Case Report

Prolonged QT Syndrome: Perioperative Management

ROBERT A. STRICKLAND, M.D., MARSHALL S. STANTON, M.D., AND KERRY D. OLSEN, M.D.

Intraoperative cardiac arrhythmias related to prolonged QT syndrome are uncommon. We describe a26-year-old woman in whom ventricular fibrillation occurred during the final minutes of a partialglossectomy and right supraomohyoid selective neck dissection and discuss the role that this specificoperation may have had in the development of the intraoperative event. In addition, we review theperioperative management of patients with prolonged QT syndrome.

Congenital prolonged QT syndrome is an uncommon butpotentially fatal entity. Jervell and Lange-Nielsen' first de­scribed this entity when they published the report of a familyin which three children died at an early age. Commoncharacteristics include the triad of prolonged QT interval,syncope, and congenital deafness. Subsequently, two otherarticles described a similar condition without the characteris­tic of deafness." Syncope is the result of malignant ven­tricular arrhythmias, which usually resemble torsades depointes." Other published case reports have described theanesthetic management of patients known preoperatively tohave prolonged QT syndromes" and those who did not havecardiac problems but in whom cardiac complications devel­oped intraoperatively.PP Herein we describe a patient whohad had an unexplained episode of cardiopulmonary arrestand who was successfully resuscitated after an episode ofintraoperative ventricular fibrillation. We also review therecent literature for the medical and anesthetic managementof patients with this potentially fatal syndrome.

REPORT OF CASEA 26-year-old woman with squamous cell carcinoma of thetongue was referred to our institution for assessment andmanagement. Her surgical history included an appendec­tomy and extraction of wisdom teeth, both of which were

From the Department of Anesthesiology (R.A.S.), Department of Car­diovascular Diseases and Internal Medicine (M.S.S.), and Departmentof Otorhinolaryngology (K.D.O.), Mayo Clinic Rochester, Rochester,Minnesota.

Address reprint requests to Dr. R. A. Strickland, Department of Anesthesi­ology, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905.

performed with use of general anesthesia and without com­plications. She had a two-pack-year history of cigarettesmoking. During her early teenage years, she had an unex­plained syncopal episode that resulted in a broken nose. Atage 18 years, she experienced a cardiac arrest: during anepisode of acute bronchitis, she took two codeine tablets(dose unknown) and drank a glass of wine to help her sleep.Sixteen hours later, she was found unresponsive, and herrespirations were shallow. Shortly thereafter, cardiopulmo­nary arrest occurred, and she was successfully resuscitated.After she had received life support and mechanical ventila­tion for 48 hours, central nervous system function began toreturn, and recovery to normal status ensued during the nextseveral days. She stated that her attending physicians at thattime believed that the cardiopulmonary arrest was attribut­able to the codeine, even though she had taken the tabletsmany hours before the arrest had occurred. Her familyhistory included the sudden death of her father at age 56years, apparently from a cardiac event.

A preoperative medical assessment of the patient revealedno physical abnormalities. The results of a complete bloodcell count, the only laboratory test that was done pre­operatively, were within normal limits; the hemoglobinconcentration was 13.4 g/dl. The findings on a 12-lead elec­trocardiogram obtained preoperatively were within normallimits.

Routine intraoperative monitoring included, but was notlimited to, an electrocardiogram (lead II), noninvasive mea­surement of the blood pressure, pulse oximetry, and massspectroscopy. Fentanyl citrate (100 ug), thiopental sodium(450 mg), and succinylcholine chloride (100 mg) were ad­ministered intravenously; nasotracheal intubation was done

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Mayo Clin Proc, October 1993, Vol 68

subsequently. Nitrous oxide (50%) and isoflurane (I to 2%)in oxygen and an additional 350 ug of fentanyl were used formaintaining anesthesia.

The anesthetic course and the operation, a partial glossec­tomy and right supraomohyoid selective neck dissection,proceeded uneventfully until the subcutaneous tissues of theneck were being closed. At that point, isolated prematureventricular contractions were noted, followed immediatelyby ventricular fibrillation. After administration of isofluraneand nitrous oxide was discontinued and 100% oxygen wasadministered, cardiopulmonary resuscitation with chestcompressions was begun. Within 60 seconds, defibrillationwith a shock of 200 joules resulted in resumption of sinusrhythm with intermittent junctional rhythm and occasionalpremature ventricular contractions. Atropine (0.4 mg) andlidocaine (l00 mg) were administered intravenously. Theskin incision was rapidly stapled; the patient awakenedshortly thereafter and was extubated. The results of theneurologic examination and findings on a 12-lead electrocar­diogram in the postanesthesia care unit were normal. Subse­quently, she was transferred to the intensive-care unit forcardiac monitoring and assessment.

An infusion of lidocaine was started prophylactically andwas discontinued 18 hours later. Serial serum electrolytesand thyroxine were normal, and serum Mg2+ was 1.6 mg/dl(normal, 1.7 to 2.1). No myocardial ischemia or injury wasapparent on the basis of serial electrocardiograms and crea­tine kinase and lactate dehydrogenase isoenzymes. Resultsof a drug screen were normal.

A review of the preoperative electrocardiogram revealeda corrected QT interval of 442 ms. Subsequent electrocar­diograms demonstrated consistently prolonged corrected QTintervals, with values approaching 530 ms (Fig. 1).

Echocardiographic findings demonstrated mild mitral re­gurgitation and ariterior mitral valve leaflet thickening with­out prolapse. During exercise, an electrocardiogram showed

PROLONGED QT SYNDROME 1017

no arrhythmias. Coronary angiography demonstrated nor­mal coronary arteries. An electrophysiologic study revealednormal atrioventricular node and His-Purkinje function anda prolonged, corrected QT interval of 517 ms. Ventriculararrhythmias could not be induced.

Congenital prolonged QT syndrome was diagnosed, and80 mg of propranolol was administered orally every 6 hours.Genetic consultation and assessment of family memberswere begun.

DISCUSSIONPatients with prolonged QT syndrome often have symptomsof syncope or dizziness, which usually begin during child­hood. Prolonged QT intervals may also be noted in anasymptomatic relative of a patient with the diagnosis. TheRomano-Ward syndrome-Y seems to have autosomal domi­nant characteristics, whereas the Jervell and Lange-Nielsensyndrome'> is autosomal recessive. A third category doesnot have any apparent genetic predisposition and occursrandomly. In relatives of patients with prolonged QT syn­drome, a history should be elicited, and electrocardiographyshould be performed.

Various clinical characteristics of this syndrome are list­ed in Table 1. Stress, anger, anxiety, loud noise, strongemotions, and physical activity increase the likelihood ofepisodes of prolonged QT syndrome.v'v" The frequencyvaries-from weekly to only a few occasions during a life­time-and may decrease with age.13,I4 The only physicalabnormality associated with some types of this syndrome isdeafness. The estimated annual mortality rate is 1 to 2%.4,5The four risk factors associated with an increased rate ofsyncope and death are congenital deafness, history of syn­cope, female gender, and history of torsades de pointes orventricular fibrillation.'

Traditionally, prolonged QT syndrome has been diag­nosed by documenting that the corrected QT interval is 440

Fig. 1. Electrocardiogram of 26-year-old woman with prolonged QT syndrome obtained 2 days postopera­tively, demonstrating corrected QT interval of 499 ms and notching of T wave,

1018 PROLONGED QT SYNDROME Mayo Clin Proc, October 1993,Vol68

*Except whereindicated otherwise-.Modified fromMoss and associates." By permission of the Ameri­can HeartAssociation.

ms or greater.':" This electrocardiographic definition willprobably be associated with misclassification of some pa­tients when the corrected interval approaches 440 ms, butfew cardiac events occur in patients with a corrected QTinterval of 440 ms or less." The resting electrocardiographicfindings are often normal; prolongation of the QT intervaloccurs only during exercise. 13.14 Associated nonspecificelectrocardiographic abnormalities include sinus brady­cardia.v" U waves.t-" premature ventricular contractionswith bigeminy and ventricular tachycardia," and torsadesde pointes.'" Moss and associates" reported that "thepathognomonic electrocardiographic finding" is a prolongedQT interval with asymmetric or notched T waves. If the rest­ing electrocardiographic findings are normal, exercise test­ing is indicated in an attempt to induce QT prolongation.

The pathogenesis of prolonged QT syndrome is uncer­tain, but several hypotheses have been proposed.' The mostwidely accepted hypothesis is an imbalance of sympatheticstimulation within the heart-the activity of the left cervicalsympathetic ganglion is greater than that of the right." Al­tered ventricular repolarization is manifested by prolonga­tion of the QT interval, and the result is the potential forventricular arrhythmias. This hypothesis is supported bystudies in a canine model in which right stellateganglionectomy or left stellate stimulation results in prolon­gation of the QT interval.'? Conversely, the QT interval isshortened when left stellate ganglionectomy or right stellatestimulation is performed. I? Alternatively, the mechanism ofarrhythmias in this syndrome may relate to afterdepolar­izations causing triggered activity.

33

786988

Experimentally, ablation of the right sympathetic stellateganglion or electrical stimulation of the left stellate ganglionincreases the QT interval. I? This finding may help explain astudy by Otteni and colleagues" that found after right, butnot left, radical neck dissections, the QT interval was oftensignificantly prolonged. Of their 32 study patients who un­derwent radical right neck dissections, torsades de pointesdeveloped postoperatively in 3.18 Our patient underwent aselective supraomohyoid right neck dissection. In this pro­cedure, the submandibular and upper and midlevel jugularlymph nodes in the neck are removed; the muscles, majorvessels, and nerves, including the cervical sympatheticchain, should be spared. Any neck dissection, whether radi­cal, modified, or selective, along the deep cervical fasciaelevates the lymph node-bearing tissue off the carotid sheathstructures and sympathetic chain. Theoretically, this maneu­ver could result in a transient or partial disruption in sympa­thetic neural transmission. Postoperatively, our patient didnot have Horner's syndrome. A transient decrease in theright cervical sympathetic activity, however, could haveaugmented the prolongation of the QT interval. This effect,plus the potential for QT prolongation related to the anes­thetics, may have been a contributing factor that resulted inventricular fibrillation.

Usually, therapy is initiated with ~-adrenergic blockers;'although these drugs may not alter the QT interval, they dodecrease the likelihood of ventricular arrhythmias. Othertreatment involves surgical excision of the left stellate gan­glion and division of the first three to five thoracic sympa­thetic ganglia.v'v'? Occasionally, ~-blockers and left stellateganglionectomy are ineffective in managing ventriculararrhythmias, or symptomatic bradycardia may occur with ~­

blockers. Two recent studies reported favorable results withuse of permanent cardiac pacemakers (with or without theother two modes of therapy) in decreasing, although noteliminating, the frequency of syncopal events. 20

•21 Implant­able defibrillators have also been advocated for poorly con­trolled ventricular arrhythmias.'

One important aspect of anesthetic management is a calm,relaxed patient. A thorough discussion of the anticipatedprocedure should help to allay fears. Premedication withsedative-hypnotic agents such as diazepam or midazolamand, possibly, morphine should also assist in producing acalm patient without a high degree of sympathetic stimula­tion. Routine doses of ~-blockersshould be continued up tothe time of operation and resumed postoperatively.

Few studies have compared general and regional anesthe­sia in patients with prolonged QT syndrome. Brown andcoworkers" mentioned two episodes of uneventful spinalanesthesia during childbirth in a patient with this syndrome.In this patient during subsequent general anesthesia, ven­tricular ectopic beats and ventricular tachycardia developed

%*

6424± 16

5716± 14

633

500± 604913

Characteristic

Table I.-Clinical Characteristics of PatientsWith Prolonged QT Syndrome

FemalesAge (yr; mean± SD)SyncopeAge at first syncopal episode(yr; mean± SD)Congenital deafnessHistory of premature ventricular beatsHistory of torsades de pointes or ventricular

fibrillationCorrected QT interval (in ms) in leadII

(mean± SD)UwavePremature ventricular beatsFamily history

SyncopeSuddendeathat <65 yr of ageCorrected QT interval >440ms

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shortly after completion of the operation; this complicationnecessitated lidocaine therapy." Two other case reportsdiscussed the merits and safety of spinal or epidural anesthe­sia.23.24 The use of heavy sedation should decrease sympa­thetic responses in patients with prolonged QT syndromewho are undergoing operations with use of local or regionalanesthesia. In addition, even though data for confirmationare lacking, empirically epinephrine should be omitted fromlarge-volume local anesthetic solutions, such as those usedfor epidural and brachial plexus anesthesia.

Various clinical studies have evaluated the effects ofanesthetics on the QT interval in normal subjects and pa­tients with prolonged QT syndrome. Thiopental increasesthe QT interval in normal subjects.P'" but in one case report,its administration did not alter the QT interval in a patientwith prolonged QT syndrome." Thiopental has also beenused safely in several other reported cases.8-12.22.28-30 Othercommonly used induction agents, such as thiamylal so­dium'" and methohexital," seem satisfactory for use in pa­tients with prolonged QT syndrome. Propofol increases theQT interval in normal subjects but less than does thio­pental." Theoretically, ketamine hydrochloride should beavoided because sympathetic stimulation may occur withuse of this agent.

During induction of anesthesia and intubation, sympa­thetic stimulation should be blunted with the use of narcoticsor ~-adrenergic blockers. Morphine and fentanyl are the twonarcotics that have been most commonly used in publishedreports. In normal adults, metoprolol has been shown to bebeneficial in decreasing the prolongation of the QT intervalafter induction with thiopental and succinylcholine, but pro­longation still occurs after intubation." Thus, the adminis­tration of ~-blockersduring induction might be beneficial inpatients with prolonged QT syndrome.

Succinylcholine, which has a duration of action of 3 to 5minutes, results in prolongation of the QT interval in normaladults, an effect that can be blunted by defasciculating dosesof tubocurarine (but not alcuronium chloride or pancuro­nium bromide).25,26 Succinylcholine, administered at induc­tion, was used without adverse effects in our patient and inpatients in other case reports,7·8.29.30 but it should be used withcaution because of its potential adverse effects on the cardiacpostganglionic muscarinic receptors. In some case reports,episodes of ventricular arrhythmias were noted during theinduction and intubation sequence when succinylcholinewas used.!':" Pancuronium, possibly as a result of its sympa­thomimetic effects, was associated with ventricular fibrilla­tion in one case report." Other muscle relaxants such asvecuronium bromide, atracurium besylate, and metocurineiodide should be satisfactory because minimal, if any, sym­pathetic stimulation or direct cardiac effects occur with useof these drugs.

PROLONGED QT SYNDROME 1019

Several reports have advocated isoflurane as the inhala­tional agent of choice because of its apparent safety,7·l2.28.3land it was reported to decrease the QT interval in one patientwith prolonged QT syndrome." Isoflurane and nitrous ox­ide, however, were the predominant anesthetic agents in ourpatient. In their study of normal human subjects, Schmelingand coworkers" demonstrated that halothane, enflurane, andisoflurane each significantly prolonged the corrected QTinterval and that halothane alone prolonged the uncorrectedQT interval. Halothane also sensitizes the heart to cat­echolamines more than does enflurane or isofluranev" andprobably should be avoided.

REFERENCES1. Jervell A, Lange-Nielsen F. Congenital deaf-mutism, func­

tional heart disease with prolongation of the Q-T interval, andsudden death. Am Heart J 1957; 54:59-68

2. Romano C, Gemme G, Pongiglione R. Aritmie cardiacherare dell' eta' pediatrica. II. Accessi sincopali perfibrillazione ventricolare parossistica. (Presentazione delprimo caso della letteratura pediatrica ltaliana.) Clin Pediatr(Bologna) 1963; 45:656-683

3. Ward OC. A new familial cardiac syndrome in children. JIrish Med Assoc 1964; 54:103-106

4. Moss AJ, Schwartz PJ, Crampton RS, Locati E, Carleen E.The long QT syndrome: a prospective international study.Circulation 1985; 71:17-21

5. Moss AJ. Prolonged QT-interval syndromes. JAMA 1986;256:2985-2987

6. Callaghan ML, Nichols AB, Sweet RB. Anesthetic manage­ment of prolonged Q-T interval syndrome. Anesthesiology1977; 47:67-69

7. Carlock FI, Brown M, Brown EM. Isoflurane anaesthesia fora patient with long Q-T syndrome. Can Anaesth Soc J 1984;31:83-85

8. Owitz S, Pratilas V, Pratila MG, Dimich I. Anaestheticconsiderations in the prolonged Q-T interval (LQTS): a casereport. Can Anaesth Soc J 1979; 26:50-54

9. Ponte J, Lund J. Prolongation of the Q-T interval (Romano­Ward syndrome): anaesthetic management. Br J Anaesth1981; 53:1347-1349

10. Wig J, Bali 1M, Singh RG, Kataria RN, Khattri HN. Pro­longed Q-T interval syndrome: sudden cardiac arrest duringanaesthesia. Anaesthesia 1979; 34:37-40

11. Forbes RB, Morton GH. Ventricular fibrillation in a patientwith unsuspected mitral valve prolapse and a prolonged Q-Tinterval. Can Anaesth Soc J 1979; 26:424-427

12. Medak R, Benumof JL. Perioperative management of theprolonged Q-T interval syndrome. Br J Anaesth 1983;55:361-364

13. Schwartz PJ, Periti M, Malliani A. The long Q-T syndrome.Am Heart J 1975; 89:378-390

14. Vincent GM, Abildskov JA, Burgess MJ. Q-T interval syn­dromes. Prog Cardiovasc Dis 1974; 16:523-530

15. Moss AJ, Schwartz PJ, Crampton RS, Tzivoni D, Locati EH,MacCluer J, et al. The long QT syndrome: prospectivelongitudinal study of 328 families. Circulation 1991;84:1136-1144

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16. Schwartz PJ, Locati E. The idiopathic long QT syndrome:pathogenetic mechanisms and therapy. Eur Heart J 1985;6(Suppl D):103-114

17. Yanowitz F, Preston JB, Abildskov JA. Functional distribu­tion of right and left stellate innervation to the ventricles:production of neurogenic electrocardiographic changes byunilateral alteration of sympathetic tone. Circ Res 1966;18:416-428

18. Otteni JC, Pottecher T, Bronner G, Flesch H, Diebolt JR.Prolongation of the Q-T interval and sudden cardiac arrestfollowing right radical neck dissection. Anesthesiology1983; 59:358-361

19. Moss AJ, McDonald J. Unilateral cervicothoracic sympa­thetic ganglionectomy for the treatment of long QT intervalsyndrome. N Engl J Med 1971; 285:903-904

20. Eldar M, Griffin JC, Abbott JA, Benditt D, Bhandari A, HerreJM, et al. Permanent cardiac pacing in patients with the longQT syndrome. J Am Coli Cardiol 1987; 10:600-607

21. Moss AJ, Liu IE, Gottlieb S, Locati EH, Schwartz PJ,Robinson JL. Efficacy of permanent pacing in the manage­ment of high-risk patients with long QT syndrome. Circula­tion 1991; 84:1524-1529

22. Brown M, Liberthson RR, Ali HH, Lowenstein E. Peri­operative anesthetic management of a patient with long Q-Tsyndrome (LQTS). Anesthesiology 1981; 55:586-589

23. Palkar NV, Crawford MW. Spinal anaesthesia in prolongedQ-T interval syndrome [letter]. Br J Anaesth 1986; 58:575-576 .

24. Ryan H. Anaesthesia for caesarean section in a patient withJervell, Lange-Nielsen syndrome. Can J Anaesth 1988;35:422-424

25. Saarnivaara L, Lindgren L. Prolongation of QT intervalduring induction of anaesthesia. Acta Anaesthesiol Scand1983; 27:126-130

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26. Saarnivaara L, Lindgren L, Hynynen M. Effects ofpractololand metoprolol on QT interval, heart rate and arterial pressureduring induction of anaesthesia. Acta Anaesthesiol Scand1984; 28:644-648

27. McConachie I, Keaveny JP, Healy TEJ, Vohra S, Million L.Effect of anaesthesia on the QT interval. Br J Anaesth 1989;63:558-560

28. Wilton NCT, Hantler CB. Congenital long QT syndrome:changes in QT interval during anesthesia with thiopental,vecuronium, fentanyl, and isoflurane. Anesth Analg 1987;66:357-360

29. O'Callaghan AC, Normandale JP, Morgan M. The prolongedQ-T syndrome: a review with anaesthetic implications and areport of two cases. Anaesth Intensive Care 1982; 10:50­55

30. Freshwater JV. Anaesthesia for caesarean section and theJervell, Lange-Nielsen syndrome (prolonged Q-T intervalsyndrome). Br J Anaesth 1984; 56:655-657

31. Adu-Gyamfi Y, Said A, Chowdhary UM, Abomelha A,Sanyal SK. Anaesthetic-induced ventricular tachyarrhythmiain Jervell and Lange-Nielsen syndrome. Can J Anaesth1991; 38:345-346

32. Schmeling WT, Warltier DC, McDonald DJ, Madsen KE,Atlee JL, Kampine JP. Prolongation of the QT interval byenflurane, isoflurane, and halothane in humans. AnesthAnalg 1991; 72:137-144

33. Joas TA, Stevens We. Comparison of the arrhythmic dosesof epinephrine during Forane, halothane, and fluroxene anes­thesia in dogs. Anesthesiology 1971; 35:48-53

34. Johnston RR, Eger EI II, Wilson C. A comparative interac­tion of epinephrine with enflurane, isoflurane, and halothanein man. Anesth Analg 1976; 55:709-712