Effects of dexmedetomidine on delirium duration of non-intubated ICU patients (4D trial): study protocol for a randomized trial

被引:11
作者
Louis, Clemence [1 ]
Godet, Thomas [1 ,2 ,3 ,4 ,5 ,8 ]
Chanques, Gerald [6 ]
Bourguignon, Nathalie [1 ]
Morand, Dominique [1 ]
Pereira, Bruno [7 ]
Constantin, Jean-Michel [1 ,2 ,3 ,4 ,5 ]
机构
[1] CHU Clermont Ferrand, Dept Med Perioperatoire MPO, F-63003 Clermont Ferrand, France
[2] GReD, F-63003 Clermont Ferrand, France
[3] UMR CNRS6293, F-63003 Clermont Ferrand, France
[4] Univ Clermont Auvergne, F-63003 Clermont Ferrand, France
[5] INSERM U1103, F-63003 Clermont Ferrand, France
[6] CHU Montpellier, Hop St Eloi, Dept Anesthesie Reanimat B, F-34090 Montpellier, France
[7] CHU Clermont Ferrand, DRCI, F-63000 Clermont Ferrand, France
[8] CHU Clermont Ferrand, Hop Estaing, Dept Med Perioperatoire MPO, 1 Pl Lucie Aubrac, F-63003 Clermont Ferrand, France
来源
TRIALS | 2018年 / 19卷
关键词
Dexmedetomidine; Haloperidol; Delirium; ICU patients; Sedation; Mechanical ventilation; Intubation; INTENSIVE-CARE-UNIT; MECHANICALLY VENTILATED PATIENTS; CRITICALLY-ILL PATIENTS; AGITATED DELIRIUM; CLINICAL-TRIAL; HALOPERIDOL; RELIABILITY; SEDATION; VALIDITY; SCALE;
D O I
10.1186/s13063-018-2656-x
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: Delirium during intensive care unit (ICU) stay is frequent and associated with significant morbidity, mortality and healthcare-related costs. International guidelines suggest its prevention. However, curative treatment remains unclearly established. Despite contradictory and ambiguous academic literature, international guidelines suggest the use of second-generation (atypical) antipsychotics over haloperidol. However, haloperidol remains the most widely used neuroleptic worldwide as a first-line treatment of agitation and/or delirium. Dexmedetomidine, an alpha2-adrenergic receptors agonist, has shown its efficiency in the treatment of delirium in intubated patients but also in its prevention. Dexmedetomidine represents a widely used alternative to haloperidol. Only few studies have compared the efficacy of dexmedetomidine in non-intubated ICU patients as a first-line curative treatment of delirium. The main objective of the 4D trial is to demonstrate that dexmedetomidine decreases delirium duration compared to placebo. Methods/design: The 4D trial is an investigator-initiated, prospective, multicenter, randomized, double-blinded, two-arm trial, randomizing 300 non-intubated ICU patients with a diagnosis of agitated delirium to receive dexmedetomidine or placebo as a cure. In case of agitation (RASS >= + 2), immediate haloperidol administration will be allowed, to protect patient and staff in charge, while waiting for study treatment action. The primary outcome measure is a composite of duration of agitation or delirium or the use of intubation with deep sedation and mechanical ventilation. Secondary outcomes include mortalities at 7 and 30 days, ICU length of stay and occurrence of adverse effects related to dexmedetomidine use (bradycardia or hypotension requesting any treatment; or haloperidol use (neuroleptic malignant syndrome, extrapyramidal syndrome, prolonged QTc). The sample size will allow the detection of a 50% decrease of agitation duration (120 min), of an absolute reduction of delirium duration (1 day) and of a 50% relative decrease of intubation and mechanical ventilation, with a type 1 error rate of 1.8% (error risk inflation due to components of composite) and power of 90%, assuming a 15% incidence of intubation and mechanical ventilation requirements, an agitation duration of 240 min and a delirium duration of 3 days. One hundred and ten patients by group will be needed. An intermediate analysis is scheduled and requires the inclusion of 150 patients. Discussion: The 4D trial may provide important data on the safety of commonly used sedative dexmedetomidine and could have a significant impact on future treatment of non-intubated ICU patients presenting with agitated delirium.
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页数:11
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