Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2013

Open Access 01-12-2013 | Study protocol

Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial

Authors: Mark van den Boogaard, Arjen J Slooter, Roger JM Brüggemann, Lisette Schoonhoven, Michael A Kuiper, Peter HJ van der Voort, Marga E Hoogendoorn, Albert Beishuizen, Jeroen A Schouten, Peter E Spronk, Saskia Houterman, Johannes G van der Hoeven, Peter Pickkers

Published in: Trials | Issue 1/2013

Login to get access

Abstract

Background

Delirium is a frequent disorder in intensive care unit (ICU) patients with serious consequences. Therefore, preventive treatment for delirium may be beneficial. Worldwide, haloperidol is the first choice for pharmacological treatment of delirious patients. In daily clinical practice, a lower dose is sometimes used as prophylaxis. Some studies have shown the beneficial effects of prophylactic haloperidol on delirium incidence as well as on mortality, but evidence for effectiveness in ICU patients is limited. The primary objective of our study is to determine the effect of haloperidol prophylaxis on 28-day survival. Secondary objectives include the incidence of delirium and delirium-related outcome and the side effects of haloperidol prophylaxis.

Methods

This will be a multicenter three-armed randomized, double-blind, placebo-controlled, prophylactic intervention study in critically ill patients. We will include consecutive non-neurological ICU patients, aged ≥18 years with an expected ICU length of stay >1 day. To be able to demonstrate a 15% increase in 28-day survival time with a power of 80% and alpha of 0.05 in both intervention groups, a total of 2,145 patients will be randomized; 715 in each group. The anticipated mortality rate in the placebo group is 12%. The intervention groups will receive prophylactic treatment with intravenous haloperidol 1 mg/q8h or 2 mg/q8h, and patients in the control group will receive placebo (sodium chloride 0.9%), both for a maximum period of 28-days. In patients who develop delirium, study medication will be stopped and patients will subsequently receive open label treatment with a higher (therapeutic) dose of haloperidol. We will use descriptive summary statistics as well as Cox proportional hazard regression analyses, adjusted for covariates.

Discussion

This will be the first large-scale multicenter randomized controlled prevention study with haloperidol in ICU patients with a high risk of delirium, adequately powered to demonstrate an effect on 28-day survival.

Trial registration

Clinicaltrials.gov: NCT01785290.
EudraCT number: 2012-004012-66.
Appendix
Available only for authorised users
Literature
1.
Association AP: Diagnostic and statistical manual of mental disorders (DSM-V). 2013, Arlington, VA: American Psychiatric Publishing
2.
Dubois MJ, Bergeron N, Dumont M, Dial S, Skrobik Y: Delirium in an intensive care unit: a study of risk factors. Intensive Care Med. 2001, 27: 1297-1304. 10.1007/s001340101017.CrossRefPubMed
3.
American college of chest physicians/society of critical care medicine consensus conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992, 20: 864-874. 10.1097/00003246-199206000-00025.
4.
Ely EW, Gautam S, Margolin R, Francis J, May L, Speroff T, Truman B, Dittus R, Bernard R, Inouye SK: The impact of delirium in the intensive care unit on hospital length of stay. Intensive Care Med. 2001, 27: 1892-1900. 10.1007/s00134-001-1132-2.CrossRefPubMed
5.
Ouimet S, Kavanagh BP, Gottfried SB, Skrobik Y: Incidence, risk factors and consequences of ICU delirium. Intensive Care Med. 2007, 33: 66-73. 10.1007/s00134-006-0399-8.CrossRefPubMed
6.
van den Boogaard M, Schoonhoven L, van der Hoeven JG, van Achterberg T, Pickkers P: Incidence and short-term consequences of delirium in critically ill patients: a prospective observational cohort study. Int J Nurs Stud. 2012, 49: 775-783. 10.1016/j.ijnurstu.2011.11.016.CrossRefPubMed
7.
van den Boogaard M, Peters SA, van der Hoeven JG, Dagnelie PC, Leffers P, Pickkers P, Schoonhoven L: The impact of delirium on the prediction of in-hospital mortality in intensive care patients. Crit Care. 2010, 14: R146-10.1186/cc9214.CrossRefPubMedPubMedCentral
8.
Ely EW, Shintani A, Truman B, Speroff T, Gordon SM, Harrell FE, Inouye SK, Bernard GR, Dittus R: Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. J Amer Med Assoc. 2004, 292: 168-169.
9.
van den Boogaard M, Schoonhoven L, Evers AW, van der Hoeven JG, van Achterberg T, Pickkers P: Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. Crit Care Med. 2012, 40: 112-118. 10.1097/CCM.0b013e31822e9fc9.CrossRefPubMed
10.
Girard TD, Jackson JC, Pandharipande PP, Pun BT, Thompson JL, Shintani AK, Gordon SM, Canonico AE, Dittus RS, Bernard GR, Ely EW: Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med. 2010, 38: 1513-1520. 10.1097/CCM.0b013e3181e47be1.CrossRefPubMedPubMedCentral
11.
Kalisvaart KJ, de Jonghe JF, Bogaards MJ, Vreeswijk R, Egberts TC, Burger BJ, Eikelenboom P, van Gool WA: Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study. J Am Geriatr Soc. 2005, 53: 1658-1666. 10.1111/j.1532-5415.2005.53503.x.CrossRefPubMed
12.
Kaneko T, Cai J, Ishikura T, Kobayashi M, Naka T, Kaibara N: Prophylactic consecutive administration of haloperidol can reduce the occurrence of postoperative delirium in gastrointestinal surgery. Yonago Acta Med. 1999, 42: 179-184.
13.
Prakanrattana U, Prapaitrakool S: Efficacy of risperidone for prevention of postoperative delirium in cardiac surgery. Anaesth Intensive Care. 2007, 35: 714-719.PubMed
14.
Gamberini M, Bolliger D, Lurati Buse GA, Burkhart CS, Grapow M, Gagneux A, Filipovic M, Seeberger MD, Pargger H, Siegemund M, Carrel T, Seiler WO, Berres M, Strebel SP, Monsch AU, Steiner LA: Rivastigmine for the prevention of postoperative delirium in elderly patients undergoing elective cardiac surgery–a randomized controlled trial. Crit Care Med. 2009, 37: 1762-1768. 10.1097/CCM.0b013e31819da780.CrossRefPubMed
15.
Girard TD, Pandharipande PP, Carson SS, Schmidt GA, Wright PE, Canonico AE, Pun BT, Thompson JL, Shintani AK, Meltzer HY, Bernard GR, Dittus RS, Ely EW, MIND Trial Investigators: Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med. 2010, 38: 428-437. 10.1097/CCM.0b013e3181c58715.CrossRefPubMedPubMedCentral
16.
Milbrandt EB, Kersten A, Kong L, Weissfeld LA, Clermont G, Fink MP, Angus DC: Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients. Crit Care Med. 2005, 33: 226-229. 10.1097/01.CCM.0000150743.16005.9A.CrossRefPubMed
17.
Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, Chen KS, Gu XE, Zhu SN: Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial. Crit Care Med. 2012, 40: 1-9.
18.
van den Boogaard M, Pickkers P, Slooter AJ, Kuiper MA, Spronk PE, van dV, van der Hoeven JG, Donders R, van AT, Schoonhoven L: Development and validation of PRE-DELIRIC (PREdiction of DELIRium in ICu patients) delirium prediction model for intensive care patients: observational multicentre study. BMJ. 2012, 344: e420-e420. 10.1136/bmj.e420.CrossRefPubMedPubMedCentral
19.
van den Boogaard M, Schoonhoven L, Van Achterberg T, Van der Hoeven JG, Pickkers P: Haloperidol prophylaxis in critically ill patients with a high risk for delirium. Crit Care. 2013, 17: R9-10.1186/cc11933.CrossRefPubMedPubMedCentral
20.
de Smet AM, Kluytmans JA, Cooper BS, Mascini EM, Benus RF, van der Werf TS, van der Hoeven JG, Pickkers P, Bogaers-Hofman D, van der Meer NJ, Bernards AT, Kuijper EJ, Joore JC, Leverstein-van Hall MA, Bindels AJ, Jansz AR, Wesselink RM, de Jongh BM, Dennesen PJ, van Asselt GJ, te Velde LF, Frenay IH, Kaasjager K, Bosch FH, van Iterson M, Thijsen SF, Kluge GH, Pauw W, de Vries JW, Kaan JA: Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009, 360: 20-31. 10.1056/NEJMoa0800394.CrossRefPubMed
21.
Heyland DK, Dhaliwal R, Jiang X, Day AG: Identifying critically ill patients who benefit the most from nutrition therapy: the development and initial validation of a novel risk assessment tool. Crit Care. 2011, 15: R268-10.1186/cc10546.CrossRefPubMedPubMedCentral
22.
Ginwalla M, Biblo LA, Paydak H: Torsade de pointes following intravenous haloperidol administration in a patient with complete heart block. WMJ. 2009, 108: 48-50.PubMed
23.
O’Brien JM, Rockwood RP, Suh KI: Haloperidol-induced torsade de pointes. Ann Pharmacother. 1999, 33: 1046-1050. 10.1345/aph.19017.CrossRefPubMed
24.
Perrault LP, Denault AY, Carrier M, Cartier R, Belisle S: Torsades de Pointes secondary to intravenous haloperidol after coronary bypass grafting surgery. Can J Anaesth. 2000, 47: 251-254. 10.1007/BF03018922.CrossRefPubMed
25.
Sharma ND, Rosman HS, Padhi ID, Tisdale JE: Torsades de Pointes associated with intravenous haloperidol in critically ill patients. Am J Cardiol. 1998, 81: 238-240. 10.1016/S0002-9149(97)00888-6.CrossRefPubMed
26.
Moher D, Schulz KF, Altman DG: Consort: the CONSORT statement: revised recommendations for improving the quality of reports of parallel group randomized trials. BMC Med Res Methodol. 2001, 1: 2-10.1186/1471-2288-1-2.CrossRefPubMedPubMedCentral
27.
Ely EW, Inouye SK, Bernard GR, Gordon S, Francis J, May L, Truman B, Speroff T, Gautam S, Margolin R, Hart RP, Dittus R: Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001, 286: 2703-2710. 10.1001/jama.286.21.2703.CrossRefPubMed
28.
Ely EW, Margolin R, Francis J, May L, Truman B, Dittus R, Speroff T, Gautam S, Bernard GR, Inouye SK: Evaluation of delirium in critically ill patients: validation of the confusion assessment method for the intensive care unit (CAM-ICU). Crit Care Med. 2001, 29: 1370-1379. 10.1097/00003246-200107000-00012.CrossRefPubMed
29.
Vreeswijk R, Toornvliet A, Honing MLH, Bakker K, de Man T, Daas G, Spronk P, de Jonghe JF, Kalisvaart KJ: Validation of the Dutch version of the confusion assessment method (CAM-ICU) for delirium screening in the intensive care unit. Netherlands Journal of Critical Care. 2009, 13: 73-78.
30.
Schuurmans MJ, Shortridge-Baggett LM, Duursma SA: The delirium observation screening scale: a screening instrument for delirium. Res Theory Nurs Pract. 2003, 17: 31-50. 10.1891/rtnp.17.1.31.53169.CrossRefPubMed
31.
Abdo WF, van de Warrenburg BP, Burn DJ, Quinn NP, Bloem BR: The clinical approach to movement disorders. Nat Rev Neurol. 2010, 6: 29-37. 10.1038/nrneurol.2009.196.CrossRefPubMed
32.
Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R, American College of Critical Care Medicine: Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013, 41: 263-306.CrossRefPubMed
33.
Schweickert WD, Pohlman MC, Pohlman AS, Nigos C, Pawlik AJ, Esbrook CL, Spears L, Miller M, Franczyk M, Deprizio D, Schmidt GA, Bowman A, Barr R, McCallister KE, Hall JB, Kress JP: Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009, 373: 1874-1882. 10.1016/S0140-6736(09)60658-9.CrossRefPubMed
34.
Kompas F: Farmacotherapeutisch Kompas 2012. 2012, Amstelveen: Prelum Uitgevers
35.
Gandek B, Ware JE, Aaronson NK, Apolone G, Bjorner JB, Brazier JE, Bullinger M, Kaasa S, Leplege A, Prieto L, Sullivan M: Cross-validation of item selection and scoring for the SF-12 health survey in nine countries: results from the IQOLA project. International Quality of Life Assessment. J Clin Epidemiol. 1998, 51: 1171-1178. 10.1016/S0895-4356(98)00109-7.CrossRefPubMed
36.
O’Brien PC, Fleming TR: A multiple testing procedure for clinical trials. Biometrics. 1979, 35: 549-556. 10.2307/2530245.CrossRefPubMed
37.
Heymann A, Radtke F, Schiemann A, Lutz A, MacGuill M, Wernecke KD, Spies C: Delayed treatment of delirium increases mortality rate in intensive care unit patients. J Int Med Res. 2010, 38: 1584-1595. 10.1177/147323001003800503.CrossRefPubMed
Metadata
Title
Prevention of ICU delirium and delirium-related outcome with haloperidol: a study protocol for a multicenter randomized controlled trial
Authors
Mark van den Boogaard
Arjen J Slooter
Roger JM Brüggemann
Lisette Schoonhoven
Michael A Kuiper
Peter HJ van der Voort
Marga E Hoogendoorn
Albert Beishuizen
Jeroen A Schouten
Peter E Spronk
Saskia Houterman
Johannes G van der Hoeven
Peter Pickkers
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Trials / Issue 1/2013
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-14-400

Other articles of this Issue 1/2013

Trials 1/2013 Go to the issue

Study protocol

The Good Schools Toolkit to prevent violence against children in Ugandan primary schools: study protocol for a cluster randomised controlled trial

Research

Homeopathic drug proving of Okoubaka aubrevillei: a randomised placebo-controlled trial

Review

Active ingredients are reported more often for pharmacologic than non-pharmacologic interventions: an illustrative review of reporting practices in titles and abstracts

Study protocol

PARot – assessing platelet-rich plasma plus arthroscopic subacromial decompression in the treatment of rotator cuff tendinopathy: study protocol for a randomized controlled trial

Study protocol

The effect of Baduanjin exercise for physical and psychological wellbeing of college students: study protocol for a randomized controlled trial

Study protocol

Comparing the effects of individualized, standard, sham and no acupuncture in the treatment of knee osteoarthritis: a multicenter randomized controlled trial