The Effect of Intravenous Haloperidol on QT Interval Dispersion in Critically Ill Patients: Comparison with QT Interval Prolongation for Assessment of Risk of Torsades de Pointes

Tisdale, James E.; Rasty, Saeed; Padhi, I. Desmond; Sharma, Nagaraja D.; Rosman, Howard

doi:10.1177/00912700122012896

Cited by 63 publications

(31 citation statements)

References 21 publications

(28 reference statements)

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“…However, after controlling for coronary risk factors, only QTc dispersion and not QTc prolongation remained a strong predictor of cardiovascular mortality (14). Likewise, a controlled study comparing patients with and without TdP after intravenous administration of haloperidol found that QTc dispersion was significantly greater in patients who experienced TdP, particularly when associated with a QTc duration >500 msec (17). Thus, the absence of any clinical or electrocardiographic evidence for arrhythmias in our youth treated with ziprasidone, including one quarter who developed electrocardiographic abnormalities of QTc or QTc dispersion, suggests that the absence of concurrently abnormal QTc dispersion and QTc prolongation might be protective.…”

Section: Discussionmentioning

confidence: 99%

“…A QTc dispersion >120 msec was shown to be a strong correlate of inducible ventricular tachycardia and its predictive value was not influenced by gender, mean QTc, and left ventricular systolic function (13). QTc dispersion is also a stronger predictor for cardiovascular mortality than QTc duration in the general population (14), patients with myocardial infarction (15), subjects with congenital long QT syndromes (16) and patients who developed TdP after intravenous administration of haloperidol (17). …”

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confidence: 99%

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QT Interval Duration and Dispersion in Children and Adolescents Treated With Ziprasidone

Correll¹,

Lops²,

Figen³

et al. 2011

J. Clin. Psychiatry

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Objective To assess the incidence of symptoms (palpitations, syncope) and electrocardiographic signs (increased QT duration and dispersion) of an increased risk of torsades de pointes in youth treated with ziprasidone. Method Prospective, observational study of 29 youth (15.3±2.9 years) receiving ziprasidone (112.8±50.6 mg/day, range: 20–240mg/day) for 99.3±108.7 days. All patients had normal electrocardiograms (EKGs) and no serious medical illness at baseline. Patients had a mean of 2.7±1.3 (median=3, range: 1–7, total: 49) follow-up EKGs performed monthly for 3 months and every three months thereafter, with concurrent ziprasidone blood level measurements. Heart rate-corrected QT (QTc) duration and dispersion were measured manually in ≥6 EKG leads. QTc interval > 450msec or ≥60msec increase, and QTc dispersion >100msec were considered abnormal. Results No patient reported syncope or symptomatic arrhythmias. Seven patients (24.1%) developed EKG abnormalities; 5 had peak QTc durations >450msec and 2 had peak QTc dispersion >100 msec. The baseline-to-peak QTc duration increased by 22.9±21msec (p<0.0001). The baseline-to-peak QTc dispersion increased by 6.1±31.4msec (p=0.30). The peak QTc duration and dispersion occurred after 47.6±45.2 and 60.4±72.1 treatment days, respectively. Baseline-to-peak QTc duration and dispersion changes were not correlated with ziprasidone dose (p=0.67) or plasma levels (p=0.37). Conclusions Ziprasidone was associated with a dose- and level-independent, significant prolongation of QTc duration in one quarter of youth. However, prolongation of QTc dispersion was non-significant, and no patient experienced concomitant abnormal prolongation of both QTc duration and QTc dispersion. The dissociation between prolonged QTc duration and dispersion suggests low arrhythmogenic potential in youth with normal baseline EKGs.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

QT Interval Duration and Dispersion in Children and Adolescents Treated With Ziprasidone

Correll¹,

Lops²,

Figen³

et al. 2011

J. Clin. Psychiatry

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show abstract

“…haloperidol, eight developed torsade de pointes and they assumed the highest dose in the shortest period (Nagaraja et al 1998). Another study on 30 critically ill patients in haloperidol treatment for delusional agitations unmasked a correlation between QT prolongation and torsade de pointes episodes (Tisdale et al 2001).…”

Section: Butyrophenonesmentioning

confidence: 99%

Drug-induced block of cardiac HERG potassium channels and development oftorsade de pointesarrhythmias: the case of antipsychotics

Calderone

Testai

Martinotti

et al. 2005

Journal of Pharmacy and Pharmacology

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The prolongation of the cardiac repolarization process, a result of the blocking of the Human Ether-ago-go Related Gene potassium channel, is an undesired accessory property shared by many pharmacological classes of non-cardiovascular drugs. Often the delayed cardiac repolarization process can be identified by a prolongation of the QT interval of the electrocardiograph. In these conditions, premature action potentials can trigger a dangerous polymorphic ventricular tachyarrhythmia, known as torsade de pointes, which occasionally can result in lethal ventricular fibrillation. In this work, brief descriptions of the electrophysiological basis of torsade de pointes and of the several pharmacological classes of torsadogenic drugs are given. Attention is focused on antipsychotics, with a deeper overview on the experimental and clinical reports about their torsadogenic properties. The cardiac action potentialCardiac action potentials are generated by trans-membrane movements of ion species, flowing principally through specific channels. In a typical human cardiac action potential ( Figure 1A), five different phases can be recognized. Phase 0 is a rapid depolarization process resulting from a massive inward flow of Na þ (current I Na ). The following phase 1 is linked to the inactivation of the I Na current and to a weak and transient repolarization due to an outward flow of K þ (current I to ). Phase 2 reflects an almost iso-electric plateau generated by the simultaneous activation of a depolarizing inward Ca þþ current, a repolarizing outward rapidly activated K þ current (current I Kr ) and a repolarizing outward slowly activated K þ current (current I Ks ). Phase 3 reflects the complete membrane repolarization due to many K þ currents (mainly I Ks and I Kr ), which leads the cell to the recovery of resting membrane potential. Finally, phase 4 is the resting period, ensured by inward rectifier K þ currents (I K1 ), before a new following cardiac cycle. The QT intervalA typical electrocardiograph (ECG) tracing of a human cardiac cycle ( Figure 1B) starts with a P wave (80-110 ms) representing the atrial depolarization. The following iso-electric time (about 100 ms) reflects the propagation of the depolarization through the atrio-ventricular node to the ventricular conduction system. The QRS complex (<120 ms) represents the whole ventricular depolarization, followed by an isoelectric time (about 120 ms) starting from the J point. Finally, the T wave (230-300 ms) represents the final ventricular repolarization and the end of the cycle. Among the various ECG parameters that are useful in analysing the cardiac functions, the QT interval is the most usual one for estimating the ventricular repolarization process. Drug-induced torsade de pointesMany drugs belonging to different pharmacological classes (Table 1) can trigger lifethreatening polymorphic ventricular tachyarrhythmias, such as torsade de pointes. In particular, many non-cardiovascular drugs in common clinical use cause the prolongation

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“…Hassaballa [2] reported 19 cases of Torsades after haloperidol and Huyse [6] reported a case of cardiac arrest after 7.5 mg of haloperidol. Tisdale [3] performed an interesting study that demonstrated that haloperidol always causes a prolonged QT interval and advocates cardiac monitoring and extra caution with a QT interval over 521 ms.…”

Section: Comment(s)mentioning

confidence: 99%

Is haloperidol or a benzodiazepine the safest treatment for acute psychosis in the critically ill patient?

Khasati

Thompson

Dunning

2004

Interactive Cardiovascular and Thoracic Surgery

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A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether haloperidol or a benzodiazepine is the safest treatment for acute psychosis in the critically ill patient. Altogether 294 papers were found using the reported search, of which nine presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that haloperidol should be considered the first line drug for agitated patients post cardiac surgery, however lorazepam either alone or in conjunction with haloperidol is an acceptable alternative.

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The Effect of Intravenous Haloperidol on QT Interval Dispersion in Critically Ill Patients: Comparison with QT Interval Prolongation for Assessment of Risk of Torsades de Pointes

Cited by 63 publications

References 21 publications

QT Interval Duration and Dispersion in Children and Adolescents Treated With Ziprasidone

QT Interval Duration and Dispersion in Children and Adolescents Treated With Ziprasidone

Drug-induced block of cardiac HERG potassium channels and development oftorsade de pointesarrhythmias: the case of antipsychotics

Is haloperidol or a benzodiazepine the safest treatment for acute psychosis in the critically ill patient?

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