Halothane Anesthesia In Dogs Research Articles

Romifidine or medetomidine premedication before propofol‐sevoflurane anaesthesia in dogs

Romifidine is an a2-adrenergic agonist sedative used in smallanimals, with similar sedative actions to other drugs of itspharmacological group (England et al., 1996a). Romifidineinduces dose-dependent cardiovascular changes in dogs andthese changes are similar to those observed with other a2-adrenergic agonists: a marked decrease in heart rate (HR),atrioventricular blocks, biphasic effect of arterial blood pressureand reduction in cardiac output have been described (Englandet al., 1996a; England & Alibhai, 1997; Lemke, 1999; Pypendop& Verstegen, 2001; Sinclair et al., 2003).Propofol is an alternative to thiopentone for induction ofgeneral anaesthesia in dogs sedated with romifidine (Redondoet al., 2000), and has been shown to be effective in combinationwith romifidine and halothane anaesthesia in dogs (Redondoet al., 1999).Sevoflurane is a volatile anaesthetic that provides anaesthesiawith rapid and smooth induction and recovery (Clarke, 1999).Sevoflurane has a variable effect on HR, causes systemicvasodilation and produces dose-dependent decreases in meanarterial pressure (MAP), total peripheral resistance and cardiacoutput (Mutoh et al., 1997). Sevoflurane causes dose-relatedrespiratory depression characterized by a fall in respiratory rate(RR) (Mutoh et al., 1997; Clarke, 1999). Several preanaestheticcombinations have been used prior to sevoflurane anaesthesia(Branson et al., 2001; Mutoh et al., 2002; Polis et al., 2004), butthere have been no studies of the use of sevoflurane in dogssedated with romifidine.Marked synergism between premedication with a2-agonistsedatives and propofol has been reported, demonstrated by adose-related reduction in induction and infusion requirementsfor propofol (Cullen & Reynoldson, 1993; Hammond & England,1994; England et al., 1996b). Romifidine has also been shown tohave a marked anaesthetic-sparing effect on thiopentone andhalothane induction and maintenance of anaesthesia (England H 1 mg/mL) at 40 lg/kg i.v.• R80: romifidine at 80 lg/kg, i.v.• MED: medetomidine (Domtor, Pfizer Salud Animal SA, Madrid,Spain; 1 mg/mL) at 10 lg/kg, i.v.In all protocols, 15 min after sedative administration anaesthe-sia was induced with propofol (Diprivan; ICIFarma, SA Porrin˜oPontevedra, Spain; 10 mg/mL) administered i.v. at a slow dose-to-effect rate with small boluses (0.5 mg/kg, every 30 sec) until

The effect of CGRP-induced hypotension on organ blood flow during halothane anesthesia in dogs: a comparison with trimetaphan.

Calcitonin gene-related peptide (CGRP) is an endogenous 37-amino-acid peptide which is a powerful vasodilator of the splanchnic circulation. To elucidate the effects of CGRP-induced hypotension on the organ blood flow, we compared the renal, hepatic, and pancreatic organ flows of CGRP-induced hypotension with those of trimetaphan (TMP) in halothane-anesthetized dogs. Systemic hemodynamics and organ blood flow were determined in 18 mongrel dogs allocated to one of two groups: CGRP group (n=10) and TMP group (n=8). CGRP of TMP was infused at a rate sufficient to decrease the mean arterial pressure (MAP) to near 60 mmHg from the baseline values for a 60 min-hypotensive period. Organ blood flow was measured using the hydrogen clearance technique. The decrease in MAP was approximately 50% of baseline values (P<0.01). The hypotension induced by either CGRP or TMP was associated with a reduction (P<0.01) in systemic vascular resistance in both groups. Cardiac index (CI) in the CGRP group did not change significantly throughout the experiment. On the other hand, CI decreased at 30 min (P<0.01) and 60 min (P<0.01) during the hypotensive period in the TMP group. No changes were observed in renal, hepatic, and pancreatic blood flows in the CGRP group. Renal blood flow in the TMP group did not change significantly throughout the experiment. In contrast, hepatic blood flow resulted in a significant decrease (P<0.01) during TMP-induced hypotension. Pancreatic blood flow decreased during the hypotensive period (P<0.01) and at 30 min (P<0.05) after termination of TMP. These findings show that CGRP does not adversely affect renal, hepatic, and pancreatic organ blood flows even in the presence of profound hypotension in halothane-anesthetized dogs. The results of this study suggest that CGRP may preserve organ blood flow during induced hypotension.

Thoracic Epidural Anesthesia and the Patient with Heart Disease

Thoracic Epidural Anesthesia and the Patient with Heart Disease

The effect of CGRP-induced hypotension on organ blood flow during halothane anesthesia in dogs: a comparison with trimetaphan

The effect of CGRP-induced hypotension on organ blood flow during halothane anesthesia in dogs: a comparison with trimetaphan

Effect of Esmolol upon Sodium Nitroprusside-Induced Hypotension under Halothane Anesthesia in Dog : Impact on the Hemodynamic Parameters and the Sodium Nitroprusside Dose Requirement

Effect of Esmolol upon Sodium Nitroprusside-Induced Hypotension under Halothane Anesthesia in Dog : Impact on the Hemodynamic Parameters and the Sodium Nitroprusside Dose Requirement

Rate of Anterior Chamber Aqueous Formation, Trabecular Outflow Facility, and Intraocular Compliance During Desflurane or Halothane Anesthesia in Dogs

Rate of Anterior Chamber Aqueous Formation, Trabecular Outflow Facility, and Intraocular Compliance During Desflurane or Halothane Anesthesia in Dogs

Effects of phenylephrine and prostaglandin E on ventriculo-arterial matching during halothane anaesthesia

We have investigated the effects of phenylephrine alone and combined with prostaglandin E1 (PGE1) on ventriculo-arterial matching during halothane anaesthesia in dogs. The ratio of left ventricular end-systolic elastance (Ees) to effective arterial elastance (Ea) was used as an index of ventriculo-arterial matching. In group 1 (n = 7), measurements were performed at control, 1.5% halothane, halothane+phenylephrine 1-10 micrograms kg-1 min-1, and halothane+phenylephrine+PGE1 0.2-1.0 or 1.0-2.0 micrograms kg-1 min-1. In group 2 (n = 5), dobutamine 2 and 5 micrograms kg-1 min-1 was infused during halothane anaesthesia. Halothane 1.5% decreased mean arterial pressure (MAP), cardiac output and Ees. Phenylephrine restored MAP, but further decreased cardiac output. The decrease in Ees produced by halothane was reversed by phenylephrine. PGE1 increased cardiac output and reversed the increases in Ea and Ea/Ees during phenylephrine infusion. Dobutamine also reversed halothane-induced decreases in MAP, cardiac output and Ees, and improved Ea/Ees. Our results indicate that combined use of PGE1 with phenylephrine can eliminate the vasoconstrictive property of phenylephrine, resulting in an improvement in ventriculo-arterial matching.

Rilmenidine Prevents Epinephrine-Induced Arrhythmias in Halothane-Anesthetized Dogs

Stimulation of central alpha 2-adrenoceptors has been known to prevent epinephrine-induced arrhythmias in halothane-anesthetized dogs. Because recent studies suggested that several physiological processes that were traditionally attributed to activation of alpha 2-adrenoceptors, such as hypotensive action, are mediated through imidazoline receptors (IRs), it may be likely that IRs are involved in the antiarrhythmic action. We investigated the hypotensive effect of rilmenidine, a selective IR agonist (1, 3, and 10 micrograms/kg i.v.), and the antiarrhythmic effects of the drug on epinephrine-induced arrhythmias during halothane anesthesia in dogs. Although the hypotensive effect of rilmenidine was not remarkable in the dose range we tested, rilmenidine increased the arrhythmogenic threshold for epinephrine in a dose-dependent manner during halothane anesthesia, achieving statistical significance at 10 micrograms/kg, the highest dose we examined. These results suggest that rilmenidine prevents epinephrine-induced arrhythmias during halothane anesthesia and that this effect is more potent than its hypotensive action.

Oral Dexmedetomidine Preserves Baroreceptor Function and Decreases Anesthetic Requirements of Halothane-anesthetized Dogs

The alpha 2-adrenergic agonist, dexmedetomidine, alters hemodynamics by diminishing sympathetic and/or augmenting parasympathetic neurogenic tone to the heart and peripheral vasculature. However, the specific actions of dexmedetomidine on baroreceptor function are unknown. The purpose of the current investigation was to determine baroreceptor function during an anesthetic state produced by halothane and a similar anesthetic state produced by halothane after dexmedetomidine pretreatment. Dogs were instrumented for measurement of arterial and left ventricular pressures, coronary blood flow velocity, segment shortening and cardiac output. Five experimental conditions were studied in the same dogs (n = 8). Measurements of baroreceptor sensitivity (via abrupt decreases and increases in arterial pressure resulting in changes in the cardiac cycle) and hemodynamics were made in the conscious state in dogs in conditions 1 and 2 before and after 25 and 50 micrograms.kg-1 of oral dexmedetomidine, respectively. Dogs in conditions 3 and 4 received the same doses of dexmedetomidine and were then anesthetized with halothane. Baroreceptor sensitivity was determined after 60 min of halothane anesthesia. For comparison, dogs in condition 5 had baroreceptor sensitivity measured after 60 min of halothane anesthesia in the absence of dexmedetomidine. Dexmedetomidine decreased heart rate, rate-pressure product, rate of increase of left ventricular pressure at 50 mmHg, cardiac output and percent segment shortening. Diastolic coronary vascular resistance and systemic vascular resistance were increased with both oral doses. In addition, diastolic coronary blood flow velocity and stroke volume were significantly reduced by the high dose of dexmedetomidine. Anesthesia with halothane increased heart rate and decreased mean arterial pressure, left ventricular systolic pressure, rate of increase of left ventricular pressure at 50 mmHg, stroke volume and segment shortening. Administration of dexmedetomidine before halothane anesthesia in dogs pretreated with dexmedetomidine resulted in small increases in heart rate and decreases mean arterial pressure and left ventricular systolic pressure. Both doses of dexmedetomidine demonstrated anesthetic-sparing effects. The end-tidal concentration of halothane to maintain dogs unconscious and unresponsive was reduced by 30% and 40% (1.03 +/- 0.08% to 0.67 +/- 0.09% and to 0.58 +/- 0.06% end-tidal, respectively) at 25 and 50 micrograms.kg-1, respectively. Baroreceptor sensitivity was profoundly depressed by halothane alone. Dexmedetomidine did not significantly change the slope of the baroreflex response when compared with conscious control measurements. After pretreatment with dexmedetomidine, the reduction in halothane concentration required for a comparable level of anesthesia resulted in significant preservation of baroreceptor sensitivity. The results indicate that dexmedetomidine alone does not alter baroreflex sensitivity. In addition, possibly through an anesthetic-sparing action, dexmedetomidine preserves baroreflex responses during halothane anesthesia. Such a preservation of the baroreceptor reflex by dexmedetomidine might provide an important mechanism for maintenance of cardiovascular stability by retaining buffer reflexes during general anesthesia.

Esmolol prevents and suppresses arrhythmias during halothane anaesthesia in dogs.

The antiarrhythmic effect of esmolol, a selective beta 1 adrenoreceptor blocker, was evaluated in the presence of epinephrine induced arrhythmias in dogs (n = 6). The arrhythmogenic dose of epinephrine (ADE) during 1.2 MAC halothane in dogs was increased from 3.23 +/- 0.25 (mean +/- SD) to 30.90 +/- 3.56 micrograms.kg-1.min-1 (P less than 0.001) by the prior administration of esmolol 0.5 microgram.kg-1 bolus followed by an infusion at the rate of 150 micrograms.kg-1.min-1. Higher esmolol infusion doses of 200 micrograms.kg-1.min-1 further increased ADE to 99.0 +/- 2.92 micrograms.kg-1.min-1 (P less than 0.001). After discontinuation of esmolol and during continued halothane anaesthesia, ventricular tachycardia was induced by increasing the infusion rate of the 100 micrograms.ml-1 solution of epinephrine. In all dogs ventricular tachycardia was restored to sinus rhythm by a bolus dose of esmolol (1 microgram.kg-1). We conclude that esmolol pretreatment increases the ADE during halothane anaesthesia in dogs. Our data suggest that esmolol may be useful as an antiarrhythmic agent in the management of epinephrine-related ventricular arrhythmias during anaesthesia in man.

The Studies on the Epinephrine - Induced Arrhythmias During Halothane Anesthesia in Dogs

The Studies on the Epinephrine - Induced Arrhythmias During Halothane Anesthesia in Dogs

Pharmacokinetic Drug Interactions in Anaesthetic Practice

Patients receive on average 10 different drugs while in hospital; when fewer than 6 are administered the probability of an adverse drug interaction is about 5%, but when more than 15 are given the probability increases to over 40%. Patients presenting for anaesthesia and surgery are likely to receive multiple preoperative drug therapy and also many perioperative medications as part of their anaesthetic regimen. Thus, there is a considerable potential for interactions to occur in anaesthetic practice. Pharmacokinetic interactions occur when the administration of 1 drug alters the disposition of another, and hence alters the concentration of drug at the receptor site, leading to altered drug response. These changes in drug concentration at the receptor site may be produced by alteration of (a) drug absorption and uptake into the body, (b) drug distribution, (c) drug metabolism and (d) drug elimination or excretion by nonmetabolic routes. Interactions affecting the absorption of orally administered medications are often due to the indirect effect of 1 drug on gastric motility and emptying, which leads to reduced, delayed or variable systemic drug availability. Gastric emptying time before elective surgery is normal, but premedication with morphine, pethidine (meperidine) and anticholinergics all delay gastric emptying and hence drug absorption. Inhalational anaesthesia of short duration does not appear to affect drug absorption, although halothane anaesthetic used for longer periods produces a slight delay in gastric emptying. Volatile anaesthetics have been shown to delay the intramuscular absorption of ketamine. Anaesthetic agents may affect drug distribution, and peak concentrations of propranolol, for example, are 4 times higher during halothane anaesthesia in dogs, accompanied by a marked decrease in volume of distribution. This effect has been noted for other drugs, including thiopental and verapamil. Volatile anaesthetics also affect plasma protein binding, leading to displacement interactions in some cases. Volatile anaesthetics affect the metabolism of concomitantly administered drug (a) by altering the rate of delivery to the organ of clearance (e.g. decreasing hepatic blood flow) and (b) by altering the activity of drug metabolising enzymes. It is now well recognised that all the volatile anaesthetics currently in use inhibit the metabolism of a large variety of drugs, e.g. propranolol, lidocaine (lignocaine), fentanyl and pethidine. Other examples of interactions of clinical importance to anaesthesiologists include those between cimetidine and the local anaesthetics and benzodiazepines; inhibition of plasma cholinesterase by drugs such as ecothiopate; interactions between monoamine oxidase inhibitors and sympathomimetics or pethidine and between monoamine oxidase inhibitors and sympathomimetics or pethidine and between isoniazid and enflurane.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of Anesthesia on Norepinephrine Kinetics Comparison of Propofol and Halothane Anesthesia in Dogs

Alteration of sympathetic function is a major determinant of the cardiovascular effects of anesthetic agents. Plasma norepinephrine (NE) concentrations are determined not only by the rate of NE release from sympathetic nerves but also by NE clearance rate. Therefore, NE concentration in plasma may be an inadequate index of sympathetic activity. We used an isotope dilution technique to investigate the effects of halothane and propofol anesthesia on NE kinetics. A relationship of NE kinetics to halothane dose was determined in six dogs. Halothane 1.0 MAC reduced plasma NE concentration by 35 +/- 9% versus awake (P less than 0.05). This was due to a reduction of 52 +/- 9% in NE spillover (P less than 0.05) accompanied by a reduction of 27 +/- 5% in NE clearance (P less than 0.005). The clearance changes were dose-dependent: reductions were 34 +/- 4% at 1.5 MAC (P less than 0.05 vs. 1.0 MAC) and 45 +/- 5% at 2.0 MAC (P less than 0.05 vs. 1.5 MAC). Six dogs were studied with a single halothane dose (1.0 MAC) and NE concentration, spillover, and clearance were found to be stable over a period of 5.5 h of anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Roles of beta 1- and beta 2-adrenoceptors in the mechanism of halothane myocardial sensitization in dogs.

The authors investigated the comparative roles of beta 1- and beta 2-adrenoceptors in myocardial sensitization by halothane in dogs. The arrhythmogenic dose (AD) of isoproterenol was determined in the presence of various doses of phenylephrine during halothane anesthesia in dogs, and the influences of 1-metoprolol (beta 1-antagonist) and ICI-118,551 (beta 2-antagonist) on the AD were examined. In the presence of 1-metoprolol, the AD of isoproterenol was significantly greater than the control, but in the presence of ICI-118,551, the AD of isoproterenol was lower. Blood pressure during the arrhythmias was higher in the presence of ICI-118,551 than that in controls. In addition, the AD of ritodrine (beta 2-agonist) was also determined at various doses of phenylephrine. The interaction between phenylephrine and ritodrine in inducing arrhythmias showed hyperbolic isoboles. However, 1-metoprolol completely inhibited the occurrence of arrhythmias induced by ritodrine and phenylephrine. The results suggest that myocardial beta 1-adrenoceptors play an essential role in the genesis of arrhythmias during halothane anesthesia in dogs, whereas beta 2-adrenoceptors do not.

Hemodynamic Interactions of Lidocaine and Diltiazem During Halothane Anesthesia in Dogs

Hemodynamic Interactions of Lidocaine and Diltiazem During Halothane Anesthesia in Dogs

Effect of Dexmedetomidine, a Selective and Potent ??2-Agonist, on Cerebral Blood Flow and Oxygen Consumption During Halothane Anesthesia in Dogs

The effect of the alpha 2-agonist dexmedetomidine on the cerebral blood flow (CBF) and the metabolic rate for oxygen was studied by a sagittal sinus outflow technique in dogs during halothane anesthesia. Dexmedetomidine was given in a dose (10 micrograms/kg) reported to reduce the anesthetic requirement of halothane by 90%. During 0.9% halothane anesthesia dexmedetomidine caused a significant reduction in CBF without influencing the metabolic rate for oxygen. Reducing the halothane concentration to 0.1% caused no further change in CBF, but increased the metabolic rate for oxygen 19%. The cerebral vasoconstrictive effect, combined with the 90% reduction in MAC for halothane, indicates that dexmedetomidine might be a useful adjunct to inhalation anesthetics during neurosurgery in situations where an increase in CBF should be avoided.

Hemodynamics Actions of Lidocaine during Halothane Anesthesia in Dogs

Hemodynamics Actions of Lidocaine during Halothane Anesthesia in Dogs

CARDIAC CONDUCTION INTERACTIONS OF PROPRANOLOL AND VERAPAMIL WITH HALOTHANE IN PENTOBARBITONE-ANAESTHETIZED DOGS

We have studied the effects of propranolol 0.25 mg kg-1 and verapamil 0.075 mg kg-1 on cardiac conduction and refractoriness in 21 dogs anaesthetized with pentobarbitone 30 mg kg-1 using His bundle electrocardiography and programmed stimulation. After baseline studies under pentobarbitone and halothane (1.3 MAC) anaesthesia, the dogs were allocated randomly to two groups: group 1 received verapamil followed by propranolol; group 2 received propranolol followed by verapamil; the drugs were given in a continuous infusion over 10 min. The atrial-His (AH) interval, the atrioventricular node effective (AVERP), and functional (AVFRP) refractory periods, were prolonged by verapamil in both groups, but not the His-ventricle (HV) interval or the ventricular effective refractory period (VERP). AVFRP and VERP were prolonged by propranolol in both groups. Corrected sinus node recovery times were normal after each drug. Heart rate and the rate required to produce Wenckebach were decreased by each drug. The combination of verapamil and propranolol during halothane anaesthesia in dogs has significant cardiac conduction effects; however, no spontaneous AV block occurred during the study.

Synergistic interaction of alpha 1- and beta-adrenoceptor agonists on induction arrhythmias during halothane anesthesia in dogs.

The authors investigated the role of alpha 1- and beta-adrenoceptors on the induction of arrhythmias during halothane anesthesia in the dog. The arrhythmogenic doses (ADs) of various combinations of alpha 1- and beta-adrenoceptor agonists were determined in dogs (N = 105) during halothane anesthesia. Isoproterenol (ISP) and phenylephrine (PHE) administered separately failed to induce arrhythmias in doses up to 4 micrograms/kg and 200 micrograms/kg, respectively. The interaction between ISP and PHE in inducing arrhythmias showed typical hyperbolic isoboles. At a systolic pressure of 140 mmHg, the AD of ISP in the presence of PHE was significantly lower than that in the presence of angiotensin II (ANG II). At a systolic pressure of 150, 160, 170, or 180 mmHg, there was no significant difference between the AD of ISP in the presence of PHE and that in the presence of ANG II. Increasing heart rate by electrical pacing did not replace ISP in the arrhythmogenic interaction between ISP and PHE. The results indicate that both alpha 1- and beta-adrenoceptor agonists are important for producing arrhythmias during halothane anesthesia, and that these agonists synergistically interact on the heart by different mechanisms.

Epinephrine arrhythmogenicity is enhanced by acute, but not chronic, aminophylline administration during halothane anesthesia in dogs.

The authors determined the effect of acute and chronic aminophylline treatment on the arrhythmogenicity of epinephrine during halothane anesthesia. The dose of epinephrine required to achieve an arrhythmia threshold (ADE) was determined in nine unpremedicated dogs anesthetized with halothane (1.5% v/v) in oxygen (A0). Aminophylline was then infused to achieve and sustain a therapeutic theophylline level (mean +/- SD) of 17 +/- 2 micrograms X ml-1 (A1), at which time the ADE was reassessed. The aminophylline infusion regimen was then adjusted to provide a supratherapeutic level of theophylline of 34 micrograms X ml-1 (A2) and the ADE was reassessed. In an additional seven dogs the ADE was assessed before and after 6 weeks of oral aminophylline treatment that yielded a plasma theophylline level of 18 +/- 3 micrograms X ml-1. The ADE was significantly (P less than 0.01) reduced from a basal value (mean +/- SD) of 2.63 +/- 0.97 micrograms X kg X -1 X min-1 to 1.39 +/- 0.47 in the A1 state. There was no further decrement in the ADE at the A2 state (1.17 +/- 0.36). The plasma epinephrine level at the arrhythmia threshold decreased commensurately from 50.7 +/- 40.2 ng X ml-1 (A0) to 20.0 +/- 7.9 and 19.2 +/- 7.6 in the A1 and A2 states, respectively (P less than 0.01). In contrast to these acute treatment experiments, neither the ADE (2.65 +/- 0.95 vs. 2.97 +/- 1.49 micrograms X kg-1 X min-1) nor the plasma epinephrine levels at the arrhythmia threshold (47.2 +/- 13.7 vs. 51.1 +/- 22.0 ng X ml-1) were different after chronic aminophylline treatment.(ABSTRACT TRUNCATED AT 250 WORDS)