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Long QT syndrome incidence is increasing in general population. A careful pre-, peri- and post-operative management is needed for patients with this syndrome because of the risk of Torsades de Pointes and malignant arrhythmias. The available data regarding prevention of lethal Torsades de Pointes during anesthesia in patients with long QT syndrome is scant and conflicting: only case reports and small case series with different outcomes have been published. Actually, there are no definitive guidelines on pre-, peri- and post-operative anesthetic management of congenital long QT syndrome. Our review focuses on anesthetic recommendations for patients diagnosed with congenital long QT syndrome furnishing some key points for preoperative optimization, intraoperative anesthetic agents and postoperative care plan, which could be the best for patients with c-long QT syndrome who undergo surgery.

• Citation:Fazio G, Vernuccio F, Grutta G, Re GL. Drugs to be avoided in patients with long QT syndrome: Focus on the anaesthesiological management. World J Cardiol 2013; 5(4): 87-93
• URL:https://www.wjgnet.com/1949-8462/full/v5/i4/87.htm
• DOI:https://dx.doi.org/10.4330/wjc.v5.i4.87

Long QT syndrome (LQTS) is a cardiac conduction disorder characterized by prolongation and increased dispersion of ventricular repolarization, manifested by lengthening of the QT interval on the surface electrocardiography (ECG). This abnormal repolarization, when amplified by sympathetic activity, can lead to the formation of reentry circuits and may present with syncope, seizures, or torsades de pointes (TdP), ventricular fibrillation and, therefore sudden cardiac death[1]. Moreover, there are other signs of the torsadogenic property of a drug: QT dispersion (difference between the longest and the shortest QT interval) and the transmural dispersion of repolarization (TDR) (time between the peak and the end of the T wave in a precordial lead)[2]. Traditionally, LQTS is divided into congenital (c-LQTS) and acquired (a-LQTS) forms. Drug-induced LQTS is the most common cause of a-LQTS; as a matter of fact, a survey by Schwartzet al[3] of 670 patients in the International LQTS Registry revealed that anesthesia can trigger LQTS.

Ninety-five percent of drug-induced LQTS is due to the obstruction of the rapid component of the late correcting potassium current (I_k-r), which physiologically allows the rapid potassium outflow[4]. I_kr and the slow component of the same channel (I_k-s) are responsible for the repolarization of cardiomyocytes. Some anesthetics and some drugs used in premedication may lead to QT-prolongation. The available data on the prevention of lethal TdP during anesthesia in patients with c-LQTS is scant and conflicting: only case reports and small case series with different outcomes, even when using the same anesthetic agent, have been published[2,5-19]. Although a-LQTS is of significant interest, this review focuses on the anesthetic recommendations for patients diagnosed with c-LQTS. Our aim is to provide some key points which could help both the cardiologists and the anesthetists when approaching a patient with LQTS candidate for anaesthesiological procedures. Firstly, we describe which drugs should be avoided in LQTS and then we move on the specific topic of the review describing the anaesthesiological management of patients with LQTS.

Certain drugs, including some anesthetics, are known to contribute to QT prolongation. Considering that not all agents that prolong the QT interval increase TDR, drugs can be distinguished into the following groups depending on their simultaneous effects on the QT corrected using the Bazzet’s formula (QTc) interval and on TDR[20]: (1) drugs inducing both QTc prolongation and increased TDR, characterized by a high torsadogenic potential; (2) drugs causing QTc prolongation but with a slight effect on TDR and little, if any, ability to induce TdP; and (3) drugs causing both QTc prolongation and increased TDR below a certain concentration, but inducing TdP once a critical value of TDR is exceeded.

Drugs that prolong the QT interval and/or induce Torsades de Pointes in patients with diagnosed or suspected c-LQTS are shown on Table1[21] and can be found on the web pageshttp://www.torsades.org. Some of these drugs are not available in every country (many of them have been withdrawn from the market in several countries). However, this list doesn’t include some anesthetic agents which have an influence on cardiac conduction and can lead to intraoperative TdP; hence, they are discussed throughout the text.

Despite an adequate β-blocking, patients with LQTS candidate to surgical or anesthetic procedure have an increased risk of developing perioperative ventricular arrhythmias. The probability of developing these arrhythmias significantly decreases with a careful pre-, intra- and post-operative management.

The prevalence of Long QT syndrome is close to 1/3000-1/5000[68,69]. The QT interval duration is physiologically variable : the QTc is calculated using the Bazett’s formula [(QTc = QT/√RR), Table2][70,71]. Genetic testing can help to recognize specific subtypes of c-LQTS. The most common phenotypes are LQT1, LQT2 and LQT3. People with LQT1, the most common variant of LQTS, are more likely to have a cardiac event during exercise than patients with LQT2 or LQT3. LQT1 is associated with a mutation in theKvLQT1 gene (also known as KCNQ1), which codes for a protein that co-assembles with another protein (minK) to form the I_k-s[72]. In patients with LQT2 arrhythmic events are usually triggered by auditory stimuli or sudden startle[73]. LQT2 is caused by the loss of Ikr[72]. Patients with LQT3 are prone to syncope or cardiac arrest at rest or during sleep; as a matter of fact, their electrocardiographic abnormalities become less marked at increased heart rate[72,74]. Table3 shows the electrocardiographic patterns of the most common phenotypes of LQTS. Both in the a-LQTS and in the c-LQTS, the blockade of ionic channels, the lengthening of the QT interval and the intensification of QTD can provoke the induction of TdP[75]. A careful pre-, peri- and post-operative management is needed for patients with this syndrome because of the risk of TdP and malignant arrhythmias. We speculate that genetic subtyping of patients with LQTS could help tailor anesthetic therapy for these high-risk patients.

Actually, there are no definitive guidelines for pre-, peri- and post-operative anesthetic management of c-LQTS. After reviewing the literature, we furnish some key points for preoperative optimization, intraoperative anesthetic agents and postoperative care plan that may be the best for patients with c-LQTS who undergo surgery. In the preoperative period it is necessary to calculate QTc, perform a 12-lead ECG at rest, discontinue or decrease the dose of drugs which could increase QTc interval and trigger a TdP in these patients (Table1), continue beta-blocking therapy until the operating day and maintain calm and quiet environment. Defibrillator must be available for immediate use during the perioperative period.

In the perioperative period, it would be better to do premedication with midazolam, sedoanalgesia with morphine or fentanyl, induction and maintenance of anesthesia with thiopental or propofol TIVA avoiding halogenated volatile anesthetics and ketamine. Before intubation and extubation, the use of a topic anesthetic, an analgesic or a beta-blocker could be recommended. Among muscle relaxant drugs, we should prefer vecuronium and atracurium. It is important to monitor not only heart rate, blood pressure, oximetry, capnometry but also ECG in at least two leads, as short episodes of TdP are hardly distinguished from monomorphic VT, when traced in one lead. In the postoperative the patient must be monitored and ECG should last until patient emerges from anesthesia and QTc turns into preoperative values. Any kind of stimulus should be avoided since they could trigger TdP and pain must be adequately controlled.