What abnormal cardiac rhythm is associated with multiple doses of Haldol (haloperidol)?

Torsades de Pointes is the Abnormal Cardiac Rhythm Associated with Multiple Doses of Haloperidol

Multiple doses of haloperidol are associated with QT interval prolongation and torsades de pointes, a potentially life-threatening polymorphic ventricular tachyarrhythmia. 1, 2

Mechanism and Risk

• Haloperidol is listed as an antipsychotic medication that causes QT interval prolongation with a mean prolongation of 7 ms, which can lead to torsades de pointes 3
• The FDA drug label specifically warns that cases of QT-prolongation and torsades de pointes have been reported in patients receiving haloperidol 2
• Higher than recommended doses of haloperidol appear to be associated with a higher risk of QT-prolongation and torsades de pointes 2
• Intravenous administration of haloperidol carries a higher risk of QT prolongation and torsades de pointes than oral or intramuscular administration 1, 3

Risk Factors for Haloperidol-Induced Torsades de Pointes

Patients with the following risk factors are at increased risk for developing torsades de pointes when receiving haloperidol:

• Female gender 1, 3
• Hypokalemia or hypomagnesemia 1, 2
• Bradycardia 1
• Recent conversion from atrial fibrillation 1
• Congestive heart failure 1
• Baseline QT prolongation 1, 2
• Left ventricular hypertrophy 1
• Congenital long QT syndrome 1, 2
• Concomitant use of other QT-prolonging medications 1, 3
• High drug concentrations, often due to drug interactions 1
• Rapid rate of intravenous drug administration 1, 4

Clinical Presentation and Diagnosis

• Torsades de pointes presents as a polymorphic ventricular tachycardia with QRS complexes that appear to spiral around the baseline of the ECG 5
• The arrhythmia is virtually always associated with prolongation of the QT interval 5
• QT intervals are generally greater than 500 msec before the development of torsades de pointes 1
• Prominent U waves may be present on the ECG 1
• Marked QTU prolongation may only be evident on post-pause beats 1

Management of Haloperidol-Induced Torsades de Pointes

When torsades de pointes is suspected or confirmed in a patient receiving haloperidol:

• Immediate discontinuation of haloperidol is indicated 1, 2
• Correction of electrolyte abnormalities, particularly potassium (to >4.5 mEq/L) and magnesium 1, 4
• Administration of intravenous magnesium sulfate, which can suppress episodes of torsades de pointes even when serum magnesium is normal 1, 6
• Temporary cardiac pacing is highly effective for managing recurrent torsades de pointes after potassium repletion and magnesium supplementation 1, 5
• Isoproterenol may be considered if pacing is not immediately available 1
• Conventional antiarrhythmic drugs that further prolong the QT interval should be avoided as they may aggravate the arrhythmia 5

Prevention Strategies

To prevent haloperidol-induced torsades de pointes:

• Consider alternative medications with lower risk of QT prolongation when possible, such as aripiprazole (0 ms QT prolongation) or olanzapine (2 ms QT prolongation) 3
• Avoid concomitant use of multiple QT-prolonging medications 1, 3
• Monitor electrolytes regularly and maintain normal levels 3
• Obtain baseline ECG before initiating haloperidol therapy 3
• Consider follow-up ECG after dose titration 3
• Adjust medication if QTc exceeds 500 ms or increases by >60 ms from baseline 3
• Use the lowest effective dose of haloperidol 2
• Prefer oral or intramuscular routes over intravenous administration 1

Important Caveats

• Cases of torsades de pointes have been reported even in the absence of predisposing factors 2
• Torsades de pointes can occur with both intravenous and oral haloperidol administration 4
• The arrhythmia may be idiosyncratic and unpredictable in select patients 7
• QTc prolongation typically precedes the development of torsades de pointes 7
• Careful serial electrocardiographic monitoring is recommended when administering high-dose haloperidol 7