Epinephrine halothane

Buzik SC, Fatal interaction Halothane, epinephrine and tooth implant surgery. Can Pharm 7(1990) 123, 68-9 and 81. 

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

Diphenhydramine hydrochloride, 3,173 Diphenoxylate hydrochloride, 7,149 Disulflram, 4, 168 Dobutamine hydrochloride, 8,139 Droperidol, 7,171 Echothiophate iodide, 3,233 Epinephrine, 7, 193 Ergotamine tartrate, 6,113 Erythromycin, 8,139 Erythromycin estolate, 1, 101 2, 573 Estradiol valerate, 4,192 Ethambutol hydrochloride, 7,231 Ethynodiol diacetate, 3,253 Fenoprofen calcium, 6,161 Flucytosine, 5,115 Fludrocortisone acetate, 3, 281 Fluorouracil, 2,221 Fluoxymesterone, 7,251 Fluphenazine enanthate, 2, 245 4,523 Fluphenazine hydrochloride, 2,263 4,518 Gluthethimide,5,139 Gramicidin, 8,179 Griseofulvin, 8,219 Halcinonide, 8,251 Halothane, 1, 119 2,573 Hexetidine, 7,277 Hydralazine hydrochloride, 8,283 Hydroflumethiazide, 7,297 Hydroxyprogesterone caproate, 4,209 Hydroxyzine dihydrochloride, 7,319 Iodipamide, 3,333 Isocarboxazid, 2, 295... 

In an undated study, HCFC-141b was administered to male SpragueDawley rats at concentrations of 5,000, 10,000, or 20,000 ppm for 30 min (Eger, unpublished data). As exposure continued, bolus intravenous epinephrine, characterized as three times the dose that produced arrhythmias in the same rats anesthetized with halothane, was administered. The dose of epinephrine was defined as a maximum of 12 fig/kg. For this study, three or more premature ventricular contractions was considered an arrhythmic response (Table 4—5). Marked arrhythmias occurred at all concentrations. The author further compared the concentrations of halothane and HCFC-141b that produced arrhythmias with administration of various doses of exogenous epinephrine. The nominal chamber concentration for HCFC-141b did not differ from that of halothane. Furthermore, the arrhythmias were characterized as relatively mild and within acceptable limits for surgical anesthesia in humans. 

Cardiac arrhythmias were induced in rats injected with exogenous epinephrine and exposed to HCFC-141 b at 5,000 ppm. However, the intravenous dose of epinephrine required was 3-fold that which induced arrhythmias in the same rats administered halothane, a common clinical anesthetic. Furthermore, the arrhythmias were characterized as mild. The threshold for cardiac sensitization for dogs was approximately 5,200 ppm. Deaths occurred in one study at 10,000 ppm and in another study at 20,000 ppm (with no deaths between concentrations of 9,000 and 19,000 ppm). 

Halothane administration can result in a marked reduction in arterial blood pressure that is due primarily to direct myocardial depression, which reduces cardiac output. The fall in pressure is not opposed by reflex sympathetic activation, however, since halothane also blunts baroreceptor and carotid reflexes. Systemic vascular resistance is unchanged, although blood flow to various tissues is redistributed. Halothane also sensitizes the heart to the arrhythmogenic effect of catecholamines. Thus, maintenance of the patient s blood pressure with epinephrine must be done cautiously. 

Enflurane produces a dose-related decrease in systemic arterial blood pressure secondary to reductions in cardiac output and systemic vascular resistance. There is evidence that cardiac output is partially maintained by a compensatory increase in heart rate. This effect seems dependent on a degree of hypercardia and does not occur during controlled ventilation. Enflurane and halothane depress myocardial contractility to a similar extent and less than isoflurane. Enflurane does not sensitise the heart to the effects of catecholamines to any significant extent and adrenaline (epinephrine) may be given subcutaneously for control of bleeding. 

The duration of action of a local anaesthetic is proportional to the time that the drug remains bound to the sodium channels. Measures that prolong contact time will prolong the duration of the local anaesthetic effect. Cocaine has a vasoconstricting effect on blood vessels and prevents its own absorption. Many local anaesthetics are prepared with adrenaline (epinephrine) in order to achieve this effect. Concentrations are usually of the order of 1 200000 or more dilute than this. Care should be exercised when using adrenaline-containing solutions in the presence of halothane as it is known to sensitise the myocardium to the effects of catecholamines. 

Halothane and Adrenaline (S) Anaesthetic sensitises other halogenated (epinephrine) and myocardium to adrenaline,... 

Kamibayachi T, Hayashi Y, Mammoto T et al. (1995) Thoracic epidural anesthesia attenuates halothane-induced myocardial sensitization to dysrhythmogenic effect of epinephrine in dogs. Anesthesiology 82 129-134 Kief H, Bahr H (1970) Epidural tolerance of artecaine in dogs. Personal communication... 

Lidocaine is used in cardiovascular medicine for its antiarrhythmic properties (see Ch. 12). More recently, studies have looked at the i.v. administration of lidocaine to horses with colic (see Ch. 6). It appears that i.v. lidocaine (without epinephrine (adrenaline)) may have some desirable effects on jejunal distension and peritoneal fluid accumulation and is well-tolerated periop-eratively in horses with colic (Brianceau et al 2002). In addition, i.v. lidocaine reduced the halothane MAC significantly (Doherty Frazier 1998) in ponies. 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, beta-blockers, cimetidine, donidine, digoxin, diltiazem, disopyramide, ephedrine, epinephrine, ergot alkaloids, guanethidine, halothane, isoprenaline, lidocaine, noradrenaline, NSAIDs, phenylephrine, quinidine, reserpine, verapamil... 

Sinus bradycardia and atrioventricular rhythms occur frequently during halothane anesthesia but usually are benign and result mainly from a direct depressive effect of halothane on sinoatrial node discharge. Halothane also can sensitize the myocardium to the arrhythmogenic effects of epinephrine. 

Intravenous anesthesia with barbiturates can increase the incidence of ventricular arrhythmias, especially when epinephrine and halothane also are present. Direct depression of cardiac contractility occurs only when doses several times those required to cause anesthesia are administered. 

Halothane sensitizes the myocardium to catecholamines arrhythmias may occur in patients with cardiac disease who have high circulating levels of epinephrine and norepinephrine (eg, patients with pheochromocytoma). Other modem anesthetics are considerably less arrhythmo-genic. The answer is (C). 

Isoflurane ha.s similar actions to halothane but is less cardiodepre.s-sant and doe.s not sensitize the heart to epinephrine (adrenaline). It causes dose-related hypotension by decreasing systemic vascular resistance. Only 0.2%i of the absorbed dose is metabolized and so isoflurane Ls very unlikely to cause hepatotoxiciiy,... 

Halothane is known to cause arrhythmias and it has been suggested that it may increase susceptibility to the adverse cardiac effect of beta-agonist bronchodilators, which can cause arrhythmias. Note that beta agonists such as terbutaline are sympathomimetics (see Table 24.1 , (p.879)), like adrenaline (epinephrine), which has also been shown to cause arrhythmias in the presence of halothane (see Anaesthetics, general + Inotropes and Vasopressors , p.99). 

Patients anaesthetised with inhalational anaesthetics (particularly cyclopropane and halothane, and to a lesser extent desflurane, enflurane, ether, isoflurane, methoxyflurane, and sevoflurane) can develop cardiac arrhythmias if they are given adrenaline (epinephrine) or noradrenaline (norepinephrine), unless the dosages are very low. Children appear to be less susceptible to this interaction. file addition of adrenaline to intrathecal tetracaine enhances the sedative effects of propofol. 

Katz RL, Matteo RS, Rapper EM. The injection of epinephrine during general anesthesia with halogenated hydrocarbons and cyclopropane in man. 2. Halothane. Anesthesiology (1962) 23, 597-600,... 

Johnston RR, Eger El, Wilson C, A comparative interaction of epinephrine with enflurane, isoflurane, and halothane in man. Anesth Analg (1976) 55, 709-12. 

Karl HW, Swedlow DB, Lee KW, Downes JJ. Epinephrine-halothane interactions in children. Anesthesiology (1983) 58, 142-5. 

Phenylephrine is a sympathomimetic, and as such may carry some risk of potentiating arrhythmias if it is used with inhalational anaesthetics such as halothane -see Anaesthetics, general + Inotropes and Vasopressors , p.99. However, it is considered that it is much less likely than adrenaline (epinephrine) to have this effect, since it has primarily alpha-agonist activity. ... 

The answer is 3 [IIC Tible 15-1]. The halocarbon compounds (e.g., chloroform, halothane, freon) and the fumes from overheated synthetic fluorine-containing resin-coated (Teflon) cookware are indirectly car-diotoxic because they sensitize the heart to sympathomimetic amines such as epinephrine. Following exposure to these substances, even the release of endogenous epinephrine associated with stress can pose a hazard. Yew plants contain a cardioactive alkaloid that inhibits depolarization and produces bradycardia and diastolic heart block. Furazolidone interferes with intermediary metabolism, resulting in a lack of energy arid a dilated, weak heart "round heart." Digitalis aflecTs potassium content in the cell. Monensin is an ionophore that alters the sodium-to-calcium ratio arid leads Id cardiac necrosis. 

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