A Prospective Observational Study in Adult Medical Intensive Care Unit Patients with Drug-Induced QTc with Correlation of Serum Potassium, Magnesium Level of Clinical Outcome

Abstract

Background:

Drug-induced QTc prolongation is a significant concern in critically ill patients, increasing the risk of life-threatening arrhythmias. This prospective observational study evaluates the association between QTc prolongation, serum potassium and magnesium levels, and clinical outcomes in adult medical intensive care unit (ICU) patients.

Methodology:

The study included 116 adult ICU patients prescribed QTc-prolonging drugs, excluding those with atrial fibrillation, pacemakers, or early transfers. Electrocardiograms (ECG) and serum electrolyte levels were analyzed to assess QTc prolongation and its correlation with arrhythmias, ICU stay, and mortality. The Tisdale risk score categorized patients into low, medium, and high-risk groups.

Results:

QTc prolongation occurred in 29 patients, with males showing a higher incidence. Common diagnoses included sepsis, myocardial infarction, and coronary artery disease. Drugs frequently implicated were ondansetron (17.24%), fluconazole (10.34%), and amiodarone (6.89%). Among these, 11 patients were high-risk, 12 moderate-risk, and 6 low-risk. Significant changes were noted in ECG and potassium levels, but not in magnesium, chloride, or creatinine.

Conclusion:

This study highlights the importance of monitoring and managing QTc-prolonging medications and associated risk factors, such as serum potassium and magnesium levels, to reduce arrhythmia risk and improve ICU outcomes.

INTRODUCTION

The QT interval on an electrocardiogram (ECG) represents ventricular depolarization and repolarization, and in critically ill patients, the use of intensive care medications can increase the risk of drug–drug interactions (DDIs), which can lead to acquired long QT syndrome.[1] A corrected QTc interval with a duration greater than 500 ms increases the risk of torsade de point (TdP), a rare but lethal form of cardiac arrhythmia. Prolonged QT intervals significantly increase hospital stay and mortality in critically ill patients.[2]

The number of intensive care unit (ICU) admissions in the United States has steadily increased over the past decade, leading to a growing population of individuals who may face long-term cognitive, physical, and psychological impairments associated with post-intensive care syndrome.[3] Ensuring safe and effective medication management during the transition from intensive care to lower acuity settings is crucial to mitigating these long-term consequences.[4]

The cell membrane, acting as a barrier, can cause hypokalemia in 20% of hospitalized patients, leading to electrocardiographic changes and potentially life-threatening cardiac dysrhythmias.[5]

The study aims to investigate drug-induced QTc with correlation of serum potassium, magnesium level of clinical outcome in adult medical ICU (MICU) patients, with the primary goal of improving patient quality of life and reducing the length of stay.

METHODOLOGY

This prospective observational study was conducted over six months at GKNM Hospital in Coimbatore. The research protocol was reviewed and approved by the Institutional Ethics Committee (2024/IEC/027), and the study involved adult patients aged 18+ with QTc-prolonging medications in the MICU, with exclusions for non-prolonging drugs, atrial fibrillation, pacemakers, or immediate discharge.

The data collection process encompassed patient demographics, electrocardiogram reports, laboratory data, medication information, and Tisdale risk score analysis. Electrolyte levels were monitored, and recommendations were provided for QTc-prolonging drugs that are primarily eliminated through the renal or hepatic systems. DDIs were analyzed, and risk scores were categorized using the Tisdale risk score. The medical team received recommendations if the QTc interval exceeded 500 ms or increased by 60 ms from the patient’s baseline. SPSS version 23.0 (Data analysis was developed by IBM Corp., Armonk, NY, USA) was utilized for data analysis.

RESULT

A study of 116 adult MICU patients revealed 29 experienced drug-induced QTc interval prolongation, with 21 over 60 and 8 below. Common conditions included sepsis, myocardial infarction, hypertension, hyperkalemia, and neurological conditions.

The most common QT-prolonging drugs identified in the study were ondansetron (17.24%), fluconazole (10.34%), amiodarone (6.89%), and metoclopramide (6.89%). Other drugs associated with QTc prolongation included amitriptyline, quetiapine, haloperidol, prednisolone, voriconazole, ciprofloxacin, azithromycin, and various drug combinations [Figure 1]. The analysis revealed that 21 out of 29 patients with prolonged QTc intervals had no identified DDIs, with four cases involving moderate and four cases involving severe interactions.

Figure 1.

Distribution of QTc prolonging drugs in prolonged cases (n = 29)

In this study, out of 116 patients, 29 patients only experienced QTc prolongation. Here, ECG, sodium, and potassium were statistically significant on the pre- and post-values [Table 1].

Table 1.

Distribution based on electrolyte level (n=29)

Parameter	n	Pre-mean±SD	Post-mean±SD	Mean difference	t	df	P	Significance
QTc interval (ms)	29	470.10±47.89	534.21±40.28	64.1	10.53	28	<0.001	***Highly significant
Sodium (mmol/L)	29	135.97±6.95	139.72±6.68	3.76	2.87	28	0.008	**Highly significant
Potassium (mmol/L)	29	4.57±1.09	3.95±0.47	0.61	3.03	28	0.005	**Highly significant
Chloride (mmol/L)	29	102.93±8.27	104.28±8.27	1.34	1.06	28	0.296	Not significant
Magnesium (mg/dL)	7	1.59±0.50	1.90±0.70	0.31	1.79	6	0.123	Not significant

The quality of life improved for 17 patients taking single QTc-prolonging medication and eight taking two or more, but recommendations were declined for four patients due to their severity [Figure 2].

Figure 2.

Distribution based on quality of life after recommendation

DISCUSSION

A study found that a significant proportion of patients admitted to the adult MICU experienced drug-induced QTc interval prolongation, highlighting the importance of vigilant monitoring and management of this vulnerable patient population. Drug interactions that enhance the risk of QTc prolongation are expected to be common, with the predominance of older patients and those with underlying cardiovascular and metabolic conditions among the prolonged QTc cases.[6] The study identified commonly implicated QTc-prolonging drugs, such as ondansetron, fluconazole, amiodarone, and metoclopramide.

The Tisdale risk assessment tool provided a nuanced and innovative approach to evaluating 29 patients with prolonged QTc intervals, revealing a granular distribution of risk levels. The majority of patients were classified as high-risk, indicating the severity of their condition and heightened potential for adverse cardiac events.[7] A substantial proportion was also classified as moderate-risk, necessitating close monitoring and tailored interventions. Interestingly, a smaller number were identified as low-risk, suggesting a need for personalized strategies.[8,9]

CONCLUSION

The study highlights the significant burden of drug-induced QTc interval prolongation in adult MICUs, highlighting patient-specific risk factors and the importance of understanding DDI.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.