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

Smit, Lisa; Trogrlić, Zoran; Devlin, John W.; Osse, Robert-Jan; Ponssen, H. H.; Slooter, Arjen J. C.; Hunfeld, Nicole; Rietdijk, Wim; Gommers, Diederik; Jagt, Mathieu van der

doi:10.1136/bmjopen-2019-036735

Cited by 11 publications

(27 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We conducted a multi-center randomized, double-blind, placebo-controlled clinical trial in adults with delirium at eight ICUs in the Netherlands. The study protocol was approved by the Medical Ethics Committees of all participating hospitals and has been published [ 11 ]. An independent data and safety monitoring board (DSMB) provided oversight of the trial.…”

Section: Methodsmentioning

confidence: 99%

“…All adult (≥ 18 years) ICU patients were eligible unless they met one or more exclusion criteria: admission to the ICU because of a primary acute neurological condition; pregnancy or breast-feeding; known allergy to haloperidol; history of ventricular arrhythmia (including torsade de pointes); neuroleptic malignant syndrome; parkinsonism; schizophrenia or other psychotic disorder; dementia or an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) score ≥ 4[ 12 ]; expected duration of ICU admission < 24 h; inability to speak the Dutch language or to undergo a valid delirium assessment (e.g., deafness or blindness); or participation in another interventional trial [ 11 ]. Eligible patients or their legal representatives were asked for written informed consent as soon as possible after ICU admission to enable randomization as soon as possible after delirium was first diagnosed.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial

Smit,

Slooter,

Devlin

et al. 2023

Crit Care

Self Cite

View full text Add to dashboard Cite

Background The role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae. Methods This multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization. Results The trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients [mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%]. Haloperidol did not increase DCFDs (adjusted RR 0.98 [95% CI 0.73–1.31], p = 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 [95% CI 0.18–0.89], p = 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol [OR 0.43 (95% CI 0.12–1.56)] and other antipsychotics [OR 0.63 (95% CI 0.29–1.32)], self-extubation or invasive device removal [OR 0.70 (95% CI 0.22–2.18)]) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study. Conclusions Haloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation. Trial registration: ClinicalTrials.gov (#NCT03628391), October 9, 2017.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial

Smit,

Slooter,

Devlin

et al. 2023

Crit Care

Self Cite

View full text Add to dashboard Cite

show abstract

“…Pharmacologic treatment of ICU delirium with antipsychotics lacks effectiveness in resolving ICU delirium promptly [149,150,151 ▪▪ ,152 ▪ ]. One large RCT suggested haloperidol may reduce mortality in delirious patients [153 ▪ ,154 ▪▪ ], though other trials found no effect on delirium or mortality, and antipsychotics for symptoms management remains inconclusive.…”

Section: Deliriummentioning

confidence: 99%

Acute encephalopathy in the ICU: a practical approach

Kurtz,

van den Boogaard,

Girard

et al. 2024

Current Opinion in Critical Care

View full text Add to dashboard Cite

Purpose of review Acute encephalopathy (AE) – which frequently develops in critically ill patients with and without primary brain injury – is defined as an acute process that evolves rapidly and leads to changes in baseline cognitive status, ranging from delirium to coma. The diagnosis, monitoring, and management of AE is challenging. Here, we discuss advances in definitions, diagnostic approaches, therapeutic options, and implications to outcomes of the clinical spectrum of AE in ICU patients without primary brain injury. Recent findings Understanding and definitions of delirium and coma have evolved. Delirium is a neurocognitive disorder involving impairment of attention and cognition, usually fluctuating, and developing over hours to days. Coma is a state of unresponsiveness, with absence of command following, intelligible speech, or visual pursuit, with no imaging or neurophysiological evidence of cognitive motor dissociation. The CAM-ICU(−7) and the ICDSC are validated, guideline-recommended tools for clinical delirium assessment, with identification of clinical subtypes and stratification of severity. In comatose patients, the roles of continuous EEG monitoring and neuroimaging have grown for the early detection of secondary brain injury and treatment of reversible causes. Summary Evidence-based pharmacologic treatments for delirium are limited. Dexmedetomidine is effective for mechanically ventilated patients with delirium, while haloperidol has minimal effect of delirium but may have other benefits. Specific treatments for coma in nonprimary brain injury are still lacking.

show abstract

“…Foi evidenciado que o delirium ocorreu em 18,9% dos pacientes com visita flexibilizada e 20,1% dos pacientes com visitação restrita. A flexibilização da visita apresentou maior impacto para os membros da família, com redução da probabilidade clínica de ansiedade e depressão, entretanto, não foi encontrada diferença significativa entre a duração da visita familiar e a incidência do delirium 11 .…”

Section: Medidas Não Farmacológicas Para Deliriumunclassified

Delirium Na Unidade De Terapia Intensiva: Revisão Bibliográfica

Hora

Mendonça

2022

Rease

View full text Add to dashboard Cite

Esse artigo buscou revisar a literatura acerca da prevenção e tratamento do delirium em Unidades de Terapia Intensiva (UTI). O presente estudo tem o objetivo de realizar uma revisão narrativa da bibliografia acerca da prevenção e tratamento do delirium em pacientes internados em Unidade de Terapia Intensiva(UTI). Foi realizada revisão bibliográfica da literatura de caráter qualitativo e descritivo, através de dados coletados em Base de Dados Virtuais, sendo utilizadas as seguintes bases de informação: Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e National Library of Medicine (NIH), no período de março a maio de 2022. Para realização da pesquisa foram utilizados os seguintes descritores: “Delirium in ICU”, “Delirium in elderly” e “Delirium”. Foi observado que apesar da flexibilização de visitas em UTI não ter diminuído a incidência do delirium de forma geral, pacientes que não receberam visitas apresentaram risco 1,97 vezes maior de desenvolver delirium hiperativo e 2,32 vezes maior de desenvolver o subtipo misto. Ademais, o presente estudo mostrou que a dexmedetomidina utilizada em subdoses é capaz de prevenir a ocorrência do delirium, além de melhorar os desfechos de indivíduos que já desenvolveram o estado confusional agudo. Logo, ficou evidente que existem poucos mecanismos capazes de prevenir a ocorrência do delirium, sendo necessária a realização de estudos mais amplos a fim de solucionar este problema.

show abstract

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

Cited by 11 publications

References 32 publications

Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial

Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients: the EuRIDICE randomized clinical trial

Acute encephalopathy in the ICU: a practical approach

Delirium Na Unidade De Terapia Intensiva: Revisão Bibliográfica

Contact Info

Product

Resources

About