Effect of medetomidine administration on bispectral index measurements in dogs during anesthesia with isoflurane

OBJECTIVE: To determine the relationship between bispectral index (BIS) and minimum alveolar concentration (MAC) multiples of isoflurane after IM injection of medetomidine or saline (0.9% NaCl) solution in anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: Each dog was anesthetized 3 times with isoflurane. First, the MAC of isoflurane for each dog was determined by use of the tail clamp method. Second, anesthetized dogs were randomly assigned to receive an IM injection of medetomidine (8 microg x kg(-1)) or an equal volume of isotonic saline (0.9% NaCl) solution 30 minutes prior to beginning BIS measurements. Last, anesthetized dogs received the remaining treatment (medetomidine or isotonic saline solution). Dogs were anesthetized at each of 4 MAC multiples of isoflurane. Ventilation was controlled and atracurium (0.2 mg/kg followed by 6 microg/kg/min as a continuous infusion, IV) administered. After a 20-minute equilibration period at each MAC multiple of isoflurane, BIS data were collected for 5 minutes and median values of BIS calculated. RESULTS: BIS significantly decreased with increasing MAC multiples of isoflurane over the range of 0.8 to 2.0 MAC. Mean (+/- SD) MAC of isoflurane was 1.3 +/- 0.2%. During isoflurane-saline anesthesia, mean BIS measurements at 0.8, 1.0, 1.5, and 2.0 MAC were 65 +/- 8, 60 +/- 7 52 +/- 3, and 31 +/- 28, respectively. During isoflurane-medetomidine anesthesia, mean BIS measurements at 0.8, 1.0, 1.5, and 2.0 MAC were 77 +/- 4, 53 +/- 7, 31 +/- 24, and 9 +/- 20, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: BIS monitoring in dogs anesthetized with isoflurane has a predictive value in regard to degree of CNS depression. During isoflurane anesthesia, our results support a MAC-reducing effect of medetomidine.     

Effect of medetomidine on breathing and inspiratory neuromuscular drive in conscious dogs

OBJECTIVE: To evaluate the effects of the alpha2-adrenoceptor agonist medetomidine on respiratory rate (RR), tidal volume (V(T)), minute volume (V(M)), and central respiratory neuromuscular drive as determined by inspiratory occlusion pressure (IOP) during increasing fractional inspired concentrations of carbon dioxide (FiCO2) in conscious dogs. ANIMALS: 6 healthy dogs (3 males and 3 females). PROCEDURE: Dogs were administered 0, 5, or 10 microg of medetomidine/kg i.v. We measured RR, V(T), V(M), and IOP for the first 0.1 second of airway occlusion (IOP0.1) during FiCO2 values of 0%, 2.5%, 5.0%, and 75% at 15 minutes before and 5, 30, and 60 minutes after administration of medetomidine. RESULTS: Increases in FiCO2 significantly increased RR, V(T), and V(M). The i.v. administration of 5 and 10 microg of medetomidine/kg significantly decreased RR and V(M) at 5, 30, and 60 minutes for FiCO2 values of 2.5% and 5.0% and at 30 and 60 minutes for an FiCO2 value of 75%. The IOP0.1 was decreased after 30 minutes only for an FiCO2 value of 7.5% in dogs administered 5 and 10 microg of medetomidine/kg. The IOP0.1 was decreased at 60 minutes after administration of 10 microg of medetomidine/kg for an FiCO2 value of 7.5%. CONCLUSIONS AND CLINICAL RELEVANCE: The i.v. administration of medetomidine decreases RR, V(M), and central respiratory drive in conscious dogs. Medetomidine should be used cautiously and with careful monitoring in dogs with CNS depression or respiratory compromise.     

Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs

OBJECTIVE: To determine the effect of IV administration of perzinfotel on the minimum alveolar concentration (MAC) of isoflurane in dogs. Animals-6 healthy sexually intact male Beagles. PROCEDURES: Dogs were instrumented with a telemetry device that permitted continuous monitoring of heart rate, arterial blood pressure, and body temperature. Dogs were anesthetized with propofol (4 to 6 mg/kg, IV) and isoflurane for 30 minutes before determination of MAC of isoflurane. Isoflurane MAC values were determined 4 times, separated by a minimum of 7 days, before and after IV administration of perzinfotel (0 [control], 5, 10, and 20 mg/kg). Bispectral index and percentage hemoglobin saturation with oxygen (SpO(2)) were monitored throughout anesthesia. RESULTS: Isoflurane MAC was 1.32 +/- 0.14%. Intravenous administration of perzinfotel at 0, 5, 10, and 20 mg/kg decreased isoflurane MAC by 0%, 24%, 30%, and 47%, respectively. Perzinfotel significantly decreased isoflurane MAC values, compared with baseline and control values. The bispectral index typically increased with higher doses of perzinfotel and lower isoflurane concentrations, but not significantly. Heart rate, body temperature, and SpO(2) did not change, but systolic, mean, and diastolic arterial blood pressures significantly increased with decreases in isoflurane MAC after administration of perzinfotel at 10 and 20 mg/kg, compared with 0 and 5 mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of perzinfotel decreased isoflurane MAC values. Improved hemodynamics were associated with decreases in isoflurane concentration.     

Effects of Halothane, Enflurane, and Isoflurane on Supraventricular and Ventricular Rate in Dogs With Complete Atrioventricular Block

Complete atrioventricular (AV) block was produced in 32 chloralose-anesthetized autonomically intact dogs to determine the effects of halothane, enflurane, and isoflurane on supraventricular and ventricular rate. Halothane (n = 17), enflurane (n = 6), and isoflurane (n = 9) were administered in three separate experiments in sequential minimum alveolar concentration (MAC) multiples of 0.5, 1.0, 1.5, 2.0, 1.5, and 1.0. Supraventricular rate, ventricular rate, and mean arterial blood pressure (MAP) were measured and recorded at baseline and after a 20-minute equilibration period of each inhalation anesthetic at each MAC multiple. Increasing concentrations of enflurane and isoflurane significantly decreased supraventricular rate ( P < .05). Ventricular rate was not significantly changed by sequential MAC multiples of halothane, enflurane, and isoflurane. Increasing concentrations of halothane, enflurane, and isoflurane significantly decreased MAP with enflurane producing the most significant decrease ( P < .05). Ventricular arrhythmias occurred in 5 of 17 dogs anesthetized with halothane and 1 of 9 dogs anesthetized with isoflurane. Inhalation anesthesia can significantly decrease supraventricular rate and MAP, does not alter ventricular rate, and can produce ventricular arrhythmias in dogs with complete AV block.     

Effects of morphine,butorphanol, buprenorphine,and U50488H on the minimum alveolar concentration of isoflurane in cats

OBJECTIVE: To determine whether opioids with varying interactions at receptors induce a reduction in minimum alveolar concentration (MAC) of isoflurane in cats. ANIMALS: 12 healthy, female, spayed cats. PROCEDURE: Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Each drug was studied separately, and for each drug cats were randomly allocated to receive 2 doses. The drugs studied were morphine (0.1 or 1.0 mg/kg), butorphanol (0.08 or 0.8 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg). All drugs were diluted in 5 ml of saline (0.9% NaCl) solution and infused IV for 5 minutes. The MAC of isoflurane was determined in triplicate, the drug administered, and the MAC of isoflurane redetermined for a period of 3 hours. RESULTS: All drugs had a significant effect on MAC over time. With morphine only, the effect on MAC over time was different between doses. The greatest mean (+/- SD) reductions in MAC of isoflurane in response to morphine, butorphanol, buprenorphine, and U50488H administration were 28 +/- 9, 19 +/- 3, 14 +/- 7, and 11 +/- 7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine (1.0 mg/kg) and butorphanol (0.08 and 0.8 mg/kg) induced significant reductions in MAC of isoflurane that were considered clinically important. Although significant, reductions in MAC of isoflurane induced by morphine (0.1 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg) were not considered clinically relevant because they fell within the error of the measurement technique. Administration of morphine or butorphanol decreases the need for potent inhalant anesthetics in cats and could potentially be beneficial in combination with inhalants.     

Effects of xylazine hydrochloride during isoflurane-induced anesthesia in horses

OBJECTIVE: To quantitate dose- and time-related anesthetic-sparing effects of xylazine hydrochloride (XYL) during isoflurane-induced anesthesia in horses and to characterize selected physiologic responses of anesthetized horses to administration of XYL. ANIMALS: 6 healthy adult horses. PROCEDURE: Horses were anesthetized 2 times to determine the minimum alveolar concentration (MAC) of isoflurane in O2 and to characterize the anesthetic-sparing effect (MAC reduction) after IV administration of XYL (0.5 and 1 mg/kg of body weight, random order). Selected measures of cardiopulmonary function, blood glucose concentrations, and urinary output also were measured during the anesthetic studies. RESULTS: Isoflurane MAC (mean +/- SEM) was reduced by 24.8 +/- 0.5 and 34.2 +/- 1.9% at 42 +/- 7 and 67 +/- 10 minutes, respectively, after administration of XYL at 0.5 and 1 mg/kg. Amount of MAC reduction by XYL was dose- and time-dependent. Overall, cardiovascular and respiratory values varied little among treatments. Administration of XYL increased blood glucose concentration; the magnitude of change was dose- and time-dependent. Urine volume increased but not significantly. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of XYL reduced the anesthetic requirement for isoflurane in horses. The magnitude of the decrease is dose- and time-dependent. Administration of XYL increases blood glucose concentration in anesthetized horses in a dose-related manner.     

Effects of intramuscular administration of low doses of medetomidine and medetomidine-butorphanol in middle-aged and old dogs.

OBJECTIVE: To determine effects of low doses of medetomidine administered with and without butorphanol and glycopyrrolate to middle-aged and old dogs. DESIGN: Prospective randomized clinical trial. ANIMALS: 88 healthy dogs > or = 5 years old. PROCEDURE: Dogs were assigned randomly to receive medetomidine (2, 5, or 10 micrograms/kg [0.9, 2.3, or 4.6 micrograms/lb] of body weight, i.m.) alone or with glycopyrrolate (0.01 mg/kg [0.005 mg/lb], s.c.), medetomidine (10 micrograms/kg) and butorphanol (0.2 mg/kg [0.1 mg/lb], i.m.), or medetomidine (10 micrograms/kg), butorphanol (0.2 mg/kg), and glycopyrrolate (0.01 mg/kg). Anesthesia was induced with thiopental sodium and maintained with isoflurane. Degree of sedation and analgesia were determined before and after medetomidine administration. Respiratory rate, heart rate, and mean arterial blood pressure were determined 10 and 30 minutes after medetomidine administration. Adverse effects and amounts of thiopental and isoflurane used were recorded. RESULTS: Sedation increased after medetomidine administration in 79 of 88 dogs, but decreased in 7 dogs that received 2 or 5 micrograms of medetomidine/kg. Mean postsedation analgesia score and amounts of thiopental and isoflurane used were less in dogs that received medetomidine and butorphanol, compared with other groups. Respiratory rate, heart rate, and blood pressure were not different among groups. Significantly more adverse effects developed in dogs that did not receive glycopyrrolate. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of medetomidine (10 micrograms/kg, i.m.) and butorphanol (0.2 mg/kg, i.m.) induced sedation and analgesia and reduced amounts of thiopental and isoflurane required for anesthesia in middle-aged and old dogs. Glycopyrrolate decreased frequency of medetomidine-associated adverse effects.     

Isoflurane sparing action of epidurally administered xylazine hydrochloride in anesthetized dogs

OBJECTIVE: To evaluate the influence of epidural administration of xylazine hydrochloride on the minimum alveolar concentration of isoflurane (MAC(ISAO)) and cardiopulmonary system in anesthetized dogs. ANIMALS: 6 clinically normal dogs. PROCEDURE: Dogs were anesthetized with isoflurane in oxygen after randomly being assigned to receive 1 of the following 4 treatments: epidural administration of saline (0.9% NaCl) solution or xylazine at a dose of 0.1, 0.2, or 0.4 mg x kg(-1). Experiments were performed on 5 occasions with at least a 1-week interval between experiments; each dog received all 4 treatments. Following instrumentation, the concentration of isoflurane was maintained constant for 15 minutes at the MAC(ISO) that had been determined for each dog, and data on heart rate, arterial blood pressure, respiratory rate, tidal volume, minute volume, arterial partial pressure of oxygen, arterial partial pressure of carbon dioxide, and arterial pH were collected. The epidural treatment was administered, and 30 minutes later, data were again collected. From this point on, determination of the MAC(ISO) following epidural treatment (ie, MAC(ISO+EPI)) was initiated. Cardiopulmonary data were collected before each electrical supramaximal stimulus during MAC(ISO+EPI) determinations. RESULTS: The mean (+/-SD) MAC(ISO) was 1.29 +/- 0.04%. The epidural administration of xylazine at doses of 0.1, 0.2, and 0.4 mg x kg(-1) decreased the MAC(ISO), respectively, by 8.4 +/- 2.4%, 21.7 +/- 4.9%, and 33.4 +/- 2.64%. Cardiopulmonary effects were limited. CONCLUSIONS AND CLINICAL RELEVANCE: Epidural administration of xylazine decreases the MAC(ISO) in a dose-dependent manner and is associated with few cardiopulmonary effects in anesthetized dogs.     

Validation of several types of noxious stimuli for use in determining the minimum alveolar concentration for inhalation anesthetics in dogs and rabbits

OBJECTIVE: To compare 3 types of noxious stimuli applied to various anatomic areas of anesthetized dogs and rabbits for determination of the minimum alveolar concentration (MAC). ANIMALS: 10 dogs and 10 rabbits. PROCEDURE: Dogs were anesthetized with isoflurane and halothane in a randomized order. Rabbits were anesthetized with isoflurane. The MAC was determined by skin incision on the lateral aspect of the chest; clamping of the tail, paw of the forelimb, and paw of the hind limb; and application of electrical current to the oral mucosa (dogs only), forelimb, and hind limb. The MAC was the end-tidal concentration midway between the value permitting and preventing purposeful movement in response to noxious stimuli. RESULTS: In dogs, mean +/- SEM MAC for isoflurane was 1.27 +/- 0.05% for clamping stimuli, 1.36 +/- 0.04% for oral electrical stimulation, 1.35 +/- 0.04% for electrical stimulation to the limbs, and 1.01 +/- 0.07% for surgical incision. The MAC for halothane was 0.97 +/- 0.03% for tail clamping, 0.96 +/- 0.03% for clamping of the limbs, 1.04 +/- 0.03% for electrical stimulation, and 0.75 +/- 0.06% for surgical incision. In rabbits, MAC for isoflurane was 2.08 +/- 0.02% for clamping stimuli, 2.04 +/- 0.02% for electrical stimulation, and 0.90 +/- 0.02% for surgical incision. The MAC for surgical incision was significantly lower than values for the other methods in both species. CONCLUSIONS AND CLINICAL RELEVANCE: Use of electrical current and clamping techniques resulted in similar MAC values. Surgical incision underestimated MAC values in dogs and rabbits.     

Cardiovascular effects of epidurally administered oxymorphone and an oxymorphone-bupivacaine combination in halothane-anesthetized dogs

OBJECTIVE: To evaluate cardiovascular effects of epidurally administered oxymorphone (OXY) and an OXY-bupivacaine combination (O/B) in halothane-anesthetized dogs. ANIMALS: 6 dogs. PROCEDURE: In a randomized crossover design study, dogs were anesthetized with halothane and given OXY, O/B, and saline solution (SAL). Eucapnia and end-tidal halothane concentration of 1.2% were established. Heart rate (HR), systemic and pulmonary arterial pressures, central venous pressure (CVP), and cardiac output were measured at baseline and 5, 15, 30, 45, 60, and 75 minutes after treatment. At 90 minutes, glycopyrrolate was administered IV, and measurements were repeated at 95 minutes. Cardiac index (CI), stroke volume, stroke index, systemic vascular resistance (SVR), and left ventricular work were calculated. End-tidal halothane concentration was decreased to 0.8% from 17 to 45 minutes and to 0.5% from 47 to 95 minutes for OXY and O/B, whereas for SAL, it was maintained at 1.5 and 1.2%, respectively. Samples were obtained at 0, 2, 5, 15, 30, 45, 60, and 95 minutes for measurement of serum opiate concentration and comparison with values after IM administration of OXY. RESULTS: HR decreased, but CVP and SVR increased in response to OXY and O/B. These changes were reversed after IV administration of glycopyrrolate, resulting in significant increase in CI, compared with that in response to SAL. Serum opiate concentration increased markedly and peaked within 15 minutes after OXY and O/B administration but did not differ from values after IM administration. CONCLUSIONS: Epidural administration of OXY results in rapid systemic uptake and decreased HR. Glycopyrrolate administration improves HR, resulting in improved CI at equipotent halothane concentrations.     

Cardiorespiratory responses and plasma cortisol concentrations in dogs treated with medetomidine before undergoing ovariohysterectomy

OBJECTIVE: To evaluate effects of medetomidine on anesthetic dose requirements, cardiorespiratory variables, plasma cortisol concentrations, and behavioral pain scores in dogs undergoing ovariohysterectomy. DESIGN: Randomized, prospective study. ANIMALS: 12 healthy Walker-type hound dogs. PROCEDURE: Dogs received medetomidine (40 micrograms/kg [18.2 micrograms/lb] of body weight, i.m.; n = 6) or saline (0.9% NaCl) solution (1 ml, i.m.; 6) prior to anesthesia induction with thiopental; thiopental dose needed for endotracheal intubation was compared between groups. Ovariohysterectomy was performed during halothane anesthesia. Blood samples were obtained at various times before drug administration until 300 minutes after extubation. Various physiologic measurements and end-tidal halothane concentrations were recorded. RESULTS: In medetomidine-treated dogs, heart rate was significantly lower than in controls, and blood pressure did not change significantly from baseline. Plasma cortisol concentrations did not increase significantly until 60 minutes after extubation in medetomidine-treated dogs, whereas values in control dogs were increased from time of surgery until the end of the recording period. Control dogs had higher pain scores than treated dogs from extubation until the end of the recording period. CONCLUSION AND CLINICAL RELEVANCE: Administration of medetomidine reduced dose requirements for thiopental and halothane and provided postoperative analgesia up to 90 minutes after extubation. Dogs undergoing ovariohysterectomy by use of thiopental induction and halothane anesthesia benefit from analgesia induced by medetomidine administered prior to anesthesia induction. Additional analgesia is appropriate 60 minutes after extubation.     

Duration of nonresponse to noxious stimulation after intramuscular administration of butorphanol, medetomidine, or a butorphanol-medetomidine combination during isoflurane administration in dogs

OBJECTIVE: To assess duration of actions of butorphanol, medetomidine, and a butorphanol-medetomidine combination in dogs given subanesthetic doses of isoflurane (ISO). ANIMALS: 6 healthy dogs. PROCEDURE: Minimum alveolar concentration (MAC) values for ISO were determined. for each dog. Subsequently, 4 treatments were administered to each dog (saline [0.9% NaCl] solution, butorphanol [0.2 mg/kg of body weight], medetomidine [5.0 microg/kg], and a combination of butorphanol [0.2 mg/kg] and medetomidine [5.0 microg/kg]). All treatments were administered IM to dogs concurrent with isoflurane; treatment order was determined, using a randomized crossover design. Treatments were given at 7-day intervals. After mask induction with ISO and instrumentation with a rectal temperature probe, end-tidal CO2 and anesthetic gas concentrations were analyzed. End-tidal ISO concentration was reduced to 90% MAC for each dog. A tail clamp was applied 15 minutes later. After a positive response, 1 of the treatments was administered. Response to application of the tail clamp was assessed at 15-minute intervals until a positive response again was detected. RESULTS: Duration of nonresponse after administration of saline solution, butorphanol, medetomidine, and butorphanol-medetomidine (mean +/- SD) was 0.0+/-0.0, 1.5+/-1.5, 2.63+/-0.49, and 5.58+/-2.28 hours, respectively. Medetomidine effects were evident significantly longer than those for saline solution, whereas effects for butorphanol-medetomidine were evident significantly longer than for each agent administered alone. CONCLUSION AND CLINICAL RELEVANCE: During ISO-induced anesthesia, administration of medetomidine, but not butorphanol, provides longer and more consistent analgesia than does saline solution, and the combination of butorphanol-medetomidine appears superior to the use of medetomidine or butorphanol alone.     

Atrial fibrillation in halothane- and isoflurane-anesthetized dogs

Programmed electrical stimulation techniques were used to evaluate the effects of halothane and isoflurane on induction of atrial fibrillation in anesthetized dogs. Experiments were performed in 16 dogs anesthetized with alpha-chloralose. Critically timed premature stimuli were applied to the right atrial appendage and Bachmann bundle to determine the atrial fibrillation threshold, defined as the minimal current required to induce rapid, irregular atrial electrical activity of at least 8 seconds' duration. Atrial fibrillation thresholds were determined at baseline (0.0% inhalational anesthetic), 0.5 minimal alveolar concentration (MAC), and 1.0 MAC of halothane (n = 8) and isoflurane (n = 8). In the absence of inhalation anesthetic, it was significantly (P less than 0.01) easier to induce atrial fibrillation at the Bachmann bundle vs the right atrial appendage. Atrial fibrillation threshold at the Bachmann bundle was not affected by increasing concentrations of halothane, but was increased by 1.0 MAC of isoflurane (P less than 0.05). It was concluded that at 1.0 MAC isoflurane, but not halothane, has antifibrillatory effects in atrial tissue.     

Effect of intravenous administration of ketamine on the minimum alveolar concentration of isoflurane in anesthetized dogs

OBJECTIVE: To determine the effect of 6 plasma ketamine concentrations on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS: 6 dogs. PROCEDURE: In experiment 1, the MAC of isoflurane was measured in each dog and the pharmacokinetics of ketamine were determined in isoflurane-anesthetized dogs after IV administration of a bolus (3 mg/kg) of ketamine. In experiment 2, the same dogs were anesthetized with isoflurane in oxygen. A target-controlled IV infusion device was used to administer ketamine and to achieve plasma ketamine concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL by use of parameters obtained from experiment 1. The MAC of isoflurane was determined at each plasma ketamine concentration, and blood samples were collected for ketamine and norketamine concentration determination. RESULTS: Actual mean +/- SD plasma ketamine concentrations were 1.07 +/- 0.42 microg/mL, 1.62 +/- 0.98 microg/mL, 3.32 +/- 0.59 microg/mL, 4.92 +/- 2.64 microg/mL, 13.03 +/- 10.49 microg/mL, and 22.80 +/- 25.56 microg/mL for target plasma concentrations of 0.5, 1, 2, 5, 8, and 11 microg/mL, respectively. At these plasma concentrations, isoflurane MAC was reduced by 10.89% to 39.48%, 26.77% to 43.74%, 25.24% to 84.89%, 44.34% to 78.16%, 69.62% to 92.31%, and 71.97% to 95.42%, respectively. The reduction in isoflurane MAC was significant, and the response had a linear and quadratic component. Salivation, regurgitation, mydriasis, increased body temperature, and spontaneous movements were some of the adverse effects associated with the high plasma ketamine concentrations. CONCLUSIONS AND CLINICAL RELEVANCE: Ketamine appears to have a potential role for balanced anesthesia in dogs.     

Influence of three anesthetic protocols on glomerular filtration rate in dogs

OBJECTIVE: To investigate renal function in clinically normal dogs when awake and during anesthesia with medetomidine; xylazine, ketamine, and halothane (XKH) combination; or propofol. ANIMALS: 10 adult female Beagles. PROCEDURES: At intervals of 15 days, dogs were administered medetomidine (0.05 mg/kg, IV); XKH combination (xylazine [1 mg/kg, IV], ketamine [5 mg/kg, IV], and halothane [1% end-tidal concentration]); or propofol (6 mg/kg, IV) to induce anesthesia or no treatment. Glomerular filtration rate was assessed on the basis of renal uptake (RU; determined via renal scintigraphy) and plasma clearance (CL) of technetium 99m-labeled diethylenetriamine pentaacetic acid ((99m)Tc-DTPA). RESULTS: In awake dogs, mean +/- SEM RU was 9.7 +/- 0.4% and CL was 3.86 +/- 0.23 mL/min/ kg. Renal uptake and CL of (99m)Tc-DTPA were not significantly modified by administration of XKH (RU, 11.4 +/- 0.9%; CL, 4.6 +/- 0.32 mL/min/kg) or propofol (RU, 9.7 +/- 0.3%; CL, 3.78 +/- 0.37 mL/min/kg). Half-life elimination time of plasma (99m)Tc-DTPA decreased significantly in XKH-anesthetized dogs, compared with the value in awake dogs (14.4 minutes and 28.9 minutes, respectively). However, glomerular filtration rate was significantly decreased by administration of medetomidine (RU, 3.9 +/- 0.1%), and the time to maximum kidney activity was significantly increased (867 +/- 56 seconds vs 181 +/- 11 seconds without anesthesia). CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that anesthesia with propofol or an XKH combination did not alter renal function in healthy Beagles, but anesthesia with medetomidine decreased early RU of (99m)Tc-DTPA.     

Pharmacokinetic variables of mivacurium chloride after intravenous administration in dogs.

OBJECTIVE: To determine pharmacokinetic variables of mivacurium chloride after IV administration in dogs. ANIMALS: 5 healthy Labrador Retrievers. PROCEDURE: Anesthesia was induced with thiopental and maintained with halothane in oxygen. Dogs were ventilated mechanically to an end-tidal P(CO)2 value between 35 and 40 mm Hg. Heart rate, direct blood pressure, and arterial pH were recorded throughout the experiment. Core temperature, end-tidal P(CO)2, and halothane concentration were kept constant throughout the experiment. Paired blood samples for determination of plasma cholinesterase activity were collected prior to administration of a bolus of mivacurium (0.05 mg/kg of body weight), which was administered IV during a 2-second period. Arterial blood samples were obtained for determination of plasma mivacurium concentration 0, 1, 3, 5, 10, 30, 60, 120, 150, and 180 minutes after administration of mivacurium. Blood was collected into tubes containing EDTA and 0.25% echothiophate. Mivacurium concentration was determined, using reversed-phase high-performance liquid chromatography. RESULTS: For the trans-trans isomer, mean +/- SEM volume of distribution was 0.18+/-0.024 L/kg, median half-life was 34.9 minutes (range, 26.7 to 53.5 minutes), and clearance was 12+/-2 ml/min/kg. For the cis-trans isomer, values were 0.31+/-0.05 L/kg, 43.4 minutes (range, 31.5 to 69.3 minutes), and 15+/-2 ml/min/kg, respectively. Values for the cis-cis isomer were not calculated, because it was not detectable in plasma 60 minutes after mivacurium administration in all 5 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: The transtrans and cis-trans isomers of mivacurium have a long half-life and slow clearance in healthy dogs anesthetized with halothane.     

Perioperative stress response in the dog: effect of pre-emptive administration of medetomidine

OBJECTIVE: To determine the effect of medetomidine on the stress response induced by ovariohysterectomy in isoflurane-anesthetized dogs. STUDY DESIGN: Prospective randomized study. ANIMALS: Twelve healthy adult female purpose-bred dogs, weighing 16.8 to 25 kg. METHODS: Two treatments were randomly administered to each of twelve dogs at weekly intervals: (1) Saline injected IM followed in 15 minutes by isoflurane anesthesia (ISO) induced by mask and maintained at an end-tidal concentration of 1.8% for 60 minutes; and (2) Medetomidine, 15 ug/lkg IM followed in 15 minutes by isoflurane anesthesia (ISO&MED) induced by mask and maintained at an end-tidal concentration of 1.0% for 60 minutes. One week after completion of these two treatments, all dogs were ovariohysterectomized. six receiving each treatment (SURG and SURG&MED). Central venous blood samples (10 mL) were obtained immediately before medetomidine or saline (baseline) and at 30, 75, and 195 minutes and 24 hours after administration of medetomidine or saline in ISO and ISO&MED. In SURG and SURG&MED, samples were obtained immediately prior to injection of medetomidine or saline (baseline) and at 30 (before skin incision), 45 (after severence of the ovarian ligament), 75 (after skin closure), 105 (30 minutes after skin closure, dog recovered and in sternal recumbency), 135, 195, 375 minutes, and 24 hours after the initial sample. Samples were analyzed for epinephrine, norepinephrine, adrenocorticotrophic hormone (ACTH), cortisol, insulin, and glucose. Data were analyzed by analysis of variance and where significant differences were found, a least significant difference test was applied. RESULTS: Premedication with medetomidine prevented or delayed the stress response induced by ovariohysterectomy in isoflurane-anesthetized dogs. CONCLUSIONS: The stress response induced by ovariohysterectomy, although significant, is of short duration. Medetomidine safely and effectively reduced surgically-induced stress responses. CLINICAL RELEVANCE: Surgically induced stress responses can be obtunded or prevented by administration of medetomidine.     

Respiratory reflexes in response to nasal administration of halothane to anesthetized, spontaneously breathing dogs

OBJECTIVE: To characterize and determine the sensory innervation of respiratory reflexes elicited by nasal administration of halothane to dogs. ANIMALS: 10 healthy Beagles. PROCEDURE: Dogs underwent permanent tracheostomy and, 2 to 3 weeks later, were anesthetized with thiopental and alpha-chloralose administered IV. The nasal passages were functionally isolated so that halothane could be administered to the nasal passages while dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to administration of halothane at concentrations of 1.25, 1.75, and 2.5 times the minimum alveolar concentration (MAC), and 5% (administered in 100% O2 at a flow rate of 5 L/min) were recorded. Reflexes in response to administration of 5% halothane were also recorded following transection of the infraorbital nerve, transection of the caudal nasal nerve, and nasal administration of lidocaine. RESULTS: Nasal administration of halothane induced an inhibition of breathing characterized by a dose-dependent increase in expiratory time and a resultant decrease in expired volume per unit time. Effects were noticeable immediately after the onset of halothane administration and lasted until its cessation. Reflex responses to halothane administration were attenuated by transection of the caudal nasal nerve and by nasal administration of lidocaine, but transection of the infraorbital nerve had no effect. CONCLUSIONS AND CLINICAL RELEVANCE: Nasal administration of halothane at concentrations generally used for mask induction of anesthesia induces reflex inhibition of breathing. Afferent fibers in the caudal nasal nerve appear to play an important role in the reflex inhibition of breathing induced by halothane administration.     

Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs anesthetized with isoflurane or a combination of isoflurane and fentanyl

OBJECTIVE: To determine the effect of a constant-rate infusion of fentanyl on minimum alveolar concentration (MAC) of isoflurane and to determine the interaction between fentanyl and a benzodiazepine agonist (diazepam) and antagonist (flumazenil) in isoflurane-anesthetized dogs. ANIMALS: 8 mixed-breed adult dogs. PROCEDURE: Dogs were anesthetized with isoflurane 3 times during a 6-week period. After a 30-minute equilibration period, each MAC determination was performed in triplicate, using standard techniques. Fentanyl was administered as a bolus (10 microg/kg of body weight, IV) that was followed by a constant infusion (0.3 microg/kg per min, IV) throughout the remainder of the experiment. After determining isoflurane-fentanyl MAC in triplicate, each dog received saline (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was determined again. RESULTS: Fentanyl significantly decreased isoflurane MAC (corrected to a barometric pressure of 760 mm Hg) from 1.80+/-0.21 to 0.85+/-0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48+/-0.29%) was significantly less than isoflurane-fentanyl-saline MAC (0.79+/-0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyl-diazepam (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean fentanyl concentrations for the entire experiment were increased over time and were higher in the diazepam group than the saline or flumazenil groups. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl markedly decreased isoflurane MAC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC. Our results indicate that diazepam enhances, whereas flumazenil does not affect, opioid-induced CNS depression and, possibly, analgesia in dogs.     

Hemodynamic effects of ionized calcium in horses anesthetized with halothane or isoflurane

OBJECTIVES: To evaluate the effects of halothane and isoflurane on cardiovascular function and serum total and ionized calcium concentrations in horses, and to determine whether administration of calcium gluconate would attenuate these effects. ANIMALS: 6 clinically normal adult Thoroughbreds. PROCEDURE: Catheters were inserted for measurement of arterial blood pressures, pulmonary arterial blood pressures, right ventricular pressure (for determination of myocardial contractility), right atrial pressure, and cardiac output and for collection of arterial blood samples. Anesthesia was then induced with xylazine hydrochloride and ketamine hydrochloride and maintained with halothane or isoflurane. An i.v. infusion of calcium gluconate was begun 75 minutes after anesthetic induction; dosage of calcium gluconate was 0.1 mg/kg of body weight/min for the first 15 minutes, 0.2 mg/kg/min for the next 15 minutes, and 0.4 mg/kg/min for an additional 15 minutes. Data were collected before, during, and after administration of calcium gluconate. RESULTS: Halothane and isoflurane decreased myocardial contractility, cardiac index, and mean arterial pressure, but halothane caused greater depression than isoflurane. Calcium gluconate attenuated the anesthetic-induced depression in cardiac index, stroke index, and maximal rate of increase in right ventricular pressure when horses were anesthetized with isoflurane. When horses were anesthetized with halothane, a higher dosage of calcium gluconate was required to attenuate the depression in stroke index and maximal rate of increase in right ventricular pressure; cardiac index was not changed with calcium administration. CONCLUSIONS AND CLINICAL RELEVANCE: I.v. administration of calcium gluconate may support myocardial function in horses anesthetized with isoflurane.