Search Results

You are looking at 1 - 10 of 12 items for :

  • Author or Editor: Jan E. Ilkiw x
  • Pharmacology x
  • Refine by Access: Content accessible to me x
Clear All Modify Search

SUMMARY

The cardiovascular and respiratory effects of 3 rapidly acting barbiturates, thiopental sodium, thiamylal sodium, and methohexital sodium, were studied in dogs from completion of injection until 12.5 minutes after injection. The doses administered were 19.4 mg of thiopental/kg of body weight, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg, which were chosen as equipotent doses necessary to inhibit the laryngoscopic reflex in 50% of the population. To determine the cardiovascular and respiratory effects for each drug, the values at each measurement time following injection were compared with baseline values (T0). At the 15- and 30-second measurement times following thiopental administration, stroke volume (sv) decreased; heart rate (hr), left atrial pressure, and mean pulmonary arterial pressure increased; and cardiac index (ci), myocardial contractility, and systemic and pulmonary vascular resistances were not different from baseline values. Mean arterial pressure (map) was not different from the baseline value at 15 seconds, but was increased from 30 seconds to 2 minutes. All values except hr had returned to baseline values by 7.5 minutes. At all measurement times, arterial oxygen tension and arterial pH were decreased, and arterial carbon dioxide tension increased from baseline values.

Although the cardiovascular and respiratory changes following administration of thiamylal and methohexital were similar to those described for thiopental, some differences were found. Following thiamylal administration, systemic vascular resistance increased at 1 minute, pulmonary vascular resistance increased at 1 and 2 minutes, and myocardial contractility increased at 1 and 2 minutes. Following methohexital administration, map decreased at 15 seconds, and sv decreased at all measurement times. Cardiac index increased at 30 seconds, 1 minute, and 2 minutes; myocardial contractility increased at 1, 2, and 2.5 minutes; and blood-gas and pH had returned to baseline by 12.5 minutes. To determine differences between drugs, the cardiovascular and respiratory values for each drug were compared at each measurement time. Changes in hr and sv induced by the 3 drugs were similar at all measurement times. Mean arterial pressure at 15 and 30 seconds was lower following methohexital administration than after thiopental or thiamylal administration. Cardiac index was higher at 1 minute following methohexital administration, compared with that after thiamylal administration, whereas systemic vascular resistance was higher at 1 minute following thiamylal administration, compared with that after methohexital administration. The increase in left atrial pressure was greater following thiamylal administration than after thiopental administration at 30 seconds to 5 minutes or after methohexital administration at 1 to 5 minutes. Mean pulmonary arterial pressure was significantly higher at 2 to 4 minutes following thiamylal administration than after methohexital administration. Pulmonary vascular resistance was higher at 1 minute following thiamylal administration, compared with that after thiopental and methohexital administration. At 1 and 2 minutes, myocardial contractility was significantly higher following methohexital administration, compared with that after thiobarbiturate administration. Arterial oxygen tension was lower at 12.5 minutes following administration of the thiobarbiturates, compared with that after methohexital administration. When compared with methohexital administration, arterial carbon dioxide tension was higher at 7.5 and 12.5 minutes following thiamylal administration. The decrease in pH following thiamylal administration was greater at all measurement times, compared with that after thiopental and methohexital administration.

Free access
in American Journal of Veterinary Research

Summary

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered to 24 isoflurane-anesthetized domestic chickens. Birds were randomly assigned to 4 groups, and atracurium was administered at dosage of 0.15, 0.25, 0.35 or 0.45 mg/kg of body weight. The time of onset of twitch depression, the amount of maximal twitch depression, and the duration of muscular relaxation were recorded. After return to control twitch height, atracurium was further administered to achieve > 75% twitch depression. When twitch depression reached 75% during noninduced recovery, 0 5 mg of edrophonium/kg was administered to reverse the muscle relaxation. Throughout the experimental period, cardiovascular, arterial blood gas, and acid-base variables were monitored.

The effective dosage of atracurium to result in 95% twitch depression in 50% of birds, (ed 95/50) was calculated, using probit analysis, to be 0.25 mg/kg, whereas the ed 95/95, the dosage of atracurium to result in 95% twitch depression in 95% of birds, was calculated by probit analysis to be 0.46 mg/kg. The total duration of action at dosage of 0.25 mg/kg was 34.5 ± 5.8 minutes; at the highest dosage (0 45 mg/kg), total duration increased 0 47.8 ± 10.3 minutes. The return to control twitch height was greatly hastened by administration of edrophonium. Small, but statistically significant changes in heart rate and systolic blood pressure, were associated with administration of atracurium and edrophonium. These changes would not be clinically relevant.

In this study, atracurium was found to be safe and reliable for induction of muscle relaxation in isoflurane-anesthetized chickens.

Free access
in American Journal of Veterinary Research

SUMMARY

Thiopental, thiamylal, and methohexital were administered to 30 dogs to determine equipotent doses necessary to inhibit laryngeal reflexes. The doses studied were 7.1, 10.0, 14.1, 20.0, and 28.3 mg of thiopental/kg of body weight; 5.7, 8.0, 11.3, 16.0, and 22.6 mg of thiamylal/kg; and 3.5, 5.0, 7.1, 10.0, and 14.1 mg of methohexital/kg. At 1, 2.5, 5, and 10 minutes after injection, the presence or absence of the laryngoscopic reflex, pedal reflex, and jaw tone were recorded. The times for return of each reflex, as well as the ability to walk 10 steps without assistance, were also recorded. Using the method of least squares, a probit analysis was performed on the quantal responses at 1 minute. The effective dose in 50% of the population for the laryngoscopic reflex was chosen as the end point for intubation, and the computed doses necessary to achieve this end point were 19.4 mg of thiopental/kg, 18.4 mg of thiamylal/kg, and 9.7 mg of methohexital/kg. When potencies of the drugs were compared with that of thiopental (1), thiamylal was found to be equipotent (1.06) and methohexital twice as potent (2.0). At the accepted clinical dose, recovery times for thiopental (71.1 ± 7.2 minutes) and thiamylal (75.3 ± 7.7 minutes) were similar, and twice that for methohexital (33.9 ± 4.6 minutes).

Free access
in American Journal of Veterinary Research

SUMMARY

The central arterial pharmacokinetics of alfentanil, a short-acting opioid agonist, were studied in rabbits, sheep, and dogs after short-duration infusion of the drug. Alfentanil was infused until a set end point (high-amplitude, slow-wave activity on the eeg) was reached. This required a larger alfentanil dose and a higher alfentanil arterial concentration in sheep, compared with rabbits and dogs. The plasma concentration-time data for each animal were fitted, using nonlinear regression, and in all animals, were best described by use of a triexponential function. In this study, differences in the disposition kinetics of alfentanil among the 3 species were found for only distribution clearance and initial distribution halflife. In dogs, compared with rabbits and sheep, the first distribution half-life was longer, probably because of pronounced drug-induced bradycardia (mean ± SD, 48 ± 21 beats/min). Distribution clearance was faster in sheep, compared with dogs, also probably because of better blood flow in sheep. Elimination half-life was similar in all species (rabbits, 62.4 ± 11.3 minutes; sheep, 65.1 ± 27.1 minutes; dogs, 58.3 ± 10.3 minutes). This rapid half-life resulted from a small steady-state volume of distribution (rabbits, 908.3 ± 269.0 ml/kg; sheep, 720.0 ± 306.7 ml/ kg; dogs, 597.7 ± 290.2 ml/kg) and rapid systemic clearance (rabbits, 19.4 ± 5.3 ml/min/kg; sheep, 13.3 ± 3.0 ml/min/kg; dogs, 18.7 ± 7.5 ml/min/kg). On the basis of these pharmacokinetic variables, alfentanil should have short duration of action in rabbits, sheep, and dogs. This may be beneficial in veterinary practice where rapid recovery would be expected after bolus administration for short procedures or after infusion for longer procedures.

Free access
in American Journal of Veterinary Research

SUMMARY

Atracurium besylate, a nondepolarizing neuromuscular blocking agent, was administered as an infusion to 8 anesthetized cats in which neuromuscular blockade was assessed, using the train-of-four response. Once 50% depression of the first-twitch (T1) response was achieved, the infusion was held constant for 60 minutes before being discontinued and the recovery time was determined. The time for recovery was recorded as the time for the train-of-four ratio (T4 ratio) to increase from 50% to 75%. After-recovery, atracurium infusion was reinstituted and the cats were again maintained for 60 minutes at 50% depression. A single bolus of gentamicin sulfate (2.0 mg/kg of body weight) was administered iv, and the infusion was continued for another 60 minutes before it was discontinued and the time for recovery was recorded.

Within 1 minute of gentamicin administration, the mean ± SD T1 response decreased from 49 ± 5% to 33 ± 8% of baseline and the T4 ratio decreased from 28 ± 19% to 14 ± 11%. Peak effect occurred at 5 minutes, with a T1 response of 29 ± 6% of baseline and a T4 ratio of 13 ± 12%. By 60 minutes after gentamicin administration, the T1 response had increased to 38 ± 7% of baseline and the T4 ratio had increased to 21 ± 13%. The time for recovery significantly (P < 0.03) increased from 9.9 ± 3.4 minutes during the control study to 18.1 ± 10.7 minutes during the gentamicin study.

In this study, gentamicin potentiated the neuromuscular blockade induced by atracurium and increased the recovery time. Residual blockade, observed after gentamicin administration was reversed with edrophonium.

Free access
in American Journal of Veterinary Research

SUMMARY

Objective

To evaluate effect of incremental doses of alfentanil on isoflurane minimum alveolar concentration (MAC) in cats to determine whether alfentanil reduces isoflurane MAC and, if so, maximal isoflurane MAC reduction.

Animals

6 healthy spayed female cats.

Procedure

Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood for measurement of gas tensions, pH, and plasma alfentanil concentration and to measure arterial blood pressure. Isoflurane MAC was determined in triplicate, and alfentanil was administered IV, using a computer-driven syringe pump to achieve estimated plasma alfentanil concentrations of 50, 100, 250, 500, 750, and 1,000 ng/ml; isoflurane MAC was determined at each alfentanil concentration. Cats were allowed to recover, and the process was graded as poor, good, or excellent.

Results

Alfentanil had a significant dose effect on isoflurane MAC reduction. Significant regression was found for normalized isoflurane MAC versus estimated plasma alfentanil concentration. A quadratic term was necessary to fit the model and, using this curve, MAC reduction (35.0 ± 6.6%) was estimated to be maximal at a plasma alfentanil concentration of 500 ng/ml. Significant differences were evident in rectal temperature, bicarbonate concentration, base deficit, arterial carbon dioxide and oxygen tensions, and arterial pH between isoflurane alone and some plasma alfentanil concentration and the corresponding reduction in isoflurane concentration.

Conclusions

Infusion of alfentanil resulted in maximal MAC reduction midway between that reported for horses and dogs. At such plasma alfentanil concentration, adverse effects were minimal, but included increase in rectal temperature, metabolic acidosis, and decrease in Pao2 . Provided cats were not handled during the recovery period, recovery was smooth and quiet.

Clinical Relevance

Infusion of alfentanil decreases the need for potent inhalant anesthetics in cats and could potentially be a clinically useful anesthetic regimen in sick cats. (Am J Vet Res 1997;58:1274–1279)

Free access
in American Journal of Veterinary Research

SUMMARY

Objective

To determine whether administration of opioids to anesthetized cats induced less cardiovascular depression than that induced by an equivalent amount of anesthetic alone, and to measure endocrine responses to a noxious stimulus.

Animals

6 healthy female cats.

Procedure

Anesthesia was induced with isoflurane and was maintained for 60 minutes at 1.3 isoflurane MAC. Blood gas tensions, pH, and plasma alfentanil and hormone concentrations, blood pressures, and cardiac output were measured. A noxious stimulus was applied for 5 minutes, while blood acquisition and measurements were repeated. Alfentanil was administered IV to achieve estimated plasma concentration of 500 ng/ml, and end-tidal isoflurane concentration was reduced by 35%. After another 60 minutes, blood was obtained and measurements were taken, then a second 5-minute noxious stimulus was applied while blood acquisition and measurements were retaken.

Results

Alfentanil administration and reduction of isoflurane concentration significantly increased body temperature, heart rate, mean arterial pressure, mean pulmonary arterial pressure, stroke index, cardiac index, hemoglobin, oxygen delivery index, Pvo2 and Pvco2 , dopamine, epinephrine (EPI), norepinephrine (NOREPI), and cortisol values, and significantly decreased arterial and venous pH. Application of a noxious stimulus significantly increased heart rate, stroke index, cardiac index, Pao2 , oxygen delivery index, arterial and venous pH, and NOREPI values, and decreased bicarbonate, Paco2 , Pvco2 , and EPI values. Alfentanil administration blunted cardiac index, Paco2 , oxygen delivery index, arterial pH, Pao2 , and EPI, and NOREPI responses to a noxious stimulus.

Conclusions

Compared with isoflurane alone, alfentanil administration and reduction of isoflurane MAC improved cardiovascular variables, and blunted respiratory, hormonal, and most hemodynamic responses to a noxious stimulus in cats.

Clinical Relevance

Use of the balanced opioid anesthesia regimen induced some beneficial effects in healthy cats; effects were similar to, although greater in nature, than effects induced by a noxious stimulus. (Am J Vet Res 1997;58:1267–1273)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of gabapentin in cats after IV and oral administration.

Animals—6 healthy female adult domestic shorthair cats.

Procedures—Gabapentin was administered IV (4 mg/kg) or orally (10 mg/kg) in a crossover randomized design. Blood samples were obtained immediately before gabapentin administration and at various times up to 960 minutes after IV administration or up to 1,440 minutes after oral administration. Blood samples were immediately transferred to tubes that contained EDTA and were centrifuged at 4°C. Plasma was harvested and stored at −20°C until analysis. Plasma concentrations of gabapentin were determined by use of liquid chromatography-mass spectrometry. Gabapentin concentration-time data were fit to compartment models.

Results—A 3-compartment model with elimination from the central compartment best described the disposition of gabapentin administered IV to cats, but a 1-compartment model best described the disposition of gabapentin administered orally to cats. After IV administration, the mean ± SEM apparent volume of the central compartment, apparent volume of distribution at steady state, and clearance and the harmonic mean ± jackknife pseudo-SD for terminal half-life were 90.4 ± 11.3 mL/kg, 650 ± 14 mL/kg, 3 ± 0.2 mL/min/kg, and 170 ± 21 minutes, respectively. Mean ± SD systemic availability and harmonic mean ± jackknife pseudo-SD terminal half-life after oral administration were 88.7 ± 11.1% and 177 ± 25 minutes, respectively.

Conclusions and Clinical Relevance—The disposition of gabapentin in cats was characterized by a small volume of distribution and a low clearance.

Full access
in American Journal of Veterinary Research

Summary

Cardiopulmonary effects of propofol were studied in hypovolemic dogs from completion of, until 1 hour after administration. Hypovolemia was induced by withdrawal of blood from dogs until mean arterial pressure of 60 mm of Hg was achieved. After stabilization at this pressure for 1 hour, 6 mg of propofol/kg of body weight was administered iv to 7 dogs, and cardiopulmonary effects were measured. After blood withdrawal and prior to propofol administration, oxygen utilization ratio increased, whereas mean arterial pressure, mean pulmonary arterial pressure, central venous pressure, pulmonary capillary wedge pressure, cardiac index, oxygen delivery, mixed venous oxygen tension, and mixed venous oxygen content decreased from baseline. Three minutes after propofol administration, mean pulmonary arterial pressure, pulmonary vascular resistance, oxygen utilization ratio, venous admixture, and arterial and mixed venous carbon dioxide tensions increased, whereas mean arterial pressure, arterial oxygen tension, mixed venous oxygen content, arterial and mixed venous pH decreased from values measured prior to propofol administration. Fifteen minutes after propofol administration, mixed venous carbon dioxide tension was still increased; however by 30 minutes after propofol administration, all measurements had returned to values similar to those measured prior to propofol administration.

Free access
in American Journal of Veterinary Research

Summary

Cardiopulmonary effects of halothane administration were studied in hypovolemic dogs. Baseline cardiopulmonary data were recorded from conscious dogs after instrumentation. Hypovolemia was induced by withdrawal of blood from dogs until mean arterial pressure of 60 mm of Hg was achieved. Blood pressure was maintained at 60 mm of Hg for 1 hour, by further removal or replacement of blood. Halothane was delivered by face mask, dogs were intubated, then halothane end-tidal concentration of 1.13 ± 0.02% was maintained, and cardiopulmonary effects were measured 3, 15, 30, and 60 minutes later. After blood withdrawal and prior to halothane administration, systemic vascular resistance index, oxygen extraction, and base deficit increased. Compared with baseline values, these variables were decreased: mean arterial pressure, mean pulmonary arterial pressure, pulmonary arterial occlusion pressure, cardiac index, oxygen delivery index, oxygen consumption index, mixed venous oxygen tension, mixed venous oxygen content, venous admixture, arterial bicarbonate concentration, and mixed venous pH. At all times after intubation, arterial and venous oxygen tensions and mixed venous carbon dioxide tensions were increased. Three minutes after intubation, base deficit and mixed venous carbon dioxide tension increased, and mean arterial pressure and arterial and venous pH decreased, compared with values measured immediately prior to halothane administration. Fifteen minutes after intubation, systemic vascular resistance index decreased and, at 15 and 30 minutes, mean arterial pressure and arterial and venous pH remained decreased. At 60 minutes, mean pulmonary arterial pressure and pulmonary arterial occlusion pressure were increased and mixed venous pH was decreased, compared with values measured before halothane administration. Results of this study indicated that induction of anesthesia with halothane and maintenance at an end-tidal halothane concentration of 1.13% induced significant changes in blood pressure, with minimal effects on cardiac output and pulmonary function, when administered to hypovolemic dogs.

Free access
in American Journal of Veterinary Research