious stimulus was applied for 5 minutes, while blood acquisition and measurements were repeated. Alfentanil was administered i.v. to achieve estimated plasma concentration of 500 ng/ml, and end-tidal isoflurane concentration was reduced by 35%. After another 60 minutes, blood was obtained and measurements were taken, then a second 5-minute noxious stimulus was applied while blood acquisition and measurements were retaken. RESULTS: Alfentanil administration and reduction of isoflurane concentration significantly increased body temperature, heart rate, mean arterial pressure, mean pulmonary arterial pressure, stroke index, cardiac index, hemoglobin, oxygen delivery index, PvO2 and PvCO2, dopamine, epinephrine (EPI), norepinephrine (NOREPI), and cortisol values, and significantly decreased arterial and venous pH. Application of a noxious stimulus significantly increased heart rate, stroke index, cardiac index, PaO2, oxygen delivery index, arterial and venous pH, and NOREPI values, and decreased bicarbonate, PaCO2, PvCO2, and EPI values. Alfentanil administration blunted cardiac index, PaCO2, oxygen delivery index, arterial pH, PaO2, and EPI, and NOREPI responses to a noxious stimulus. CONCLUSIONS: Compared with isoflurane alone, alfentanil administration and reduction of isoflurane MAC improved cardiovascular variables, and blunted respiratory, hormonal, and most hemodynamic responses to a noxious stimulus in cats. CLINICAL RELEVANCE: Use of the balanced opioid anesthesia regimen induced some beneficial effects in healthy cats; effects were similar to, although greater in nature, than effects induced by a noxious stimulus.

Effect of alfentanil on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To evaluate effect of incremental doses of alfentanil on isoflurane minimum alveolar concentration (MAC) in cats to determine whether alfentanil reduces isoflurane MAC and, if so, maximal isoflurane MAC reduction. ANIMALS: 6 healthy spayed female cats. PROCEDURE: Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood for measurement of gas tensions, pH, and plasma alfentanil concentration and to measure arterial blood pressure. Isoflurane MAC was determined in triplicate, and alfentanil was administered i.v., using a computer-driven syringe pump to achieve estimated plasma alfentanil concentrations of 50, 100, 250, 500, 750, and 1,000 ng/ml; isoflurane MAC was determined at each alfentanil concentration. Cats were allowed to recover, and the process was graded as poor, good, or excellent. RESULTS: Alfentanil had a significant dose effect on isoflurane MAC reduction. Significant regression was found for normalized isoflurane MAC versus estimated plasma alfentanil concentration. A quadratic term was necessary to fit the model and, using this curve, MAC reduction (35.0 +/- 6.6%) was estimated to be maximal at a plasma alfentanil concentration of 500 ng/ml. Significant differences were evident in rectal temperature, bicarbonate concentration, base deficit, arterial carbon dioxide and oxygen tensions, and arterial pH between isoflurane alone and some plasma alfentanil concentration and the corresponding reduction in isoflurane concentration. CONCLUSIONS: Infusion of alfentanil resulted in maximal MAC reduction midway between that reported for horses and dogs. At such plasma alfentanil concentration, adverse effects were minimal, but included increase in rectal temperature, metabolic acidosis, and decrease in PaO2. Provided cats were not handled during the recovery period, recovery was smooth and quiet. CLINICAL RELEVANCE: Infusion of alfentanil decreases the need for potent inhalant anesthetics in cats and could potentially be a clinically useful anesthetic regimen in sick cats.