scholarly journals Dexmedetomidine reduces ventricular arrhythmias in a model of drug-induced QT-prolongation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Frommeyer ◽  
J Brandt ◽  
C Ellermann ◽  
J Wolfes ◽  
L Eckardt
Keyword(s):  
Qt Interval ◽  
Ventricular Arrhythmias ◽  
Spatial Dispersion ◽  
Torsade De Pointes ◽  
Qt Prolongation ◽  
Recent Experimental Data ◽  
Moderate Increase ◽  
Drug Induced ◽  
Dispersion Of Repolarization ◽  
Significant Prolongation

Abstract Background Dexmedetomidine is increasingly employed for conscious sedation during electrophysiological procedures. Recent experimental data have suggested direct effects of dexmedetomidine on cardiac electrophysiology. The aim of the present study was to assess the effects of dexmedetomidin on drug-induced QT-prolongation. Methods and results In 12 isolated rabbit hearts the macrolide antibiotic erythromycin (300μM) was infused as a potent Ikr blocker after obtaining baseline data. Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant prolongation of QT-interval (+25ms, p<0.05) accompanied by a moderate increase of action potential duration (APD, +5ms, p=ns) after infusion of erythromycin as compared with baseline. Effective refractory period (ERP) was also elevated (+33ms, p<0.05). Erythromycin (+26ms, p<0.05) also significantly increased spatial dispersion of repolarisation. Additional infusion of dexmedetomidine (3μM) resulted in a rather stable QT-interval (+7ms, p=ns) and APD (+7ms, p=ns) as compared with sole erythromycin treatment. Of note, a significant decrease of spatial dispersion (−24ms, p<0.05) was observed while ERP was moderately increased (+13ms, p=ns). Lowering of potassium concentration in bradycardic AV-blocked hearts resulted in the occurrence of early afterdepolarizations (EAD) and drug induced proarrhythmia with torsade de pointes in 6 of 12 erythromycin-treated hearts (40 episodes). Additional infusion of dexmedetomidine reduced the occurrence of torsade de pointes (4 of 12 hearts, 9 episodes). Conclusion Infusion of dexmedetomidine resulted in a reduction of spatial dispersion of repolarization in the presence of a prolonged repolarization period. This resulted in a reduction of torsade de pointes with dexmedetomidine. Furthermore, an increase of ventricular refractory periods reduced inducibility of ventricular arrhythmias. Thus, in an experimental setting dexmedetomidine shows significant antiarrhythmic effects, which may influence electrophysiologic findings during clinical electrophysiologic studies. This needs to be studied in the clinical setting. Funding Acknowledgement Type of funding source: None

scholarly journals Prolonged QT Interval in a Patient With Coronavirus Disease-2019: Beyond Hydroxychloroquine and Azithromycin

2020 ◽  
Vol 8 ◽  
pp. 232470962094840
Author(s):  
B K Anupama ◽  
Soumya Adhikari ◽  
Debanik Chaudhuri
Keyword(s):  
Qt Interval ◽  
Ventricular Arrhythmias ◽  
Torsade De Pointes ◽  
Cardiac Pacing ◽  
Qt Prolongation ◽  
Medication Effects ◽  
Increased Risk ◽  
Repolarization Reserve ◽  
Prolonged Qt Interval ◽  
Prolonged Qt

Recent reports have suggested an increased risk of QT prolongation and subsequent life-threatening ventricular arrhythmias, particularly torsade de pointes, in patients with coronavirus disease-2019 (COVID-19) treated with hydroxychloroquine and azithromycin. In this article, we report the case of a 75-year-old female with a baseline prolonged QT interval in whom the COVID-19 illness resulted in further remarkable QT prolongation (>700 ms), precipitating recurrent self-terminating episodes of torsade de pointes that necessitated temporary cardiac pacing. Despite the correction of hypoxemia and the absence of reversible factors, such as adverse medication effects, electrolyte derangements, and usage of hydroxychloroquine/azithromycin, the QT interval remained persistently prolonged compared with the baseline with subsequent degeneration into ventricular tachycardia and death. Thus, we highlight that COVID-19 illness itself can potentially lead to further prolongation of QT interval and unmask fatal ventricular arrhythmias in patients who have a prolonged QT and low repolarization reserve at baseline.

Terfenadine-Induced Torsade de Pointes: Risk Factors and Mechanisms

1997 ◽  
Vol 13 (3) ◽  
pp. 127-132 ◽  
Author(s):  
Thomas Yk Chan
Keyword(s):  
Risk Factors ◽  
Liver Dysfunction ◽  
Qt Interval ◽  
Torsade De Pointes ◽  
Pharmacokinetic Studies ◽  
Drug Induced ◽  
Significant Prolongation ◽  
Concurrent Use ◽  
Cyp3a4 Inhibitors

Objective: To review the risk factors and mechanisms of terfenadine-induced torsade de pointes and to discuss how this adverse reaction might be avoided. Data Sources: Previous reports of terfenadine-induced torsade de pointes and studies of the underlying mechanisms were identified by a MEDLINE search or from the reference lists of pertinent articles. Study Selection and Data Extraction: All relevant articles were included in the review. Pertinent information was selected for discussion. Data Synthesis: Terfenadine is extensively (99%) metabolized by CYP3A4 to an active acid metabolite (terfenadine carboxylate), and with therapeutic dosages, unchanged terfenadine is usually undetectable in plasma. A review of all the reported cases of torsade de pointes indicated that most patients had one or more factors that would be expected to cause excessively high concentrations of unchanged terfenadine, such as overdose; use of supratherapeutic dosages; concurrent use of CYP3A4 inhibitors such as ketoconazole, itraconazole, erythromycin, and troleandomycin; and liver dysfunction. Many patients had one or more factors known to predispose to drug-induced torsade de pointes (e.g., preexisting prolonged QT interval, ischemic heart disease, hypokalemia). Pharmacokinetic studies in healthy volunteers have shown that ketoconazole, itraconazole, erythromycin, and clarithromycin can alter the metabolism of terfenadine and result in the accumulation of unchanged terfenadine, which is associated with significant prolongation of the QT interval. In vitro studies have shown that the proarrhythmic effects of terfenadine are secondary to the blockade of cardiac potassium channels. Terfenadine carboxylate does not have such an effect. Conclusions: Supratherapeutic dosages of terfenadine should never be used. The concurrent use of CYP3A4 inhibitors should be avoided. Terfenadine should be avoided in patients with liver dysfunction or factors known to predispose to drug-induced torsade de pointes.

Torsade De Pointes Resulting from the Addition of Droperidol to an Existing Cytochrome P450 Drug Interaction

1998 ◽  
Vol 32 (7-8) ◽  
pp. 761-765 ◽  
Author(s):  
Elizabeth Landrum Michalets ◽  
Laura K Smith ◽  
Eric D Van Tassel
Keyword(s):  
Cytochrome P450 ◽  
Qt Interval ◽  
Tricyclic Antidepressants ◽  
Torsade De Pointes ◽  
Tendon Repair ◽  
Qt Prolongation ◽  
Drug Induced ◽  
Case Summary ◽  
P450 Inhibitors

OBJECTIVE: To report a case of QT prolongation associated with concomitant cyclobenzaprine and fluoxetine administration followed by torsade de pointes potentiated by droperidol. CASE SUMMARY: A 59-year-old white woman who had been receiving long-term fluoxetine and cyclobenzaprine therapy was admitted for Achilles tendon repair. Baseline QTc was prolonged at 497 msec. Prior to surgery, the patient received droperidol, an agent known to prolong the QT interval. During surgery the patient developed torsade de pointes, which progressed into ventricular fibrillation. On postoperative day 1, after cyclobenzaprine discontinuation, the QTc decreased toward normal (440 msec). DISCUSSION: Cyclobenzaprine shares anticholinergic effects, tachycardia, and dysrhythmic potential with the tricyclic antidepressants (TCAs). Fluoxetine is a known inhibitor of the CYP2D6 isoenzyme (along with CYP3A4 and CYP2C) and has been shown to increase TCA serum concentrations. The combination of cyclobenzaprine and fluoxetine resulted in significant QT prolongation in our patient that progressed to torsade de pointes after preoperative droperidol administration. Resolution of QT abnormalities after cyclobenzaprine discontinuation provided further evidence of a drug-induced etiology. Other possible medical and drug-related causes of torsade de pointes are reviewed and ruled out. CONCLUSIONS: Clinicians should be aware of the dysrhythmic potential of cyclobenzaprine and fluoxetine, monitor for other cytochrome P450 inhibitors, and avoid concomitant drugs known to prolong the QT interval.

scholarly journals Torsades de Pointes after Ondansetron Infusion in 2 Patients

2017 ◽  
Vol 44 (5) ◽  
pp. 366-369 ◽  
Author(s):  
Danny Y. Lee ◽  
Tri Trinh ◽  
Sion K. Roy
Keyword(s):  
Risk Factors ◽  
Receptor Antagonist ◽  
Qt Interval ◽  
Ventricular Arrhythmias ◽  
Torsades De Pointes ◽  
Qt Prolongation ◽  
Drug Induced ◽  
Qt Intervals ◽  
Type 3

Drugs that prolong the electrocardiographic QT interval increase the risk of ventricular arrhythmias, particularly torsades de pointes. Ondansetron, a 5-hydroxytryptamine type 3 receptor antagonist antiemetic, is one such drug. We present the cases of 2 patients who were given intravenous ondansetron and subsequently developed torsades de pointes. Both had normal QT intervals at baseline but were discovered to have risk factors that predisposed them to drug-induced QT prolongation and ventricular arrhythmias. We briefly review the mechanisms for torsades de pointes caused by QT-prolonging medications, describe characteristics that increase patients' susceptibility to drug-induced QT prolongation, and call attention to the risk of ventricular arrhythmias in patients who are given ondansetron.

Abstract 14311: Qt Interval Correlation Between Telemetry and 12-lead Electrocardiogram

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Mohamed Farhan Nasser ◽  
Ahmad Jabri ◽  
Saima Karim ◽  
Elizabeth Kaufman
Keyword(s):  
Qt Interval ◽  
Ventricular Arrhythmias ◽  
Qt Prolongation ◽  
T Wave ◽  
Qt Intervals ◽  
Increased Risk ◽  
Tangent Method ◽  
Wave Morphology ◽  
Monitoring Service ◽  
Inpatient Units

Introduction: QT prolongation is associated with increased risk of ventricular arrhythmias.As many patients with COVID19 may be started on QT prolonging drugs, measuring and monitoring QT is imperative to prevent fatal ventricular arrhythmias. However, we need to limit exposure of staff to patients with confirmed COVID19 and judiciously use personal protective equipment. Thus, it is important to find alternatives to doing frequent 12-lead ECGs. Hypothesis: We hypothesize that the QT interval measured from telemetry is similar to the QT interval on 12-lead ECG. Methods: Telemetry recordings and 12-lead ECGs were obtained from 15 patients at the same time and identical heart rates. Patients were from two different inpatient units with the same telemetry monitoring service. QT intervals were measured manually using calipers with the tangent method, excluding U waves. Telemetry recordings included lead I and II or a precordial lead. QT from telemetry was compared to the corresponding leads and to the longest QT on the 12-lead ECG. In cases of atrial fibrillation (AF), the QT from all the complexes was averaged. Results: Of 15 patients, 2 were in AF and 2 had RBBB. One patient had abnormal T-wave morphology and QT prolongation (abnormal repolarization). In all patients, QT intervals from the same leads as telemetry matched the QT measured from 12-lead. In 14 of 15 patients, telemetry QT matched the longest QT on the 12-lead ECG. However, in the patient with abnormal repolarization, maximum QT on 12-lead ECG was substantially longer than telemetry QT (Figure 1). Conclusion: When using the same lead, QT intervals were identical on telemetry and 12-lead ECG. However, in the patient with abnormal repolarization, the longest QT on 12-lead ECG was not represented on telemetry. In patients with abnormal repolarization on 12-lead ECG, we recommend serial 12-lead ECGs while on QT-prolonging drugs. Telemetry may suffice as a surrogate for 12-lead ECG to follow QT intervals in most patients.

scholarly journals Drug-induced QT interval prolongation in cancer patients

2011 ◽  
Vol 4 (4) ◽  
pp. 223
Author(s):  
Torben K. Becker ◽  
Sai-Ching J. Yeung
Keyword(s):  
Cancer Patients ◽  
Qt Interval ◽  
Alkylating Agents ◽  
Torsade De Pointes ◽  
Interval Prolongation ◽  
Drug Induced ◽  
Vascular Disruption ◽  
Qt Interval Prolongation ◽  
Increased Risk ◽  
Multiple Drugs

Cancer patients are at an increased risk for QT interval prolongation and subsequent potentially fatal Torsade de pointes tachycardia due to the multiple drugs used for treatment of malignancies and the associated symptoms and complications. Based on a systematic review of the literature, this article analyzes the risk for prolongation of the QT interval with antineoplastic agents and commonly used concomitant drugs. This includes anthracyclines, fluorouracil, alkylating agents, and new molecularly targeted therapeutics, such as vascular disruption agents. Medications used in the supportive care can also prolong QT intervals, such as methadone, 5-HT3-antagonists and antihistamines, some antibiotics, antifungals, and antivirals. We describe the presumed mechanism of QT interval prolongation, drug-specific considerations, as well as important clinical interactions. Multiple risk factors and drug–drug interactions increase this risk for dangerous arrhythmias. We propose a systematic approach to evaluate cancer patients for the risk of QT interval prolongation and how to prevent adverse effects.

scholarly journals Managing drug-induced QT prolongation in clinical practice

2020 ◽  
pp. postgradmedj-2020-138661
Author(s):  
Rani Khatib ◽  
Fatima R N Sabir ◽  
Caroline Omari ◽  
Chris Pepper ◽  
Muzahir Hassan Tayebjee
Keyword(s):  
Qt Interval ◽  
Simple Algorithm ◽  
Torsades De Pointes ◽  
Daily Practice ◽  
Qt Prolongation ◽  
Key Factors ◽  
Drug Induced ◽  
Electrolyte Disturbances ◽  
Related Risk ◽  
Life Threatening

Many drug therapies are associated with prolongation of the QT interval. This may increase the risk of Torsades de Pointes (TdP), a potentially life-threatening cardiac arrhythmia. As the QT interval varies with a change in heart rate, various formulae can adjust for this, producing a ‘corrected QT’ (QTc) value. Normal QTc intervals are typically <450 ms for men and <460 ms for women. For every 10 ms increase, there is a ~5% increase in the risk of arrhythmic events. When prescribing drugs associated with QT prolongation, three key factors should be considered: patient-related risk factors (eg, female sex, age >65 years, uncorrected electrolyte disturbances); the potential risk and degree of QT prolongation associated with the proposed drug; and co-prescribed medicines that could increase the risk of QT prolongation. To support clinicians, who are likely to prescribe such medicines in their daily practice, we developed a simple algorithm to help guide clinical management in patients who are at risk of QT prolongation/TdP, those exposed to QT-prolonging medication or have QT prolongation.

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