Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes

Gupta, Akshay; Lawrence, Andrew; Krishnan, K. Ranga Rama; Kavinsky, Clifford J.; Trohman, Richard G.

doi:10.1016/j.ahj.2007.01.040

Cited by 316 publications

(211 citation statements)

References 91 publications

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“…Such arrhythmias can cause syncope, seizures, and sudden cardiac death. 1,2 Most patients who develop torsades de pointes have predisposing risk factors such as prolonged QT (acquired or congenital), electrolyte abnormalities, or female gender. The QT interval is dynamic, varying with each beat, and is also affected by age, autonomic tone, myocardial ischemia, and structural heart disease.…”

Section: Discussionmentioning

confidence: 99%

Quinine and the ABCs of Long QT: A Patient’s Misfortune with Arthritis, (Alcoholic) Beverages, and Cramps

et al. 2016

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A 91-year-old woman presented to the emergency department by ambulance after her family found her minimally responsive. Telemetry monitoring demonstrated episodes of non-sustained polymorphic ventricular tachycardia (PMVT) associated with significantly prolonged repolarization. Her medical history revealed that she was taking quinine or a derivative in three different forms: hydroxychloroquine, quinine sulfate (for leg cramps), and her gin mixed with tonic water (containing quinine). The present case is illustrative of classic etiologies and findings of acquired long QT syndrome, and serves as an important reminder for providers to take a complete medication history, including use of duplicative and alternative medicines and type of alcohol consumption.KEY WORDS: cardiac arrhythmia; prolonged QT; quinine; gin and tonic.

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Section: Discussionmentioning

confidence: 99%

Quinine and the ABCs of Long QT: A Patient’s Misfortune with Arthritis, (Alcoholic) Beverages, and Cramps

et al. 2016

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“…8 It is well known that individuals with normal cardiac ion channels can also acquire a prolonged QT interval, usually as a consequence of consuming one or more of a host of QT-prolonging medications. 11 In 2001, the FDA issued a black box warning regarding droperidol, on the basis that it prolonged the QT interval, thereby increasing the risk of malignant dysrhythmias such as torsades de pointes. This warning was met with protest by the anesthesiology community, given droperidol's effectiveness as an antiemetic, its low cost and its established safety record when used at antiemetic doses.…”

Section: Discussionmentioning

confidence: 99%

“…14 This characteristic is shared by several other medications that are better known for their QT prolonging effects, including class III antidysrhythmics, cisapride, and droperidol. 11 Other antiemetic medications have variable effects on the QT interval. Dimenhydrinate is a first generation H-1 antagonist that has not been linked with significant changes in the QT interval.…”

Section: Discussionmentioning

confidence: 99%

Ventricular tachycardia after ondansetron administration in a child with undiagnosed long QT syndrome

McKechnie

Froese

2010

Can J Anesth/J Can Anesth

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Purpose To describe a case of ventricular tachycardia after co-administration of ondansetron and dimenhydrinate to a child with occult congenital QT prolongation. Clinical features A previously healthy 11-yr-old girl presented for surgical excision of a thyroglossal duct cyst under general anesthesia. Induction and maintenance of anesthesia were unremarkable, and the surgery was carried out without incident. Prior to emergence, ondansetron 0.1 mgÁkg -1 and dimenhydrinate 0.4 mgÁkg -1 were administered. Within approximately two minutes, polymorphic premature ventricular contractions developed and, subsequently, polymorphic ventricular tachycardia ensued. A 12-lead electrocardiogram revealed a profoundly prolonged QT interval that decreased but failed to normalize completely postoperatively. Our patient was diagnosed subsequently with congenital QT prolongation. Conclusion The QT interval is prolonged by the administration of ondansetron in a manner similar to that seen with droperidol, whereas dimenhydrinate is not considered to exert significant effects on the QT interval. Individuals with occult QT prolongation are at risk of experiencing malignant dysrhythmias when ondansetron is administered, especially in conjunction with anesthetic agents that also prolong the QT.

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“…Known risk factors for drug-induced TdP are female sex, hypokalaemia, hypomagnesaemia, bradycardia, simultaneous administration of inhibitor compounds, and genetic factors [4][5][6]. Serum electrolytes, especially potassium and magnesium, were normal.…”

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confidence: 99%

“…Although hepatic dysfunction decreased clearance of solifenacin [1], hepatic function was also normal. Anti-infective agents that were administered intravenously did not include CYP3A4 inhibitors such as erythromycin [4][5][6]. She had no other structural heart diseases, nor any family history of sudden death.…”

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confidence: 99%

QT prolongation and torsade de pointes associated with solifenacin in an 81‐year‐old woman

Asajima

Sekiguchi

Matsushima

et al. 2008

Brit J Clinical Pharma

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Solifenacin, an antimuscarinic drug, has been widely used for the treatment of overactive bladder (OAB), but severe cardiac adverse effects have not been reported. An 81-year-old woman was prescribed solifenacin 5 mg day -1 for OAB. Two weeks later she developed the first syncope. Nine days after the first syncope she developed recurrent syncope, and electrocardiogram monitoring showed marked QT prolongation and torsade de pointes (TdP). Concomitant drugs remained unchanged. Serum electrolytes and hepatic function were normal. Calculated creatinine clearance was mildly decreased. We considered that the loss of consciousness was associated with solifenacin. Although intravenous magnesium sulphate could not terminate the recurrence of TdP, increasing the pacing rate prevented further attacks of TdP. Solifenacin might be a possible cause of QT prolongation and TdP.Solifenacin is a newer bladder-selective antimuscarinic drug for the treatment of OAB [1]. Although terodiline, an older antimuscarinic drug for OAB, has been reported to predispose to QT prolongation and TdP and was withdrawn from the market in the early 1990s [2-4], solifenacin has not been reported to have severe cardiac adverse effects [1].An 81-year-old woman was admitted to the division of orthopaedics with dislocation of hip joint and infection of decubitus. One year before admission she had undergone total hip arthroplasty. Her past medical history included hypertension and pacemaker implantation for sick sinus syndrome. Her medication included amlodipine, but not any over-the-counter drugs or herbals. Electrocardiogram (ECG) on admission showed sinus rhythm with normal QT interval (QT400 ms/QTc360 ms) (Figure 1a). Solifenacin 5 mg day -1 was started for OAB after admission. Her infection was initially treated with intravenous cefazolin, but was changed to intravenous teicoplanin because of methicillin-resistant Staphylococcus aureus infection. Two weeks later she suddenly developed loss of consciousness, but she spontaneously regained full consciousness.Although ECG was not recorded during the episode, ECG monitoring showed QT prolongation (QT600 ms/ QTc581 ms) after regaining consciousness (Figure 1b). Nine days after the first syncope she developed recurrent loss of consciousness and ECG monitoring showed TdP (Figure 1c). She was resuscitated with a single DC shock. She was immediately transferred to the division of cardiology. ECG monitoring showed QT prolongation (QT600 ms) and recurrent TdP. Serum electrolytes and hepatic function were normal. Calculated creatinine clearance was 60 ml min -1 . We considered that solifenacin was closely related to syncope and TdP. We stopped solifenacin. Intravenous magnesium sulphate could not terminate recurrent episodes of TdP. The pacing rate was increased 60 to 90 beats min -1 to shorten the QT interval, resulting in a QT interval of 600 to 500 ms (QTc 408 ms). There were no further attacks of TdP. Electrocardiographic abnormalities resolved a few days after solifenacin was discontinued.The high bladder ...

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Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes

Cited by 316 publications

References 91 publications

Quinine and the ABCs of Long QT: A Patient’s Misfortune with Arthritis, (Alcoholic) Beverages, and Cramps

Quinine and the ABCs of Long QT: A Patient’s Misfortune with Arthritis, (Alcoholic) Beverages, and Cramps

Ventricular tachycardia after ondansetron administration in a child with undiagnosed long QT syndrome

QT prolongation and torsade de pointes associated with solifenacin in an 81‐year‐old woman

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