For some time now we had planned to do a column on “Torsade de Pointes” and its relationship to a variety of commonly used medications. We kept putting it off because of a lack of consensus of how to best monitor for it and how to treat when the risk becomes obvious. But now the American Heart Association/American College of Cardiology Foundation) has published the AHA/ACCF statement on Torsade de Pointes (Drew et al 2010).
Torsade de Pointes is a form of ventricular tachycardia, often fatal, in which the QRS complexes become “twisted” (changing in amplitude and morphology) but is best known for its occurrence in patients with long QT intervals. Though cases of the long QT interval syndrome (LQTS) may be congenital, many are acquired and due to a variety of drugs that we prescribe. The syndrome is more common in females and many have a genetic predisposition. And there are a number of reasons why this syndrome is more likely to both occur and result in death in hospitalized patients. Hospitalized patients have a whole host of other factors that may help precipitate malignant arrhythmias in vulnerable patients. They tend to have underlying heart disease, electrolyte abnormalities (eg. hypokalemia, hypomagnesemia, hypocalcemia), renal or hepatic impairment, and bradycardia, all of which may be precipitating factors. More importantly they may have the sorts of conditions for which we prescribe the drugs that are primarily responsible for prolonging the QT interval (eg. haloperidol, antiarrhythmic agents, etc.). And many of those drugs are given intravenously and in high doses in the hospital as compared to the outpatient arena. Rapid intravenous infusion of such drugs may be more likely to precipitate Torsade de Pointes than slow infusion.
The drugs most commonly associated with Torsade de Pointes are haloperidol, methadone, thioridazine, amiodarone, quinidine, sotalol, procainamide, erythromycin, azithromycin, the antihistamine terfenadine and certain antifungals. Though the newer antipsychotic agents have been less often implicated in torsade de pointes, quetiapine has been reported to be associated with it occasionally (Vieweg 2005). For a full list of drugs that commonly cause prolongation of the QT interval and may lead to Torsade de Pointes, go to the Arizona CERT website. That site also has a list of drugs that prolong the QT interval and might possibly cause Torsade de Pointes and another list of drugs that have conditional risk (eg. only when combined with other drugs). Some drugs (eg. cisapride (Propulsid), a drug formerly used to promote GI motility) have actually been withdrawn from the market because of serious cardiac side effects, including prolongation of the QT interval and torsade de pointes.
One study of Torsade de Pointes associated with psychotropic drugs (Justo et al 2005) found that most patients had multiple risk factors for Torsade de Pointes before they were begun on the psychotropic drugs. 73% had 2 or more risk factors that were easily identifiable prior to initiation of the psychotropic drugs. While female sex is the most common risk factor (71%), 34% had advanced heart disease, 30% were on a second drug known to prolong the QT interval, and 27% had high doses of the offending psychotropic drugs. 18% had either a family history of LQTS, a prior episode of Torsade de Pointes, or prolonged QT on baseline EKG. 14% had hypokalemia. Most of these could have been determined by simple history, baseline EKG, and serum potassium levels. Thus, they made the recommendation that prior to initiating treatment with psychotropic agents, patients be assessed for these risk factors. Yet we see very few behavioral health units monitoring for QT prolongation when patients are begun on such agents.
One must keep in mind that the incidence of Torsade de Pointes is still quite low overall. The potential benefits of many of these psychotropic agents may outweigh the risks of Torsade. But identifying the risk factors should at least flag such patients for closer monitoring during treatment with psychotropic drugs.
When seeing patients in the ED who have overdosed on unknown medications, prompt performance of EKG may be important in case one or more of the ingested drugs prolongs the QT interval and predisposes to torsade de pointes.
There are numerous issues when the patient with a long QT interval must undergo anesthesia and surgery. A review on anesthesia in such cases (Booker 2003) focused primarily on patients with congenital long QT syndrome but most of the issues apply to any patient with QT prolongation irrespective of etiology. Most commonly used anesthetic agents (halothane, enflurane, isoflurane, and sevoflurane) can prolong the QT interval. A variety of drugs used in the OR may further prolong the QT and lead to torsade de pointes (Saussine 2006). These include ketamine, succinylcholine, pancuronium, droperidol, sufentanil, and neostigmine. They also note that adrenergic stimulation, such as occurs with anxiety or tracheal intubation/extubation or pain may precipitate arrhythmias in such patients. In addition, Saussine et al (Saussine 2006) described precipitation of ventricular arrhythmias by sevoflurane in a patient with congenital LQTS. These resolved promptly when the sevoflurane was discontinued and propofol was added. They note that propofol has been shown to shorten the QT interval in normal patients and suggested it might be wise to use in patients with prolonged QT syndromes.
Unfortunately, at this time, there is no validated scoring tool that can identify for you the magnitude of an individual patient’s risk for torsade de pointes. Therefore, the best you can do is look for the presence of the individual risk factors and monitor the QT interval more closely in those patients.
We refer you to the AHA/ACCF scientific statement for details on the nuances of measuring the QT interval and the QTc (corrected QT). Note that it is not as straight forward as you’d expect. In fact, a study on a large group of patients diagnosed with congenital LQTS seen for second opinion at the Mayo clinic (Taggart 2007) noted almost 40% of patients erroneously diagnosed, often because of inaccurate measurement of the QTc. The AHA/ACCF statement also notes that the morphology of some EKG’s may make it more difficult to measure the QT so alternative methods may need to be considered. Also, they provide advice about the EKG in the setting of conduction block, bradycardia, or atrial fibrillation. Perhaps most important are their comments about being consistent about which lead you use to measure the QT. They discuss manual measurement and monitoring, using “electronic calipers”, and doing fully automated monitoring.
So who should you monitor? Continuous monitoring might be personnel- and resource-intensive and you might consider that only in those at-risk patients who will be receiving one of the drugs known to be most likely to cause QT prolongation and torsade de pointes. Most hospitals may have to just periodically monitor the QT in at-risk patients. No one could be expected to remember all the drugs or drug-drug interactions that may potentially prolong the QT interval and all the other conditions that predispose to QT prolongation and torsade de pointes. Therefore, it is incumbent to develop and use computer algorithms that will prompt staff to do appropriate QT monitoring. You can usually build “rules” into most hospital computer systems that will check laboratory and other clinical data and pharmacy data and generate an alert to an appropriate caregiver to check the QT interval. If your system is actually capturing the QTc in a data field, your alert could even be triggered by a rule that says something like “if the QTc increases by more than x% or x msec. over baseline or if the exceeds x msec., alert physician…”. Remember also that it is not only addition of new drugs you must be concerned about. Risk factors are not static. On admission a patient may have normal potassium and magnesium levels but both may become depleted after even several days of diuretic therapy so your algorithm must take such into account and look for the most current risk factor data. When you already have a prolonged QT you should have a second algorithm that triggers an alert when a physician attempts to order a drug known to prolong the QT or one that interacts with other drugs potentially prolonging the QT.
The AHA/ACCF scientific statement has a good section on management of patients who have drug-induced QT prolongation and/or torsade de pointes, including comments on cadioversion, use of intravenous magnesium sulfate, repletion of potassium, temporary pacing, etc.
A patient you have identified as at risk should be given an up-to-date list of the drugs that may prolong the QT either alone or in combination with other drugs and the patients should be told to avoid those drugs.
Remember also that the genetic predisposition to prolongation of the QT may be placing other family members at risk as well. So you need to consider when to recommend EKG’s and even genetic testing on family members.
Is there a downside to such monitoring for patients at risk? The study by Taggart et al., which related to congenital LQTS, found many patients erroneously diagnosed also received unnecessary treatment (such as implantable defibrillators) or advice that significantly curtailed their activities or unnecessary anxiety. On the other hand, the editorial on that study (Vetter 2007) stresses the risks of failure to diagnose and the risk of sudden cardiac death.
So what should your healthcare organization be doing?
Torsade de pointes is a relatively uncommon cause of sudden unexpected death but one that is potentially preventable. Being aware of the risk factors and having systems that identify when potentially dangerous drugs are being given to at-risk patients may potentially save lives.
Drew BJ, Ackerman MJ, Funk M on behalf of the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology, the Council on Cardiovascular Nursing, and the American College of Cardiology Foundation
Prevention of Torsade de Pointes in Hospital Settings: A Scientific Statement From the American Heart Association and the American College of Cardiology Foundation
Circulation 2010;121;1047-1060; originally published online Feb 8, 2010
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