Cardiopulmonary evaluation of the use of medetomidine hydrochloride in cats.

OBJECTIVE: To evaluate the cardiovascular effects of the alpha2-adrenergic receptor agonist medetomidine hydrochloride in clinically normal cats. ANIMALS: 7 clinically normal cats. PROCEDURE: Cats were anesthetized with isoflurane, and thermodilution catheters were placed for measurement of central venous, pulmonary, and pulmonary capillary wedge pressures and for determination of cardiac output. The dorsal pedal artery was catheterized for measurement of arterial blood pressures and blood gas tensions. Baseline variables were recorded, and medetomidine (20 microg/kg of body weight, IM) was administered. Hemodynamic measurements were repeated 15 and 30 minutes after medetomidine administration. RESULTS: Heart rate, cardiac index, stroke index, rate-pressure product, and right and left ventricular stroke work index significantly decreased from baseline after medetomidine administration, whereas systemic vascular resistance and central venous pressure increased. However, systolic, mean, and diastolic arterial pressures as well as arterial pH, and oxygen and carbon dioxide tensions were not significantly different from baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: When administered alone to clinically normal cats, medetomidine (20 microg/kg, IM) induced a significant decrease in cardiac output, stroke volume, and heart rate. Arterial blood pressures did not increase, which may reflect a predominant central alpha2-adrenergic effect over peripheral vascular effects.

The effect of a combination of medetomidine-butorphanol and medetomidine, butorphanol, atropine on glomerular filtration rate in dogs.

The effects of intramuscularly administered medetomidine and butorphanol (MB), and medetomidine, butorphanol, atropine (MBA) on glomerular filtration rate (GFR) were determined in six dogs as measured by 99m-Tc-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) nuclear scintigraphy. Direct systolic, diastolic, and mean arterial blood pressures and heart rate were measured at regular time intervals before, during, and after GFR calculations. The mean GFR measurement following MB was significantly greater (4.44 ml/min/kg) than following MBA (3.82 ml/min/kg) or saline treatment (3.41 ml/min/kg). There was no significant difference between the mean GFR measurements following MBA injection and following saline injection. Diastolic and mean arterial pressures following MBA injection were significantly higher than the values recorded after either MB or saline alone. Heart rate following MB administration was significantly lower than that recorded for dogs receiving MBA or saline alone. The results of this study indicate that the administration of medetomidine in combination with butorphanol significantly increases total GFR in healthy dogs, while the administration of the combination of medetomidine, butorphanol, and atropine does not.

Fumonisin B(1) increases serum sphinganine concentration but does not alter serum sphingosine concentration or induce cardiovascular changes in milk-fed calves.

Fumonisin B(1) is the most toxic and commonly occurring form of a group of mycotoxins that alter sphingolipid biosynthesis and induce leukoencephalomalacia in horses and pulmonary edema in pigs. Purified fumonisin B(1) (1 mg/kg, iv, daily) increased serum sphinganine and sphingosine concentrations and decreased cardiovascular function in pigs within 5 days. We therefore examined whether the same dosage schedule of fumonisin B(1) produced a similar effect in calves. Ten milk-fed male Holstein calves were instrumented to obtain blood and cardiovascular measurements. Treated calves (n = 5) were administered purified fumonisin B(1) at 1 mg/kg, iv, daily for 7 days and controls (n = 5) were administered 10 ml 0.9% NaCl, iv, daily. Each calf was euthanized on day 7. In treated calves, serum sphinganine concentration increased from day 3 onward (day 7, 0.237 +/- 0.388 micromol/l; baseline, 0.010 +/- 0.007 micromol/l; mean +/- SD), whereas, serum sphingosine concentration was unchanged (day 7, 0.044 +/- 0.065 micromol/l; baseline, 0.021 +/- 0.025 micromol/l). Heart rate, cardiac output, stroke volume, mean arterial pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, central venous pressure, plasma volume, base-apex electrocardiogram, arterial Po(2), and systemic oxygen delivery were unchanged in treated and control calves. Fumonisin-treated calves developed metabolic acidosis (arterial blood pH, 7.27 +/- 0.11; base excess, -9.1 +/- 7.6 mEq/l), but all survived for 7 days. We conclude that calves are more resistant to fumonisin B(1) cardiovascular toxicity than pigs.

Anesthetic and cardiopulmonary effects of propofol in dogs premedicated with atropine, butorphanol, and medetomidine.

This study evaluated the anesthetic and cardiorespiratory effects of a combination of intravenous propofol (2.2 mg/kg), intramuscular medetomidine (22.0 pg/kg), intravenous butorphanol (0.22 mg/kg), and intravenous atropine (0.022 mg/kg) in healthy dogs. Anesthesia was characterized by muscle relaxation and analgesia. Heart rate decreased after medetomidine and propofol administration (131 to 113 beats/min) but returned to baseline after intravenous atipamezole (110 microg/kg). Mild acidemia, hypercapnia, hypoxemia, and decreased SaO2 developed after premedication. PaO2 and SaO2 were further decreased by propofol injection. In conclusion, this combination proved to be an effective anesthetic protocol for healthy dogs and should be adequate for minor surgical procedures.

Physiology of pain.

The substantial increase in our collective knowledge of pain physiology and pharmacology over the past decade has had a significant effect on the practice of clinical veterinary medicine. An overview of the basic anatomical and physiologic components of nociceptive processing is presented, as well as a discussion of the sensitizing events that occur within the nervous system in acute and chronic pathologic pain states. The unique features of visceral and neuropathic pain are also outlined. With the goal of improving the success of our therapeutic interventions, the final section is devoted to the various classes of analgesic drugs and techniques, and how they are best incorporated into pain management strategies.

Adjunctive analgesic therapy.

Adjuvant analgesics are drugs that have weak or nonexistent analgesic action when administered alone but can enhance analgesic actions when coadministered with known analgesic agents. Such agents are often administered in cases of refractory pain. For some chronic pain syndromes, however, they may constitute a first-line approach. Because pain is such an individual experience, analgesic regimens may require several drugs at varying dosages to confer a comfortable state. Adjunctive therapies such as the tricyclic antidepressants, anticonvulsants, N-methyl-D-aspartic acid receptor antagonists and low-dose intravenous local anesthetics, to name a few, have proved to be efficacious in relieving certain types of pain, especially neuropathic and cancer pain. Their use in animals is increasing, with anecdotal reports of some success.

Safety of moxidectin in avermectin-sensitive collies.

OBJECTIVE: To evaluate the safety of moxidectin administration at doses of 30, 60, and 90 microg/kg of body weight (10, 20, and 30 times the manufacturer's recommended dose) in avermectin-sensitive Collies. ANIMALS: 24 Collies. PROCEDURE: Collies with mild to severe reactions to ivermectin challenge (120 mg/kg; 20 times the recommended dose for heartworm prevention) were used. Six replicates of 4 dogs each were formed on the basis of body weight and severity of reaction to ivermectin test dose. Within replicates, each dog was randomly allocated to treatment with oral administration of 30, 60, or 90 microg of moxidectin/kg or was given a comparable volume of placebo tablet formulation. Dogs were observed hourly for the first 8 hours and twice daily thereafter for 1 month for signs of toxicosis. RESULTS: Signs of toxicosis were not observed in any control group dog throughout the treatment observation period. Likewise, signs of toxicosis were not observed in any dog receiving moxidectin at 30, 60, or 90 microg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: The moxidectin formulation used in the study reported here appears to have a wider margin of safety than ivermectin or milbemycin in avermectin-sensitive Collies.

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.

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.

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.

Techniques for evaluation of right ventricular relaxation rate in horses and effects of inhalant anesthetics with and without intravenous administration of calcium gluconate.

OBJECTIVES: To determine the most repeatable method for evaluating right ventricular relaxation rate in horses and to determine and compare effects of isoflurane or halothane with and without the added influence of intravenously administered calcium gluconate on right ventricular relaxation rates in horses. ANIMALS: 6 Thoroughbred horses from 2 to 4 years old. PROCEDURE: 6 models (2 for monoexponential decay with zero asymptote, 3 for monoexponential decay with variable asymptote, and 1 for biexponential decay) for determining right ventricular relaxation rate were assessed in conscious and anesthetized horses. The 2 methods yielding the most repeatable results then were used to determine right ventricular relaxation rates in horses anesthetized with isoflurane or halothane before, during, and after i.v. administration of calcium gluconate. Right ventricular pressure was measured, using a catheter-tip high-fidelity pressure transducer, and results were digitized at 500 Hz from minimum rate of change in ventricular pressure. RESULTS: 2 models that used monoexponential decay with zero asymptote repeatedly produced an estimate for relaxation rate and were used to analyze effects of anesthesia and calcium gluconate administration on relaxation rate. Isoflurane and halothane each prolonged right ventricular relaxation rate, with greater prolongation evident in halothane-anesthetized horses. Calcium gluconate attenuated the anesthesia-induced prolongation in right ventricular relaxation rate, with greater response obtained in isoflurane-anesthetized horses. CONCLUSIONS AND CLINICAL RELEVANCE: Right ventricular relaxation rate in horses is assessed best by use of a monoexponential decay model with zero asymptote and nonlinear regression. Intravenous administration of calcium gluconate to isoflurane-anesthetized horses best preserves myocardial relaxant function.

The pharmacodynamics of thiopental, medetomidine, butorphanol and atropine in beagle dogs.

This study evaluated the quality of anaesthesia and some of the haemodynamic effects induced by a combination of thiopental, medetomidine, butorphanol and atropine in healthy beagle dogs (n = 12). Following premedication with atropine (ATR, 0.022 mg/kg intravenously (i.v.)) and butorphanol (BUT, 0.22 mg/kg i.v.), medetomidine (MED, 22 micrograms/kg intramuscularly (i.m.)) was administered followed in 5 min by thiopental (THIO, 2.2 mg/kg i.v.). Heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MBP) were monitored continuously with an ECG and direct arterial blood pressure monitor. Atipamezole (ATI, 110 micrograms/kg i.v.) was administered to half of the dogs (n = 6) following surgery to evaluate the speed and quality of arousal from anaesthesia. Anaesthesia was characterized by excellent muscle relaxation, analgesia and absence of purposeful movement in response to surgical castration. Arousal following antagonism of medetomidine was significantly faster (P < 0.05) than in unantagonized dogs. Recoveries were smooth but recovery times following atipamezole administration were highly variable among dogs (sternal time range 6-38 min, standing time range 9-56 min). Medetomidine caused a significant (P < 0.05) increase in SBP, DBP and MBP. Atropine prevented the medetomidine induced bradycardia. In conclusion, this combination provided adequate surgical anaesthesia in healthy beagle dogs. At the dosages used in this study, it seems prudent that this combination should be reserved for dogs free of myocardial disease.

Hemodynamic effects of epidural ketamine in isoflurane-anesthetized dogs.

OBJECTIVE: The purpose of this study was to determine the hemodynamic effects of epidural ketamine administered during isoflurane anesthesia in dogs. STUDY DESIGN: Prospective, single-dose trial. ANIMALS: Six healthy dogs (five males, one female) weighing 25.3 +/- 3.88 kg. METHODS: Once anesthesia was induced, dogs were maintained at 1.5 times the predetermined, individual minimum alveolar concentration (MAC) of isoflurane. Dogs were instrumented and allowed to stabilize for 30 minutes before baseline measurements were recorded. Injection of 2 mg/kg of ketamine in 1 mL saline/4.5 kg body weight was then performed at the lumbosacral epidural space. Hemodynamic data were recorded at 5, 10, 15, 20, 30, 45, 60, and 75 minutes after epidural ketamine injection. Statistical analysis included an analysis of variance (ANOVA) for repeated measures over time. All data were compared with baseline values. A P < .05 was considered significant. RESULTS: Baseline values +/- standard error of the mean (X +/- SEM) for heart rate, mean arterial pressure, mean pulmonary artery pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, stroke index, systemic vascular resistance, pulmonary vascular resistance, and rate-pressure product were 108 +/- 6 beats/min, 85 +/- 10 mm Hg, 10 +/- 2 mm Hg, 3 +/- 1 mm Hg, 5 +/- 2 mm Hg, 2.3 +/- 0.3 L/min/m2, 21.4 +/- 1.9 mL/beat/m2, 3386 +/- 350 dynes/sec/cm5, 240 +/- 37 dynes/sec/cm5, and 12376 +/- 1988 beats/min x mm Hg. No significant differences were detected from baseline values at any time after ketamine injection. CONCLUSIONS: The epidural injection of 2 mg/kg of ketamine is associated with minimal hemodynamic effects during isoflurane anesthesia. CLINICAL RELEVANCE: These results suggest that if epidural ketamine is used for analgesia in dogs, it will induce minimal changes in cardiovascular function.

Pharmacology of drugs used for anesthesia and sedation.

This article reviews and defines the concepts underlying modern pharmacologic science, such as the study of pharmacokinetics, pharmodynamics, and drug interactions. Differences in anesthetic and sedative effects observed among species may be explained in part, by varying pharmacokinetics and dynamics unique to each species. Pharmacokinetic data from ruminants and swine for many of the commonly used anesthetics and adjunctive sedatives are included. The receptor mechanism mediating the actions of anesthetics and sedatives is also reviewed. Rationale for combining CNS depressant drugs and analgesics to achieve "balanced anesthesia" and other favorable drug interactions is discussed. Several drug combinations used in ruminants and swine are provided in table form.

Hemodynamic effects of calcium gluconate administered to conscious horses.

Calcium gluconate was administered to conscious horses at 3 different rates (0.1, 0.2, and 0.4 mg/kg/min for 15 minutes each). Serum calcium concentrations and parameters of cardiovascular function were evaluated. All 3 calcium administration rates caused marked increases in both ionized and total calcium concentrations, cardiac index, stroke index, and cardiac contractility (dP/dtmax). Mean arterial pressure and right atrial pressure were unchanged; heart rate decreased markedly during calcium administration. Ionized calcium concentration remained between 54% and 57% of total calcium concentration throughout the study. We conclude that calcium gluconate can safely be administered to conscious horses at 0.1 to 0.4 mg/kg/min and that administration will result in improved cardiac function.

Ability of flumazenil, butorphanol, and naloxone to reverse the anesthetic effects of oxymorphone-diazepam in dogs.

OBJECTIVE: To evaluate the ability of flumazenil (FLU), butorphanol (BUT), and naloxone (NAL) to reverse the anesthetic effects of oxymorphone-diazepam in dogs. ANIMALS: 6 healthy adult mixed-bread dogs. PROCEDURE: Dogs were randomly assigned to each of 6 reversal treatment groups. In each experiment, oxymorphone (0.22 mg/kg of body weight, i.v.) and diazepam (0.22 mg/kg. i.v.) were given sequentially 15 minutes after glycopyrrolate (0.01 mg/kg, i.v.) administration. Physiologic saline solution (SAL; 1 ml), FLU (0.01 mg/kg), BUT (0.44 mg/kg), or NAL (0.06 mg/kg) alone, or FLU-BUT or FLU-NAL (same dosages) was given i.v. as a reversal treatment 15 minutes after oxymorphone-diazepam administration. An individual unaware of the treatment protocol recorded time to extubation, sternal recumbency, and walking. RESULTS: Time to extubation was significantly (P < 0.05) less with BUT, NAL, FLU-BUT, or FLU-NAL treatment, compared with that for SAL treatment. Time to sternal recumbency was less with BUT, NAL, FLU-BUT, or FLU-NAL treatment, compared with that for SAL treatment. Time to walking was less with FLU-BUT or FLU-NAL treatment, compared with that for SAL treatment. CLINICAL IMPLICATIONS: Flumazenil, in combination with BUT or NAL, can be used to reverse the anesthetic effects of oxymorphone-diazepam in dogs.

Hemodynamic and anesthetic effects of etomidate infusion in medetomidine-premedicated dogs.

Hemodynamic and analgesic effects of medetomidine (15 micrograms/kg of body weight, IM) and etomidate (0.5 mg/kg, IV, loading dose; 50 micrograms/kg/min, constant infusion) were evaluated in 6 healthy adult Beagles. Instrumentation was performed during isoflurane/oxygen-maintained anesthesia. Before initiation of the study, isoflurane was allowed to reach end-tidal concentration < or = 0.5%, when baseline measurements were recorded. Medetomidine and atropine (0.044 mg/kg) were given IM after recording of baseline values. Ten minutes later, the loading dose of etomidate was given IM, and constant infusion was begun and continued for 60 minutes. Oxygen was administered via endotracheal tube throughout the study. Analgesia was evaluated by use of the standard tail clamp technique and a direct-current nerve stimulator. Sinoatrial and atrial-ventricular blocks occurred in 4 of 6 dogs within 2 minutes after administration of a medetomidine-atropine combination, but disappeared within 8 minutes. Apnea did not occur after administration of the etomidate loading dose. Analgesia was complete and consistent throughout 60 minutes of etomidate infusion. Medetomidine significantly (P < 0.05) increased systemic vascular resistance and decreased cardiac output. Etomidate infusion caused a decrease in respiratory function, but minimal changes in hemodynamic values. Time from termination of etomidate infusion to extubation, sternal recumbency, standing normally, and walking normally were 17.3 +/- 9.4, 43.8 +/- 14.2, 53.7 +/- 11.9, and 61.0 +/- 10.9 minutes, respectively. All recoveries were smooth and unremarkable. We concluded that this anesthetic drug combination, at the dosages used, is a safe technique in healthy Beagles.