Multivariate Analysis of Risk Factors for QT Prolongation
Background: Subarachnoid hemorrhage (SAH) often causes a prolongation of the corrected QT (QTc) interval during the acute phase. The aim of the present study was to examine independent risk factors for QTc prolongation in patients with SAH by means of multivariate analysis.
Method: We studied 100 patients who were admitted within 24 hours after onset of SAH. Standard 12-lead electrocardiography (ECG) was performed immediately after admission. QT intervals were measured from the ECG and were corrected for heart rate using the Bazett formula. We measured serum levels of sodium, potassium, calcium, adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, antidiuretic hormone, and glucose.
Results: The average QTc interval was 466 ± 46 ms. Patients were categorized into two groups based on the QTc interval, with a cutoff line of 470 ms. Univariate analyses showed significant relations between categories of QTc interval, and sex and serum concentrations of potassium, calcium, or glucose. Multivariate analyses showed that female sex and hypokalemia were independent risk factors for severe QTc prolongation. Hypokalemia (<3.5 mmol/l) was associated with a relative risk of 4.53 for severe QTc prolongation as compared with normokalemia, while the relative risk associated with female sex was 4.45 as compared with male sex. There was a significant inverse correlation between serum potassium levels and QTc intervals among female patients.
Conclusion: These findings suggest that female sex and hypokalemia are independent risk factors for severe QTc prolongation in patients with SAH.

Hypokalemia and many types of electrocardiographic (ECG) abnormality are observed during the acute phase of subarachnoid hemorrhage (SAH). Among ECG abnormalities, a prolongation of the QT interval, especially when associated with hypokalemia, deserves particular attention because it is frequently observed in those patients who develop life-threatening ventricular arrhythmias such as tor-sades de pointes. However, the pathogeneses of these abnormalities during the acute phase of SAH have not yet been fully investigated.

It is commonly believed that hypokalemia identified during the acute phase of SAH is caused by a catecholamine surge following SAH. In healthy male volunteers, Brown and coworkers demonstrated that serum infused adrenaline (epinephrine) caused excessive activation of the sodium/potassium-ATPase (Na/K-ATPase; Na/K pump) as a result of




₂-adrenergic receptor stimulation; this resulted in trafficking of potassium ions from extracellular to intracellu-lar spaces, leading to a decrease in serum potassium levels.


Recent work showed that there were some relationships between serum catecholamine levels and QT intervals during the acute phase of SAH. However, one cannot refute the possibility that the catecholamine surge may influence the QT interval indirectly via hypokalemia, because hypokalemia (as well as hypocalcemia and hypomagnesemia) can cause a prolongation in the QT interval.

In a previous preliminary study, we suggested that women may be more prone than men to develop both hypokalemia and prolongation in the corrected QT (QTc) interval on the first day of SAH. In the present prospective study, we assessed various possible risk factors for the QTc prolongation that is observed in SAH patients in order to examine independent risk factors by means of multivariate analysis.