QTc interval prolongation in critically ill patients: Prevalence, risk factors and associated medications

Flávia Medeiros Fernandes, Eliane Pereira Silva, Rand Randall Martins, Antonio Gouveia Oliveira, Flávia Medeiros Fernandes, Eliane Pereira Silva, Rand Randall Martins, Antonio Gouveia Oliveira

Abstract

Purpose: To investigate the prevalence and risk factors of acquired long QT syndrome (LQTS) on admission to a general Intensive Care Unit (ICU), and to assess the risk of LQTS associated with prescribed medications.

Methods: Prospective observational, cross-sectional study approved by the Institutional Review Board. Between May 2014 and July 2016, 412 patients >18 years-old consecutively admitted to the ICU of a university hospital were included. LQTS was defined as a QT interval on the admission electrocardiogram corrected using Bazett's formula (QTc) >460 ms for men and >470 ms for women. All medications administered within 24 hours before admission were recorded. Logistic regression was used.

Results: LQTS prevalence was 27.9%. In LQTS patients, 70.4% had ≥ 1 LQTS-inducing drug prescribed in the 24 hours prior to ICU admission versus 70.4% in non-LQTS patients (p = 0.99). Bradycardia and Charlson morbidity index score are independent risk factors for LQTS. Haloperidol (OR 4.416), amiodarone (OR 2.509) and furosemide (OR 1.895) were associated with LQTS, as well as another drug not yet described, namely clopidogrel (OR 2.241).

Conclusions: The LQTS is highly prevalent in critically ill patients, ICU patients are often admitted with LQTS-inducing medications, and patients with slow heart rate or with high Charlson comorbidity index should be evaluated for LQTS.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Patient accountability.
Fig 1. Patient accountability.
Fig 2. Sex-specific prevalence rates of LQTS…
Fig 2. Sex-specific prevalence rates of LQTS among patients admitted to an Intensive Care Unit.
Fig 3. Prevalence rates of LQTS among…
Fig 3. Prevalence rates of LQTS among users and non-users of QT-interval prolonging drugs in the 24 hours prior to ICU admission.

References

    1. Nelson S, Leung J. QTc prolongation in the intensive care unit: a review of offending agents. AACN advanced critical care. 2011;22(4):289–95. doi:
    1. Antzelevitch C. Arrhythmogenic mechanisms of QT prolonging drugs: is QT prolongation really the problem? J. Electrocardiol. 2004;37 Suppl:15–24.
    1. Mason PK, Mounsey JP. Drug-induced long QT syndrome: molecular mechanisms for congenital and acquired QT prolongation. Drug Discov Today Dis Mech. 2007;4(3):159–63.
    1. Gowda RM, Khan IA, Wilbur SL, Vasavada BC, Sacchi TJ. Torsade de pointes: the clinical considerations. Int. J. Cardiol. 2004;96(1):1–6. doi:
    1. Pickham D, Helfenbein E, Shinn JA, Chan G, Funk M, Drew BJ. How many patients need QT interval monitoring in critical care units? Preliminary report of the QT in Practice study. J. Electrocardiol. 2010;43(6):572–6. doi:
    1. Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. J. Am. Coll. Cardiol. 2010;55(9):934–47. doi:
    1. Park E, Willard J, Bi D, Fiszman M, Kozeli D, Koerner J. The impact of drug-related QT prolongation on FDA regulatory decisions. Int. J. Cardiol. 2013;168(5):4975–6. doi:
    1. Pickham D, Helfenbein E, Shinn JA, Chan G, Funk M, Weinacker A, et al. High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: Results of the QT in Practice (QTIP) Study*. Crit Care Med. 2012;40(2):394–9. doi:
    1. Ng TM, Olsen KM, McCartan MA, Speidel KM, Miller MA, Levit AV. Pharmacologic predictors of qtc prolongation and proarrhythmia in the adult medical Intensive Care Unit. Crit Care Med. 2004;32(12):A40.
    1. Tisdale JE, Wroblewski HA, Overholser BR, Kingery JR, Trujillo TN, Kovacs RJ. Prevalence of QT interval prolongation in patients admitted to cardiac care units and frequency of subsequent administration of QT interval-prolonging drugs: a prospective, observational study in a large urban academic medical center in the US. Drug Saf. 2012;35(6):459–70. doi:
    1. Ng TM, Bell AM, Hong C, Hara JM, Touchette DR, Danskey KN, et al. Pharmacist monitoring of QTc interval-prolonging medications in critically ill medical patients: a pilot study. Ann Pharmacother. 2008;42(4):475–82. doi:
    1. Ng TM, Olsen KM, McCartan MA, Puumala SE, Speidel KM, Miller MA, et al. Drug-induced QTc-interval prolongation in the intensive care unit: incidence and predictors. J Pharm Pract. 2010;23(1):19–24. doi:
    1. Hoogstraaten E, Rijkenberg S, van der Voort PH. Corrected QT-interval prolongation and variability in intensive care patients. J Crit Care Med. 2014;29(5):835–9.
    1. Vandenberk B, Vandael E, Robyns T, Vandenberghe J, Garweg C, Foulon V, et al. Which QT Correction Formulae to Use for QT Monitoring? J Am Heart Assoc. 2016;5(6):e003264 doi:
    1. Green SM. Cheerio, laddie! Bidding farewell to the Glasgow Coma Scale. Ann Emerg Med. 2011;58(5):427–30. doi:
    1. Allyn J, Ferdynus C, Bohrer M, Dalban C, Valance D, Allou N. Simplified Acute Physiology Score II as Predictor of Mortality in Intensive Care Units: A Decision Curve Analysis. PloS one. 2016;11(10):e0164828 doi:
    1. Safari S, Shojaee M, Rahmati F, Barartloo A, Hahshemi B, Forouzanfar MM, et al. Accuracy of SOFA score in prediction of 30-day outcome of critically ill patients. Turk J Emerg Med. 2016;16(4):146–50. doi:
    1. Fraccaro P, Kontopantelis E, Sperrin M, Peek N, Mallen C, Urban P, et al. Predicting mortality from change-over-time in the Charlson Comorbidity Index: A retrospective cohort study in a data-intensive UK health system. Medicine. 2016;95(43):e4973 doi:
    1. Vlachos K, Georgopoulos S, Efremidis M, Sideris A, Letsas KP. An update on risk factors for drug-induced arrhythmias. Expert Rev Clin Pharmacol. 2016;9(1):117–27. doi:
    1. Kallergis EM, Goudis CA, Simantirakis EN, Kochiadakis GE, Vardas PE. Mechanisms, risk factors, and management of acquired long QT syndrome: a comprehensive review. ScientificWorldJournal. 2012;2012:212178 doi:
    1. Chiladakis J, Kalogeropoulos A, Arvanitis P, Koutsogiannis N, Zagli F, Alexopoulos D. Preferred QT correction formula for the assessment of drug-induced QT interval prolongation. J Cardiovasc Electrophysiol. 2010;21(8):905–13. doi:
    1. Michels G, Kochanek M, Pfister R. Life-threatening cardiac arrhythmias due to drug-induced QT prolongation: A retrospective study over 6 years from a medical intensive care unit. Med Klin Intensivmed Notfmed. 2016;111(4):302–9. doi:
    1. Kozik TM, Wung SF. Acquired long QT syndrome: frequency, onset, and risk factors in intensive care patients. Crit Care Nurse. 2012;32(5):32–41. doi:
    1. Ridruejo R, Zalba Etayo B, Civeira Murillo E, Montes Castro N, Munárriz Hinojosa J. Síndrome de QT largo adquirido en pacientes ingresados en UCI. Med Intensiva. 2005;29(7):379–83.
    1. Riad FS, Davis AM, Moranville MP, Beshai JF. Drug-Induced QTc Prolongation. Am J Cardiol. 2017;119(2):280–3. doi:
    1. Sarganas G, Garbe E, Klimpel A, Hering RC, Bronder E, Haverkamp W. Epidemiology of symptomatic drug-induced long QT syndrome and Torsade de Pointes in Germany. Europace. 2014;16(1):101–8. doi:
    1. Seftchick MW, Adler PH, Hsieh M, Wolfson AB, Chan ST, Webster BW, et al. The prevalence and factors associated with QTc prolongation among emergency department patients. Ann Emerg Med. 2009;54(6):763–8. doi:
    1. Pham JC, Banks MC, Narotsky DL, Dorman T, Winters BD. The prevalence of long QT interval in post-operative intensive care unit patients. J Clin Monit Comput. 2016;30(4):437–43. doi:
    1. Tisdale JE, Jaynes HA, Kingery JR, Overholser BR, Mourad NA, Trujillo TN, et al. Effectiveness of a clinical decision support system for reducing the risk of QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes. 2014;7(3):381–90. doi:
    1. Katoh T. Clinical Background and Evaluation of Drug-Induced Prolongation of QT Interval. Journal of Arrhythmia. 2009;25(2):56–62.
    1. Isbister GK, Page CB. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice. Br J Clin Pharmacol. 2013;76(1):48–57. doi:
    1. Li G, Cheng G, Wu J, Zhou X, Liu P, Sun C. Drug-induced long QT syndrome in women. Adv ther. 2013;30(9):793–802. doi:
    1. Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J. 2016;149(3):139–52.
    1. Schwartz PJ, Woosley RL. Predicting the Unpredictable: Drug-Induced QT Prolongation and Torsades de Pointes. J Am Coll Cardiol. 2016;67(13):1639–50. doi:
    1. Poluzzi E, Raschi E, Moretti U, De Ponti F. Drug-induced torsades de pointes: data mining of the public version of the FDA Adverse Event Reporting System (AERS). Pharmacoepidemiol Drug Saf. 2009;18(6):512–8. doi:
    1. Allen LaPointe NM, Curtis LH, Chan KA, Kramer JM, Lafata JE, Gurwitz JH, et al. Frequency of high-risk use of QT-prolonging medications. Pharmacoepidemiol Drug Saf. 2006;15(6):361–8. doi:
    1. Woosley RL, Romero K. QT drug List, 2013. AZCERT, Inc. Available from: .
    1. Keller GA, Alvarez PA, Ponte ML, Belloso WH, Bagnes C, Sparanochia C, et al. Drug-Induced QTc Interval Prolongation: A Multicenter Study to Detect Drugs and Clinical Factors Involved in Every Day Practice. Curr Drug Saf. 2016;11(1):86–98.

Source: PubMed

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