Antiarrhythmic effect of diltiazem during halothane anesthesia in dogs and in humans

The antiarrhythmic effects of diltiazem (DL), a slow channel inhibitor, were evaluated in the presence of epinephrine-halothane-induced arrhythmias in dogs, of premature ventricular contractions (PVCs) during anesthesia in patients (n = 10), and of tachyarrhythmias with associated atrial fibrillation (AF) during anesthesia in patients (n = 9). The arrhythmogenic dose of epinephrine (ADE) during one MAC of halothane in dogs was increased from 1.13 +/- 0.21 to 3.14 +/- 0.89 microgram X kg-1 X min-1 by the administration of 0.3 mg/kg of DL. This suggests that DL significantly increases the threshold for the induction of arrhythmias associated with epinephrine and halothane. In 10 patients, PVCs that appeared spontaneously during halothane anesthesia were eliminated by the intravenous administration of DL (0.1 mg/kg). With an additional nine patients who had had AF preoperatively and suffered tachyarrhythmias during anesthesia, the intraoperative intravenous administration of DL significantly decreased heart rate (to less than 100 beats/min) within 10-15 min. Diltiazem is an effective means for the treatment of PVCs and AF-mediated tachyarrhythmias during anesthesia. Because of the pharmacologic properties of DL (e.g., depressing sinus and atrioventricular (AV) node function), DL should be used with caution in patients with a sick sinus syndrome or an AV block, or in the presence of beta-adrenergic antagonists.     

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)     

Increasing myocardial oxygen demand during prolonged halothane anesthesia in dogs

The effect of prolonged halothane anesthesia on myocardial oxygen uptake and coronary blood flow is unknown. This 5.5-hr study was undertaken to determine whether myocardial changes occur in dogs during prolonged steady-state halothane anesthesia. Hourly data were collected beginning 1.5 hr after induction of steady-state anesthesia. When compared to values obtained at 1.5 hr of halothane anesthesia, no significant myocardial changes were observed during the initial 3.5 hr. However, after 4.5 hr, mean arterial blood pressure increased 14% (P less than 0.01), coronary sinus flow increased 22% (P less than 0.05), and myocardial oxygen uptake increased 19% (P less than 0.05). At 5.5 hr mean arterial pressure was 18% (P less than 0.01), coronary sinus flow 31% (P less than 0.01), and myocardial oxygen uptake 21% (P less than 0.05) above levels measured at 1.5 hr. At 5.5 hr whole body oxygen uptake was 6% (P less than 0.01) above the 1.5 hr value. Cardiac output, heart rate, and systemic and coronary vascular resistances did not change significantly. This study demonstrates that duration of anesthesia is an important factor in determining the metabolic oxygen requirements of the heart. During prolonged anesthesia, the increase in myocardial oxygen demands may have an unfavorable effect on the myocardial oxygen supply-demand relationship.     

The hemodynamic and cardiovascular effects of isoflurane and halothane anesthesia in children

The hemodynamic and cardiovascular effects of isoflurane and halothane anesthesia were studied in 15 unpremedicated ASA I children using measurements of heart rate, blood pressure and M-mode echocardiography (echo). The children (ages 2 to 7.3 yr) were randomly assigned to receive either isoflurane (N = 8) or halothane (N = 7) with oxygen. End-tidal carbon dioxide concentrations (range 30-44 mmHg) were monitored throughout the study in each child. The experimental protocol was completed prior to intubation and the initiation of surgery. Within each anesthetic group, preinduction (control) hemodynamic and echo measurements were compared with measurements obtained at two sequential equipotent end-tidal anesthetic concentrations (0.74% and 2.22% isoflurane; or 0.5% and 1.5% halothane). We also compared the data of the isoflurane group with that of the halothane group at each equipotent end-tidal anesthetic concentration. Preinduction hemodynamic (heart rate, blood pressure) and echo measurements (left ventricular dimensions and function) were similar between the two anesthetic groups. With isoflurane or halothane administration, blood pressure decreased significantly, while heart rate remained essentially unchanged. The observed alterations in heart rate and blood pressure were similar in both study groups at each equipotent end-tidal anesthetic concentration. In contrast, there were marked differences in the echo measurements of the two anesthetic groups. Halothane was associated with a significant dose-dependent decrease in echo-measured left-ventricular shortening fraction and mean velocity of circumferential fiber shortening. These echo measurements were not significantly altered by isoflurane at either end-tidal anesthetic concentration. These alterations suggest halothane is associated with significant myocardial depression in normal children, while myocardial function is well preserved during isoflurane anesthesia.     

Oral atropine premedication in infants attenuates cardiovascular depression during halothane anesthesia

The efficacy of oral atropine premedication in attenuation of the cardiovascular depression associated with halothane anesthesia has not been previously evaluated. A solution containing either oral atropine 0.04 mg/kg (HI), 0.02 mg/kg (LO), or a placebo (NO) was randomly administered to 36 infants 1-6 months old and 36 infants 7-15 months old 30-90 minutes before induction of anesthesia. The onset of action of atropine was approximately 25 minutes after administration as determined by a 15% increase in heart rate (HR) above baseline levels. Heart rate, systolic blood pressure (SBP), and mean arterial blood pressure (MAP) were then measured at 1-minute intervals starting just before induction of anesthesia and continuing until onset of surgical stimulation during anesthesia with halothane (up to 3%), nitrous oxide (60%), and oxygen (40%). In infants 1-6 months old, either dosage of oral atropine preserved HR and SBP as compared with placebo. In infants 7-15 months old, either dosage preserved HR but not SBP. The severity of hypotension was greatest in infants 1-6 months of age given placebos. No significant differences existed between oral atropine 0.04 mg/kg or 0.02 mg/kg in either age range. It is concluded that premedication with oral atropine 0.02 mg/kg is effective in attenuating the cardiovascular depression associated with halothane anesthesia in infants.     

Cardiovascular effects of atropine sulfate preparations in vagotomized dogs under halothane anesthesia

The cardiovascular effects of 3 preparations of atropine sulfate were studied acutely in open-chest, vagotomized dogs under endotracheal halothane anesthesia. Indices of myocardial performance (LVdp/dt/CPIP and maximum ascending aortic blood acceleration) showed insignificant changes when varying doses of IV atropine (0.04 mg/kg and 0.04 mg/kg) were given. However, mean ascending aortic pressure fell by 20 percent following the larger doses of 2 commercial preparations containing antibacterial preservatives, and only 9 percent following a "pure" (USP) atropine preparation. Calculated changes in systemic vascular resistance closely followed actual pressure values. These results indicate that atropine, even in large doses, causes little or no depression of ventricular function independently of its chronotropic action. However, atropine does cause a fall in blood pressure, seemingly due to peripheral vasodilation, particularly in commercial preparations containing preservatives.     

Landiolol decreases a dysrhythmogenic dose of epinephrine in dogs during halothane anesthesia

PURPOSE: To examine the effect of landiolol (ONO-1101), a new ultra-short acting and highly selective beta blocker, on epinephrine-induced ventricular arrhythmias in halothane-anesthetized dogs. METHODS: We administered five different doses (0, 0.1, 0.5, 1.0, 10 microg x kg(-1) x min(-1)) landiolol and determined the dysrhythmogenic dose of epinephrine (DDE), defined as the smallest dose producing four or more PVCs within 15 sec, at each dose of landiolol and after cessation of infusion. RESULTS: The control value of DDE during 1.3 MAC halothane anesthesia was 1.26 +/- 0.44 (mean +/- SD) microg x kg(-1) x min(-1) and the corresponding plasma concentration of epinephrine (PCE) was 12.2 +/- 8.3 ng x ml(-1). Concomitant administration of 10 microg x kg(-1) x min(-1) landiolol increased DDE and corresponding PCE (P < 0.05). At 30 min after cessation of landiolol infusion, DDE and corresponding PCE returned to the control values. CONCLUSIONS: Landiolol, at a dose of 10 microg x kg(-1) x min(-1), has an antiarrhythmic effect on epinephrine-induced ventricular arrhythmias in dogs during anesthesia with halothane.     

Epidurally administered halothane vapor potentiates mepivacaine-induced epidural anesthesia : A report of 10 Cases

Key words  halothane vapor - epidural halothane - potentiation of epidural anesthesia     

The effects of ketamine on cardiovascular dynamics during halothane and enflurane anesthesia.

The cardiovascular effects of a single dose of ketamine administered during halothane or enflurane anesthesia were studied in 24 patients. During halothane anesthesia, ketamine caused a rapid and significant increase in arteriolar peripheral resistance (p less than 0.01) and a decrease in cardiac output, stroke volume, and systolic diastolic, and mean arterial blood pressures. Heart rate was not significantly changed. Ketamine resulted in similar, though less dramatic and slower developing, changes in patients anesthetized with enflurane. These results demonstrate that general anesthesia blocks the cardiovascular-stimulating properties of ketamine. They also indicate that ketamine has significant cardiovascular-depressant qualities when used during halothane or enflurane anesthesia.     

Alpha-adrenergic responsiveness correlates with epinephrine dose for arrhythmias during halothane anesthesia in dogs

The dose of epinephrine required to elicit ventricular arrhythmias during halothane anesthesia may depend on end-organ sensitivity. We determined whether the arrhythmogenic dose for epinephrine (ADE) could be correlated with either alpha- or beta-adrenergic responsiveness. After ADE was determined in 26 dogs anesthetized with 1.2 MAC halothane, an in vivo assessment of adrenergic responsiveness was made. The alpha-adrenergic responsiveness was defined as the dose of phenylephrine required to increase mean arterial pressure by 75% (alpha 75), while the dose of isoproterenol causing a 75% increase in heart rate was a measure of beta-adrenergic responsiveness (beta 75). The correlation coefficients for alpha 75 and beta 75 vs ADE then were determined by multiple linear regression analysis. There was a highly significant correlation with the alpha 75 (F = 9.06; P less than 0.01), while no relationship existed with beta 75 (F = 0.52; P greater than 0.05). Thus the alpha-adrenergic responsiveness in individual patients may be used to predict the threshold for epinephrine-induced arrhythmias during halothane anesthesia.     

Effects of halothane and enflurane anesthesia on sympathetic beta-adrenoreceptor-mediated pulmonary vasodilation in chronically instrumented dogs

BACKGROUND: The authors previously reported that the pulmonary vasodilator response to the sympathetic beta-adrenoreceptor agonist isoproterenol is potentiated during isoflurane anesthesia compared with the conscious state. In the present in vivo study, the authors tested the hypothesis that halothane and enflurane anesthesia also enhance sympathetic beta adrenoreceptor-mediated pulmonary vasodilation. The authors also used the membrane-permeable analog of cyclic adenosine monophosphate (cAMP), dibutyryl cAMP, to help delineate the site in the signaling pathway for an anesthesia-induced effect on beta adrenoreceptor-mediated pulmonary vasodilation. METHODS: Mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were measured on separate days in the conscious, halothane-, and enflurane-anesthetized states at baseline, after preconstriction with the thromboxane analog U46619, and during the cumulative intravenous administration of isoproterenol. LPQ plots were also measured in conscious, halothane-, and isoflurane-anesthetized dogs after U46619 preconstriction and during the cumulative intravenous administration of dibutyryl cAMP. RESULTS: Compared with the conscious state, neither halothane nor enflurane had an effect on the baseline LPQ relationship. The magnitude of the pulmonary vasodilator response to isoproterenol was potentiated during halothane anesthesia but unchanged during enflurane anesthesia. The pulmonary vasodilator response to dibutyryl cAMP was not altered during either halothane or isoflurane anesthesia compared with the conscious state. CONCLUSIONS: These results indicate that inhalational anesthetic agents can exert differential effects on the pulmonary vasodilator response to sympathetic beta-adrenoreceptor activation. The potentiated vasodilator response observed during halothane and isoflurane anesthesia is the result of effects proximal to cAMP accumulation in the beta-adrenoreceptor signaling pathway.     

Comparative cardiovascular effects of verapamil, nifedipine, and diltiazem during halothane anesthesia in swine

Controversy persists about the cardiac toxicity of bupivacaine if accidentally administered intravenously during regional anesthesia. Using awake, unanesthetized sheep, we evaluated the cardiac effects of low and high equivalent doses of lidocaine and bupivacaine given intravenously over 10 s. All animals convulsed within 30 s of injections. Although both drugs significantly increased heart rate and systemic and pulmonary arterial blood pressure for up to 10 min, cardiac output was affected variably. The magnitude of hemodynamic changes that each drug produced did not differ significantly from each other at either dose level. However, of the sheep receiving intravenous lidocaine, none developed arrhythmias other than mild sinus tachycardia and minimal ST-T wave changes (which occurred in 25% of the animals). After intravenous bupivacaine injection, all sheep had transient changes on the EKG and/or arrhythmias (e.g., supraventricular tachycardia; atrioventricular condition blocks; ventricular tachycardia; multiform premature ventricular contractions; wide QRS complexes; ST-T wave changes; and in one animal, fatal ventricular fibrillation). Normal sinus rhythm usually returned within 8-10 min. Arterial blood gas and acid-base values stayed within the normal range during the studies, and serum potassium did not change significantly from control. In conclusion, in conscious adult sheep, equivalent doses of lidocaine or bupivacaine produced similar central nervous system (CNS) toxicity when rapidly injected intravenously. In the absence of marked hypoxia, respiratory or metabolic acidosis, hyperkalemia, or hypotension, serious cardiac arrhythmias occurred after bupivacaine but not lidocaine.     

Nitrous oxide: cardiovascular effects in infants and small children during halothane and isoflurane anesthesia

Two-dimensional and pulsed Doppler echocardiography were used to measure cardiovascular function in 31 unmedicated infants and small children. In 15 patients, the cardiovascular effects of equipotent levels of halothane were compared with and without N2O. In 16 patients, the cardiovascular effects of isoflurane with and without N2O were compared. Prior to anesthesia induction, cardiovascular measurements of heart rate (HR), mean blood pressure (MBP), and two-dimensional and pulsed Doppler echocardiography were recorded. The echocardiographic measurements were used to determine cardiac output (CO), stroke volume (SV), ejection fraction (EF), and left ventricular end-diastolic and end-systolic volume (LVEDV and LVESV). Twenty minutes after mask inhalation induction with halothane or isoflurane with N2O and O2 (3:2 liters/min), cardiovascular measurements were repeated with end-expired halothane or isoflurane maintained at 0.9 MAC. A third set of cardiovascular data was collected 10 minutes after the discontinuation of N2O, with inspired isoflurane or halothane levels in O2 (5 liters/min) increased to maintain 1.5 MAC end-expired levels. Ventilation was controlled throughout the study period and the study was completed before intubation and the start of elective surgery. Heart rate and MBP decreased to similar degrees below awake levels in both patient groups during N2O with halothane or isoflurane. When N2O was discontinued and end-expired levels of halothane or isoflurane increased, MBP remained at levels observed during N2O-O2 with halothane or isoflurane. Heart rate increased during isoflurane in O2. Cardiac output decreased significantly and similarly below awake levels during both halothane of isoflurane with and without N2O.     

Epidural anesthesia modifies cardiovascular responses to severe hypoxia in dogs

Hypoxia is a critical and sometimes fatal complication of anesthesia. Since there is little information on the cardiovascular response to hypoxia during epidural anesthesia, we assessed the effects of epidural anesthesia on the cardiovascular response to hypoxia and on survival in dogs.
We randomly assigned 36 mongrel dogs to one of three groups according to the anesthede technique used: the thoracic group (n=12) received thoracic epidural anesthesia plus general anesthesia, the thoracolumbar group (n=12) received thoracolumbar epidural anesthesia plus general anesthesia, and the control group (n=12) received general anesthesia alone. We monitored hemodynamics and plasma catecholamine concentrations and assessed survival in these groups during normocapnic hypoxia (FiO₂, 0.09 for 120 min).
During hypoxic challenge, PaCO₂ and PaO₂ values were similar in all groups. In both groups that received epidural anesthesia, heart rate, systolic and diastolic arterial pressures, and plasma epinephrine and norepine-phrine concentrations were lower and arterial pH was greater than in the control group. There was no significant difference in survival among groups.
Epidural anesthesia modified both the physiologic cardiovascular and catecholamine responses to hypoxia. Epidural anesthesia of the thoracic region did not appear to accelerate cardiac arrest, but it attenuated the development of metabolic acidosis during hypoxia.     

Reversal by acupuncture of cardiovascular depression induced with morphine during halothane anaesthesia in dogs

The cardiovascular effects of morphine sulphate and/or acupuncture by means of electrocautery at Jen Chung (Go-26) were studied in 35 dogs. All animals were maintained under anaesthesia with halothane 0.75 per cent supplemented by the intravenous administration of succinylcholine to allow controlled ventilation during a two hour period of monitoring. Cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure, central venous pressure, total peripheral resistance, [H⁺] (pH) PaC0₂, Pa0₂ and base deficit were measured in each dog. Morphine 0.5 mg ·kg^-1, administered alone as a single bolus, significantly (P < 0.05) decreased cardiac output, heart rate, mean arterial pressure, and significantly increased stroke volume and pulse pressure in dogs under halothane anaesthesia. Acupuncture by electrocautery alone induced a significant increase in cardiac output, stroke volume, heart rate, mean arterial pressure and pulse pressure with a significant decrease in total peripheral resistance following halothane. Acupuncture at Jen Chung (Go-26) for 10 minutes following the intravenous administration of morphine caused a significant increase in cardiac output, heart rate and mean arterial pressure with a significant decrease in central venous pressure and total peripheral resistance during halothane anaesthesia. The depressant effect of morphine on cardiac output, heart rate and mean arterial pressure in dogs under halothane anaesthesia appears to be reversed by acupuncture by electrocautery at Jen Chung (Go-26). Stimulation of this acupuncture locus could be helpful in resuscitating patients whose cardiovascular system is depressed by morphine and/or halothane anaes-thesia.