QT Prolongation

Description

The QT interval (QT) refers to the time between the start of ventricular depolarization to the end of repolarization; normally between 0.3 and 0.44 seconds.
A prolonged QT interval is affiliated with ventricular arrhythmias, particularly the development of Torsades de Pointes. This condition is otherwise known as long QT syndrome (LQTS) and can be either congenital or "acquired."
Surgical stimulation and several perioperative medications can have adverse effects on patients with LQTS.

Epidemiology

Prevalence

US: 1:1,100–5,000 people

Morbidity

Although some patients present initially with syncope to the emergency department, for many patients there is no pre-morbid state prior to collapse and out-of-hospital cardiac arrest.

Mortality

US: 4,000/year

Risk Factors

Increased sympathetic tone can precipitate Torsades de Pointes.
Electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia)
Drugs (see Table 1)
Anorexia nervosa (severe starvation)
Subarachnoid hemorrhage
Hypothermia

Table 1. Medications that affect the QT interval

Strong Association
Droperidol, Methadone, Amiodarone, Procainamide, Quinidine, Sotalol, Disopyramide, Chloroquine, Clarithromycin, Erythromycin, Pentamidine, Chlorpromazine, Haloperidol, Thioridazine, Cisapride, Domperidone, Organophosphates, Ibutilide, Probucol, Sparfloxacin, Pimozide, Halofantrine, Levomethadyl, Mesoridazine
Moderate Association
Dolasetron, Granisetron, Ondansetron, Oxytocin, Chloral hydrate, Salmeterol, Octreotide, Tacrolimus, Flecainide, Nicardipine, Azithromycin, Gatifloxacin, Levofloxacin, Moxifloxacin, Lithium, Quetiapine, Risperidone, Venlafaxine, Ziprasidone, Amantadine, Tamoxifen, Voriconazole, AlfuzosinAtazanavir, Clozapine, Vardenafil
Increased risk for Congenital LQTS patients
Amitriptyline, Ciprofloxacin, Citalopram, Clomipramine, Desipramine, Diphenhydramine, Doxepin, Fluconazole, Fluoxetine, Galantamine, Imipramine, Itraconazole, Ketoconazole, Mexiletine, Nortriptyline, Paroxetine, Protriptyline, Ritonavir, Sertraline, Solifenacin, Trazodone, Trimethoprim-Sulfa, Trimipramine, Dobutamine, Dopamine, Ephedrine, Epinephrine, Isoproterenol, Norepinephrine, Albuterol, Cocaine, Ketamine, Phenteramine, Ritodrine, Succinylcholine, Pancuronium

Physiology/Pathophysiology

Normal ventricular depolarization: After the sinoatrial (SA) node spontaneously depolarizes (sodium channel influx), the signal is spread via 3 accessory conduction tracts in the atrium to the atrioventricular (AV) node. Adjacent myocardial cells depolarize in a domino fashion. Electrical depolarization is followed by mechanical contraction of the atrium, with blood being pumped into the ventricles. The conduction fibers from the atrium are connected to those in the ventricle via the bundle of His (preceded by the AV node); in the ventricles, the signal is then transmitted along the left and right bundle branches onto the Purkinje fibers. In the same manner, the adjacent muscle cells are depolarized in a domino fashion, and depolarization is followed by ventricular contraction and blood ejection.
Normal early myocardial repolarization in the ventricle begins with a rapid, transient efflux of potassium. Potassium efflux continues via slowly activating (iKs) and rapidly activating (iKr) delayed rectifier channels. However, this process is counteracted by an influx of calcium and sodium that prolongs repolarization and allows time for mechanical contraction and systolic ejection of blood. The complex interactions between these ions and their respective channels dictate the duration and characteristics of repolarization.
Heterogenous rate of repolarization: The rate of repolarization is not equal between the epicardium, mid-myocardium, and endocardium. The mid-myocardial cells have less iKs channels and more iNa channels; therefore, the rate of repolarization is slower than the other 2 layers. This causes a transmural dispersion of repolarization (TDR).
- EKG: The peak of the T wave represents epicardial cell repolarization and the end of the T wave represents mid-myocardial cell repolarization (where repolarizatoin is slowest).
- TDR is manifested on the EKG by the interval between the peak of the T wave to the end of the T wave (Tp-e).
The QT interval represents the time period during which ventricular depolarization and repolarization occur. It is rate-dependent; bradycardia has longer intervals whereas tachycardia has shorter intervals. Thus, its assessment and interpretation must factor in, and be corrected for, heart rate. The corrected QT (QTc) is calculated using Bazett's formula, QTc = [QT/(R–R)]. R-R is the R-to-R interval in seconds.
LQTS is caused by the malfunction of cardiac ion channels. Any condition that qualitatively or quantitatively decreases the iK channel function or increases the iNa channel function will prolong the QT interval, exaggerate the TDR, and prolong repolarization. This heterogeneity of repolarization leads to an increased potential for self-sustaining re-entrant circuits and early after-depolarizations (EADs), which can degenerate into Torsades de Pointes.
- Prolonged QT is defined as a corrected QT interval (QTc) >0.45–0.47 seconds in males and 0.47–0.48 seconds in females.
"Acquired" LQTS is thought to occur in silent gene carriers until symptoms manifest after being exposed to a provoking drug or sympathetic stimulation.

Anesthetic Goals/Guiding Principles

Preoperative assessment of the patient may reveal historical and/or ECG characteristics diagnostic for LQTS. It is necessary to correct for heart rate; most modern EKG machines provide a QTc value.
Anesthesia in patients with untreated LQTS carries a very high risk for malignant ventricular arrhythmias. They should be optimized prior to surgery and should be on a maintenance beta-blocker regimen.
Avoidance of sympathetic outflow is necessary as this predisposes to re-entrant ventricular arrhythmias and Torsades de Pointes.

Symptoms

60% of patients are asymptomatic until a presenting syncopal or pseudoseizure episode (usually in childhood or early adulthood).
Occasionally, the first symptom may present as Torsades de Pointes under anesthesia.

History

In patients without known LQTS, some "red flags" to watch out for are syncope with or without stress, unexplained sudden cardiac death before age 30 in immediate family members, and family members with known LQTS. It will often manifest as a child or in early adulthood. If concern for LQTS is raised in an elective case, referral to a cardiologist should be made for a possible electrophysiology study.
Patients with a known history of LQTS should be on scheduled beta-blockers that are continued perioperatively. Serum electrolytes should be within normal limits.

Signs/Physical Exam

Often nonspecific physical examination
Adequately beta-blocked patients should (ideally) not have any change in QT interval during a Valsalva maneuver.

Medications

Beta-blockers help reduce the incidence of cardiac events, but they are not entirely effective for preventing sudden death.

Diagnostic Tests & Interpretation

Labs/Studies

ECG: Prolonged QTc, T wave alternans, notched T wave in 3 leads
Serum electrolytes should be assessed and abnormalities should be corrected.
If a pacemaker or ICD is present, follow appropriate perioperative management.

Concomitant Organ Dysfunction

In Jervell and Lange-Nielsen syndrome, patients also have congenital deafness.
In andersen syndrome (LQT7), patients have periodic paralysis.

Circumstances to delay/Conditions

Inadequate beta-blockade
Abnormalities in electrolytes can delay repolarization (hypokalemia, hypomagnesemia, and hypocalcemia).

Classifications

Acquired LQTS: It is now thought that these cases have common nucleotide polymorphisms that alter ion channel repolarization behavior in the presence of drugs, electrolyte abnormalities, or in certain disease states.
Congenital LQTS: 8 different genotypes (LQT1-8) have been identified. Romano–Ward syndrome is the most common presentation of congenital LQTS and is inherited in an autosomal dominant manner. Jervell and Lange-Nielsen syndrome is autosomal recessive and is associated with deafness.

PREOPERATIVE PREPARATION

Premedications

Consider preoperative sedation when appropriate. Limiting anxiety and sympathetic outflow is crucial.
Avoid abrupt and loud noises; may trigger Torsades de Pointes.

INTRAOPERATIVE CARE

Choice of Anesthesia

Epidurals, spinals, and general anesthetics have all been administered safely; there is no evidence that one mode is safer than the other.

Monitors

Low threshold for intra-arterial monitoring
Low threshold for central venous access, as it can facilitate transvenous pacing.

Induction/Airway Management

Midazolam, fentanyl, morphine, and propofol appear to be benign in LQTS. Thiopental prolongs the QT interval but may reduce dispersion of depolarization and has been safely used in congenital LQTS. Ketamine should be avoided.
Succinylcholine may prolong the QT interval.
Laryngoscopy, intubation, suctioning, and cold-inspired gases can cause a sympathetic outflow; these potent stimuli may be attenuated by a short-acting opioid and/or esmolol.
Consider topical anesthesia to vocal cords prior to intubation.
Total IV anesthesia with a propofol and remifentanil infusion may provide excellent attenuation of sympathetic outflow throughout induction, intraoperative maintenance, and emergence; with the advantage of a short context sensitive half-life.

Maintenance

Avoid sympathetic stimulation by maintaining normocarbia, normothermia, normoglycemia, normovolemia, and normoxia.
Volatile anesthetics prolong the QT interval, but isoflurane and sevoflurane have been used safely in congenital LQTS.
Keep patient "deep" or adequately anesthetized; otherwise innocuous stimuli can result in increased sympathetic outflow.
High ventilatory pressures should be avoided as this may cause QT prolongation.
Pancuronium has vagolytic properties and should be avoided.
Avoid sympathomimetic drugs such as ephedrine.
Droperidol should be avoided in LQTS. Ondansetron is considered a medication with possible risk for prolonging the QT interval.

Extubation/Emergence

Consider "deep" extubation while the patient is in a surgical plane of anesthesia, if appropriate.
Neostigmine, edrophonium, atropine, and glycopyrrolate should be avoided because each may cause QT interval prolongation.

Bed Acuity

Will need postoperative ECG monitoring, as the perioperative period may exacerbate QT prolongation.
Good pain control can avoid sympathetic stimulation.

Complications

Torsades de Pointes:
- Some episodes will be short and self terminating.
- Can occur at any point in the perioperative period.
- Can manifest in hemodynamic instability and degenerate into ventricular fibrillation.
Treatment consists of:
- If unstable, ACLS should be instituted immediately with early chest compressions, asynchronous defibrillation, and magnesium sulfate (30 mg/kg).
- Magnesium dose can be repeated after 15 minutes, followed by an infusion of 3–20 mg/min if arrhythmias persist.
- If resistant to magnesium, Torsades can be treated with pacing to accelerate the heart rate.

Kies SJ , Pabelick CM , Hurley HA , et al. Anesthesia for patients with congenital long QT syndrome. Anesthesiology. 2005;102:204–210.
Hunter J , Sharma P , Rathi S. Long QT syndrome. Continuing education in anaesthesia. Critical Care and Pain. 2008;8(2):67–70.
Schwartz PJ , Moss AJ , Vincent GM. Diagnostic criteria for the long QT syndrome: An update. Circulation. 1993;88:782–784.

www.torsades.org

See Also (Topic, Algorithm, Electronic Media Element)

ICD9

426.82 Long QT syndrome
794.31 Nonspecific abnormal electrocardiogram [ECG] [EKG]

ICD10

I45.81 Long QT syndrome

LQTS is a significant cause of sudden death in young people, and is probably underdiagnosed.
for a significant number of patients with LQTS, their first manifestation may be under anesthesia.
Avoid stimuli that evoke sympathetic outflow including hypothermia, pain, hypoxia, excessive ventilatory pressure, and hypovolemia.
for patients with known LQTS, ensure that they are not hypokalemic, hypocalcemic, or hypomagnesemic. Ensure that they are adequately beta blocked.

Marc A. Logarta , MD, DBA, FANZCA

section name header

Basics ⬇

Prevalence

Morbidity

Mortality

Risk Factors

Table 1. Medications that affect the QT interval

Diagnosis ⬆ ⬇

History

Signs/Physical Exam

Labs/Studies

Treatment ⬆ ⬇

Premedications

Choice of Anesthesia

Monitors

Induction/Airway Management

Maintenance

Extubation/Emergence

Follow-Up ⬆ ⬇

References ⬆ ⬇

Additional Reading ⬆ ⬇

Codes ⬆ ⬇

Clinical Pearls ⬆ ⬇

Author(s) ⬆