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QTc prolongation after haloperidol administration in critically ill patients post cardiovascular surgery: A cohort study and review of the literature

Published online by Cambridge University Press:  29 April 2020

Burbuqe Ibrahimi ,
Soenke Boettger Open the ORCID record for Soenke Boettger [Opens in a new window] ,
Maria Schubert ,
Dominique Bettex  and
Alain Rudiger
Burbuqe Ibrahimi*
Affiliation:
Institute of Anaesthesiology, University of Zurich, University Hospital Zurich, Zurich, Switzerland Department of Cardiology, University of Zurich, University Hospital Zurich, Zurich, Switzerland
Soenke Boettger
Affiliation:
Department of Consultation-Liaison Psychiatry and Psychosomatics, University of Zurich, University Hospital Zurich, Zurich, Switzerland
Maria Schubert
Affiliation:
Department of Consultation-Liaison Psychiatry and Psychosomatics, University of Zurich, University Hospital Zurich, Zurich, Switzerland
Dominique Bettex
Affiliation:
Institute of Anaesthesiology, University of Zurich, University Hospital Zurich, Zurich, Switzerland
Alain Rudiger
Affiliation:
Institute of Anaesthesiology, University of Zurich, University Hospital Zurich, Zurich, Switzerland
*
Author for correspondence: Burbuqe Ibrahimi, Institute of Anaesthesiology and Department of Cardiology, University of Zurich, University Hospital Zurich, Ramistrasse 100, 8091 Zurich, Switzerland. E-mail: burbuqe.ibrahimi@usz.ch
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Abstract

Objective

From case reports, haloperidol administration has been associated with QTc prolongation, torsades de pointes, and sudden cardiac death. In a vulnerable population of critically ill patients after cardiac surgery, however, it is unclear whether haloperidol administration affects the QTc interval. Thus, the aim of this study is to explore the effect of haloperidol in low doses on this interval.

Method

This retrospective cohort study was performed on a cardio-surgical intensive care unit (ICU), screened 2,216 patients and eventually included 68 patients with delirium managed with oral and intravenous haloperidol. In this retrospective analysis, electrocardiograms were taken prior and within 24 h after haloperidol administration. The effect of haloperidol on QTc was determined with a Person correlation, and inter-group differences were measured with new long QT comparisons.

Results

In total, 68 patients were included, the median age was 71 (64–79) years and predominantly male (77%). Haloperidol administration followed ICU admission by three days and the cumulative dose was 4 (2–9) mg. As a result, haloperidol administration did not affect the QTc (r = 0.144, p = 0.23). In total, 31% (21/68 patients) had a long QT before and 27.9% (19/68 patients) after haloperidol administration. Only 12% (8/68 patients) developed a newly onset long QT. These patients were not different in the route of administration, cumulative haloperidol doses, comorbidities, laboratory findings, or medications.

Significance of results

These results indicated that low-dose intravenous haloperidol was safe and not clinically relevant for the development of a newly onset long QT syndrome or adverse outcomes and support recent findings inside and outside the ICU setting.

Keywords

Cardiac surgeryDeliriumHaloperidolICULong QTQTc time

Information

Type
Original Article
Information
Palliative & Supportive Care , Volume 18 , Special Issue 4: Palliative and Supportive Care During The COVID-19 Pandemic , August 2020 , pp. 447 - 459
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Copyright
Copyright © Cambridge University Press 2020

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Footnotes

*

These authors shared first authorship.

†

This article has been updated since its original publication. See https://doi.org/10.1017/S1478951521000559.

References

Al Qadheeb, NS, Skrobik, Y, Schumaker, G, et al. (2016) Preventing ICU subsyndromal delirium conversion to delirium with low-dose IV haloperidol: A double-blind, placebo-controlled pilot study. Critical Care Medicine 44, 583–591.CrossRefGoogle ScholarPubMed
American Psychiatric Association (1987) Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised. Washington, DC: American Psychiatric Association.Google Scholar
American Psychiatric Association (1999) Practice guideline for the treatment of patients with delirium. American Journal of Psychiatry 156, 1–20.Google Scholar
American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association.Google Scholar
Attin, M and Davidson, JE (2011) Using QRS morphology and QTc interval to prevent complications and cardiac death. Critical Care Nursing Quarterly 34, 246–253.CrossRefGoogle ScholarPubMed
Barbateskovic, M, Larsen, LK, Oxenboll-Collet, M, et al. (2016) Pharmacological interventions for delirium in intensive care patients: A protocol for an overview of reviews. Systematic Reviews 5, 211–391.CrossRefGoogle ScholarPubMed
Bergeron, N, Dubois, MJ, Dumont, M, et al. (2001) Intensive Care Delirium Screening Checklist: Evaluation of a new screening tool. Intensive Care Medicine 27, 859–864.CrossRefGoogle ScholarPubMed
Blom, MT, Jansen, S, de Jonghe, A, et al. (2015) In-hospital haloperidol use and perioperative changes in QTc-duration. Journal of Nutrition, Health and Aging 19, 583–589.CrossRefGoogle ScholarPubMed
Burry, L, Mehta, S, Perreault, MM, et al. (2018) Antipsychotics for treatment of delirium in hospitalised non-ICU patients. Cochrane Database of Systematic Reviews 6, CD005594. doi:10.1002/14651858.CD005594.pub3.Google ScholarPubMed
Chu, CC, Shieh, JP, Tzeng, JI, et al. (2008) The prophylactic effect of haloperidol plus dexamethasone on postoperative nausea and vomiting in patients undergoing laparoscopically assisted vaginal hysterectomy. Anesthesia and Analgesia 106, 1402–1406, table of contents.CrossRefGoogle ScholarPubMed
Crumb, WJ Jr., Ekins, S, Sarazan, RD, et al. (2006) Effects of antipsychotic drugs on I(to), I (Na), I (sus), I (K1), and hERG: QT prolongation, structure activity relationship, and network analysis. Pharmaceutical Research 23, 1133–1143.CrossRefGoogle ScholarPubMed
Czekalla, J, Beasley, CM Jr., Dellva, MA, et al. (2001) Analysis of the QTc interval during olanzapine treatment of patients with schizophrenia and related psychosis. Journal of Clinical Psychiatry 62, 191–198.CrossRefGoogle ScholarPubMed
Desai, M, Li, L, Desta, Z, et al. (2003a) Variability of heart rate correction methods for the QT interval. British Journal of Clinical Pharmacology 55, 511–517.CrossRefGoogle Scholar
Desai, M, Tanus-Santos, JE, Li, L, et al. (2003b) Pharmacokinetics and QT interval pharmacodynamics of oral haloperidol in poor and extensive metabolizers of CYP2D6. Pharmacogenomics Journal 3, 105–113.CrossRefGoogle Scholar
Devlin, JW, Fong, JJ, Schumaker, G, et al. (2007) Use of a validated delirium assessment tool improves the ability of physicians to identify delirium in medical intensive care unit patients. Critical Care Medicine 35, 2721–2724.CrossRefGoogle ScholarPubMed
Devlin, JW, Roberts, RJ, Fong, JJ, et al. (2010) Efficacy and safety of quetiapine in critically ill patients with delirium: A prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Critical Care Medicine 38, 419–427.CrossRefGoogle ScholarPubMed
Duprey, MS, Al Qadheeb, N, Roberts, R, et al. (2016) The use of low-dose IV haloperidol is not associated with QTc prolongation: Post hoc analysis of a randomized, placebo-controlled trial. Intensive Care Medicine 42, 1818–1819.CrossRefGoogle Scholar
Ely, EW, Margolin, R, Francis, J, et al. (2001) Evaluation of delirium in critically ill patients: Validation of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). Critical Care Medicine 29, 1370–1379.CrossRefGoogle Scholar
Gaffigan, ME, Bruner, DI, Wason, C, et al. (2015) A randomized controlled trial of intravenous haloperidol vs. intravenous metoclopramide for acute migraine therapy in the emergency department. Journal of Emergency Medicine 49, 326–334.CrossRefGoogle ScholarPubMed
Garcia, E, Robert, M, Peris, F, et al. (2009) The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia: A randomized, double-blind, placebo-controlled, multicentre study. CNS Drugs 23, 615–625.CrossRefGoogle ScholarPubMed
Girard, TD, Exline, MC, Carson, SS, et al. (2018) Haloperidol and ziprasidone for treatment of delirium in critical illness. New England Journal of Medicine 379, 2506–2516.CrossRefGoogle ScholarPubMed
Grecu, L, Bittner, EA, Kher, J, et al. (2008) Haloperidol plus ondansetron versus ondansetron alone for prophylaxis of postoperative nausea and vomiting. Anesthesia and Analgesia 106, 1410–1413, table of contents.CrossRefGoogle ScholarPubMed
Harrigan, EP, Miceli, JJ, Anziano, R, et al. (2004) A randomized evaluation of the effects of six antipsychotic agents on QTc, in the absence and presence of metabolic inhibition. Journal of Clinical Psychopharmacology 24, 62–69.CrossRefGoogle ScholarPubMed
Harvey, AT, Flockhart, D, Gorski, JC, et al. (2004) Intramuscular haloperidol or lorazepam and QT intervals in schizophrenia. Journal of Clinical Pharmacology 44, 1173–1184.CrossRefGoogle ScholarPubMed
Hauffe, T, Kruger, B, Bettex, D, et al. (2015) Shock management for cardio-surgical ICU patients — The golden hours. Cardiac Failure Review 1, 75–82.CrossRefGoogle Scholar
Hauffe, T, Kruger, B, Bettex, D, et al. (2016) Shock management for cardio-surgical intensive care unit patient: The silver days. Cardiac Failure Review 2, 56–62.CrossRefGoogle ScholarPubMed
Henderson, RA, Lane, S and Henry, JA (1991) Life-threatening ventricular arrhythmia (torsades de pointes) after haloperidol overdose. Human & Experimental Toxicology 10, 59–62.CrossRefGoogle ScholarPubMed
Inouye, SK, van Dyck, CH, Alessi, CA, et al. (1990) Clarifying confusion: The confusion assessment method. A new method for detection of delirium. Annals of Internal Medicine 113, 941–948.CrossRefGoogle Scholar
Kane, JM, Carson, WH, Saha, AR, et al. (2002) Efficacy and safety of aripiprazole and haloperidol versus placebo in patients with schizophrenia and schizoaffective disorder. Journal of Clinical Psychiatry 63, 763–771.CrossRefGoogle ScholarPubMed
Kane, JM, Potkin, SG, Daniel, DG, et al. (2011) A double-blind, randomized study comparing the efficacy and safety of sertindole and risperidone in patients with treatment-resistant schizophrenia. Journal of Clinical Psychiatry 72, 194–204.CrossRefGoogle ScholarPubMed
Kishi, T, Hirota, T, Matsunaga, S, et al. (2016) Antipsychotic medications for the treatment of delirium: A systematic review and meta-analysis of randomised controlled trials. Journal of Neurology, Neurosurgery, and Psychiatry 87, 767–774.CrossRefGoogle ScholarPubMed
Kornick, CA, Kilborn, MJ, Santiago-Palma, J, et al. (2003) QTc interval prolongation associated with intravenous methadone. Pain 105, 499–506.CrossRefGoogle ScholarPubMed
Lee, Y, Wang, PK, Lai, HY, et al. (2007) Haloperidol is as effective as ondansetron for preventing postoperative nausea and vomiting. Canadian Journal of Anaesthesia 54, 349–354.CrossRefGoogle ScholarPubMed
Le Gall, JR, Lemeshow, S and Saulnier, F (1993) A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA 270, 2957–2963.CrossRefGoogle ScholarPubMed
Lin, CH, Kuo, CC, Chou, LS, et al. (2010) A randomized, double-blind comparison of risperidone versus low-dose risperidone plus low-dose haloperidol in treating schizophrenia. Journal of Clinical Psychopharmacology 30, 518–525.CrossRefGoogle ScholarPubMed
Lindborg, SR, Beasley, CM, Alaka, K, et al. (2003) Effects of intramuscular olanzapine vs. haloperidol and placebo on QTc intervals in acutely agitated patients. Psychiatry Research 119, 113–123.CrossRefGoogle ScholarPubMed
McNicoll, L, Pisani, MA, Ely, EW, et al. (2005) Detection of delirium in the intensive care unit: Comparison of confusion assessment method for the intensive care unit with confusion assessment method ratings. Journal of the American Geriatrics Society 53, 495–500.CrossRefGoogle ScholarPubMed
Metzger, E and Friedman, R (1993) Prolongation of the corrected QT and torsades de pointes cardiac arrhythmia associated with intravenous haloperidol in the medically ill. Journal of Clinical Psychopharmacology 13, 128–132.CrossRefGoogle ScholarPubMed
Meyer-Massetti, C, Cheng, CM, Sharpe, BA, et al. (2010) The FDA extended warning for intravenous haloperidol and torsades de pointes: how should institutions respond? Journal of Hospital Medicine 5, E8–16.CrossRefGoogle ScholarPubMed
Miceli, JJ, Tensfeldt, TG, Shiovitz, T, et al. (2010) Effects of high-dose ziprasidone and haloperidol on the QTc interval after intramuscular administration: A randomized, single-blind, parallel-group study in patients with schizophrenia or schizoaffective disorder. Clinical Therapeutics 32, 472–491.CrossRefGoogle ScholarPubMed
Nasrallah, HA and Chen, AT (2017) Multiple neurotoxic effects of haloperidol resulting in neuronal death. Annals of Clinical Psychiatry 29, 195–202.Google ScholarPubMed
Neufeld, KJ, Yue, J, Robinson, TN, et al. (2016) Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: A systematic review and meta-analysis. Journal of the American Geriatrics Society 64, 705–714.CrossRefGoogle ScholarPubMed
Nikooie, R, Neufeld, KJ, Oh, ES, et al. (2019) Antipsychotics for treating delirium in hospitalized adults: A systematic review. Annals of Internal Medicine 171, 485–494.CrossRefGoogle ScholarPubMed
Page, VJ, Ely, EW, Gates, S, et al. (2013) Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): A randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine 1, 515–523.CrossRefGoogle ScholarPubMed
Park, JY, Shon, JH, Kim, KA, et al. (2006) Combined effects of itraconazole and CYP2D6*10 genetic polymorphism on the pharmacokinetics and pharmacodynamics of haloperidol in healthy subjects. Journal of Clinical Psychopharmacology 26, 135–142.CrossRefGoogle ScholarPubMed
Rautaharju, PM, Surawicz, B, Gettes, LS, et al. (2009) AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: Part IV: The ST segment, T and U waves, and the QT interval: A scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology. Journal of American College of Cardiology 53, 982–991.CrossRefGoogle Scholar
Reade, MC, O'Sullivan, K, Bates, S, et al. (2009) Dexmedetomidine vs. haloperidol in delirious, agitated, intubated patients: A randomised open-label trial. Critical Care 13, R75.CrossRefGoogle ScholarPubMed
Riviere, J, van der Mast, RC, Vandenberghe, J, et al. (2019) Efficacy and tolerability of atypical antipsychotics in the treatment of delirium: A systematic review of the literature. Psychosomatics 60, 18–26.CrossRefGoogle ScholarPubMed
Royal College of Physicians (UK) (2010) National Institute for Health and Clinical Excellence: Guidance. Delirium: Diagnosis, Prevention and Management.Google Scholar
Rudiger, A, Begdeda, H, Babic, D, et al. (2016) Intra-operative events during cardiac surgery are risk factors for the development of delirium in the ICU. Critical Care 20, 264. doi:10.1186/s13054-016-1445-8.CrossRefGoogle ScholarPubMed
Schubert, M, Schurch, R, Boettger, S, et al. (2018) A hospital-wide evaluation of delirium prevalence and outcomes in acute care patients — A cohort study. BMC Health Services Research 18, 550.CrossRefGoogle ScholarPubMed
Spellmann, I, Reinhard, MA, Veverka, D, et al. (2018) QTc prolongation in short-term treatment of schizophrenia patients: Effects of different antipsychotics and genetic factors. European Archives of Psychiatry and Clinical Neuroscience 268, 383–390.CrossRefGoogle ScholarPubMed
Su, KP, Shen, WW, Chuang, CL, et al. (2003) A pilot cross-over design study on QTc interval prolongation associated with sulpiride and haloperidol. Schizophrenia Research 59, 93–94.CrossRefGoogle Scholar
van den Boogaard, M, Schoonhoven, L, van Achterberg, T, et al. (2013) Haloperidol prophylaxis in critically ill patients with a high risk for delirium. Critical Care 17, R9.CrossRefGoogle ScholarPubMed
van den Boogaard, M, Slooter, AJC, Bruggemann, RJM, et al. (2018) Effect of haloperidol on survival among critically Ill adults with a high risk of delirium: The REDUCE randomized clinical trial. JAMA 319, 680–690.CrossRefGoogle ScholarPubMed
von Elm, E, Altman, DG, Egger, M, et al. (2014) The strengthening the reporting of observational studies in epidemiology (STROBE) statement: Guidelines for reporting observational studies. International Journal of Surgery 12, 1495–1499.CrossRefGoogle ScholarPubMed
Wang, PK, Tsay, PJ, Huang, CC, et al. (2012) Comparison of dexamethasone with ondansetron or haloperidol for prevention of patient-controlled analgesia-related postoperative nausea and vomiting: A randomized clinical trial. World Journal of Surgery 36, 775–781.CrossRefGoogle ScholarPubMed
Wu, YC, Tseng, PT, Tu, YK, et al. (2019) Association of delirium response and safety of pharmacological interventions for the management and prevention of delirium: A network meta-analysis. JAMA Psychiatry 76, 526–535.CrossRefGoogle ScholarPubMed