Localization of molecular halothane in phospholipid bilayer model nerve membranes.

The molecular motion and distribution of the inhalation anesthetic halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) in a phospholipid bilayer model nerve membrane preparation was studied using fluorine nuclear magnetic resonance. Bilayers containing stable free radicals at known depths were studied to measure possible localization of halothane within certain areas of the bilayer. Bilayer suspensions containing manganese ions in the aqueous phase were used to test the partition of halothane between the aqueous and lipid phases. It was found that halothane rapidly achieves complete exchange throughout the bilayer and the surrounding aqueous phase. The results provide experimental evidence against the formation of anesthetic clathrates hypothesized by Pauling and Miller in their theories of anesthesia.     

Effects of halothane on the pharmacokinetics of lidocaine in digitalis-toxic dogs

Following the production of digitalis toxicity in dogs as manifested by ventricular tachycardia, the pharmacokinetics of lidocaine treatment of the arrhythmia were determined during pentobarbitone anaesthesia and pentobarbitone-halothane anaesthesia. The elimination rate constants, beta and Ke, and the biological half life T1/2beta were statistically significantly increased during halothane anaesthesia. The volume of distribution was unchanged. The results indicate that the therapeutic loading dose of lidocaine need not be altered during halothane anaesthesia but if a constant infusion is used, the rate of infusion would have to be decreased four fold to avoid toxic plasma levels of lidocaine.     

Effects of halothane, isoflurane, enflurane, thiopental, and fentanyl on blood gas values in rats exposed to hypoxia

In rats pretreated with phenobarbital breathing 10% oxygen, subanesthetic doses of halothane, isoflurane, enflurane, thiopental, and fentanyl caused hepatic injury. Because hypoxia per se can produce such injury, we hypothesized that the anesthetic-induced injury resulted from increased hypoxemia secondary to respiratory depression. Male Sprague-Dawley rats were pretreated with phenobarbital; half of the rats were fed and the other half were deprived of food for the 24 h before study. Isoflurane anesthesia was given for the placement of a catheter into the femoral artery. After 1 h of recovery, the rats were exposed to 10% oxygen. Control samples were obtained and halothane, isoflurane, enflurane, thiopental, or fentanyl was administered. Rats given food had higher PaCO2 and lower pH values than starved rats. Also, arterial oxygen saturation (SaO2) tended to be lower in rats given food. At concentrations of 0.15-0.2 MAC or higher, halothane, isoflurane, and enflurane slightly increased PaCO2 values relative to values for a control group exposed only to hypoxia. However, SaO2 and PaO2 did not show significant drug-induced changes. Fentanyl transiently decreased PaO2 and SaO2. Thiopental caused no changes. Thus, we conclude that subanesthetic doses of anesthetics may depress the ventilatory response to hypoxia but that this depression is inconsistent and appears to be too small to cause hepatic damage.     

Effects of thiopental and halothane on spontaneous contractile activity induced in isolated ventricular muscles of the rabbit

To see if the known properties of thiopental of reducing Ca2+ and K+ fluxes across the myocardial sarcolemma account for its arrhythmogenic action, we have evaluated the effect of the anesthetic on spontaneous contractile activity induced in isolated rabbit papillary muscles. Thiopental (20 mg/l) prolonged the duration of sustained automaticity induced by stimulation at 1-2 Hz in the presence of 1 mumol/l isoproterenol. Thiopental (10, 20 mg/l) shortened the delay before the onset of Ba(2+)-induced automaticity, which involves a decrease in a K+ current. The minimum concentration of Ba2+ required to induce automaticity was lowered by thiopental. Whether spontaneous activities were induced by high frequency stimulation in the presence of isoproterenol or by Ba2+, thiopental lowered the frequency of spontaneous beats. Thus, thiopental appears to have both arrhythmogenic and antiarrhythmic actions, and the former may be unmasked when catecholamines counteract the latter by increasing Ca2+ influx. Like thiopental, halothane (1.0%) decreased the frequency and force of Ba(2+)-induced automatic beats but, unlike thiopental, prolonged the delay before the onset of Ba(2+)-induced automaticity, indicating that halothane acts as a purely antiarrhythmic agent in this type of automaticity.     

Differences in the myocardial depressant action of thiopental and halothane

The negative inotropic effects of thiopental (10-30 mg/L) and halothane (0.5-1.5%) were compared in rabbit papillary muscles under various stimulation conditions to gain insight into the action of these anesthetics on the availability of Ca2+ for the activation of myocardial contractile activity. The negative inotropic effect of thiopental was more pronounced at short (0.5 sec) than at long (1 sec) beat-to-beat intervals under steady-state conditions, and thiopental's effect on potentiated state contractions was less than that on steady-state contractions. For all variables studied, the effect of halothane was opposite that of thiopental. These results suggest that thiopental reduces the influx of extracellular Ca2+ and the amount of Ca2+ in sarcolemmal sites and slows the transport of intracellular Ca2+ within the sarcoplasmic reticulum from sites of uptake to sites of release without markedly diminishing the amount of intracellular Ca2+. Halothane does not appreciably affect the transport but does diminish the amount of Ca2+ within the sarcoplasmic reticulum that is available for the activation of myocardial contractile activity.     

Selective synaptic actions of thiopental and its enantiomers

BACKGROUND: There is conflicting evidence concerning the extent to which the intravenous general anesthetic thiopental acts by enhancing inhibitory gamma-aminobutyric acid-mediated (GABAergic) synaptic transmission or by inhibiting excitatory glutamatergic transmission. Yet there are remarkably few studies on the effects of thiopental on functional synapses. In addition, the degree of stereoselectivity of thiopental acting at synapses has yet to be tested. METHODS: The actions of thiopental and its enantiomers on GABAergic and glutamatergic synapses were investigated using voltage clamp techniques on microisland cultures of rat hippocampal neurons, a preparation that avoids the confounding effects of complex neuronal networks. RESULTS: Racemic thiopental markedly enhanced the charge transfer at GABAergic synapses without significantly affecting the peak of the postsynaptic current. At a surgically relevant concentration (25 microm), charge transfer was increased by approximately 230%. However, even at twice this concentration there were no significant effects on glutamatergic postsynaptic currents. At GABAergic synapses, thiopental acted stereoselectively, with the S(-) enantiomer being approximately twice as effective as the R(+) enantiomer at enhancing charge transfer. CONCLUSIONS: Thiopental stereoselectively enhances inhibitory GABAergic synaptic transmission in a way that reflects animal potencies, supporting the idea that this is a principal mode of action for this drug. The absence of any effect on glutamatergic synapses at surgically relevant concentrations suggests that the inhibition of these excitatory synapses is not an important factor in producing thiopental general anesthesia.     

Painless injection of propofol: pretreatment with ketamine vs thiopental, meperidine, and lidocaine

Propofol, a commonly used anesthetic, often causes pain on injection. Several methods have been described to reduce this pain, however, complete inhibition has not been achieved. Our randomized, placebo controlled, double blind study has been conducted to compare the analgesic efficacy of iv pretreatment of ketamine, meperidine, thiopental, lidocaine to minimize the injection pain of propofol. 125 patients ASA I and II were randomly allocated into 5 groups and received. Group K, ketamine 0.4 mg/kg; Group T, thiopental 0.5 mg/kg; Group M, meperidine 0.5 [corrected] mg/kg; Group L, lidocaine 1 mg/kg; Group S, saline 3 ml. All pretreatment drugs were made into 4 ml solutions and were accompanied by manual venous occlusion for 1 min, followed by tourniquet release and slowly IV administration of propofol. Pain was assessed with a four point scale. All treatment groups had a significantly lower incidence of pain than placebo group (p <0.05). However, it has been observed that pretreatment with ketamine was the most effective in attenuating pain associated with propofol injection (p <0.05). For painless injection of propofol, routine pretreatment with ketamine 0.4 mg/kg along with venous occlusion is recommended.     

The influence of halothane and thiopental on respiratory-related nerve activities in decerebrate cats

The effects of halothane and thiopental on the respiratory efferent activities in the phrenic, recurrent laryngeal and hypoglossal nerves were studied in decerebrate, paralyzed and artificially ventilated cats. Inhalation of halothane (2%, 90 s) and intravenous injection of thiopental (2-3 mg/kg) produced a similar change in the breathing pattern, characterized by an increase in respiratory frequency and a decrease in the respiratory burst discharge in the three nerves studied. Depression of the respiratory activity was greatest in the hypoglossal nerve, intermediate in the recurrent laryngeal nerve, and least in the phrenic nerve. Both drugs diminished the whole power spectral densities of the three nerves. Thiopental selectively attenuated the high frequency peaks of these spectra and shifted the peak frequencies to lower values. Bilateral section of the vagus and carotid sinus nerves had no effect on the action of thiopental on the respiratory neural activities, whereas it decreased, but did not eliminate, the action of halothane. The present results demonstrate that both halothane and thiopental produce a selective depression of the upper airway motor activities, with stronger effects on the hypoglossal nerve. Effects on the peripheral receptors and the central respiratory drives differ between the two drugs.     

Effects of lidocaine with and without epinephrine on plasma epinephrine and lidocaine concentrations and hemodynamic values during third molar surgery.

Lidocaine with epinephrine is currently the most common local anesthetic agent used for impacted third molar surgery. The purpose of the present study was to define the adverse hemodynamic effects and plasma concentrations of lidocaine and epinephrine on 17 healthy patients during the impacted teeth operations. Arterial blood pressure (systolic blood pressure, diastolic blood pressure), heart rate, peripheral oxygen saturation range, and electrocardiography were measured by an automatic noninvasive pressure device and monitor. High-performance liquid chromatography was used to measure the changes of plasma concentrations of epinephrine and lidocaine from blood samples taken 5 different times during the operation. We concluded that lidocaine-epinephrine is effective local anesthetic and had no important adverse events in healthy patients during the third molar surgery.     

Effects of halothane on synaptic neurotransmission to medullary expiratory neurons in the ventral respiratory group of dogs.

BACKGROUND: The activity of canine expiratory neurons is primarily dependent on N-methyl-D-aspartic acid (NMDA)-receptor mediated excitatory chemodrive inputs and a powerful inhibitory gain modulatory mechanism mediated via gamma-aminobutyric acidA (GABA(A)) receptors. We examined whether the depressant effect of halothane on expiratory neuronal activity is primarily caused by a reduction in glutamatergic excitation or a potentiation of the inhibitory mechanism. METHODS: Experiments were performed in halothane-anesthetized, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of a halothane dose increase from one minimum alveolar concentration (MAC) to 2 MAC on extracellularly recorded expiratory neuronal activity was studied before and during complete GABA(A) receptor blockade by localized picoejection of bicuculline close to the neuron. Complete blockade of the inhibitory mechanism allowed differentiation between the effects of halothane on overall NMDA-mediated excitation and on GABA(A)-mediated inhibition. RESULTS: The spontaneous activity of 12 expiratory neurons was significantly depressed (18.1%) by the 1-MAC halothane dose increase. Overall glutamatergic excitation was depressed 38.3+/-12.3% (mean +/- SD) by the 1-MAC halothane increase. The prevailing GABA(A)ergic attenuation of neuronal output decreased significantly from 49.5+/-10 to 32.0+/-10.4%. Thus overall inhibition was reduced by halothane by 33.5+/-17.2%. CONCLUSIONS: These results suggest that the depressive effect of a 1-MAC halothane dose increase on expiratory neuronal activity in our in vivo preparation with an intact neural network was mainly caused by a reduction of synaptic excitatory mechanisms and not an enhancement of synaptic inhibitory mechanisms.     

The volatile anesthetics, halothane, enflurane and isoflurane, influence the distribution of thiopental in man differently

In man, a change of thiopental pharmacokinetics was observed under halothane anesthesia, but not when patients were anesthetized with enflurane and isoflurane. After an initial subanesthetic dose of 50 mg thiopental, the concentrations in serum (T) were determined over 15 min (4 samples). From these T-values the pharmacokinetic parameters Vc (central volume of distribution), t1/2 alpha and Cl were established (control). 16 min after the first thiopental dose, one of the inhalation anesthetics was administered (randomized). After 45 min exposure to the respective inhalation anesthetic (2-3 MAC in combination with N2O, steady-state a second dose of 50 mg thiopental was injected and the T-values were determined again over 15 min. The T-values of the control course varied considerably; the logarithmic frequency distribution revealed two distinct subgroups of patients, A and B, with characteristic Vc and t1/2 alpha. Both subgroups were influenced by the volatile anesthetics in a similar way with regard to pharmacokinetic parameters. With halothane, Vc was decreased and t1/2 alpha was shortened. In contrast, enflurane and isoflurane did not affect the pharmacokinetic parameters.     

Anesthesia for arthroscopy of the knee: propofol versus thiopental and halothane

Sixty ASA I or II patients, who underwent general anaesthesia for arthroscopy of the knee, were separated into two groups. Induction was performed either with thiopentone 7 mg . kg-1 (group I) or with propofol 2.5 mg . kg-1 (group II). All patients were intubated and ventilated. Dextromoramide was used as analgesic. Maintenance of anaesthesia was obtained with halothane inhalation (group I) or by continuous automatic injection of propofol at a dose of 9 mg . kg-1 . h-1 (group II). Induction and maintenance were satisfactory in both groups. Pulse rate was stable at induction and intubation for the propofol group, whereas it increased at both stages of anaesthesia with thiopentone; it fell moderately in both groups afterwards. Systolic and diastolic blood pressures dropped more in the propofol group after induction, with a maximum decrease of 20%. Recovery was significantly more rapid and comfortable with propofol than with thiopentone.     

Effects of halothane and fentanyl anesthesia on plasma beta-endorphin immunoreactivity during cardiac surgery

We studied the effects of halothane anesthesia (n = 6) and fentanyl anesthesia (n = 9; 50-100 micrograms/kg) on plasma beta-endorphin immunoreactivity as a measure of stress response during coronary artery bypass grafting, including cardiopulmonary bypass. Plasma levels of beta-endorphin immunoreactivity measured prior to induction, after induction, after intubation, after skin incision, during cardiopulmonary bypass, and on leaving the operating room were significantly higher in patients given halothane during cardiopulmonary bypass and on leaving the operating room than they were in patients given fentanyl.