American Journal of Emergency Medicine 32 (2014) 683.e5-683.e7

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Case Report

The use of isoproterenol and phenytoin to reverse Torsade de pointes?,??,?

Abstract

Torsade de pointes is a form of Polymorphic ventricular tachycardia that differs from other forms of ventricular tachycardia in its morphology, precipitating factors, and therapeutic approach. Its recognition is of utmost importance, as the standard anti- arrythmic drugs not only might be ineffective in its termination but also may aggravate it. Herein, we report a case of antipsychotic- induced torsade de pointes and describe the use of magnesium sulfate, isoproterenol, and phenytoin and their proposed mecha- nism of action.

A 31-year-old morbidly obese woman with a medical history of obstructive Sleep apnea and schizophrenia presented to the hospital with progressive shortness of breath. There was clinical and radiographic evidence of pulmonary edema, so intravenous diuresis was initiated for a working diagnosis of congestive heart failure. Admission electrocardiogram revealed low voltage, sinus tachycardia, and Corrected QT interval (QTc) of 489 milliseconds. Echocardiogra- phy revealed an ejection fraction of 30 % and severe pulmonary hypertension. Because of the patient’s agitation in-hospital, she was initially given 200 mg of depot haloperidol (which she receives monthly) in addition to 2 mg of intravenous haloperidol every 6 hours as needed. Ziprasidone was added later in a dose of 80 mg twice daily because of continued symptoms. Over the next 3 hospital days, there was slight improvement in her oxygenation. Her electrocardiogram was not monitored to follow the progression of the QTc interval. On hospital day 4, the patient developed altered mental status; and an arterial blood gas analysis revealed acute on top of chronic respiratory acidosis. Bi-level positive airway pressure (BiPAP) mask was placed without improvement in oxygenation or mental status, and she was not able to maintain her airway. The patient’s trachea was intubated, and the patient was transferred to the intensive care unit and mechanically ventilated. Two hours later, the patient developed 3 successive episodes of torsade de pointes (TdP) (Fig. 1) requiring repeated defibrillation. Electrocardiogram after restoration of normal sinus rhythm revealed a QTc interval of 850 milliseconds (Fig. 2). The diagnosis of antipsychotic-induced TdP was estab- lished. The patient immediately received 2 g of intravenous magnesium sulfate. laboratory investigations revealed a magne- sium level of 1.6 mg/dL and a potassium level of 3.7 mmol/L, and both were immediately corrected. antipsychotic drugs were

? This manuscript is not under consideration for publication elsewhere.

?? All authors have approved the final manuscript.

? This manuscript was presented as a poster in the American Society of

Anesthesiology Annual Meeting, October 2013.

discontinued.Amiodarone infusion that was initially administered was discontinued, and isoproterenol infusion was started to maintain the heart rate above 90 beats per minute, in addition to initiating phenytoin infusion. This was followed by normalization of the QTc interval in 24 hours. TdP did not reoccur during the remainder of the patient’s hospital course. Fig. 3 is an illustration of the various drugs responsible for QTc prolongation and their time course. Fig. 4 shows the in-hospital progression of the QTc interval.

TdP is an uncommon form of polymorphic ventricular tachycardia first described by Dessertenne in 1966 [1]. It differs from other forms of ventricular tachycardia in its morphological features, precipitating factors, and therapeutic interventions. Its recognition is of utmost importance because of its propensity to worsen with certain antiarrythmic drugs. Frequent culprits are antipsychotic medications, antibiotics, certain gastric motility agents (cisapride), and certain antiarrythmic drugs, all which cause prolongation of the QT interval. It is characterized by a change in the amplitude and twisting of the QRS complexes around the isoelectric line. Treatment strategy involves correction of electrolyte abnormalities especially hypomagnesaemia and acceleration of the heart rate to shorten the QTc interval. Magnesium sulfate therapy is the recommended first-line therapy in TdP, however, its mechanism of action is not fully understood. Because magnesium is a cofactor in the sodium potassium ATPase activity, it may prevent TdP by facilitating the influx of potassium into the cells, thereby stabilizing membrane potential, correcting the dispersed repolarization process without shortening it [2]. Isoproter- enol infusion has been used successfully in TdP. A continuous infusion of 2 to 10 ug/min to target heart rate above 90 beats per minute causes shortening of the QTc interval and suppression of the arrhythmia. It should be noted that isoproterenol is contraindicated in a large proportion of patients, such as those with acute myocardial infarction, severe angina pectoris, and hypertension. Furthermore, isoproterenol may be fatal if given to patients with a ventricular tachycardia that is not TdP (no QT prolongation). In such cases, isoproterenol infusion may cause degeneration into ventricular fibrillation and worse outcome [1]. Acetylcholine injection is known to cause QT prolonga- tion and TdP in patients with congenital Long QT syndrome [3]. Atropine is expected to increase the heart rate, thereby shortening the QTc interval and suppressing the arrhythmia, and has been success- fully used in previous case reports [4]. Atropine, however, often fails to maintain rapid heart rate and may induce paradoxical bradycardia, increasing the risk of TdP [5]. Phenytoin has also been successfully used for treatment of TdP. The proposed antiarrythmic actions of phenytoin include the decrease in ventricular automaticity especially in Purkinje fibers and a central antiarrythmic effect through decrease in sympathetic discharge and increase in the atrioventricular conduction velocity in addition to blocking calcium-dependent

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683.e6 H.R. Omar et al. / American Journal of Emergency Medicine 32 (2014) 683.e5-683.e7

Fig. 1. Torsade de pointes.

depolarization in the plateau phase of action potential favoring repolarization of purkinje fibers and preventing early after depolar- ization (EAD) and inhibiting EAD conduction from the purkinje network to the surrounding myocardium (through its sodium-

Fig. 2. Electrocardiogram after TdP showing QTc of 850 milliseconds, ventricular couplets, and extrasystoles.

channel blocking effect) [6]. cardiac pacing is another therapeutic modality for treatment of TdP. The most agreed upon mechanism for arrhythmia precipitation in TdP is pause-dependent arrhythmia; and in most times, it is a postextrasystolic pause. The role of pacing is to prevent, or at least shorten, the postextrasystolic pauses that facilitate the onset of TdP. One way of achieving this goal is to increase the lower rate limit. Faster pacing will shorten postextrasystolic pauses, potentially reducing the risk of pause-induced TdP [7]. In our patient, several comorbidities contributed together to the occurrence of TdP. First, the baseline QT prolongation, the liberal use of antipsychotics (including intravenous haloperidol that is off-label), intravenous diuretics with subsequent hypomagnesaemia, underlying congestive heart failure, and congestive hepatomegaly. In conclusion, we aim to emphasize the value of isoproterenol and phenytoin in reversing prolonged QTc-induced TdP.

Hesham R. Omar, MD Internal Medicine Department Mercy Medical Center

Clinton, IA, USA E-mail address: [email protected]

Collin Sprenker, BS Rachel Karlnoski, PhD Devanand Mangar, MD Anesthesia Department Tampa General Hospital and

Florida Gulf to Bay Anesthesiology Associates LLC

Tampa, FL, USA

Enrico M. Camporesi, MD

Department of Surgery/Anesthesiology Department of Molecular Pharmacology and Physiology

University of South Florida

Tampa, FL, USA

http://dx.doi.org/10.1016/j.ajem.2013.11.037

References

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3. Aizawa Y, Washizuka T, Igarashi Y, Kitazawa H, Chinushi M, Abe A, et al. Acetylcholine-induced prolongation of the QT interval in idiopathic long QT syndrome. Am J Cardiol 1996;77:879-82.
4. Tan HL, Wilde AA, Peters RJ. Suppression of Torsades de pointes by atropine. Heart 1998;79(1):99-100.
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7. Viskin S, Glikson M, Fish R, Glick A, Copperman Y, Saxon LA. Rate smoothing with cardiac pacing for preventing torsade de pointes. Am J Cardiol 2000;86(9A): 111K-5K.

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   Fig. 3. An illustration of the various drugs responsible for QTc prolongation and their time course. N, number of doses administered; TdP, torsade de pointes.

   

   Fig. 4. Progression of the QTc interval in relation to various interventions. D/C, discontinue; AP, antipsychotics; MG, Magnesium sulphate; Amio, amiodarone; ED, emergency department; TdP, torsade de pointes.