Skip to main content
SpringerLink
Log in

QT interval abnormalities: risk factors and perioperative management in long QT syndromes and Torsades de Pointes

  • Review Article
  • Published:
Journal of Anesthesia Aims and scope Submit manuscript

Abstract

Electrophysiological abnormalities of the QT interval of the standard electrocardiogram are not uncommon. Congenital long QT syndrome is due to mutations of several possible genes (genotype) that result in prolongation of the corrected QT interval (phenotype). Abnormalities of the QT interval can be acquired and are often drug-induced. Torsades de Pointes (TP) is an arrhythmia that is a result of aberrant repolarization/QT abnormalities. If not recognized and corrected quickly, QT interval abnormalities may precipitate potentially fatal ventricular dysrhythmias. The main mechanism responsible for the development of QT prolongation is blockade of the rapid component of the delayed rectifier potassium current (I kr), encoded for by the human-ether-a-go-go-related gene (hERG). The objectives of this review were (1) to describe the electrical pathophysiology of QT interval abnormalities, (2) to differentiate congenital from acquired QT interval abnormalities, (3) to describe the currently known risk factors for QT interval abnormalities, (4) to identify current drug-induced causes of acquired QT interval abnormalities, and (5) to recommend immediate and effective management strategies to prevent unanticipated dysrhythmias and deaths from QT abnormalities in the perioperative period.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Gupta A, Lawrence AT, Krishnan K, Kavinsky CJ, Trohman RG. Current concepts in the mechanism and management of drug-induced QT prolongation and torsades de pointes. Am Heart J. 2007;153:891–9.

    Article  PubMed  Google Scholar 

  2. Lawrence CL, Pollard CE, Hammond TG, Valentin JP. Nonclinical proarrhythmia models: predicting Torsades de Pointes. J Pharmacol Toxicol Methods. 2005;52(1):46–59.

    Article  PubMed  CAS  Google Scholar 

  3. Dessertenne F. Ventricular tachycardia with 2 variable opposing foci. Arch Mal Coeur Vaiss. 1966;59:263–72.

    PubMed  CAS  Google Scholar 

  4. Drew BJ, Ackerman MJ, Funk M, Gibler WB, Kligfield P, Menon V, Philippides GJ, Roden DM, Zareba W. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Cardiology. 2010;121:1047–60.

    Google Scholar 

  5. Molokhia M, Pathak A, Lapeyre-Mestre M, Caturla L, Montastruc JL, McKeigue P. Case ascertainment and estimated incidence of drug-induced long-QT syndrome: study in Southwest France. Br J Clin Pharmacol. 2008;66:386–95.

    Article  PubMed  Google Scholar 

  6. Viskin S. The QT interval: too long, too short or just right. Heart Rhythm. 2009;6(5):711–5.

    Article  PubMed  Google Scholar 

  7. Murgatroyd F, Krahn AD, Klein GJ, Yee R, Skanes A (eds). Handbook of cardiac electrophysiology: a practical guide to invasive EP studies and catheter ablation. London: ReMEDICA Publishing Limited; 2002.

  8. Roden DM, Woosley RL, Primm RK. Incidence and clinical features of the quinidine-associated long QT syndrome: implications for patient care. Am Heart J. 1986;111:1088–93.

    Article  PubMed  CAS  Google Scholar 

  9. Sauer AJ, Moss AJ, McNitt S, Peterson DR, Zareba W, Robinson JL, Qi M, Goldenberg I, Hobbs JB, Ackerman MJ, Benhorin J, Hall WJ, Kaufman ES, Locati EH, Napolitano C, Priori SG, Schwartz PJ, Towbin JA, Vincent GM, Zhang L. Long QT syndrome in adults. J Am Coll Cardiol. 2007;49:329–37.

    Article  PubMed  Google Scholar 

  10. Cupp M. Drug-induced long QT interval. Pharm Lett. 2010;26(4):260421.

    Google Scholar 

  11. Indik JH, Pearson EC, Fried K, Woosley RL. Bazett and Fridericia QT correction formulas interfere with measurement of drug-induced changes in QT interval. Heart Rhythm. 2006;3:1003–7.

    Article  PubMed  Google Scholar 

  12. Dogan A, Tunc E, Varol E, Ozaydin M, Ozturk M. Comparison of the four formulas of adjusting QT interval for the heart rate in middle-aged healthy Turkish men. Ann Noninvasive Electrocardiol. 2005;10:134–41.

    Article  PubMed  Google Scholar 

  13. Yap YG, Camm AJ. Drug induced QT prolongation and Torsade de Pointes. Heart. 2003;89:1363–72.

    Article  PubMed  CAS  Google Scholar 

  14. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013–22.

    Article  PubMed  CAS  Google Scholar 

  15. Yan GX, Antzelevitch C. Cellular basis for the normal T wave and the electrocardiographic manifestations of the long-QT syndrome. Circulation. 1998;98:1928–36.

    Article  PubMed  CAS  Google Scholar 

  16. Antzelevitch C. Role of transmural dispersion of repolarization in the genesis of drug-induced torsades de pointes. Heart Rhythm. 2005;2:S9–15.

    Article  PubMed  Google Scholar 

  17. Antzelevitch C, Sicouri S. Clinical relevance of cardiac arrhythmias generated by afterdepolarization: role of M cells in the generation of U wave, triggered activity, and Torsade de Pointes. J Am Coll Cardiol. 1994;23:259–77.

    Article  PubMed  CAS  Google Scholar 

  18. Burke JH, Ehlert FA, Kruse JT, Parker MA, Goldberger JJ, Kadish AH. Gender-specific differences in the QT interval and the effect of autonomic tone and menstrual cycle in healthy adults. Am J Cardiol. 1997;79:178–81.

    Article  PubMed  CAS  Google Scholar 

  19. Rodriguez I, Kilborn MJ, Liu XK, Pezzullo JC, Woosley RL. Drug-induced prolongation in women during the menstrual cycle. JAMA. 2001;285:1322–6.

    Article  PubMed  CAS  Google Scholar 

  20. Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswnathan PC, Hohnloser SH, Shimizu W, Schwartz PJ, Stanton M, Murray KT, Norris K, George AL Jr, Roden DM. Allelic variants in long-QT disease genes in patients with drug-associated Torsade de Pointes. Circulation. 2002;105:1943–8.

    Article  PubMed  CAS  Google Scholar 

  21. Roden DM. Long QT syndrome: reduced repolarization reserve and the genetic link. J Intern Med. 2006;259:59–69.

    Article  PubMed  CAS  Google Scholar 

  22. Carmeliet E. Repolarization reserve in cardiac cells. J Med Biomed Eng. 2006;26:98–105.

    Google Scholar 

  23. Priori SG, Napolitano C, Schwartz PJ. Low penetrance in the long-QT syndrome. Circulation. 1999;99:529–33.

    Article  PubMed  CAS  Google Scholar 

  24. Vincent GM. Controversies in arrhythmia and electrophysiology: genotypying has a minor role in selecting therapy for congenital long-QT syndromes at present. Circ Arrhythm Electrophysiol. 2008;1:227–33.

    Article  PubMed  Google Scholar 

  25. Hondeghem LM, Carlsson L, Duker G. Instability and triangulation of the action potential predict serious proarrhythmia, but action potential duration and prolongation is antiarryhthmic. Circulation. 2001;103:2004–13.

    Article  PubMed  CAS  Google Scholar 

  26. Hondeghem LM, Hoffman P. Blinded test in isolated female rabbit heart reliably identifies action potential duration prolongation and proarrhythmic drugs: importance of triangulation, reverse use dependence, and instability. J Cardiovasc Pharmacol. 2003;41(1):14–24.

    Article  PubMed  CAS  Google Scholar 

  27. Thomsen MB, Verduyn SC, Stengl M, Beekman JD, de Pater G, van Opstal J, Volders PG, Vos MA. Increased short-term variability of repolarization predicts d-sotalol-induced torsades de pointes in dogs. Circulation. 2004;110:2453–9.

    Article  PubMed  Google Scholar 

  28. Milberg P, Ramtin S, Monnig G, Osada N, Wasmer K, Breithardt G, Haverkamp W, Eckardt L. Comparison of the in vitro electrophysiologic and proarrhythmic effects of amiodarone and sotalol in a rabbit model of acute atrioventricular block. J Cardiovasc Pharmacol. 2004;44:278–86.

    Article  PubMed  CAS  Google Scholar 

  29. Pratt CM, Ruberg S, Morganroth J, McNutt B, Woodward J, Harris S, Ruskin J, Moye L. Dose–response relation between terfenadine (Seldane) and the QTc interval on the scalar electrocardiogram: distinguishing a drug effect from spontaneous variability. Am Heart J. 1996;131:472–80.

    Article  PubMed  CAS  Google Scholar 

  30. Jacobsen I, Carlsson L, Duker G. Beat-by-beat QT interval variability, but not QT prolongation per se, predicts drug-induced torsades de pointes in the anaesthetized methoxamine-sensitized rabbit. J Pharmacol Toxicol Methods. 2011;63:40–6.

    Article  Google Scholar 

  31. Antzelevitch C, Shimizu W. Cellular mechanisms underlying the long QT syndrome. Curr Opin Cardiol. 2002;17:43–51.

    Article  PubMed  Google Scholar 

  32. Antzelevitch C. Ionic, molecular, and cellular bases of QT interval prolongation and torsades de pointes. Eurospace. 2007;9:4–15.

    Google Scholar 

  33. Yan GX, Wu Y, Liu T, Wang J, Marinchak RA, Kowy PR. Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome: direct evidence from intracellular recordings in the intact left ventricular wall. Circulation. 2001;103:2851–6.

    Article  PubMed  CAS  Google Scholar 

  34. Antzelevitch C. Arrhythmogenic mechanisms of QT-prolonging drugs: is QT prolongation really the problem? J Electrocardiol. 2004;37:15–24.

    Article  PubMed  Google Scholar 

  35. Fossa AA, Wisialowski T, Wolfgang E, Wang E, Avery M, Raunig DL, Fermini B. Differential effect of HERG blocking agents on cardiac electrical alternans in guinea pig. Eur J Pharmacol. 2004;486:209–21.

    Article  PubMed  CAS  Google Scholar 

  36. De Bruin ML, Pettersson M, Meyboom RH, Hoes AW, Leufkens HG. Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death. Eur Heart J. 2005;26:590–7.

    Article  PubMed  Google Scholar 

  37. Kim HT, Lee JH, Park IB, Heo HE, Kim TY, Lee MJ. Long QT syndrome provoked by induction of general anesthesia—a case report. Korean J Anesthesiol. 2010;59:114–8.

    Article  Google Scholar 

  38. van der Heide K, de Haes A, Wietasch GJ, Wiesfeld AC, Hendriks HG. Torsades de pointes during laparoscopic adrenalectomy of pheochromoctyoma: a case report. J Med Case Rep. 2011;5:368.

    Article  PubMed  Google Scholar 

  39. Saarnivaara L, Lindgren L. Prolongation of QT interval during induction of anaesthesia. Acta Anaeasthesiol Scand. 1983;27:126–30.

    Article  CAS  Google Scholar 

  40. Michaloudis DG, Kanakoudis FS, Petrou AM, Konstantinidou AS, Pollard BJ. The effects of midazolam or propofol followed by suxamethonium on the QT interval in humans. Eur J Anaesthesiol. 1996;13:364–8.

    Article  PubMed  CAS  Google Scholar 

  41. Keller GA, Ponte ML, Di Girolamo G. Other drugs acting on nervous system associated with QT-interval prolongation. Curr Drug Saf. 2010;5:105–11.

    Article  PubMed  CAS  Google Scholar 

  42. Saarnivaara L, Klemola UM, Lindgren L. QT interval of the ECG, heart rate and arterial pressure using five non-depolarizing muscle relaxants for intubation. Acta Anaesthesiol Scand. 1988;32(8):623–8.

    Article  PubMed  CAS  Google Scholar 

  43. Aypar E, Karagoz AH, Ozer S, Celiker A, Ocal T. The effects of sevoflurane and desflurane anesthesia on QTc interval and cardíac rhythm in children. Paediatr Anaesth. 2007;17(6):563–7.

    Article  PubMed  Google Scholar 

  44. Karagoz AH, Basgul E, Celiker V, Aypar U. The effect of inhalational anaesthetics on QTc interval. Eur J Anaesthesiol. 2005;22:171–4.

    PubMed  CAS  Google Scholar 

  45. Scuderi PE. Sevoflurane and QTc prolongation: an interesting observation, or a clinically significant finding? Anesthesiology. 2010;113(4):772–5.

    Article  PubMed  Google Scholar 

  46. Riley DC, Schmeling WT, Al-Wathiqui MH, Kampine JP, Wartlier DC. Prolongation of the QT interval by volatile anesthetics in chronically instrumented dogs. Anesth Analg. 1988;67:741–9.

    Article  PubMed  CAS  Google Scholar 

  47. Schmeling WT, Warltier DC, McDonald DJ, Madsen KE, Atlee JL, Kampine JP. Prolongation of the QT interval by enflurane, isoflurane, and halothane in humans. Anesth Analg. 1991;72:137–44.

    Article  PubMed  CAS  Google Scholar 

  48. Silay E, Kati I, Tekin M, Guler N, Huseyinoglu UA, Coskuner I, Yagmur C. Comparison of the effects of desflurane and sevoflurane on the QTc interval and QT dispersion. Acta Cardiol. 2005;60:459–64.

    Article  PubMed  Google Scholar 

  49. Kazanci D, Unver S, Karadeniz U, Iyican D, Koruk S, Yilmaz MB, Erdemli O. A comparison of the effects of desflurane, sevoflurane, and propofol on QT, QTc, and P dispersion on ECG. Ann Card Anaesth. 2009;12:107–12.

    Article  PubMed  Google Scholar 

  50. Whyte SD, Booker PD, Buckley DG. The effects of propofol and sevoflurane on the QT interval and transmural dispersion of repolarization in children. Anesth Analg. 2005;100(1):71–7.

    Article  PubMed  CAS  Google Scholar 

  51. Saussine M, Massad I, Raczka F, Davy JM, Frapier JM. Torsades de pointes during sevoflurane anesthesia in a child with congenital long QT syndrome. Paediatr Anaesth. 2006;16(1):63–5.

    Article  PubMed  Google Scholar 

  52. Tacken MC, Bracke FA, Van Zundert AA. Torsades de pointes during sevoflurane anesthesia and fluconazole infusion in a patient with long QT syndrome. Acta Anaesth Belg. 2011;62:105–8.

    PubMed  CAS  Google Scholar 

  53. Cubeddu LX. QT prolongation and fatal arrhythmias: a review of clinical implications and effects of drugs. Am J Ther. 2003;10(6):452–7.

    Article  PubMed  Google Scholar 

  54. Saarnivaar L, Hiller A, Oikkonen M. QT interval, heart rate and arterial pressures using propofol, thiopentone, or methohexitone for induction of anaesthesia in children. Acta Anaesthesiol Scand. 1993;37:419–23.

    Article  Google Scholar 

  55. Irie T, Kaneko Y, Nakajima T, Saito A, Kurabayashi M. QT interval prolongation and Torsade de Pointes induced by propofol and hypoalbuminemia. Int Heart J. 2010;51:365–6.

    Article  PubMed  Google Scholar 

  56. Kies SJ, Pabelick CM, Hurley HA, White RD, Ackerman MJ. Anesthesia for patients with congenital long QT syndrome. Anesthesiology. 2005;102:204–10.

    Article  PubMed  Google Scholar 

  57. Olshansky B, Martins J, Hunt S. N-acetyl procainamide causing torsades de pointes. Am J Cardiol. 1982;50:1439–41.

    Article  PubMed  CAS  Google Scholar 

  58. Chow MJ, Piergies AA, Bowsher DJ, Murphy JJ, Kushner W, Ruo TI, Asada A, Talano JV, Atkinson AJ Jr. Torsade de Pointes induced by N-acetylprocainamide. J Am Coll Cardiol. 1984;4:621–4.

    Article  PubMed  CAS  Google Scholar 

  59. Lehmann MH, Hardy S, Archibald D, Quart B, MacNeil DJ. Sex difference in risk of Torsade de Pointes with d, l-sotalol. Circulation. 1996;94:2535–41.

    Article  PubMed  CAS  Google Scholar 

  60. Kober L, Bloch Thomsen PE, Moller M, Torp-Pedersen C, Carlsen J, Sandoe E, Egstrup K, Agner E, Videbaek J, Marchant B, Camm AJ. Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial. Lancet. 2000;356:2052–8.

    Article  PubMed  CAS  Google Scholar 

  61. Torp-Pedersen C, Moller M, Bloch-Thomsen PE, Kober L, Sandoe E, Egstrup K, Agner E, Carlsen J, Videbaek J, Marchant B, Camm AJ. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med. 1999;341:857–65.

    Article  PubMed  CAS  Google Scholar 

  62. Gowda RM, Punukollu G, Khan IA, Patiola RR, Tejani FH, Cosme-Thormann BF, Vasavada BC, Sacchi TJ. Ibutilide-induced long QT syndrome and Torsade de Pointes. Am J Ther. 2002;9:527–9.

    Article  PubMed  Google Scholar 

  63. Lazzara R. Amiodarone and Torsade de Pointes. Ann Intern Med. 1989;111:549–51.

    Article  PubMed  CAS  Google Scholar 

  64. Hohnloser SH, Klingenheben T, Singh BN. Amiodarone-associated proarrhythmic effects. A review with special reference to Torsade de Pointes tachycardia. Ann Intern Med. 1994;121:529–35.

    Article  PubMed  CAS  Google Scholar 

  65. Drouin E, Lande G, Charpentier F. Amiodarone reduces transmural heterogeneity of repolarization in the human heart. J Am Coll Cardiol. 1998;32:1063–7.

    Article  PubMed  CAS  Google Scholar 

  66. Antzelevitch C, Belardinelli L, Wu L, Fraser H, Zygmunt AC, Burashnikov A, Di Diego JM, Fish JM, Cordeiro JM, Goodrow RJ Jr, Scornik F, Perez G. Electrophysiologic properties and antiarrhythmic actions of a novel antianginal agent. J Cardiovasc Pharmacol Ther. 2004;9:S65–83.

    Article  PubMed  CAS  Google Scholar 

  67. Turner S, Matthews L, Pandharipande P, Thompson R. Dolasetron-induced Torsade de Pointes. J Clin Anesth. 2007;19:622–5.

    Article  PubMed  Google Scholar 

  68. White PF. Droperidol: a cost-effective antiemetic for over thirty years. Anesth Analg. 2002;95(4):789–90.

    PubMed  CAS  Google Scholar 

  69. Halloran K, Barash PG. Inside the black box: current policies and concerns with the United States Food and Drug Administration’s highest drug safety warning system. Curr Opin Anaesthesiol. 2010;23(3):423–7.

    Article  PubMed  Google Scholar 

  70. Adler A, Viskin S, Bhulyan ZA, Eisenberg E, Rosso R. Propoxyphene-induced Torsade de Pointes. Heart Rhythm. 2011;8:1952–4.

    Article  PubMed  Google Scholar 

  71. Krantz MJ, Kutinsky IB, Robertson AD, Mehler PS. Dose-related effects of methadone on QT prolongation in a series of patients with Torsade de Pointes. Pharmacotherapy. 2003;23:802–5.

    Article  PubMed  CAS  Google Scholar 

  72. Stringer J, Welsh C, Tommaselio A. Methadone-associated QT interval prolongation and torsades de pointes. Am J Health Syst Pharm. 2009;66:825–33.

    Article  PubMed  CAS  Google Scholar 

  73. Krantz MJ, Garcia JA, Mehler PS. Effects of buprenorphine on cardiac repolarization in a patient with methadone-related torsades de pointes. Pharmocotherapy. 2005;25:611–4.

    Article  Google Scholar 

  74. Wieneke H, Conrads H, Wolstein J, Breuckmann F, Gastpar M, Erbel R, Scherbaum N. Levo-alpha-acetylmethadol (LAAM) induced QTc-prolongation-results from a controlled clinical trial. Eur J Med Res. 2009;14:7–12.

    Article  PubMed  CAS  Google Scholar 

  75. Deamer RL, Wilson DR, Clark DS, Prichard JG. Torsades de pointes associated with high dose levomethadyl acetate (ORLAM). J Addict Dis. 2001;20:7–14.

    Article  PubMed  CAS  Google Scholar 

  76. Khan IA. Long QT syndrome: diagnosis and management. Am Heart J. 2002;143(1):7–14.

    Article  PubMed  Google Scholar 

  77. Pinski SL, Equia LE, Trohman RG. What is the minimal pacing rate that prevents Torsade de Pointes? Insights from patients with permanent pacemakers. Pacing Clin Electrophysiol. 2002;25:1612–5.

    Article  PubMed  Google Scholar 

  78. Nathan AT, Berkowitz DH, Montenegro LM, Nicolson SC, Vetter VL, Jobes DR. Implications of anesthesia in children with long QT syndrome. Anesth Analg. 2011;112:1163–8.

    Article  PubMed  CAS  Google Scholar 

  79. Nagele P, Pal S, Brown F, Blood J, Miller JP, Johnston J. Postoperative QT interval prolongation in patients undergoing noncardiac surgery under general anesthesia. Anesthesiology. 2012;117:321–8.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

Alan David Kaye received honoraria from Depomed and research funding from Depomed. J. Michael Bensler received honoraria from Boehringer Ingelheim and is on the advisory board for Medtronics. Jacqueline Volpi Abadie, Adam M. Kaye, and James H. Diaz report no conflicts of interest.

Author information

Author notes

  1. Jacqueline Volpi-Abadie

    Present address: Department of Anesthesiology, Alton Ochsner Clinic, New Orleans, 70121, USA

  2. J. Michael Bensler

    Present address: Cardiovascular Consultants of Nevada, Henderson, USA

Authors and Affiliations

  1. Department of Anesthesiology, LSU School of Medicine, Room 656, 1542 Tulane Ave., New Orleans, LA, 70112, USA

    Alan David Kaye, Jacqueline Volpi-Abadie & James H. Diaz

  2. Jackson Heart Clinic, Baptist Hospital, Jackson, MS, 39202, USA

    J. Michael Bensler

  3. Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, 3601 Pacific Avenue, Stockton, CA, 95211, USA

    Adam M. Kaye

Authors
  1. Alan David Kaye
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacqueline Volpi-Abadie
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Michael Bensler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adam M. Kaye
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James H. Diaz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alan David Kaye.

About this article

Cite this article

Kaye, A.D., Volpi-Abadie, J., Bensler, J.M. et al. QT interval abnormalities: risk factors and perioperative management in long QT syndromes and Torsades de Pointes. J Anesth 27, 575–587 (2013). https://doi.org/10.1007/s00540-013-1564-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00540-013-1564-1

Keywords

Search

Navigation