Clinical Factors Associated With Ventricular Dysrhythmia in Emergency Department Patients With Severe QTc Prolongation After Drug Overdose

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Severe QTc prolongation after drug overdose (n=1265). Intervention: Shock vs. Absence of shock. Primary outcome: Ventricular dysrhythmia (aOR 4.54, 95% CI 2.07-9.75).

Q: What does this research mean for the field?

In emergency department patients with severe QTc prolongation following drug overdose, shock (aOR 4.54), bradycardia, and acidosis are independently associated with ventricular dysrhythmia. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

M.D.C. Simpson; Katherine B. Tang; Michael W. Donnino; Peter R. Chai; Rachel Culbreth; Sharan Campleman; Paul M. Wax; Alex F. Manini; Michele M. Burns

doi:10.1111/acem.70083

June 10, 2025Academic Emergency MedicineOpen Access

Clinical Factors Associated With Ventricular Dysrhythmia in Emergency Department Patients With Severe QTc Prolongation After Drug Overdose

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Key result

Shock is linked to ~4.5-fold higher ventricular dysrhythmia risk in drug overdose with severe QTc prolongation.

aOR 4.54
95% CI 2.07-9.75
n=1,265

Why the study?

Severe QTc prolongation after acute drug overdose is challenging to manage because ventricular dysrhythmias are rare but life-threatening, making it unclear which presenting patients will develop these outcomes.

Does the presence of bradycardia, acidosis, or shock predict ventricular dysrhythmia in patients with severe QTc prolongation after drug overdose?

Key Points

To identify clinical factors associated with ventricular dysrhythmias and adverse cardiovascular outcomes in emergency department patients presenting with severe QTc prolongation following drug overdose.
Secondary analysis of 1265 patients aged ≥ 13 years with acute or acute-on-chronic drug overdose and initial emergency department electrocardiogram QTc ≥ 500 ms in the Toxicology Investigators Consortium Core Registry (2013–2023).
Multivariable logistic regression adjusted for age, sex, and race/ethnicity to identify independent predictors of ventricular dysrhythmia, with diagnostic test characteristics calculated for identified risk factors.
Ventricular dysrhythmias developed in 48 of 1265 patients (3.79%).
Shock (aOR 4.54, 95% CI 2.07–9.75), bradycardia (aOR 3.12, 95% CI 1.35–6.90), and acidosis (aOR 3.02, 95% CI 1.42–6.23) were independently associated with ventricular dysrhythmia and each secondary outcome.
The absence of bradycardia, acidosis, and shock had a negative predictive value of 98.2% (95% CI 97.2%–98.9%) for developing ventricular dysrhythmia.

Study Design

Type

Cohort (n=1,265)

Multicenter

Yes

Structured PICO

Does the presence of bradycardia, acidosis, or shock predict ventricular dysrhythmia in patients with severe QTc prolongation after drug overdose?

P

Population

1,265 patients aged 13 years or older presenting to the emergency department with acute drug overdose and severe QTc prolongation (≥ 500 ms).

E

Exposure

Presence of bradycardia, acidosis, or shock

C

Comparator

Absence of bradycardia, acidosis, and shock

O

Outcome

Ventricular dysrhythmia (ventricular tachycardia or ventricular fibrillation) during the encounterhard clinical

Main Result

Odds Ratio: 4.54 (95% CI 2.07–9.75)

The presence of bradycardia, acidosis, or shock strongly predicts ventricular dysrhythmias in patients with severe QTc prolongation post-overdose, while their absence has a 98.2% negative predictive value, aiding in triage decisions.

Limitations

Requirement of toxicology consultation may bias the cohort toward more critically ill patients
Most facilities are tertiary academic institutions, limiting generalizability
Timing of outcomes in relation to clinical data is not documented, limiting causal conclusions
Electrolyte abnormalities and hypothermia were not routinely recorded or analyzed
Electrocardiograms were not uploaded, preventing independent confirmation of QTc values
Selection bias due to requirement of toxicology consultation
Predominantly tertiary academic institutions
Lack of granular timing data to establish causation
Unable to analyze electrolyte abnormalities
Electrocardiograms not uploaded to confirm QTc interpretation

Implication

Shock was associated with ventricular dysrhythmia in severe QTc prolongation post-overdose; leaves open whether these factors improve risk stratification or triage.

Abstract

BACKGROUND: Management of severe prolongation of the corrected QT interval (QTc) following acute drug overdose presents a challenge to clinicians, as resulting ventricular dysrhythmias are rare but life-threatening. This study aimed to identify which patients with severe QTc prolongation on presentation to the emergency department (ED) after overdose will develop ventricular dysrhythmias, death, cardiac arrest, the need for rhythm control, or extracorporeal membrane oxygenation utilization. METHODS: Secondary analysis of Toxicology Investigators Consortium Core Registry data from 2013 to 2023. We included patients ≥ 13 years old with acute or acute-on-chronic overdose, toxicology consultation in the inpatient or ED setting, and initial ED electrocardiogram QTc ≥ 500 ms. We excluded patients with no or unknown toxicologic exposure, symptoms unlikely or unknown whether related to exposure, or missing data. The primary outcome was ventricular dysrhythmia. Secondary outcomes included death, cardiac arrest, rhythm control, and extracorporeal membrane oxygenation. Independent variables included patient and overdose characteristics, initial QTc and bicarbonate values, clinical findings, and drug exposures. Multivariable logistic regression was performed with ventricular dysrhythmia as the dependent variable to identify potential predictors. Diagnostic test characteristics were calculated for risk factors identified in the regression model. RESULTS: Of 2764 patients screened, 1265 were included. Forty-eight (3.79%) patients developed ventricular dysrhythmias. Bradycardia (aOR 3.12, 95% CI 1.35-6.90), acidosis (aOR 3.02, 95% CI 1.42-6.23), and shock (aOR 4.54, 95% CI 2.07-9.75) were independently associated with ventricular dysrhythmia on regression analysis and were each associated with every secondary outcome. The absence of any of these findings had a negative predictive value of 98.2% (97.2%-98.9%) for developing ventricular dysrhythmia. CONCLUSIONS: In this large international data registry, we identified predictors of ventricular dysrhythmia in patients presenting to the ED after overdose in the setting of severe QTc prolongation.

Discussion

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Cite This Study

Simpson et al. (2025) conducted a cohort in Severe QTc prolongation after drug overdose (n=1,265). Shock vs. Absence of shock was evaluated on Ventricular dysrhythmia (aOR 4.54, 95% CI 2.07-9.75). In patients with severe QTc prolongation after drug overdose, shock was independently associated with an increased risk of ventricular dysrhythmia (aOR 4.54).

synapsesocial.com/papers/6a58f8c7d848c9ced74cf7ab https://doi.org/10.1111/acem.70083

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Clinical Factors Associated With Ventricular Dysrhythmia in Emergency Department Patients With Severe QTc Prolongation After Drug Overdose

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Clinical Factors Associated With Ventricular Dysrhythmia in Emergency Department Patients With Severe QTc Prolongation After Drug Overdose

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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