Effects of acepromazine or dexmedetomidine on fentanyl disposition in dogs during recovery from isoflurane anesthesia.

OBJECTIVE: To describe fentanyl pharmacokinetics during isoflurane anesthesia and on recovery from anesthesia with concurrent administration of acepromazine, dexmedetomidine or saline in dogs. STUDY DESIGN: Experimental blinded, randomized, crossover study. ANIMALS: Seven adult hound dogs. METHODS: Dogs were administered intravenous (IV) fentanyl as a bolus (5 µg kg(-1)) followed by an infusion (5 µg kg(-1) hour(-1)) for 120 minutes during isoflurane anesthesia and emergence from anesthesia, and for 60 minutes after extubation during recovery from anesthesia. At the time of extubation, dexmedetomidine (2.5 µg kg(-1)), acepromazine (0.05 mg kg(-1)) or saline were administered IV. Venous blood was sampled during the maintenance and recovery periods. Fentanyl plasma concentrations were measured using high-performance liquid chromatography-mass spectrometry and population pharmacokinetic analyses were performed. RESULTS: Mean fentanyl plasma concentrations were 1.6-4.5 ng mL(-1) during isoflurane anesthesia and 1.6-2.0 ng mL(-1) during recovery from anesthesia. Recovery from isoflurane anesthesia without sedation was associated with an increase in the volume of the central compartment from 0.80 to 1.02 L kg(-1). After administration of acepromazine, systemic clearance of fentanyl increased from 31.5 to 40.3 mL minute(-1) kg(-1) and the volume of the central compartment increased from 0.70 to 0.94 L kg(-1). Administration of dexmedetomidine did not significantly change fentanyl pharmacokinetics. Inter-individual variability for fentanyl parameter estimates in all treatments ranged from 2.2% to 54.5%, and residual error ranged from 6.3% to 13.4%. CONCLUSIONS AND CLINICAL RELEVANCE: The dose rates of fentanyl used in this study achieved previously established analgesic plasma concentrations for the duration of the infusion. Despite alterations in fentanyl pharmacokinetics, differences in fentanyl plasma concentrations among treatments during recovery from anesthesia were small and were unlikely to be of clinical significance.

Effects of hypercapnia, hypocapnia, and hyperoxemia on brain morphometrics determined by use of T1-weighted magnetic resonance imaging in isoflurane-anesthetized dogs.

OBJECTIVE: To evaluate the effects of various combinations of PaCO2 and PaO2 values on brain morphometrics. ANIMALS: 6 healthy adult dogs. PROCEDURES: A modified Latin square design for randomization was used. Dogs were anesthetized with propofol (6 to 8 mg/kg, IV), and anesthesia was maintained with isoflurane (1.7%) and atracurium (0.2 mg/kg, IV, q 30 min). Three targeted values of PaCO2 (20, 40, and 80 mm Hg) and 2 values of PaO2 (100 and 500 mm Hg) were achieved in each dog, yielding 6 combinations during a single magnetic resonance (MR) imaging session. When the endpoints were reached, dogs were given at least 5 minutes for physiologic variables to stabilize before T1-weighted MR images were obtained. Total brain volume (TBV) and lateral ventricular volume (LVV) were calculated from manually drawn contours of areas of interest by use of a software program, with each dog serving as its own control animal. Three blinded investigators subjectively evaluated the lateral ventricular size (LVS) and the cerebral sulci width (CSW). Brain morphometric values were compared among the target blood gas states. RESULTS: No significant differences in TBV were found among target states. The LVV was significantly greater during hypocapnia, compared with hypercapnia at the same PaO2 value. With regard to the subjective evaluations, there were no significant differences among evaluators or among combinations of PaO2 and PaCO2 values. CONCLUSIONS AND CLINICAL RELEVANCE: The changes observed in LVV during hypocapnia and hypercapnia may serve as a potential confounding factor when neuromorphometric evaluations are performed in anesthetized dogs.

Effects of hypercapnia, hypocapnia, and hyperoxemia on blood oxygenation level-dependent signal intensity determined by use of susceptibility-weighted magnetic resonance imaging in isoflurane-anesthetized dogs.

OBJECTIVE: To assess the effects of alterations in PaCO(2) and PaO(2) on blood oxygenation level-dependent (BOLD) signal intensity determined by use of susceptibility-weighted magnetic resonance imaging in brains of isoflurane-anesthetized dogs. ANIMALS: 6 healthy dogs. PROCEDURES: In each dog, anesthesia was induced with propofol (6 to 8 mg/kg, IV) and maintained with isoflurane (1.7%) and atracurium (0.2 mg/kg, IV, q 30 min). During 1 magnetic resonance imaging session in each dog, targeted values of PaCO(2) (20, 40, or 80 mm Hg) and PaO(2) (100 or 500 mm Hg) were combined to establish 6 experimental conditions, including a control condition (PaCO(2), 40 mm Hg; PaO(2), 100 mm Hg). Dogs were randomly assigned to different sequences of conditions. Each condition was established for a period of >or= 5 minutes before susceptibility-weighted imaging was performed. Signal intensity was measured in 6 regions of interest in the brain, and data were analyzed by use of an ANCOVA and post hoc Tukey-Kramer adjustments. RESULTS: Compared with control condition findings, BOLD signal intensity did not differ significantly in any region of interest. However, signal intensities in the thalamus and diencephalic gray matter decreased significantly during both hypocapnic conditions, compared with all other conditions except for the control condition. CONCLUSIONS AND CLINICAL RELEVANCE: In isoflurane-anesthetized dogs, certain regions of gray matter appeared to have greater cerebrovascular responses to changes in PaCO(2) and PaO(2) than did others. Both PaO(2) and PaCO(2) should be controlled during magnetic resonance imaging procedures that involve BOLD signaling and taken into account when interpreting findings.

Cardiopulmonary effects of diazepam-ketamine-isoflurane or xylazine-ketamine-isoflurane during abdominal surgery in foals.

OBJECTIVE: To evaluate cardiopulmonary effects of anesthetic induction with diazepam and ketamine or xylazine and ketamine, with subsequent maintenance of anesthesia with isoflurane, in foals undergoing abdominal surgery. ANIMALS: 17 pony foals. PROCEDURES: Foals underwent laparotomy at 7 to 15 days of age and laparoscopy 7 to 10 days later. Foals were randomly assigned to receive diazepam, ketamine, and isoflurane (D/K/Iso; n = 8) or xylazine, ketamine, and isoflurane (X/K/Iso; 9) for both procedures. RESULTS: During anesthesia for laparotomy, cardiac index, and mean arterial blood pressure ranged from 110 to 180 mL/kg/min and 57 to 81 mm Hg, respectively, in the D/K/Iso group and 98 to 171 mL/kg/min and 50 to 66 mm Hg, respectively, in the X/K/Iso group. Cardiac index, heart rate, and arterial blood pressures were significantly higher in the D/K/Iso group, compared with the X/K/Iso group. During anesthesia for laparoscopy, cardiac index and mean arterial blood pressure ranged from 85 to 165 mL/kg/min and 67 to 83 mm Hg, respectively, in the D/K/Iso group, and 98 to 171 mL/kg/min and 48 to 67 mm Hg, respectively, in the X/K/Iso group. Heart rates and arterial blood pressures were significantly higher in the D/K/Iso group, compared with the X/K/Iso group. There were no significant differences between groups during either experimental period for percentage end-tidal isoflurane, arterial blood gas partial pressures, or pH values. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthesia of foals for abdominal surgery with D/K/Iso was associated with less hemodynamic depression than with X/K/Iso.

Sedative and cardiopulmonary effects of medetomidine hydrochloride and xylazine hydrochloride and their reversal with atipamezole hydrochloride in calves.

OBJECTIVE: To assess the sedative and cardiopulmonary effects of medetomidine and xylazine and their reversal with atipamezole in calves. ANIMALS: 25 calves. PROCEDURES: A 2-phase (7-day interval) study was performed. Sedative characteristics (phase I) and cardiopulmonary effects (phase II) of medetomidine hydrochloride and xylazine hydrochloride administration followed by atipamezole hydrochloride administration were evaluated. In both phases, calves were randomly allocated to receive 1 of 4 treatments IV: medetomidine (0.03 mg/kg) followed by atipamezole (0.1 mg/kg; n = 6), xylazine (0.3 mg/kg) followed by atipamezole (0.04 mg/kg; 7), medetomidine (0.03 mg/kg) followed by saline (0.9% NaCl; 6) solution (10 mL), and xylazine (0.3 mg/kg) followed by saline solution (10 mL; 6). Atipamezole or saline solution was administered 20 minutes after the first injection. Cardiopulmonary variables were recorded at intervals for 35 minutes after medetomidine or xylazine administration. RESULTS: At the doses evaluated, xylazine and medetomidine induced a similar degree of sedation in calves; however, the duration of medetomidine-associated sedation was longer. Compared with pretreatment values, heart rate, cardiac index, and PaO(2) decreased, whereas central venous pressure, PaCO(2), and pulmonary artery pressures increased with medetomidine or xylazine. Systemic arterial blood pressures and vascular resistance increased with medetomidine and decreased with xylazine. Atipamezole reversed the sedative and most of the cardiopulmonary effects of both drugs. CONCLUSIONS AND CLINICAL RELEVANCE: At these doses, xylazine and medetomidine induced similar degrees of sedation and cardiopulmonary depression in calves, although medetomidine administration resulted in increases in systemic arterial blood pressures. Atipamezole effectively reversed medetomidine- and xylazine-associated sedative and cardiopulmonary effects in calves.

Cardiopulmonary effects of anesthetic induction with thiopental, propofol, or a combination of ketamine hydrochloride and diazepam in dogs sedated with a combination of medetomidine and hydromorphone.

OBJECTIVE: To evaluate the cardiopulmonary effects of anesthetic induction with thiopental, propofol, or ketamine hydrochloride and diazepam in dogs sedated with medetomidine and hydromorphone. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs received 3 induction regimens in a randomized crossover study. Twenty minutes after sedation with medetomidine (10 microg/kg, IV) and hydromorphone (0.05 mg/kg, IV), anesthesia was induced with ketamine-diazepam, propofol, or thiopental and then maintained with isoflurane in oxygen. Measurements were obtained prior to sedation (baseline), 10 minutes after administration of preanesthetic medications, after induction before receiving oxygen, and after the start of isoflurane-oxygen administration. RESULTS: Doses required for induction were 1.25 mg of ketamine/kg with 0.0625 mg of diazepam/kg, 1 mg of propofol/kg, and 2.5 mg of thiopental/kg. After administration of preanesthetic medications, heart rate (HR), cardiac index, and PaO(2) values were significantly lower and mean arterial blood pressure, central venous pressure, and PaCO(2) values were significantly higher than baseline values for all regimens. After induction of anesthesia, compared with postsedation values, HR was greater for ketamine-diazepam and thiopental regimens, whereas PaCO(2) tension was greater and stroke index values were lower for all regimens. After induction, PaO(2) values were significantly lower and HR and cardiac index values significantly higher for the ketamine-diazepam regimen, compared with values for the propofol and thiopental regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine and hydromorphone caused dramatic hemodynamic alterations, and at the doses used, the 3 induction regimens did not induce important additional cardiovascular alterations. However, administration of supplemental oxygen is recommended.

Effects of a peripheral alpha2 adrenergic-receptor antagonist on the hemodynamic changes induced by medetomidine administration in conscious dogs.

OBJECTIVE: To evaluate the effects of administration of a peripheral alpha(2)-adrenergic receptor antagonist (L-659,066), with and without concurrent administration of glycopyrrolate, on cardiopulmonary effects of medetomidine administration in dogs. ANIMALS: 6 healthy adult dogs. PROCEDURES: Dogs received saline (0.9% NaCl) solution (saline group), L-659,066 (group L), or L-659,066 with glycopyrrolate (group LG). These pretreatments were followed 10 minutes later by administration of medetomidine in a randomized crossover study. Hemodynamic measurements and arterial and mixed-venous blood samples for blood gas analysis were obtained prior to pretreatment, 5 minutes after pretreatment, and after medetomidine administration at intervals up to 60 minutes. RESULTS: After pretreatment in the L and LG groups, heart rate, cardiac index, and partial pressure of oxygen in mixed-venous blood (PvO2) values were higher than those in the saline group. After medetomidine administration, heart rate, cardiac index, and PvO2 were higher and systemic vascular resistance, mean arterial blood pressure, and central venous pressure were lower in the L and LG groups than in the saline group. When the L and LG groups were compared, heart rate was greater at 5 minutes after medetomidine administration, mean arterial blood pressure was greater at 5 and 15 minutes after medetomidine administration, and central venous pressure was lower during the 60-minute period after medetomidine administration in the LG group. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of L-659,066 prior to administration of medetomidine reduced medetomidine-induced cardiovascular changes in healthy dogs. No advantage was detected with concurrent administration of L-659,066 and glycopyrrolate.

Cardiopulmonary effects of administration of a combination solution of xylazine, guaifenesin, and ketamine or inhaled isoflurane in mechanically ventilated calves.

OBJECTIVE: To compare the cardiopulmonary effects of administration of a solution of xylazine, guaifenesin, and ketamine (XGK) or inhaled isoflurane in mechanically ventilated calves undergoing surgery. ANIMALS: 13 male calves 2 to 26 days of age. Procedures-In calves in the XGK group, anesthesia was induced (0.5 mL/kg) and maintained (2.5 mL/kg/h) with a combination solution of xylazine (0.1 mg/mL), guaifenesin (50 mg/mL), and ketamine (1.0 mg/mL). For calves in the isoflurane group, anesthesia was induced and maintained with isoflurane in oxygen. The rates of XGK infusion and isoflurane administration were adjusted to achieve suitable anesthetic depth. All calves received 100% oxygen and were mechanically ventilated to maintain end-tidal carbon dioxide concentrations from 35 to 40 mm Hg and underwent laparoscopic bladder surgery through an abdominal approach. Cardiopulmonary variables were measured before induction and at intervals up to 90 minutes after anesthetic induction. RESULTS: The quality of induction was excellent in all calves. The XGK requirements were 0.57 +/- 0.18 mL/kg and 2.70 +/- 0.40 mL/kg/h to induce and maintain anesthesia, respectively. Heart rate was significantly lower than baseline throughout the anesthetic period in the XGK group. Systolic arterial blood pressure was significantly higher in the XGK group, compared with the isoflurane group, from 5 to 90 minutes. Cardiac index was lower than baseline in both groups. Differences between groups in cardiac index and arterial blood gas values were not significant. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of XGK resulted in excellent anesthetic induction and maintenance with cardiopulmonary alterations similar to those associated with isoflurane in mechanically ventilated calves.

Postoperative effects of anesthesia and surgery on resting energy expenditure in horses as measured by indirect calorimetry.

In this study, we aimed to define the effects of anesthesia and surgery on the resting energy expenditure of horses in experimental conditions. Six horses were used in a longitudinal study with 2 study periods: before and after anesthesia and surgery. Every horse underwent a standard 90-min ventral midline exploratory laparotomy. Oxygen uptake (VO2) and carbon dioxide output (VCO2) were measured, with the use of a closed-circuit spirometry system, on 5 consecutive days immediately before and after the surgery. In 3 consecutive 5-min periods each day, the expired air was collected in a Collins spirometer. Samples of the expired gas were drawn from the spirometer through a drying column into O2 and CO2 analyzers. Resting energy expenditure was calculated as [(VO2 STPD*3.94) + (VCO2 STPD*1.11)]*1.44. This study showed that anesthesia and ventral midline exploratory laparotomy in experimental conditions increase the postoperative caloric demand in horses by an average of 1.0 Mcal/d, which represents approximately a 10% increase (P = 0.03). Additional studies in critically ill horses after surgery are needed to determine their caloric needs and to optimize their nutritional management.

Comparison of hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of anesthesia with isoflurane and halothane in horses undergoing arthroscopic surgery.

OBJECTIVE: To compare hemodynamic, clinicopathologic, and gastrointestinal motility effects and recovery characteristics of halothane and isoflurane in horses undergoing arthroscopic surgery. ANIMALS: 8 healthy adult horses. PROCEDURE: Anesthesia was maintained with isoflurane or halothane (crossover study). At 6 intervals during anesthesia and surgery, cardiopulmonary variables and related derived values were recorded. Recovery from anesthesia was assessed; gastrointestinal tract motility was subjectively monitored for 72 hours after anesthesia. Horses were administered chromium, and fecal chromium concentration was used to assess intestinal transit time. Venous blood samples were collected for clinicopathologic analyses before and 2, 24, and 48 hours after anesthesia. RESULTS: Compared with halothane-anesthetized horses, cardiac index, oxygen delivery, and heart rate were higher and systemic vascular resistance was lower in isoflurane-anesthetized horses. Mean arterial blood pressure and the dobutamine dose required to maintain blood pressure were similar for both treatments. Duration and quality of recovery from anesthesia did not differ between treatments, although the recovery periods were somewhat shorter with isoflurane. After isoflurane anesthesia, gastrointestinal motility normalized earlier and intestinal transit time of chromium was shorter than that detected after halothane anesthesia. Compared with isoflurane, halothane was associated with increases in serum aspartate transaminase and glutamate dehydrogenase activities, but there were no other important differences in clinicopathologic variables between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with halothane, isoflurane appears to be associated with better hemodynamic stability during anesthesia, less hepatic and muscle damage, and more rapid return of normal intestinal motility after anesthesia in horses undergoing arthroscopic procedures.

In vivo interaction of pulmonary intravascular macrophages with activated platelets in microvessels of equine lung after multiple exposures to halothane, isoflurane, and thiamylal: a comparative ultrastructural and cytochemical study.

The pulmonary intravascular macrophages (PIMs) of equines contain a unique electron-dense surface coat that is predominantly composed of lipoproteins. A single exposure of inhalatory halothane causes mobilization of the surface coat into the endocytotic system of the PIMs, followed by expansion of the Golgi apparatus and its enrichment with acid phosphatase. Simultaneously, the cells of the lymphocytic series show hyperplasia in the form of mitotic changes inside the microvascular compartment of the lung. Halothane is known to cause acute and chronic hepatotoxicity because of its biotransformation into trifluoroacytelated polypeptides. The present study was designed to examine the comparative effects of reexposures of inhalatory doses of halothane, isoflurane, and the intravenous barbiturate thiamylal sodium in ponies to evoke a stronger response in the PIMs after four exposures at increasing intervals of 1, 2, and 6 weeks. Ultrastructural and cytochemical evidence is presented that halothane induced translocation of the surface coat into the vacuolar system of the PIMs, followed by expansion of the Golgi apparatus and its enrichment with acid phosphatase. The cell membrane was thrown into extraordinary lamellipodial extensions, which enabled the PIMs to interact with platelets within the narrow confines of the pulmonary capillaries. The relationship between PIMs and platelets developed into large platelet aggregates. Isoflurane and thiamylal sodium did not affect the circulating platelets, although the surface coat was translocated into the endolysosomes in both situations. Although isoflurane is a lipid-soluble inhalant anesthetic similar to halothane, it is subject to very little biotransformation after use and in the present model demonstrates no immune response.

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

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

Comparison of arterial pressure waveform analysis with the lithium dilution technique to monitor cardiac output in anesthetized dogs.

OBJECTIVE: To assess agreement between arterial pressure waveform-derived cardiac output (PCO) and lithium dilution cardiac output (LiDCO) systems in measurements of various levels of cardiac output (CO) induced by changes in anesthetic depth and administration of inotropic drugs in dogs. ANIMALS: 6 healthy dogs. PROCEDURE: Dogs were anesthetized on 2 occasions separated by at least 5 days. Inotropic drug administration (dopamine or dobutamine) was randomly assigned in a crossover manner. Following initial calibration of PCO measurements with a LiDCO measurement, 4 randomly assigned treatments were administered to vary CO; subsequently, concurrent pairs of PCO and LiDCO measurements were obtained. Treatments included a light plane of anesthesia, deep plane of anesthesia, continuous infusion of an inotropic drug (rate adjusted to achieve a mean arterial pressure of 65 to 80 mm Hg), and continuous infusion of an inotropic drug (7 microg/kg/min). RESULTS: Significant differences in PCO and LiDCO measurements were found during deep planes of anesthesia and with dopamine infusions but not during the light plane of anesthesia or with dobutamine infusions. The PCO system provided higher CO measurements than the LiDCO system during deep planes of anesthesia but lower CO measurements during dopamine infusions. CONCLUSIONS AND CLINICAL RELEVANCE: The PCO system tracked changes in CO in a similar direction as the LiDCO system. The PCO system provided better agreement with LiDCO measurements over time when hemodynamic conditions were similar to those during initial calibration. Recalibration of the PCO system is recommended when hemodynamic conditions or pressure waveforms are altered appreciably.

Accuracy of pulse oximetry and capnography in healthy and compromised horses during spontaneous and controlled ventilation.

The objective of this prospective clinical study was to evaluate the accuracy of pulse oximetry and capnography in healthy and compromised horses during general anesthesia with spontaneous and controlled ventilation. Horses anesthetized in a dorsal recumbency position for arthroscopy (n = 20) or colic surgery (n = 16) were instrumented with an earlobe probe from the pulse oximeter positioned on the tip of the tongue and a sample line inserted at the Y-piece for capnography. The horses were allowed to breathe spontaneously (SV) for the first 20 min after induction, and thereafter ventilation was controlled (IPPV). Arterial blood, for blood gas analysis, was drawn 20 min after induction and 20 min after IPPV was started. Relationships between oxygen saturation as determined by pulse oximetry (SpO2), arterial oxygen saturation (SaO2), arterial carbon dioxide partial pressure (PaCO2), and end tidal carbon dioxide (P(et)CO2), several physiological variables, and the accuracy of pulse oximetry and capnography, were evaluated by Bland-Altman or regression analysis. In the present study, both SpO2 and P(et)CO2 provided a relatively poor indication of SaO2 and PaCO2, respectively, in both healthy and compromised horses, especially during SV. A difference in heart rate obtained by pulse oximetry, ECG, or palpation is significantly correlated with any pulse oximeter inaccuracy. If blood gas analysis is not available, ventilation to P(et)CO2 of 35 to 45 mmHg should maintain the PaCO2 within a normal range. However, especially in compromised horses, it should never substitute blood gas analysis.

Cardiopulmonary effects of romifidine/ketamine or xylazine/ketamine when used for short duration anesthesia in the horse.

The cardiovascular changes associated with anesthesia induced and maintained with romifidine/ketamine versus xylazine/ ketamine were compared using 6 horses in a cross over design. Anesthesia was induced and maintained with romifidine (100 microg/kg, IV)/ketamine (2.0 mg/kg, IV) and ketamine (0.1 mg/kg/min, IV), respectively, in horses assigned to the romifidine/ ketamine group. Horses assigned to the xylazine/ketamine group had anesthesia induced and maintained with xylazine (1.0 mg/kg, IV)/ketamine (2.0 mg/kg, IV) and a combination of xylazine (0.05 mg/kg/min, IV) and ketamine (0.1 mg/kg/min, IV), respectively. Cardiopulmonary variables were measured at intervals up to 40 min after induction. All horses showed effective sedation following intravenous romifidine or xylazine and achieved recumbency after ketamine administration. There were no significant differences between groups in heart rate, arterial oxygen partial pressures, arterial carbon dioxide partial pressures, cardiac index, stroke index, oxygen delivery, oxygen utilization, systemic vascular resistance, left ventricular work, or any of the measured systemic arterial blood pressures. Cardiac index and left ventricular work fell significantly from baseline while systemic vascular resistance increased from baseline in both groups. The oxygen utilization ratio was higher in the xylazine group at 5 and 15 min after induction. In conclusion, the combination of romifidine/ketamine results in similar cardiopulmonary alterations as a xylazine/ketamine regime, and is a suitable alternative for clinical anesthesia of the horse from a cardiopulmonary viewpoint.

Comparison of a central and a peripheral (cephalic vein) injection site for the measurement of cardiac output using the lithium-dilution cardiac output technique in anesthetized dogs.

The objective of this study was to determine the agreement between cardiac output measured by central (cranial vena cava) versus peripheral (cephalic vein) venous injection of lithium chloride for lithium-dilution cardiac output (LiDCO) determination in the dog. Five dogs (2 males, 3 females), anesthetized with halothane, were used. With each dog, 12 alternating central and peripheral LiDCO measurements were made, resulting in 10 paired comparisons. A total of 50 comparisons were obtained, the cardiac output measurements ranging from 1.11 to 2.76 L/min. The LiDCO measurement from the cephalic vein was similar to that obtained from the recommended central venous site: the difference between the central and cephalic vein determinations for all measurements was 0.098+/-0.336 L/min (mean +/- 2 standard deviations). Linear regression analysis demonstrated a slope of 1.050 (95% confidence interval 0.904 to 1.196) and a y intercept of 0.005 (r = 0.902). Therefore, although the central venous site is recommended by the manufacturer, the cephalic vein can be used instead in the dog, eliminating the need for central venous catheterization and thus reducing time and expense.

Effects of glycopyrrolate on cardiorespiratory function in horses anesthetized with halothane and xylazine.

OBJECTIVE: To evaluate cardiopulmonary effects of glycopyrrolate in horses anesthetized with halothane and xylazine. ANIMALS: 6 horses. PROCEDURE: Horses were allocated to 2 treatment groups in a randomized complete block design. Anesthesia was maintained in mechanically ventilated horses by administration of halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, i.v.). Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of glycopyrrolate or saline (0.9% NaCl) solution. Glycopyrrolate (2.5 microg/kg, i.v.) was administered at 10-minute intervals until heart rate (HR) increased at least 30% above baseline or a maximum cumulative dose of 7.5 microg/kg had been injected. Recovery characteristics and intestinal auscultation scores were evaluated for 24 hours after the end of anesthesia. RESULTS: Cumulative dose of glycopyrrolate administered to 5 horses was 5 microg/kg, whereas 1 horse received 7.5 microg/kg. The positive chronotropic effects of glycopyrrolate were accompanied by an increase in cardiac output, arterial blood pressure, and tissue oxygen delivery. Whereas HR increased by 53% above baseline values at 20 minutes after the last glycopyrrolate injection, cardiac output and mean arterial pressure increased by 38% and 31%, respectively. Glycopyrrolate administration was associated with impaction of the large colon in 1 horse and low intestinal auscultation scores lasting 24 hours in 3 horses. CONCLUSIONS AND CLINICAL RELEVANCE: The positive chronotropic effects of glycopyrrolate resulted in improvement of hemodynamic function in horses anesthetized with halothane and xylazine. However, prolonged intestinal stasis and colic may limit its use during anesthesia.

Effects of a muscarinic type-2 antagonist on cardiorespiratory function and intestinal transit in horses anesthetized with halothane and xylazine.

OBJECTIVE: To evaluate the cardiorespiratory and intestinal effects of the muscarinic type-2 (M2) antagonist, methoctramine, in anesthetized horses. ANIMALS: 6 horses. PROCEDURE: Horses were allocated to 2 treatments in a randomized complete block design. Anesthesia was maintained with halothane (1% end-tidal concentration) combined with a constant-rate infusion of xylazine hydrochloride (1 mg/kg/h, i.v.) and mechanical ventilation. Hemodynamic variables were monitored after induction of anesthesia and for 120 minutes after administration of methoctramine or saline (0.9% NaCl) solution (control treatment). Methoctramine was given at 10-minute intervals (10 microg/kg, i.v.) until heart rate (HR) increased at least 30% above baseline values or until a maximum cumulative dose of 30 microg/kg had been administered. Recovery characteristics, intestinal auscultation scores, and intestinal transit determined by use of chromium oxide were assessed during the postanesthetic period. RESULTS: Methoctramine was given at a total cumulative dose of 30 microg/kg to 4 horses, whereas 2 horses received 10 microg/kg. Administration of methoctramine resulted in increases in HR, cardiac output, arterial blood pressure, and tissue oxygen delivery. Intestinal auscultation scores and intestinal transit time (interval to first and last detection of chromium oxide in the feces) did not differ between treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE: Methoctramine improved hemodynamic function in horses anesthetized by use of halothane and xylazine without causing a clinically detectable delay in the return to normal intestinal motility during the postanesthetic period. Because of their selective positive chronotropic effects, M2 antagonists may represent a safe alternative for treatment of horses with intraoperative bradycardia.

Effect of background serum lithium concentrations on the accuracy of lithium dilution cardiac output determination in dogs.

OBJECTIVES: To assess the effect of increasing serum lithium concentrations on lithium dilution cardiac output (LiDCO) determination and to determine the ability to predict the serum lithium concentration from the cumulative lithium chloride dosage. ANIMALS: 10 dogs (7 males, 3 females). PROCEDURE: Cardiac output (CO) was determined in anesthetized dogs by measuring LiDCO and thermodilution cardiac output (TDCO). The effect of the serum lithium concentration on LiDCO was assessed by observing the agreement between TDCO and LiDCO at various serum lithium concentrations. Also, cumulative lithium chloride dosage was compared with the corresponding serum lithium concentrations. RESULTS: 44 paired observations were used. The linear regression analysis for the effect of the serum lithium concentration on the agreement between TDCO and LiDCO revealed a slope of -1.530 (95% confidence interval [CI], -2.388 to -0.671) and a y-intercept of 0.011 (r2 = 0.235). The linear regression analysis for the effect of the cumulative lithium chloride dosage on the serum lithium concentration revealed a slope of 2.291 (95% CI, 2.153 to 2.429) and a y-intercept of 0.008 (r2 = 0.969). CONCLUSIONS AND CLINICAL RELEVANCE: The LiDCO measurement increased slightly as the serum lithium concentration increased. This error was not clinically relevant and was minimal at a serum lithium concentration of 0.1 mmol/L and modest at a concentration of 0.4 mmol/L. The serum lithium concentration can be reliably predicted from the cumulative lithium dosage if lithium chloride is administered often within a short period.

The cardiopulmonary effects of romifidine in dogs with and without prior or concurrent administration of glycopyrrolate.

OBJECTIVE: To determine the electrocardiographic and cardiopulmonary effects of romifidine with and without prior or concurrent administration of glycopyrrolate. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: Six (three male, three female) cross-bred dogs weighing 23 ± 2.4 kg. METHODS: Baseline cardiopulmonary measurements were obtained in conscious dogs and one of five treatments was administered. Glycopyrrolate (G) 0.01 mg kg-1, or saline (S) 0.5 mL, were administered IM as premedication (Gp or Sp), or G was administered concurrently (Gc) with romifidine (RO). Treatments were as follows T1, Sp + RO 40 µg kg-1; T2, Gp + RO (40 µg kg-1); T3, Sp + RO 120 µg kg-1; T4, Gp + RO (120 µg kg-1); T5, Sp + Gc + RO (120 µg kg-1). Romifidine or RO + Gc was administered subcutaneously 20 minutes after premedication (time 0), and further measurements were taken 10, 20, 30, 60 and 90 minutes after RO. The main treatment effect was evaluated using two-way anova for repeated measures, followed by one-way anova and a post-hoc least squares difference test with a modified Bonferroni correction (p < 0.02). A Student's t-test was used to compare the effect of romifidine at 20 and 60 minutes versus baseline values (p < 0.05). RESULTS: Both low- and high-dose RO (T1, T3) significantly decreased heart rate (HR), respiratory rate (RR), cardiac index (CI) and stroke volume index, and increased arterial blood pressure (SAP), systemic vascular resistance (SVR), pulmonary arterial occlusion pressure (PAOP) and central venous pressure. High-dose RO produced greater increases in SVR and SAP measurements. Neither dose of RO produced an alteration in blood gas values or the alveolar to arterial oxygen gradient. Glycopyrrolate significantly increased HR and CI from 10 to 90 minutes between T1/T2 and T3/T4. Increases in SAP were dose related with significant differences between T1/T3 and T2/T4 at 90 and 10 minutes, respectively, and were highest in animals receiving Gp or Gc. High-dose RO groups (T3, T4) had higher values for SVR than low-dose RO groups (T1, T2), unrelated to G administration. There was an increase in PAOP in all treatments. The oxygen extraction ratio was increased with all treatments: larger increases were observed in T1, T3 and T4 compared with only minimal changes in T2. Concurrent G administration was associated with an increased frequency of high-grade second-degree atrioventricular heart block with variable conduction at 10 and 20 minutes. CONCLUSIONS: Romifidine produced effects consistent with other selective α2-adrenoreceptor agonists. Glycopyrrolate offset the decrease in HR and partially offset the decrease in CI associated with RO administration. Glycopyrrolate premedication produced an initial tachycardia and added to the increase in SAP associated with RO. Concurrent G administration was associated with a higher frequency of dysrhythmias and is not recommended. Despite the decrease in RR, RO sedation did not alter blood gas values. CLINICAL RELEVANCE: It appears likely that G administration prior to or concurrent with RO produces an increase in myocardial workload and oxygen demand suggesting that this combination should not be used in dogs with cardiomyopathy or heart failure. The improvement in oxygen extraction ratio with T2 suggests that G may be beneficial with lower doses of RO, nevertheless, the use of G and RO in cardiovascularly compromised patients is not advised.