Ventricular fibrillation refractory

Pharmacology Therapeutic concentrations of lidocaine attenuate phase 4 diastolic depolarization, decrease automaticity and cause a decrease or no change in excitability and membrane responsiveness. Action potential duration and effective refractory period (ERP) of Purkinje fibers and ventricular muscle are decreased, while the ratio of ERP to action potential duration is increased. Lidocaine raises ventricular fibrillation threshold. AV nodal conduction time is unchanged or shortened. Lidocaine increases the electrical stimulation threshold of the ventricle during diastole. 

It is indicated in tachyarrhythmias associated with WPW syndrome, atrial flutter and fibrillation, paroxysmal tachyarrhythmias not responding to other agents. Ventricular tachycardia and ventricular arrhythmia refractory to other treatment. 

Mouritzen C. V. and Andersen M. N. (1966) Mechanisms of ventricular fibrillation during hypothermia relative changes in myocardial refractory period and conduction velocity. J. Thorac. Cardiovasc. Surg. 51, 585-589. 

Actions Bretylium has a number of direct and indirect electro-physiological actions, the most prominent of which are prolongation of the refractory period and raising of the intensity of the electrical current necessary to induce ventricular fibrillation in the His-Purkinje system. 

Erythromycin has antidysrhythmic properties similar to those of Class lA antidysrhythmic drugs, and causes an increase in atrial and ventricular refractory periods. This is only likely to be a problem in patients with heart disease or in those who are receiving drugs that delay ventricular repolarization (5). High-doses intravenously have caused ventricular fibrillation and torsade de pointes (6). Each episode of dysrhythmia, QT interval prolongation, and myocardial dysfunction occurred 1-1.5 hours after erythromycin infusion and resolved after withdrawal. 

Arrhythmias occur within a few seconds after reperfusion, following ischemic periods of 10-30 min long. They start by a spontaneous stimulus in the reperfused zone and change afterward in a re-entry multiple wavelet type of ventricular tachycardia (VT) or ventricular fibrillation (VF). Extremely short action potential, short refractory period and slow conduction are the main contributing factors. Increased hyperpolarization and elevated intracellular calcium that act negatively on gap conductance impair conduction. Unidirectional conduction is favored by the marked heterogeneity in extracellular potassium, action potential and refractory period. The extra stimulus is initiated in the reperfused zone, probably by early (EAD) and late (DAD) afterdepolirizations. 

Harrison EE. Lidocaine in prehospital countershock refractory ventricular fibrillation. Ann Emerg Med 1981 10 420M23. 96. 

Van Dongen and Sanchez (29) compared the antifibrillatory activity of hydroquinidine with a specially purified quinidine. They present the viewpoint that the activity of commercially prepared quinidine in auricular fibrillation is based entirely on its content of dihydroquinidine. They used the rabbit as a test animal and observed that dihydroquinidine produced an increase in the electrical stimulus thresholds required to provoke premature systoles, tachycardia, auricular fibrillation, and ventricular fibrillation. With dihydroquinidine there was also a decrease in the duration of fibrillation which occurs after the electrical stimulus is ended. Dihydroquinidine, they found, could prevent the heterotropic rhythms (largely ventricular arrhythmias) provoked by the intravenous injection of barium chloride or epinephrine. They also observed that hydroquinidine, at 8 mg./kg., prolonged the auricular conduction time by 50%, the AV conduction time by 30 %, and increased the refractory period by 15%. Pure quinidine was inactive at this dosage. 

Additional evidence for an antifibrillatory action for ajmaline was supplied by van Dongen (13). He found that in the decerebrate cat 0.5 mg./kg. ajmaline increased the amount of faradic current required to produce auricular fibrillation, ventricular fibrillation, and post-stimulus arrhythmias. This action differs from that of quinidine, which prolonged auricular conduction time and atrioventricular conduction times by 52-100 %, while ajmaline did not alter refractory periods or conduction times. Heterotropic cardiac rhythms were produced by a variety of means (barium chloride, epinephrine, and strophantin-ephedrine) which in all cases may be prevented by ajmaline. 

C. Clinical Uses and Toxicities Bretylium is used only in the treatment of refractory post-myocardial infarction arrh)l hmias, eg, recurrent ventricular fibrillation. This rarely used drug may... 

Initiating factors, often multifactorial, include ectopic beats, ischemia, alteration in conduction or refractoriness, electrolyte disturbances, drugs, and autonomic perturbations. Factors that result in sudden death because of a ventricular arrhythmia are complex and understood poorly. Any simphstic medical approach that alters the arrhythmic substrate (such as drug therapy or even catheter ablation) may fail to reduce risk and may make things worse. Alternatively, a defibrillation shock, timed properly, can stop ventricular fibrillation. 

Undersensing. Inappropriate delivery of pacing stimuli when the pacemaker system fails to sense P-waves or QRS complexes defines undersensing. Delivery of stimuli can be harmful if they occur during the atrial and ventricular relative refractory periods that are predisposed to tachyarrhythmia induction. Of particular concern is the induction of ventricular tachycardia or fibrillation when ventricular pacing occurs on the terminal portion of the T-wave ( R-on-T ), especially in the critical care setting where concomitant ischemia, metabolic and electrolyte abnormalities are frequently present. 

Compound 4 is an inhibitor of the slowly activating delayed rectifier K(+) current which repolarizes the cardiac ventricular cell membrane. As a result, the refractory period of the spontaneously contracting heart muscle is prolonged and the cardiac action potential is delayed. This helps to reduce the potentially fatal cardiac ventricular fibrillation which can result from ischaemic heart damage, leading to myocardial infarction. 

Digitalis is the drug of choice in atrial fibrillation for controlling ventricular rate. Its effect is due to the prolongation of the refractory period of the conducting tissue. The dose in so adjusted as to maintain the ventricular rate of 60 to 80 beats per minute at rest and approximately 100 beats per minute during light exercise. 

Purkinje system, ventricular muscle Slight 4- refractory period Extra systoles, tachycardia, fibrillation... 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

These agents appear to be similar in efficacy to verapamil in the management of supraventricular arrhythmias, including rate control in atrial fibrillation. An intravenous form of diltiazem is available for the latter indication and causes hypotension or bradyarrhythmias relatively infrequently. Bepridil also has action potential- and QT-prolonging actions that theoretically may make it more useful in some ventricular arrhythmias but also create the risk of torsade de pointes. Bepridil is only rarely used, primarily to control refractory angina. 

Approximately 25% of all patients with hypertrophic cardiomyopathy (HCM) have latent left ventricular outflow obstruction with an intraventricular gradient (I). Pathophysiologic features are asymmetric hypertrophy of the septum and a systolic anterior movement of the anterior leaflet. Medical treatment includes betablockers, and calcium antagonists of the verapamil type. Approximately 5— 10% of the patients with outflow obstruction are refractory to such negative inotropic therapy (2). Positive inotropic drugs such as digitalis or sympathomimetics are strictly contraindicated. In the presence of atrial fibrillation, anticoagulation therapy should be started. Since endocarditis is more common in patients with HCM because of turbulence in the left ventricle, prophylactic antibiotics should be administered for periods of potential bacteraemia. 

Endogenous norepinephrine stimulates cardiac beta receptors. Receptor-linked cAMP-dependent protein kinases phosphorylate calcium channels to increase intracellular calcium. Elevated intracellular calcium increases conduction velocity (phase 0) and decreases the threshold potential in normal SA and AV node cells (see Figure 12.13). Beta blockers slow spontaneous conduction velocity in the SA node by approximately 10-20 percent. In addition, beta blockers can slow conduction velocity while increasing the refractory period of the AV node. These effects control the ventricular rate in atrial fibrillation or flutter and terminate paroxysmal supraventricular tachycardias. They are also safer, although somewhat less effective, than other drugs for suppression of premature ventricular complexes (PVCs). Drugs in this class approved by the FDA for treatment of various arrhythmias include propranolol, acebutolol, and esmolol. Problems with the beta blockers include drowsiness, fatigue, impotence, and depressed ventricular performance. 

Digoxin (see p. 158) shortens the refractory period in atrial and ventricular myocardial cells while prolonging the effective refractory period and diminishing conduction velocity in Purkinje fibers. Digoxin is used to control the ventricular response rate in atrial fibrillation and flutter. At toxic concentrations, digoxin causes ectopic ventricular beats that may result in ventricular tachycardia and fibrillation. [Note This arrhythmia is usually treated with lidocaine or phenytoin.]... 

Atrial flutter, benefiting by the vagus nerve action of shortening the refractory period of the atrial muscle so that flutter is converted to fibrillation (in which state the ventricular rate is more readily controlled). Electrical cardioversion is preferred. 

Atrial dysrhythmias (including atrial fibrillation) and less often, ventricular extra beats (including refractory ventricular tachycardia and fibrillation) (11-13). 

The adverse effects of propafenone in placebo-con-trolled trials in patients with atrial tachydysrhythmias have been reviewed (16). The following effects were reported after single intravenous oral doses to produce conversion of atrial fibrillation to sinus rhythm. Non-cardiac adverse effects included mild dizziness. Mild hypotension was also noted, but only required withdrawal of propafenone in one of 29 patients in one study. There have been prodysrhythmic effects in several studies, including atrial flutter with a broad QRS complex, which can occur in up to 5% of cases in some cases atrial flutter can have a rapid ventricular response due to 1 1 atrioventricular conduction, which has been attributed to slowing of atrial conduction and reduced refractoriness of the atrioventricular node. Other prodysrhythmic effects in a few patients included sinus bradycardia with sinus pauses and effects on atrioventricular conduction. 

A 65-year-old woman, who had had normal preoperative serum electrolytes and a normal QT interval with sinus rhythm, received hydroxyzine and atropine premedication followed by thiopental and vecuronium for anesthetic induction. Endotracheal intubation was difficult and precipitated atrial fibrillation, which was refractory to disopyramide 100 mg. Anesthesia was then maintained with sevoflurane 2% and nitrous oxide 50%. Ten minutes later ventricular tachycardia ensued, refractory to intravenous lidocaine, disopyramide, and magnesium. DC cardioversion resulted in a change to a supraventricular tachycardia, which then deteriorated to torsade de pointes. External cardiac massage and further DC cardioversion were initially unsuccessful, but the cardiac rhythm reverted to atrial fibrillation 10 minutes after the sevoflurane was switched off. Two weeks later she had her operation under combined epidural and general anesthesia, with no changes in cardiac rhythm. 

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