Survey of EKG Monitoring Practices: A Necessity or Prolonged Nuisance?

Psychotropic drugs delay cardiac repolarization prolonging the QT interval on EKGs. These medications bind cardiac potassium channels, thus blocking potassium efflux from cardiomyocytes. A prolonged QT arouses concerns in clinical practice, as it can lead to, in some cases, a life-threatening polymorphic ventricular tachyarrhythmia called torsades de pointes (1). Torsades de pointes is usually self-limited and typically manifests in convulsions, dizziness, and syncope; however, it can also result in ventricular fibrillation and sudden cardiac death (2). EKG warning signs that precede torsades de pointes include marked QTc prolongation, premature ventricular contractions, and T-wave changes. Cardiac repolarization is faster at higher heart rates, hence there is need for a rate-corrected adjustment of the QT interval (QTc) (2, 3). The most commonly used formula, Bazett's formula, defines QTc as QT/RR0.5, where RR is heart rate. This formula produces accurate calculations for heart rate in the narrow range of 60–80 beats per minute. For higher heart rates, there is the Fridericia correction formula, which defines QTc as QT/RR0.33 (3). Normal QTc range differs based on age and sex: for men it varies between 440 and 450 msec, and for women it varies between 460 and 470 msec (4, 5). The Food and Drug Administration defines threshold for potential discontinuation of a medication at a QTc >500 msec, or 60 msec above baseline, or >5-msec increase in mean value (6). The American Heart Association and American College of Cardiology mirror this threshold. QTc prolongation is not an ideal predictor for risk of torsades de pointes but rather modest at best (7).

The objective of the present study was to determine the extent to which evidence-based practices have affected clinical QTc monitoring in those prescribing antipsychotics and how closely American Psychiatric Association (APA)-outlined guidelines are being followed.

Risk

There is no threshold for QTc prolongation at which torsades de pointes is certain to occur. Data from congenital long QT syndrome studies report that a QTc >500 msec is associated with a 2-to 3-fold higher risk for torsades de pointes (5). Incidence is difficult to obtain. Sudden death is assumed to be secondary to arrhythmias; however, patients are not monitored at the time of death, and we cannot assume association with torsades de pointes. Number needed to screen would be needed. Risk factors for QTc prolongation can be divided into three categories: genetic, medication-related, and individual dependent. Genetic risk includes congenital long QT syndromes that can be attributed to mutations in potassium and sodium channels, occurring in 1/2,500 individuals in the population (8). Medication risk manifests in several drugs known to prolong QTc by way of cumulative effect or via inhibition of the cytochrome system; these most frequently inhibit potassium channels (9). Examples include antiarrhythmic class IC and III (sotalol, flecainide, and propafenone), diuretics (especially potassium sparing), all antidepressants to some degree, antipsychotics (10–12), antihistamines, macrolides, alcohol, caffeine, cocaine, and methadone. Aside from electrolyte abnormalities (hypokalemia, hypomagnesemia), individual risk factors also include female gender, 65 years of age or older, and patients with cardiac risk factors such as congenital long QT syndromes, ischemic heart disease, congestive heart failure, myocarditis, hypertension, bradycardia, and sinoatrial/atrioventricular blocks (9) The APA also mentions a personal history of syncope, as well as family history of sudden death at an early age (less than 40 years old, especially if both parents had sudden death) as risk factors (13).

APA Guidelines

Current APA guidelines recommend checking EKG and serum potassium before treatment with thioridazine, mesoridazine, or pimozide, as well as prior to treatment with ziprasidone in the presence of cardiac risk factors. It is also recommended to obtain a follow-up EKG any time a significant change in dose of thioridazine, mesoridazine, or pimozide occurs in the presence of cardiac risk factors, ziprasidone use, or with addition of other medications that can alter QTc interval. Discontinuation of any antipsychotic should be considered at a QTc >500 msec, or 60 msec above baseline, or >5 msec increase in mean value (13).

Methodology

A survey was distributed via Qualtrics Survey Software (https://www.qualtrics.com) to 52 members of the faculty/academic residency program at East Carolina University, Department of Psychiatry. Design of the survey aimed to best characterize trends in EKG monitoring practices. Survey conductors had no disclosures, and this study was exempt from institutional review board review. Target participants included a varied sample of physicians in training at any level, fellows, and faculty treating both adults and adolescents at both inpatient and outpatient levels. Level of expertise and age was very varied. Affiliate and adjunct faculty were excluded, as were any faculty members unable to write prescriptions. Initial distribution was on September 11, 2015, and was available for 1 month with three weekly reminders sent out to non-responders. Responses were completely anonymous, with no Internet protocol address or any identifiers collected. Data were gathered and further analyzed by Qualtrics. The response rate was 55%, with a 24% drop-out rate (i.e., participants who started the survey but did not complete it). Participants who reported practicing in both inpatient and outpatient settings completed 27 questions, whereas participants who reported only one practice setting completed a survey of 22 questions. The length of the survey may have been a factor in the drop-out rate. The survey maintained complete confidentiality, and the surveyors remained blinded.

Results

Upon consulting with a statistician (although there was no statistically significant difference between those practicing in outpatient versus inpatient settings), there was a significantly large proportion of psychiatrists who did not screen for personal history of syncope, family history of sudden death, electrolyte abnormalities, and long QT syndrome (see Figure 1 and Figure 2).

Discussion and Treatment Recommendations

In our practice, the use of psychotropic medications that affect repolarization cannot be avoided. Physicians should be aware of the risk associated when combining multiple drugs that prolong QTc and avoid these prescribing habits. Personalized risk assessments should also be undertaken with a goal of risk reduction. Electrolyte evaluation and EKG recording appear to be warranted prior to treatment initiation and later under steady conditions. Slow dose titration and regular EKG monitoring of patients at high risk or of those prescribed additional medications that can prolong QTc are recommended. Throughout the course, it is prudent to be mindful of potential electrolyte imbalance during episodes of diarrhea, sweating, malnutrition, diuretic therapy, alcohol/drug use, and eating disorders. Arrhythmia should be considered when patients present with palpitations, dizziness, syncope, or convulsions. In the event of a markedly elevated QTc, magnesium sulfate, either orally or intravenously, should be considered. Medication discontinuation should always be considered when QTc is >500 msec, despite normal serum potassium, normal QRS duration, and lack of symptoms.

Conclusions

At present, no quantitative multivariate risk index exists for the prediction of torsades de pointes. Providers in our survey share differing opinions on the exact QTc interval at which discontinuation of antipsychotics is necessary. Our survey shows that most providers turn to current literature to guide their treatment decisions, indicating the older existing APA guidelines are lagging behind current literature. Current APA guidelines need to be updated to reflect data relevant to today's prescribing practices. Our survey demonstrated that antipsychotics that appear to have providers concerned about QTc prolongation were identified as ziprasidone, haloperidol, prolixin, thorazine, clozapine, and quetiapine. The fact that thioridazine, medoridazine, and pimozide were not among them is likely attributed to the lack of current utilization. One common finding based on literature review is apparent—the importance of cardiac risk stratification. Our survey demonstrated that providers do not routinely screen for cardiac risk factors. Only 64% and 55% of those surveyed report screening for arrhythmias and heart disease, respectively, and more concerning is the lower proportion of providers screening for any personal history of syncope (33%), family history of sudden death (26%), or long QT syndromes (34%). Only 42% screen for electrolyte imbalance. An independent, nonprofit organization (www.crediblemeds.org) developed a risk stratification process—the Adverse Drug Event Causality Analysis [ADECA]—where drugs are placed into one of four risk categories based on their relative potential for QTc prolongation and/or cause of life-threatening ventricular arrhythmias. This, along with cardiac risk stratification, can provide guidance in treatment decisions. According to our data, outpatient providers are less likely to order EKG when prescribing antipsychotics. The literature suggests that this is attributed to financial issues and lack of access to EKG resources, especially when not practicing in a tertiary care setting. Further evaluation comparing tertiary care setting outpatient psychiatrists, as well as those with access to EKG resources, would be beneficial in identifying barriers to practice.

Limitations

This study was conducted strictly in the setting of an academic institution. Whether there is generalizability to the practices of outside providers cannot be confirmed. The number of responders participating is relatively low; however, the high response rate increases the validity.

Key Points/Clinical Pearls