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      Medical toxicologists’ practice patterns regarding drug-induced QT prolongation in overdose patients: A survey in the United States of America, Europe, and Asia Pacific region

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      Clinical Toxicology
      Informa UK Limited

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          Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation.

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            Treatment of torsade de pointes with magnesium sulfate.

            Twelve consecutive patients who developed torsade de pointes (polymorphous ventricular tachycardia with marked QT prolongation, TdP) over a 4 year period were treated with intravenous injections of magnesium sulfate. In nine of the patients a single bolus of 2 g completely abolished the TdP within 1 to 5 min, and in three others complete abolition of the TdP was achieved after a second bolus was given 5 to 15 min later. Nine of the patients also received continuous infusion of MgSO4 (3 to 20 mg/min) for 7 to 48 hr until the QT interval was below 0.50 sec. In nine of the 12 patients the TdP was induced by antiarrhythmic agents. The QT interval preceding TdP ranged from 0.54 to 0.72 sec. After the MgSO4 bolus, which prevented the recurrence of TdP, no significant changes were observed in the QT interval. There were no side effects of this treatment. In eight of the 12 patients potassium levels before the TdP were below 3.5 meq/liter; magnesium levels were available in eight patients before TdP, and were normal in all. Five additional patients with polymorphous ventricular tachycardia but normal QT intervals (non-TdP patients) received two to three boluses of MgSO4. This treatment was ineffective in all, but they responded to conventional antiarrhythmic therapy. Thus, MgSO4 is a very effective and safe treatment for TdP, and its application is rapid and simple. Its use is therefore recommended as the first line of therapy for TdP.
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              Drug-induced QT prolongation and torsades de pointes: evaluation of a QT nomogram.

              Although QT prolongation is associated with increased risk of torsade de pointes (TdP), the precise relationship is not well defined. To evaluate the performance of a QT nomogram in assessing the risk of TdP from QT-RR combinations. Systematic review. We systematically searched MEDLINE/EMBASE for cases of drug-induced TdP. Controls were patients taking non-cardiotoxic drugs in overdose. Inclusion criteria were definite TdP, normal ECG before or after the event, association with a drug/toxin and QT-RR measurements available. The upper bound of a QT-RR cloud diagram developed from human preclinical studies was converted into a QT nomogram [QT vs. heart rate (HR)]. QT-HR combinations for TdP cases and controls were plotted with the QT nomogram, and curves corresponding to a QTc = 440 ms and QTc = 500 ms for comparison (Bazett's correction). We identified 129 cases of TdP. TdP cases occurred at lower HR values with longer QT intervals, with most cases occurring at HR 30-90 bpm. Controls were more evenly distributed, with HR 40-160 bpm. The sensitivity and specificity of the QT nomogram were 96.9% (95%CI 93.9-99.9) and 98.7% (95%CI 96.8-100), respectively. For Bazett QTc = 440 ms, sensitivity and specificity were 98.5% (95%CI 96.3-100) and 66.7% (95%CI 58.6-74.7), respectively, whereas for Bazett QTc =500 ms they were 93.8% (95%CI 89.6-98.0) and 97.2% (95%CI 94.3-100), respectively. The QT nomogram is a clinically relevant risk assessment tool that accurately predicts arrhythmogenic risk for drug-induced QT prolongation. Further prospective evaluation of the nomogram is needed.
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                Author and article information

                Journal
                Clinical Toxicology
                Clinical Toxicology
                Informa UK Limited
                1556-3650
                1556-9519
                February 19 2015
                April 21 2015
                February 23 2015
                April 21 2015
                : 53
                : 4
                : 204-209
                Article
                10.3109/15563650.2015.1013547
                5d243e8e-7fd6-48fa-9f89-e70efefdd292
                © 2015
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