Improving Patient Safety: The Measurement of QT Interval as an Emerging Vital Sign for Nursing

Monitoring the clinical condition of the patients and identifying signs of deterioration is one of the traditional roles of nurses. Many of drugs that that are administered everyday by nurses such as macrolides, fluoroquinolones, Imipenem/ cilastatin, citalopram, haloperidol and Piperacillin/Tazobactam are related with QT prolongation on the electrocar-diogram, which cause an increased risk of life-threatening arrhythmias. In light of recent reports on the cardiac risks involved in administering the first drugs proposed for the treatment of COVID-19, nurses can play an important role in measuring the QT interval in each shift. Nurses should be familiar with QT interval measurement and monitoring methods, especially in patients with other risk factors such as age over 68, cardiology history, potassium and magne-sium electrolyte disturbances. Calculating and monitoring the QT interval as another vital sign is crucial for patient safety and can help reduce the risk of life-threatening arrhythmias. © 2022, Hellenic Nurses Association. All rights reserved.

Clinical efficacy of Azithromycin for COVID-19 management: A systematic meta-analysis of meta-analyses.

BACKGROUND: Azithromycin has been adopted as a component of the COVID-19 management protocol throughout the global healthcare settings but with a questionable if not downright unsubstantiated evidence base. OBJECTIVES: In order to amalgamate and critically appraise the conflicting evidence around the clinical efficacy of Azithromycin (AZO) vis a vis COVID-19 management outcomes, a meta-analysis of meta-analyses was carried out to establish an evidence-based holistic status of AZO vis a vis its efficacy as a component-in-use of the COVID-19 management protocol. METHODS: A comprehensive systematic search was carried out through PubMed/Medline, Cochrane and Epistemonikos with a subsequent appraisal of abstracts and full-texts, as required. The Quality of Reporting of Meta-analyses (QUOROM) checklist and the Assessment of Multiple Systematic Reviews (AMSTAR) methodology were adopted to assess the methodological quality of the included meta-analyses. Random-effects models were developed to calculate summarized pool Odds Ratios (with 95% confidence interval) for the afore determined primary and secondary outcomes. RESULTS: AZO, when compared with best available therapy (BAT) including or excluding Hydroxychloroquine, exhibited statistically insignificant reduction in mortality [(n= 27,204 patients) OR= 0.77 (95% CI: 0.51-1.16) (I2= 97%)], requirement of mechanical ventilation [(n= 14,908 patients) OR= 1.4 (95% CI: 0.58-3.35) (I2= 98%)], induction of arrhythmia [(n= 9,723 patients) OR= 1.21 (95% CI: 0.63-2.32) (I2= 92%)] and QTc prolongation (a surrogate for torsadogenic effect) [(n= 6,534 patients) OR= 0.62 (95% CI: 0.23-1.73) (I2= 96%)]. CONCLUSION: The meta-analysis of meta-analyses portrays AZO as a pharmacological agent that does not appear to have a comparatively superior clinical efficacy than BAT when it comes to COVID-19 management. Secondary to a very real threat of anti-bacterial resistance, it is suggested that AZO be discontinued and removed from COVID-19 management protocols.

Torsades de pointes associated with remdesivir treatment for COVID-19 pneumonia.

Background: Prolonged QT interval (QTc) can be a serious adverse event from SARS-CoV-2 infection and associated treatment, including remdesivir. Methods: We present a case of a 55-year-old woman with COVID-19 pneumonia who was treated with remdesivir. The QTc on admission was 483 ms. After three doses of remdesivir, she had an episode of non-sustained ventricular tachycardia. Repeat QTc was significantly prolonged at 609 ms. She experienced a polymorphic ventricular tachycardic cardiac arrest the next morning, thought to be secondary to torsades de pointes. Results: Transthoracic echocardiogram showed normal biventricular function. Electrolytes were within normal limits. In the absence of other QTc-prolonging medications, remdesivir was thought to be inciting agent. Following discontinuation of remdesivir, the patient's QTc returned to baseline. Conclusions: There is a risk for cardiac events from QTc prolongation effects of SARS-CoV-2 infection and associated treatment. We recommend pharmacological profile review and cardiac monitoring for patients receiving remdesivir.

Historique: Un intervalle QT prolongé (QTc) peut être un grave effet indésirable de l'infection par le SRAS-CoV-2 et du traitement qui s'y associe, y compris le remdésivir. Méthodologie: Les chercheurs présentent le cas d'une femme de 55 ans atteinte d'une pneumonie à COVID-19 qui a reçu un traitement au remdésivir. Son QTc à l'admission était de 483 ms. Après trois doses de remdésivir, elle a subi un épisode de tachycardie ventriculaire non soutenue. La reprise du QTc était particulièrement prolongé, à 609 ms. La patiente a vécu un arrêt cardiaque causé par une tachycardie ventriculaire polymorphe le lendemain matin, considéré comme secondaire à des torsades de pointe. Résultats: L'échocardiogramme transthoracique a révélé une fonction biventriculaire normale. Les électrolytes se situaient dans les limites normales. En l'absence d'autres médicaments pour prolonger le QTc, le remdésivir a été présumé comme responsable. Après l'arrêt de ce médicament, le QTc de la patiente est redevenu normal. Conclusions: La prolongation du QTc découlant de l'infection par le SRAS-CoV-2 et du traitement qui s'y associe entraîne un risque d'arrêt cardiaque. Il est recommandé de procéder à une évaluation du profil pharmacologique et d'assurer la surveillance cardiaque des patients qui reçoivent du remdésivir.

C-L Case Conference: Torsades de Pointes in a Patient with Lifelong Medical Trauma, COVID-19, Remdesivir, Citalopram, Quetiapine and Hemodialysis.

We present a case of Torsades de Pointes (TdP) in a patient with COVID-19 infection and multiple TdP risk factors including QTc prolongation, hemodialysis, bradycardia, and treatment with remdesivir, citalopram and quetiapine. The case was complicated by post-resuscitation anxiety superimposed on a history of medical trauma since childhood. Top experts in the field of consultation liaison psychiatry, trauma informed care (TIC) and cardiac electrophysiology provide perspectives on this case with a review of the literature. Key teaching topics include identification of TdP risk factors in patients with complex illness; the necessity for prompt electrophysiology consultation in clinical scenarios with high risk for TdP; and the approach to patients with medical trauma using a trauma-informed lens. We highlight the contributions of COVID-19, the pharmacokinetics of QTc-prolonging psychotropic medications, the risks of hemodialysis, and the role of remdesivir-induced bradycardia in this first reported case of TdP in a patient treated with remdesivir.

Transient Hypogonadism Is Associated With Heart Rate-Corrected QT Prolongation and Torsades de Pointes Risk During Active Systemic Inflammation in Men.

Background Systemic inflammation and male hypogonadism are 2 increasingly recognized "nonconventional" risk factors for long-QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate-corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men. We hypothesized that, during inflammatory activation in men, testosterone levels decrease and that this enhances TdP risk by contributing to the overall prolonging effect of inflammation on QTc. Methods and Results We investigated (1) the levels of sex hormones and their relationship with inflammatory markers and QTc in male patients with different types of inflammatory diseases, during active phase and recovery; and (2) the association between inflammatory markers and sex hormones in a cohort of male patients who developed extreme QTc prolongation and TdP, consecutively collected over 10 years. In men with active inflammatory diseases, testosterone levels were significantly reduced, but promptly normalized in association with the decrease in C-reactive protein and interleukin-6 levels. Reduction of testosterone levels, which also inversely correlated with 17-ß estradiol over time, significantly contributed to inflammation-induced QTc prolongation. In men with TdP, both active systemic inflammation and hypogonadism were frequently present, with significant correlations between C-reactive protein, testosterone, and 17-ß estradiol levels; in these patients, increased C-reactive protein and reduced testosterone were associated with a worse short-term outcome of the arrhythmia. Conclusions During systemic inflammatory activation, interleukin-6 elevation is associated with reduced testosterone levels in males, possibly deriving from an enhanced androgen-to-estrogen conversion. While transient, inflammatory hypotestosteronemia is significantly associated with an increased long-QT syndrome/TdP risk in men.

Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine: A Meta-analysis.

Introduction Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown. Objective To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with HCQ. Data Sources PubMed, EMBASE, Google Scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv, Research Square) were searched for studies published between December 2019 and June 30, 2020. Methods Effect statistics were pooled using random effects. The quality of observational studies and randomized controlled trials was appraised with STROBE and the Cochrane Risk of Bias Assessment tools, respectively. Outcomes Critical LQT was defined as: (1) maximum QT corrected (QTc)≥500 ms (if QRS<120 ms) or QTc≥550 ms (if QRS≥120 ms), and (2) QTc increase ≥60 ms. Results In the 28 studies included (n=9124), the frequency of LQT during HCQ treatment was 6.7% (95% confidence interval [CI]: 3.7-10.2). In 20 studies (n=7825), patients were also taking other QT-prolonging drugs. The frequency of LQT in the other 8 studies (n=1299) was 1.7% (95% CI: 0.3-3.9). Twenty studies (n=6869) reported HCQ discontinuation due to LQT, with a frequency of 3.7% (95% CI: 1.5-6.6). The frequency of ventricular arrhythmias during HCQ treatment was 1.68% (127/7539) and that of arrhythmogenic death was 0.69% (39/5648). Torsades de Pointes occurred in 0.06% (3/5066). Patients aged >60 years were at highest risk of HCQ-associated LQT (P<0.001). Conclusions HCQ-associated cardiotoxicity in SARS-CoV-2 patients is uncommon but requires ECG monitoring, particularly in those aged >60 years and/or taking other QT-prolonging drugs.

Acquired Long QT and Ventricular Arrhythmias in the Setting of Acute Inflammation: A Case Series.

We report a case series of 4 patients with transient marked QTc prolongation and ventricular arrhythmias in the setting of inflammation with very high ferritin levels. Three patients were positive for coronavirus disease-2019. In the setting of an acute rise in inflammatory markers, electrocardiography screening for QTc prolongation is warranted. (Level of Difficulty: Beginner.).

A tale of two extremities: A dynamic case of Covid-19 induced hypokalemia and bradycardia leading into Torsade's de pointes.

INTRODUCTION: As researchers and academics around the world scramble ahead to dissect and analyse every aspect of the SARS-CoV2 virus, one such study explored the various underlying electrolyte abnormalities that were precipitated in patients suffering from a confirmed COVID-19 infection. A significant proportion of such patients were noted to be hypokalemic. Hypokalemia can be life threatening as it is known to cause cardiac arrhythmia. CASE PRESENTATION: Our encounter with said presentation was incidental. The on-call medical team was involved in a cardiac arrest call for a 74-year -old gentleman who developed torsades de pointes, Retrospective analysis of the clinical picture pointed out the fact that he was found to be persistently hypokalemic and bradycardic solely triggered as a result of COVID-19. CONCLUSION: Although initially thought to be a pulmonary disease but along with time extra-pulmonary manifestations of Covid-19 has demonstrated significant consequences. Electrolyte abnormalities and cardiac dysfunction are examples of such extra-pulmonary pathologies. Therefore, it is important to keep close monitoring for such abnormalities otherwise could lead into life threatening arrythmias.

Effect of Hydroxychloroquine on QTc in Patients Diagnosed with COVID-19: A Systematic Review and Meta-Analysis.

BACKGROUND: Hydroxychloroquine or chloroquine with or without the concomitant use of azithromycin have been widely used to treat patients with SARS-CoV-2 infection, based on early in vitro studies, despite their potential to prolong the QTc interval of patients. OBJECTIVE: This is a systematic review and metanalysis designed to assess the effect of hydroxychloroquine with or without the addition of azithromycin on the QTc of hospitalized patients with COVID-19. MATERIALS AND METHODS: PubMed, Scopus, Cochrane and MedRxiv databases were reviewed. A random effect model meta-analysis was used, and I-square was used to assess the heterogeneity. The prespecified endpoints were ΔQTc, QTc prolongation > 500 ms and ΔQTc > 60 ms. RESULTS: A total of 18 studies and 7179 patients met the inclusion criteria and were included in this systematic review and meta-analysis. The use of hydroxychloroquine with or without the addition of azithromycin was associated with increased QTc when used as part of the management of patients with SARS-CoV-2 infection. The combination therapy with hydroxychloroquine plus azithromycin was also associated with statistically significant increases in QTc. Moreover, the use of hydroxychloroquine alone, azithromycin alone, or the combination of the two was associated with increased numbers of patients that developed QTc prolongation > 500 ms. CONCLUSION: This systematic review and metanalysis revealed that the use of hydroxychloroquine alone or in conjunction with azithromycin was linked to an increase in the QTc interval of hospitalized patients with SARS-CoV-2 infection that received these agents.

Hydroxychloroquine/Azithromycin Therapy and QT Prolongation in Hospitalized Patients With COVID-19.

OBJECTIVES: This study aimed to characterize corrected QT (QTc) prolongation in a cohort of hospitalized patients with coronavirus disease-2019 (COVID-19) who were treated with hydroxychloroquine and azithromycin (HCQ/AZM). BACKGROUND: HCQ/AZM is being widely used to treat COVID-19 despite the known risk of QT interval prolongation and the unknown risk of arrhythmogenesis in this population. METHODS: A retrospective cohort of COVID-19 hospitalized patients treated with HCQ/AZM was reviewed. The QTc interval was calculated before drug administration and for the first 5 days following initiation. The primary endpoint was the magnitude of QTc prolongation, and factors associated with QTc prolongation. Secondary endpoints were incidences of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality. RESULTS: Among 415 patients who received concomitant HCQ/AZM, the mean QTc increased from 443 ± 25 ms to a maximum of 473 ± 40 ms (87 [21%] patients had a QTc ≥500 ms). Factors associated with QTc prolongation ≥500 ms were age (p < 0.001), body mass index <30 kg/m2 (p = 0.005), heart failure (p < 0.001), elevated creatinine (p = 0.005), and peak troponin (p < 0.001). The change in QTc was not associated with death over the short period of the study in a population in which mortality was already high (hazard ratio: 0.998; p = 0.607). No primary high-grade ventricular arrhythmias were observed. CONCLUSIONS: An increase in QTc was seen in hospitalized patients with COVID-19 treated with HCQ/AZM. Several clinical factors were associated with greater QTc prolongation. Changes in QTc were not associated with increased risk of death.

Cardiac Toxicity of Chloroquine or Hydroxychloroquine in Patients With COVID-19: A Systematic Review and Meta-regression Analysis.

OBJECTIVE: To systematically review the literature and to estimate the risk of chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in patients with coronavirus disease 2019 (COVID-19). METHODS: We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled patients with COVID-19 treated with CQ or HCQ, with or without azithromycin, and reported on cardiac toxic effects. We performed a meta-analysis using the arcsine transformation of the different incidences. RESULTS: A total of 19 studies with a total of 5652 patients were included. The pooled incidence of torsades de pointes arrhythmia, ventricular tachycardia, or cardiac arrest was 3 per 1000 (95% CI, 0-21; I 2 =96%) in 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5% (95% CI, 1-11; I 2 =98%). The pooled incidence of change in QTc from baseline of 60 milliseconds or more or QTc of 500 milliseconds or more was 9% (95% CI, 3-17; I 2 =97%). Mean or median age, coronary artery disease, hypertension, diabetes, concomitant QT-prolonging medications, intensive care unit admission, and severity of illness in the study populations explained between-studies heterogeneity. CONCLUSION: Treatment of patients with COVID-19 with CQ or HCQ is associated with an important risk of drug-induced QT prolongation and relatively higher incidence of torsades de pointes, ventricular tachycardia, or cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. Patients with COVID-19 who are treated with antimalarials for other indications should be adequately monitored.

Safety and Effectiveness of Hydroxychloroquine and Azithromycin Combination Therapy for Treatment of Hospitalized Patients with COVID-19: A Propensity-Matched Study.

INTRODUCTION: We sought to determine the effectiveness and safety of hydroxychloroquine-azithromycin (HCQ-AZM) therapy in hospitalized patients with COVID-19. METHODS: This was a retrospective cohort study of 613 patients hospitalized (integrated health system involving three hospitals) for RT-PCR-confirmed COVID-19 infection between March 1, 2020 and April 25, 2020. Intervention was treatment with HCQ-AZM in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Outcomes of interest were in-hospital all-cause mortality, cardiovascular mortality, pulseless electrical activity (PEA) arrest, non-lethal arrhythmias, and length of hospital stay. Secondary measures included in-hospital corrected QT (QTc) interval parameters and serum biomarkers levels. RESULTS: Propensity-matched groups were composed of 173 patients given HCQ-AZM and 173 matched patients who did not receive treatment. There was no significant difference in in-hospital mortality (odds ratio [OR] 1.52; 95% confidence interval [CI] 0.80-2.89; p = 0.2), PEA arrest (OR 1.68, CI 0.68-4.15; p = 0.27), or incidence of non-lethal arrhythmias (10.4% vs. 6.8%; p = 0.28). Length of hospital stay (10.5 ± 7.4 vs. 5.8 ± 6.1; p < 0.001), peak CRP levels (252 ± 136 vs. 166 ± 124; p < 0.0001), and degree of QTc interval prolongation was higher for the HCQ-AZM group (28 ± 32 vs. 9 ± 32; p < 0.0001), but there was no significant difference in incidence of sustained ventricular arrhythmias (2.8% vs. 1.7%; p = 0.52). HCQ-AZM was stopped in 10 patients because of QT interval prolongation and 1 patient because of drug-related polymorphic ventricular tachycardia. CONCLUSION: In this propensity-matched study, there was no difference in in-hospital mortality, life-threatening arrhythmias, or incidence of PEA arrest between the HCQ-AZM and untreated control groups. QTc intervals were longer in patients receiving HCQ-AZM, but only one patient developed drug-related ventricular tachycardia.

Hydroxychloroquine and QTc prolongation in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: Among many drugs that hold potential in COVID-19 pandemic, chloroquine (CQ), and its derivative hydroxychloroquine (HCQ) have generated unusual interest. With increasing usage, there has been growing concern about the prolongation of QTc interval and Torsades de Pointes (TdP) with HCQ, especially in combination with azithromycin. AIMS: This meta-analysis is planned to study the risk of QTc prolongation and Torsades de pointes (TdP) by a well-defined criterion for HCQ, CQ alone, and in combination with Azithromycin in patients with COVID-19. METHODS: A comprehensive literature search was made in two databases (PubMed, Embase). Three outcomes explored in the included studies were frequency of QTc > 500 ms (ms) or ΔQTc > 60 ms (Outcome 1), frequency of QTc > 500 ms (Outcome 2) and frequency of TdP (Outcome 3). Random effects method with inverse variance approach was used for computation of pooled summary and risk ratio. RESULTS: A total of 13 studies comprising of 2138 patients were included in the final analysis. The pooled prevalence of outcome 1, outcome 2 and outcome 3 for HCQ, CQ with or without Azithromycin were 10.18% (5.59-17.82%, I2 - 92%), 10.22% (6.01-16.85%, I2 - 79%), and 0.72% (0.34-1.51, I2 - 0%) respectively. The prevalence of outcome 2 in subgroup analysis for HCQ and HCQ + Azithromycin was 7.25% (3.22-15.52, I2 - 59%) and 8.61% (4.52-15.79, I2 - 76%), respectively. The risk ratio (RR) for outcome 1 and outcome 2 between HCQ + Azithromycin and HCQ was 1.22 (0.77-1.93, I2 - 0%) & 1.51 (0.79-2.87, I2 - 13%), respectively and was not significant. Heterogeneity was noted statistically as well clinically (regimen types, patient numbers, study design, and outcome definition). CONCLUSION: The use of HCQ/CQ is associated with a high prevalence of QTc prolongation. However, it is not associated with a high risk of TdP.

Arrhythmias and COVID-19: A Review.

Current understanding of the impact of coronavirus disease-2019 (COVID-19) on arrhythmias continues to evolve as new data emerge. Cardiac arrhythmias are more common in critically ill COVID-19 patients. The potential mechanisms that could result in arrhythmogenesis among COVID-19 patients include hypoxia caused by direct viral tissue involvement of lungs, myocarditis, abnormal host immune response, myocardial ischemia, myocardial strain, electrolyte derangements, intravascular volume imbalances, and drug sides effects. To manage these arrhythmias, it is imperative to increase the awareness of potential drug-drug interactions, to monitor QTc prolongation while receiving COVID therapy and provide special considerations for patients with inherited arrhythmia syndromes. It is also crucial to minimize exposure to COVID-19 infection by stratifying the need for intervention and using telemedicine. As COVID-19 infection continues to prevail with a potential for future surges, more data are required to better understand pathophysiology and to validate management strategies.