Case
An 88-year-old woman with history of osteoporosis, hyperlipidemia, and a remote myocardial infarction presents to the ED with altered mental status and agitation. The patient is admitted to the medicine service for further management. Her current medications include a thiazide and a statin. Psychiatry is consulted and recommends administering intravenous haloperidol. A baseline EKG shows a corrected QT interval (QTc) of 486 milliseconds (ms). How often should subsequent EKGs be ordered?
Overview of issue
A prolonged QT interval can predispose a patient to dangerous arrhythmias such as Torsades de pointes (TdP), which results in sudden cardiac death in about 10% of cases.1,2 A prolonged QTc interval can be caused by cardiac, renal, or hepatic dysfunction; congenital Long QT Syndrome (LQTS)2
Samantha Platt To diminish risk of TdP while taking these medications, it is necessary to monitor the QTc interval. Before commencing a QT-prolonging medication, it is recommended to get a baseline EKG, then perform EKG monitoring after administering the medication. According to American Heart Association guidelines, a prolonged QT interval is considered more than 460 ms in women or above 450 ms in men.3 If an abnormal rhythm and/or prolonged QTc is detected via EKG monitoring, then the drug dosage can be changed or an alternative therapy selected.4 However, there are no current guidelines recommending how often EKG monitoring should be performed after a QT-prolonging antipsychotic medication is administered on an inpatient medicine unit. Without guidelines, there is potential for health care providers to under- or over-order EKG monitoring, possibly putting patients at risk of TdP or wasting hospital resources, respectively. Brian Rice There are currently no universally accepted guidelines regarding inpatient EKG monitoring for patients started on QTc prolonging antipsychotic medications. A 2018 review of the literature surrounding assessment and management of patients on QTc prolonging medications was performed to analyze the available data and make recommendations; notably the evidence was limited as none of the studies were randomized controlled trials. The authors recommend assessing the drug for QTc prolonging potential, and if possible, choosing alternative treatment in patients with baseline prolonged QTc. If the QT prolonging medication is the best or only option, then the next step is assessing the patient’s risk for QTc prolongation based on that person’s current condition and medical history.5 They recommend using the QTc prolonging risk point system developed by Tisdale and colleagues, which identified patient risk factors for elevated QTc intervals based on EKG findings in cardiac care units at a large tertiary hospital center.6 Dr. Omar Mirza Based on the patient’s demographics, current condition, and medication list, the score can be used to stratify patients into low-, medium-, and high-risk categories (see Table 1). Risk factors include age over 68 years, female sex, prior MI, concurrent use of other QTc prolonging medications, and sepsis, all of which have differing ability to cause QTc prolongation and thus are weighted differentially. This scoring system is helpful in identifying high risk patients; however, the review does not include recommendations for management of these patients beyond removing the offending drug or monitoring EKGs more aggressively in higher risk patients once identified.6 Dr. Kevin Dunsky Low-risk patients can be managed expectantly. If the baseline QTc is < 500 ms, then the provider may administer the medication, but should obtain follow-up EKG monitoring to ensure the QTc does not rise above 500 ms; if it does, a management change is necessitated. For moderate- to high-risk patients with a baseline QTc > 500 ms, they recommend not administering the medication and consulting a cardiologist. The review does not provide a recommendation on how often EKG monitoring should be performed after prescribing an antipsychotic medication in an inpatient setting.5 A 2018 review article explored patient risk factors for a prolonged QTc in the setting of prescribing potentially QTc prolonging antipsychotics.7 The authors reiterate that QTc prolonging risk factors are important considerations when prescribing antipsychotics that can lead to adverse events, though they note that much of the literature associating antipsychotics with negative outcomes consists of case reports in which patients had independent risk factors for development of TdP, such as preexisting ventricular arrhythmias. Dr. David Portnoy In addition, the data regarding the risk of each individual antipsychotic agent are not comprehensive. Some medications that have been deemed “QTc prolonging” were identified as such in only a handful of cases where patients had confounding comorbid risk factors. This raises concern that some medications are being unduly stigmatized in situations where there is little chance of TdP. If there is no equivalent or alternate treatment available, this may lead to an antipsychotic medication being held unnecessarily, which may exacerbate the psychiatric illness. The authors note that the trend toward ordering baseline EKGs in the inpatient setting following administration of a new antipsychotic may be partly attributed to the ready availability of EKG testing in hospitals. They recommend a baseline EKG to assess the patient’s risk. For most agents, they recommend no further EKG monitoring unless there is a change in patient risk factors. Follow-up EKGs should be done in patients with multiple or significant risk factors to assess their QTc stability. In patients with a QTc > 500 ms on a follow-up EKG, daily monitoring is encouraged alongside reassessment of the current treatment regimen.7 Overall, the current literature suggests that providers should know which antipsychotics carry a risk for QTc prolongation and what other treatment options are available. The risk of QTc prolongation for common antipsychotic agents is provided in Table 2. Providers should assess their patients’ risk factors for QTc prolongation and order a baseline EKG to help quantify the cardiac risk associated with prescribing the drug. In patients with many risk factors or complicated medication regimens, a follow-up EKG should be performed to assess the new QTc baseline. If the subsequent QTc is > 500 ms, then an alternative medication should be strongly considered. The majority of patients, however, will not have a clinically significant increase in their QTc, in which case there is no need for a change in medication and monitoring frequency can be deescalated. 
Overview of the data
I have seen time and time again in clinic patients on antipsychotic medications, and in the hospital patients in sepsis and shock or alcoholics with myopathy or myelopathy, that the prolonged QTC interval immediately reverses with IV magnesium.
We know that the serum level of magnesium is frequently at the low end of normal in such situations, and intracellular Mg levels are not readily available. It has been frequently documented in the general older populations for IC Mg to be low while serum Mg is normal.
I suggest that every patient with a long QTC in outpatient and inpatient settings, be given Mg by appropriate route and measure the QTC after enough Mg has been given. You will be surprised how often and quickly corrects. Then prescribe Mg as a chronic necessary “supplement.”