Responsabile UAS “Trombosi Venosa Profonda ed Embolia Polmonare”
Responsabile CDF BLSD IRC “Emersan Lateranum”
SC Medicina Interna I° per l'Urgenza
TORSADES DE POINTES
KEY-WORDS: Torsades de pointes
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INTRODUCTION
CLINICAL
WORKUP
TREATMENT
MEDICATION
FOLLOW-UP
MISCELLANEOUS
BIBLIOGRAPHY
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Background: Torsades de pointes (TDP), often referred to as torsade, is an uncommon variant of ventricular tachycardia. The underlying etiology and management of torsades are, in general, quite different from garden variety ventricular tachycardia (VT). The management of torsade with group IA, antidysrhythmic drugs can have disastrous consequences. Differentiating between these entities is therefore critically important.
Pathophysiology: Torsade is defined as a polymorphous ventricular tachycardia in which the morphology of the QRS complexes vary from beat to beat. The ventricular rate can range from 150/min-250/min. In the original report, there was a regular variation of the morphology QRS vector from positive to net negative and back again. This was symbolically termed torsades de pointes or twisting of the point about the isoelectric axis because it reminded the original authors of the torsade de point dance movement in ballet. In most cases there is polymorphism, but there may not be regularity to the axis changes.
The definition also requires that the Q-T interval be markedly increased (usually to 600msec or greater). Cases of polymorphous VT, which are not associated with a prolonged Q-T interval are treated as generic VT. Torsade usually occurs in bursts that are not sustained, thus, one usually has a rhythm strip showing the patient's base-line Q-T prolongation.
The underlying basis for this rhythm disturbance is a delay inthe phase III of the action potential. This prolonged period of repolarization and the inhomogeneity of repolarization times among myocardial fibers allow the dysrhythmia to emerge. The initiating electrophysiologic mechanism may be triggered activity or reentry.
Frequency:
- In the US : The incidence of torsades is still unknown.
Mortality/Morbidity: There are 300,000 sudden cardiac deaths per year in the U.S. TDP accounts for probably less than 5%.
Sex: Females are 2-3 times more likely to develop TDP.
- Females have more QT prolongation secondary to drug therapy.
- Congenital long QT syndrome is autosomal dominant, but shows greater frequency of expression and a greater lengthening of the QT interval in females than in their male relatives.
History:
- Patients should be asked about previous cardiac events or syncope and any medications they are presently using.
- A history of congenital deafness or a family history of sudden death may indicate a long QT syndrome.
Physical: No physical findings are typical of TDP.
Causes:
- The prolongation of the Q-T interval may be congenital, as seen in the Jervell and Lange-Nielson syndrome (i.e., congenitally long Q-T, associated with congenital deafness) and the Romano Ward syndrome (i.e., isolated prolongation of Q-T interval). Both of these syndromes are associated with sudden death either due to primary ventricular fibrillation or torsade that degenerates into ventricular fibrillation.
- The acquired conditions that predispose one to torsade either decrease the outward potassium current or interfere with the inward sodium or calcium currents or fluxes.
- The electrolyte disturbances that have been reported to precipitate torsade include hypokalemia and hypomagnesemia.
- This in turn, causes a delay in phase III, reprolongation and forms the substrate for the emergence of the dysrhythmia.
- The antiarrhythmic drugs reported to be etiologic include class IA agents (e.g., quinidine procainamide and disopyramide), class IC agents (e.g., encainide and flecainide) and class III agents (e.g., sotalol and amiodarone).
- Drug interactions with the antihistamines astemizole and terfenadine can precipitate torsade and these drugs should never be used with class IA, IC or III drugs.
- Astemizole and terfenadine in high dosage or when used in combination with the azole antifungal drugs or the macrolide antibiotics, have been reported to precipitate torsade and sudden death.
- Interestingly, grapefruit juice has been shown to slow the hepatic metabolism of these antihistamines as well as other drugs and to prolong the Q-T interval in patients taking astemizole and terfenadine (recently taken off the market by the FDA).
- The clinical implications of this experiment of nature are unclear.
- Other drugs that prolong the Q-T interval that have been implicated in cases of torsade include the phenothiazines, tricyclic antidepressants, lithium carbonate and the anthracycline chemotherapeutic agents (e.g., Adriamycin and daunomycin).
- Risk Factors:
- Female gender
- History of syncope or resuscitated arrest
- Congenital deafness
- Family history of sudden death
Lab Studies:
- Potassium, magnesium and calcium levels
Other Tests:
- Electrocardiogram (ECG): Once in sinus rhythm, the QT interval should be examined.
Prehospital Care: EMS should institute immediate ACLS protocol for ventricular tachycardia.
Emergency Department Care: Torsade is an inherently unstable rhythm. As such, it is prone to revert to more stable rhythms spontaneously and also to recurrences. Unfortunately, it is also subject to degeneration into ventricular fibrillation. Therefore, the onus is on the physician to begin therapy as soon as it is clear that the rhythm fulfills the criteria for torsade.
- The first line of therapy is to treat hypokalemia if it is the precipitating factor and to administer MgSO 4 in a dose of 2.0- 4.0 gm IV as initial pharmacotherapy.
- Magnesium is usually very effective even in the patient with a normal magnesium level.
- If this fails repeat the initial dose, but the danger of hypermagnesemia (depression of neuromuscular function) requires close monitoring.
- Other therapies that have been reported to be effective include overdrive pacing and isoproterenol infusion.
- The patient with torsade in extremis should be treated with electrical cardioversion or defibrillation. There are anecdotal reports of successful conversion with Dilantin and lidocaine.
- Patients with the congenital long Q-T syndromes are thought to have an abnormality of sympathetic balance or tone and are treated with beta-blockers. If the patient breaks through this therapy and enters the ED in torsade, a short acting beta-blocker, such as esmolol can be tried.
- There are a few case reports of successful conversion using phenytoin and overdrive pacing. Electrical cardioversion should be attempted in patients unresponsive to this therapy.
- Long-term management in some cases has included cervical sympathectomy and the use of the implantable pacemaker/defibrillator.
- Shortening the action potential will decrease the likelihood of immediate recurrence. Pacing or administration of isoproterenol to a rate of 90-100 is effective.
- All QT-prolonging drugs should be withdrawn.
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Magnesium and potassium are first line therapies in the treatment of torsades de pointes. Isoproterenol and short-acting beta-blockers have also been used. In addition, for the treatment of primary torsades associated with the congenital prolonged Q-T syndromes, the drug therapy of choice is a beta-blocker. In primary and secondary torsades-overdrive, a pacemaker is an appropriate secondary therapy. Conversely, in the treatment of recurrent Torsades, implantable defibrillators are used as prophylaxis. If the patient is unstable, electrical cardioversion or defibrillation should be carried out at once.
Drug Category: Electrolytes - Electrolytes are considered therapeutic alternatives for the treatment of torsade de pointes. It is important to assess patients for underlying electrolyte abnormalities that may cause refractory dysrhythmia. Some of the electrolyte abnormalities associated with torsades de pointes include hypokalemia, and hypomagnesemia. Electrolytes also reduce the arrhythmic effects of offending drugs.
Drug Name |
Magnesium Sulfate - It is the DOC for the treatment of torsade de pointes, known or suspected hypomagnesemia, or severe refractory VF. |
Adult Dose |
Administer 1- 2 g IV diluted in 100 ml of D5W over a period of 1-2 min May repeat q4h with close monitoring of deep tendon reflexes. |
Pediatric Dose |
Torsades de pointes: Safety and efficacy have not been established. Hypomagnesemia: Administer 25-50 mg/kg/dose q4-6h for 3-4 doses. A maximum single dose of 2 g may also be administered and repeated if hypomagnesemia persists. |
Contraindications |
Avoid use in patients with documented hypersensitivity to magnesium and in those diagnosed with heart block, myocardial damage, Addison's disease, or severe hepatitis. |
Interactions |
Concurrent use with nifedipine may cause hypotension and neuromuscular blockade. Magnesium may also increase the neuromuscular blockade seen with aminoglycosides and potentiate the neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine. In addition, it may increase the CNS effects and toxicity of CNS depressants, betamethasone, and cardiotoxicity of ritodrine. |
Pregnancy |
A - Safe in pregnancy |
Precautions |
Magnesium may alter cardiac conduction leading to heart block in digitalized patients. Respiratory rate, deep tendon reflex, and renal function should be monitored when this electrolyte is administered parenterally. Use caution when administering the magnesium dose since it may produce significant hypertension or asystole. |
Drug Name |
Potassium Chloride - It is the first line therapy in the treatment of torsades de pointes. Potasium is essential for the maintenance of intracellular tonicity, transmission of nerve impulses, contraction of cardiac, skeletal, and smooth muscles, and maintenance of normal renal function. Gradual potassium depletion occurs via renal excretion, through GI loss or because of low intake. Depletion usually results from diuretic therapy, primary or secondary hyperaldosteronism, diabetic ketoacidosis, severe diarrhea, if associated with vomiting, or inadequate replacement during prolonged parenteral nutrition. Potassium depletion sufficient to cause 1 mEq/L drop in serum potassium requires a loss of about 100-200 mEq of potassium from the total body store. |
Adult Dose |
Serum levels greater than 2.5 mEq/L: Administer 10 mEq over 1 h, and prn based on frequently obtained lab values. Do not exceed 200 mEq/24h Serum levels less than 2.5 mEq/L: Administer 40 mEq over 1 h, and prn based on frequently obtained lab values. Do not exceed 400 mEq/24h |
Pediatric Dose |
Initially, administer 1 mEq/kg IV over 1-2 h and prn based on frequently obtained lab values. |
Contraindications |
Avoid use in patients diagnosed with, hyperkalemia, renal failure and conditions in which potassium retention is present and those with oliguria or azotemia, crush syndrome, severe hemolytic reactions, anuria, and adrenocortical insufficiency. |
Interactions |
Concurrent use with ACE inhibitors may result in elevated serum potassium concentrations. Potassium-sparing diuretics and potassium-containing salt substitutes can produce severe hyperkalemia. In patients taking digoxin, hypokalemia may result in digoxin toxicity. Use caution if discontinuing a potassium preparation in patients maintained on digoxin. |
Pregnancy |
A - Safe in pregnancy |
Precautions |
Do not infuse rapidly. High plasma concentrations of potassium may cause death due to cardiac depression, arrhythmias, or arrest. Plasma levels do not necessarily reflect tissue levels. Monitor potassium replacement therapy whenever possible by continuous or serial ECG. When a concentration greater than 40 mEq/L is infused, local pain and phlebitis may also follow. |
Drug Category: Adrenergic agonist - Adrenergic agents are agents that alter the electrophysiologic mechanisms responsible for arrhythmic disturbances.
Drug Name |
Isoproterenol - It has beta-1- and beta-2-adrenergic receptor activity. It binds beta-receptors of the heart, smooth muscle of the bronchi, skeletal muscle and vasculature and alimentary tract. It has positive inotropic and chronotropic actions. |
Adult Dose |
Dilute 1 ml of 1:5000 solution (0.2mg) to 10 ml with Sodium Chloride or 5% Dextrose Injection and administer an initial dose of 0.02-0.06 mg IV (1-3 ml of diluted solution). For subsequent doses, administer 0.01-0.2 mg IV (0.5-10 ml of diluted solution) to achieve a heart rate of 90-100 beats/min. Alternatively, dilute 10 ml of 1:5000 solution (2mg) in 500 ml of D5W or dilute 5ml of 1:5000 solution (1 mg) in 250 ml of D5W and administer 5 mcg/min (1.25 ml/min of diluted solution) to achieve a heart rate of 90-100 beats/min. |
Pediatric Dose |
Safety and efficacy in children have not been established. The American Heart Association recommends an initial infusion rate of 0.1 mcg/kg/min and titrate to HR effect. |
Contraindications |
Avoid use in patients diagnosed with tachyarrhythmias, ventricular arrhythmias that require inotropic therapy, tachycardia or heart block caused by digitalis intoxication, and angina pectoris. |
Interactions |
Bretylium increases the action of vasopressors on adrenergic receptors which may in turn result in arrhythmias. Guanethidine may increase the effect of direct-acting vasopressors, possibly resulting in severe hypertension. Tricyclic antidepressants may potentiate the pressor response of direct-acting vasopressors. |
Pregnancy |
C - Safety for use during pregnancy has not been established. |
Precautions |
By increasing myocardial oxygen requirements while decreasing effective coronary perfusion, isoproterenol may have a deleterious effect on the injured or failing heart. In some patients, presumably with organic disease of the AV node and its branches, isoproterenol may paradoxically worsen heart blocks or precipitate Adams-Stokes attacks. Exercise caution in patients with coronary artery disease, coronary insufficiency, diabetes or hyperthyroidism and in patients sensitive to sympathomimetic amines. If the heart rate exceeds 110 beats/min, it may be advisable to decrease the infusion rate or temporarily discontinue the infusion. |
Drug Category: Beta-adrenergic blockers - These agents are excellent drugs for use in patients at risk for experiencing complications from beta-blockade, particularly those with reactive airway disease, mild-moderate LV dysfunction, and peripheral vascular disease. The short half-life of 8 minutes allows for titration to desired effect, and the ability to stop quickly if needed.
Drug Name |
Esmolol - It is ideal for use in patients at risk for experiencing complications from beta-blockade, especially patients diagnosed with mild-moderate LV dysfunction, and peripheral vascular disease. It has a short half-life of 8 minutes and thus it is easily titrateable to the desired effect. In addition, the therapy may be stopped quickly if needed. |
Adult Dose |
Initially, administer a loading dose iv infusion of 500 mcg/kg/min for 1 min followed by a 4 min maintenance infusion of 50 mcg/kg/min. If an adequate therapeutic effect is not observed within 5 min, repeat the loading dose and follow with a maintenance infusion of 100 mcg/kg/min. Continue the titration procedure, repeating the loading infusion and increasing the maintenance infusion by increments of 50 mcg/kg/min (for 4 min). |
Pediatric Dose |
Safety and efficacy in children have not been established. The suggested dose is 100-500 mcg/kg administered over 1 min |
Contraindications |
Avoid use in patients with documented hypersensitivity to this drug or related products and in those diagnosed with uncompensated congestive heart failure, bradycardia, cardiogenic shock, and A-V conduction abnormalities. |
Interactions |
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease its bioavailability and plasma levels, possibly resulting in a decreased pharmacologic effect. Conversely, the cardiotoxicity of sotalol may increase when administered concurrently with sparfloxacin, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives. The toxicity of sotalol increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents. |
Pregnancy |
C - Safety for use during pregnancy has not been established. |
Precautions |
Beta-adrenergic blockers may mask the signs and symptoms of acute hypoglycemia and the clinical signs of hyperthyroidism. The symptoms of hyperthyroidism, including thyroid storm may worsen when this medication is abruptly withdrawn. Withdraw the drug slowly and monitor the patient closely. |
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Further Inpatient Care:
- All patients should be admitted to an ICU setting for continued monitoring and withdrawal of offending drugs.
Transfer:
- Since ICU care is warranted, patients should be transferred to a facility with acute cardiac care capabilities.
Deterrence/Prevention:
- QT-prolonging medications should be avoided.
Prognosis:
- Patients with TDP have a 50% chance of a recurrence even with therapy.
Medical/Legal Pitfalls:
- A major pitfall in the management of torsade is to fail to recognize it as separable from other forms of ventricular tachycardia.
- If one fails to differentiate this rhythm disturbance than it is likely that the therapy of the dysrhythmia will include a type IA antidysrhythmic agent, such as procainamide.
- Type IA agents perpetuate the rhythm disturbance in torsade
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