Efficacy of halopeRIdol to decrease the burden of Delirium In adult Critically ill patiEnts (EuRIDICE): study protocol for a prospective randomised multi-centre double-blind placebo-controlled clinical trial in the Netherlands

Lisa Smit, Zoran Trogrlić, John W Devlin, Robert-Jan Osse, Huibert H Ponssen, Arjen J C Slooter, Nicole G M Hunfeld, Wim J R Rietdijk, Diederik Gommers, Mathieu van der Jagt, EuRIDICE study group, M van den Boogaard, A J B W Brouwers, J A Lens, B J M van der Meer, H Ponssen, F J Schoonderbeek, K S Simons, E Berger, A Bouman, M Campo, D van Duijn, H Embden-van Donk, D van de Graaf, E Hoogendoorn, P Ormskerk, N Roovers, E Toscano, A Vileito, T van Zuylen, M van den Boogaard, A J B W Brouwers, J A Lens, B J M van der Meer, H Ponssen, F J Schoonderbeek, K S Simons, E Berger, A Bouman, M Campo, D van Duijn, H Embden-van Donk, D van de Graaf, E Hoogendoorn, P Ormskerk, N Roovers, E Toscano, A Vileito, T van Zuylen, C Exler, E van den Berg, J van Meeteren, M Koopmanschap, I Nutma, E Kuijper, Lisa Smit, Zoran Trogrlić, John W Devlin, Robert-Jan Osse, Huibert H Ponssen, Arjen J C Slooter, Nicole G M Hunfeld, Wim J R Rietdijk, Diederik Gommers, Mathieu van der Jagt, EuRIDICE study group, M van den Boogaard, A J B W Brouwers, J A Lens, B J M van der Meer, H Ponssen, F J Schoonderbeek, K S Simons, E Berger, A Bouman, M Campo, D van Duijn, H Embden-van Donk, D van de Graaf, E Hoogendoorn, P Ormskerk, N Roovers, E Toscano, A Vileito, T van Zuylen, M van den Boogaard, A J B W Brouwers, J A Lens, B J M van der Meer, H Ponssen, F J Schoonderbeek, K S Simons, E Berger, A Bouman, M Campo, D van Duijn, H Embden-van Donk, D van de Graaf, E Hoogendoorn, P Ormskerk, N Roovers, E Toscano, A Vileito, T van Zuylen, C Exler, E van den Berg, J van Meeteren, M Koopmanschap, I Nutma, E Kuijper

Abstract

Introduction: Delirium in critically ill adults is associated with prolonged hospital stay, increased mortality and greater cognitive and functional decline. Current practice guideline recommendations advocate the use of non-pharmacological strategies to reduce delirium. The routine use of scheduled haloperidol to treat delirium is not recommended given a lack of evidence regarding its ability to resolve delirium nor improve relevant short-term and longer-term outcomes. This study aims to evaluate the efficacy and safety of haloperidol for the treatment of delirium in adult critically ill patients to reduce days spent with coma or delirium.

Methods and analysis: EuRIDICE is a prospective, multi-centre, randomised, double-blind, placebo-controlled trial. Study population consists of adult intensive care unit (ICU) patients without acute neurological injury who have delirium based on a positive Intensive Care Delirium Screening Checklist (ICDSC) or Confusion Assessment Method for the ICU (CAM-ICU) assessment. Intervention is intravenous haloperidol 2.5 mg (or matching placebo) every 8 hours, titrated daily based on ICDSC or CAM-ICU positivity to a maximum of 5 mg every 8 hours, until delirium resolution or ICU discharge. Main study endpoint is delirium and coma-free days (DCFD) up to 14 days after randomisation. Secondary endpoints include (1) 28-day and 1-year mortality, (2) cognitive and functional performance at 3 and 12 months, (3) patient and family delirium and ICU experience, (4) psychological sequelae during and after ICU stay, (4) safety concerns associated with haloperidol use and (5) cost-effectiveness. Differences in DCFDs between haloperidol and placebo group will be analysed using Poisson regression analysis. Study recruitment started in February 2018 and continues.

Ethics and dissemination: The study has been approved by the Medical Ethics Committee of the Erasmus University Medical Centre Rotterdam (MEC2017-511) and by the Institutional Review Boards of the participating sites. Its results will be disseminated via peer-reviewed publication and conference presentations.

Trial registration: NCT03628391.

Keywords: adult intensive & critical care; adult neurology; delirium & cognitive disorders; intensive & critical care; mental health; therapeutics.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

References

    1. Salluh JI, Soares M, Teles JM, et al. . Delirium epidemiology in critical care (DECCA): an international study. Crit Care 2010;14:R210. 10.1186/cc9333
    1. Ely EW, Shintani A, Truman B, et al. . Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA 2004;291:1753–62. 10.1001/jama.291.14.1753
    1. Pandharipande PP, Girard TD, Ely EW. Long-term cognitive impairment after critical illness. N Engl J Med 2014;370:212–3. 10.1097/SA.0000000000000071
    1. Milbrandt EB, Deppen S, Harrison PL, et al. . Costs associated with delirium in mechanically ventilated patients. Crit Care Med 2004;32:955–62. 10.1097/01.CCM.0000119429.16055.92
    1. Reade MC, Eastwood GM, Bellomo R, et al. . Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA 2016;315:1460–8. 10.1001/jama.2016.2707
    1. Devlin JW, Skrobik Y, Gélinas C, et al. . Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med 2018;46:e825–73. 10.1097/CCM.0000000000003299
    1. Page VJ, Ely EW, Gates S, et al. . Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med 2013;1:515–23. 10.1016/S2213-2600(13)70166-8
    1. Girard TD, Pandharipande PP, Carson SS, et al. . Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med 2010;38:428–37. 10.1097/CCM.0b013e3181c58715
    1. Barnes-Daly MA, Phillips G, Ely EW. Improving hospital survival and reducing brain dysfunction at seven California community hospitals: implementing PAD guidelines via the ABCDEF bundle in 6,064 patients. Crit Care Med 2017;45:171–8. 10.1097/CCM.0000000000002149
    1. Al-Qadheeb NS, Balk EM, Fraser GL, et al. . Randomized ICU trials do not demonstrate an association between interventions that reduce delirium duration and short-term mortality: a systematic review and meta-analysis. Crit Care Med 2014;42:1442–54. 10.1097/CCM.0000000000000224
    1. Collet MO, Caballero J, Sonneville R, et al. . Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients: the multinational AID-ICU inception cohort study. Intensive Care Med 2018;44:1081–9. 10.1007/s00134-018-5204-y
    1. Jorm AF, Jacomb PA. The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE): socio-demographic correlates, reliability, validity and some norms. Psychol Med 1989;19:1015–22. 10.1017/S0033291700005742
    1. Hodgson C, Needham D, Haines K, et al. . Feasibility and inter-rater reliability of the ICU Mobility Scale. Heart Lung 2014;43:19–24. 10.1016/j.hrtlng.2013.11.003
    1. Richards KC, O'Sullivan PS, Phillips RL. Measurement of sleep in critically ill patients. J Nurs Meas 2000;8:131–44. 10.1891/1061-3749.8.2.131
    1. Simpson GM, Angus JW. A rating scale for extrapyramidal side effects. Acta Psychiatr Scand Suppl 1970;212:11–19. 10.1111/j.1600-0447.1970.tb02066.x
    1. Jones C, Griffiths RD, Humphris G, et al. . Memory, delusions, and the development of acute posttraumatic stress disorder-related symptoms after intensive care. Crit Care Med 2001;29:573–80. 10.1097/00003246-200103000-00019
    1. Breitbart W, Gibson C, Tremblay A. The delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouses/caregivers, and their nurses. Psychosomatics 2002;43:183–94. 10.1176/appi.psy.43.3.183
    1. Nasreddine ZS, Phillips NA, Bédirian V, et al. . The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695–9. 10.1111/j.1532-5415.2005.53221.x
    1. Bean J. Rey Auditory Verbal Learning Test, Rey AVLT : Kreutzer JS, DeLuca J, Caplan B, Encyclopedia of clinical neuropsychology. New York, NY: Springer New York, 2011: 2174–5.
    1. Ledoux K, Vannorsdall TD, Pickett EJ, et al. . Capturing additional information about the organization of entries in the lexicon from verbal fluency productions. J Clin Exp Neuropsychol 2014;36:205–20. 10.1080/13803395.2013.878689
    1. Wechsler D. Wechsler Adult Intelligence Scale–Fourth Edition (WAIS-IV). 22 San Antonio, TX: NCS Pearson, 2008: 498.
    1. Reitan RM, Wolfson D. The Halstead–Reitan neuropsychological test battery for adults—theoretical, methodological, and validational bases. Neuropsychological assessment of neuropsychiatric and neuromedical disorders 2009;1:3–24.
    1. Roth C. Boston Naming Test : Kreutzer JS, DeLuca J, Caplan B, Encyclopedia of clinical neuropsychology. New York, NY: Springer New York, NY, 2011: 430–3.
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70. 10.1111/j.1600-0447.1983.tb09716.x
    1. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473–83.
    1. Robinson BC. Validation of a caregiver strain index. J Gerontol 1983;38:344–8. 10.1093/geronj/38.3.344
    1. Weiss DS, Marmar CR, Wilson JP, et al. . Assessing psychological trauma and PTSD. The Impact of Events Scale 1997;19:399–411.
    1. Girard TD, Exline MC, Carson SS, et al. . Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med 2018;379:2506–16. 10.1056/NEJMoa1808217
    1. Nederlandse Vereniging voor Psychiatrie Richtlijn delirium. Amsterdam: Dries van Ingen, Uitgeverij Boom, 2004: 1–127.
    1. Barnes TRE. The Barnes Akathisia Rating Scale-revisited. J Psychopharmacol 2003;17:365–70. 10.1177/0269881103174013
    1. Fongemie JM, Al-Qadheeb NS, Estes NAM, et al. . Agreement between ICU clinicians and electrophysiology cardiologists on the decision to initiate a QTc-interval prolonging medication in critically ill patients with potential risk factors for torsade de pointes: a comparative, case-based evaluation. Pharmacotherapy 2013;33:589–97. 10.1002/phar.1242
    1. Tisdale JE, Jaynes HA, Kingery JR, et al. . Effectiveness of a clinical decision support system for reducing the risk of QT interval prolongation in hospitalized patients. Circ Cardiovasc Qual Outcomes 2014;7:381–90. 10.1161/CIRCOUTCOMES.113.000651
    1. Trogrlić Z, van der Jagt M, Lingsma H, et al. . Improved guideline adherence and reduced brain dysfunction after a multicenter multifaceted implementation of ICU delirium guidelines in 3,930 patients. Crit Care Med 2019;47:419–27. 10.1097/CCM.0000000000003596
    1. Barr J, Fraser GL, Puntillo K, et al. . 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. 10.1097/CCM.0b013e3182783b72
    1. van den Boogaard M, Slooter AJC, Brüggemann RJM, et al. . Effect of haloperidol on survival among critically ill adults with a high risk of delirium: the REDUCE randomized clinical trial. JAMA 2018;319:680–90. 10.1001/jama.2018.0160

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit