QT Prolongation in Critically Ill Patients With SARS-CoV-2 Infection

Background: Several reports linked the use of repurposed drugs such as hydroxychloroquine (HCQ), azithromycin, lopinavir/ritonavir, and favipiravir with QT interval prolongation in patients with SARS-CoV2 infection. Little is known about the risk factors for QT interval prolongation in this population. We sought to describe the prevalence and identify the main risk factors associated with clinically significant corrected QT (QTc) prolongation in this population. Methods: We conducted a retrospective analysis of critically ill patients who were admitted to our intensive care unit (ICU), had at least one electrocardiogram performed during their ICU stay, and tested positive for SARs-CoV-2. Clinically significant QTc interval prolongation was defined as QTc >500 milliseconds (ms). Results: Out of the 111 critically ill patients with SARS-CoV-2 infection, QTc was significantly prolonged in 47 cases (42.3%). Patients with a clinically significant QTc prolongation had significantly higher proportions of history of cardiac diseases/surgery (22 [46.8%] vs. 10 [15.6%], P < .001), hypokalemia (10 [21.3] vs. 5 [7.8%], P = .04), and male gender (95% vs. 82.8%, P = .036) than patients with QTc ≤500 ms, respectively. A total of 46 patients (41.4%) received HCQ, 28 (25.2%) received lopinavir/ritonavir, and 5 (4.5%) received azithromycin. Multivariate logistic regression analysis showed that a history of cardiac disease was the only independent factor associated with clinically significant QTc prolongation ( P = .004 for the likelihood-ratio test). Conclusion: The prevalence of clinically significant QTc prolongation in critically ill patients with SARS-CoV-2 infection was high and independent of drugs used. Larger prospective observational studies are warranted to elucidate independent risk factors associated with clinically significant QTc prolongation in this study population.

Drug-Induced QT Interval Prolongation

The correct measurement of the QT interval (using the QT correction formulas, preferably Fridericia and Framingham) as well as a correct interpretation of the causes and of the clinical consequences of a QT prolongation is very important in clinical practice. Drug-induced long QT syndrome (DILQTS) is one of the most common causes of LQTS. In the diagnosis and management of the DILQTS, it can be useful to follow the three-step rule presented in this article: detailed pharmacological anamnesis and correct ECG interpretation; database search and clinical interpretation; confirmatory test.

PR interval prolongation and 1-year mortality among emergency department patients: a multicentre transnational cohort study

ObjectivesEmerging evidence supports that PR interval prolongation is associated with increased mortality. However, most previous studies have limited confounder control, and clinical impact in a population of acute ill patients is unknown. The aim of this study was to investigate whether 1-year all-cause mortality was increased in patients presenting with PR interval prolongation in the emergency department (ED).Design and settingWe conducted a register-based cohort study in two Swedish and two Danish EDs. We included all adult patients with an ECG performed at arrival to the Danish EDs during March 2013 to May 2014 and Swedish EDs during January 2010 to January 2011. Using propensity score matching, we analysed HR for 1-year all-cause mortality comparing patients with PR interval prolongation (>200 ms) and normal PR interval (120–200 ms).Participants and resultsWe included 106 124 patients. PR interval prolongation occurred in 8.9% (95% CI 8.7% to 9.0%); these patients were older and had more comorbidity than those with a normal PR interval. The absolute 1-year risk of death was 13% (95% CI 12.3% to 13.7%) for patients with PR interval prolongation and 7.9% (95% CI 7.7% to 8.0%) for those without. After confounder adjustments by propensity score matching, PR interval prolongation showed no association with 1-year mortality with a HR of 1.00 (95% CI 0.93% to 1.08%).ConclusionPR interval prolongation does not constitute an independent risk factor for 1-year mortality in ED patients.

Antipsychotic Polypharmacy and Adverse Drug Reactions Among Adults in a London Mental Health Service, 2008-2018

Background: Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions. Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2+ antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of adverse drug reactions: QT interval prolongation, hyperprolactinaemia, and increased body weight (body mass index [BMI] > 25). Methods: We extracted anonymised EHR data. Patients aged 16+ receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively. Results: We identified 35,409 observations of antipsychotic prescribing among 13,391 patients. APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% C.I. 1.87-3.24) and of having a BMI > 25 (adjusted odds ratio 1.75; 95% C.I. 1.33-2.31) in the period following the APP prescribing. Conclusions: Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.