Impact of Various Sedation Regimens on the Incidence of Delirium

Study Overview
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Brief Summary
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Sedation drugs that are commonly used in ICU in treatment of ARDS, includes propofol, midazolam and dexmedetomidine . Among these, both dexmedetomidine and propofol have been reported to be used together with midazolam in ICU and the combination of propofol and midazolam is most commonly used, but things follow include a high incidence rate of delirium, But the combination of midazolam and dexmedetomidine may have complementary advantages and could have be a better choice for sedation. In this study, we attempted to observe the effects of two different drug regimens on delirium incidence rates in severe ARDS patients' : midazolam and propofol vs propofol and dexmedetomidine .

Official Title
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Impact of Various Sedation Regimens on the Incidence of Post-sedation Delirium in Patients Receiving Mechanical Ventilation

Conditions
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Delirium

Intervention / Treatment
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* Drug: Dexmedetomidine,midazolam
* Drug: Propofol,midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects willing to give written informed consent. Mild, moderate or severe ARDS patients demanding invasive mechanical ventilation. Subjects whose expected time of mechanical ventilation is longer than 24 hours. Subjects aged between 18 and 70. Exclusion Criteria: Subjects with extremely unstable circulation, whose SBP lower than 90mmHg after volume expansion or pressor agent treatment. Subjects with extremely unstable circulation, whose SBP lower than 90mmHg after volume expansion or pressor agent treatment. Subjects with heart rates less than 50 beats per minute. Subjects with second or third degree atrioventricular block. Subjects with serious cerebral injury, severe neurologic disorder (e.g acute stroke, uncontrolled epilepsy and severe dementia) or coma. Subjects with acute or severe liver disease (Child-Pugh class C), see attachment 2. ARDS patients caused by pulmonary fibrosis or COPD. Subjects on all types hemodialysis. Subjects with neuromuscular system disease, alcohol withdrawal syndrome or mental disease before entrance of ICU. Subjects suspected of narcotic analgesics abusing. Subjects needing neuromuscular blocking agents (except intubation). Subjects allergic to investigational products or with other contraindication. Subjects who are breastfeeding or pregnant Subjects participated in other study within 30 days before entrance of ICU

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dexmedetomidine,midazolam<br>Slow injection of 2mg midazolam every minute and watching patients' reaction until attaining the target level of sedation;midazolam was maintained at 0.02 0.1mg/kg/h, for 24 hours.Dexmedetomidine will be added at 0.2 1.4μg/kg/h to maintain sedation.If target sedation level (RASS score) cannot be reached in maximum dose of dexmedetomidine, continuous intravenous infusion of midazolam could be used at 0.02 0.1mg/kg/h, until the target level is reached. | Drug: Dexmedetomidine,midazolam<br> <br> |
| Active Comparator: Propofol,midazolam<br>Slow injection of 2mg midazolam every minute and watching patients' reaction until attaining the target level of sedation;midazolam was maintained at 0.02 0.1mg/kg/h, for 24 hours.Propofol will be added at 0.3 4mg/kg/h to maintain sedation.If target sedation level (RASS score) cannot be reached in maximum dose of propofol, continuous intravenous infusion of midazolam could be used at 0.02 0.1mg/kg/h, until the target level is reached. | Drug: Propofol,midazolam<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rates and duration of delirium | Incidence rates and duration of delirium within 14 days after initiation of sedation with dexmedetomidine or propofol | up to 15 days | 
| Sedation interruption | Eye opening according to the voice orders, eye tracking, clenching fist and nodding are involved in assessment, patients could do 3 of those or more is deemed as conscious and taken in delirium assessment. | up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sedation therapy effect | The frequency of assessment whose score fall within the target range. | up to 7 days | 
| Hospitalized days in ICU |  | up to 15 days | 
| Death rates | Patients' death rates with a follow-up of 28 days | 28 days | 
| Incidence rate of patients self-extubation |  | up to 7 days | 
| Injection speed, total dose and injection of sedatives in different groups. |  | 7 days | 
| Additional dose of fentanyl and midazolam |  | up to 7 days | 
| Dosage of diuretic, antiemetic, hypoglycemic, beta-receptor antagonist and vasoactive agents. |  | up to 15 days | 
| Variation degree of HR, RR, BP and SpO2 |  | up to 15 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sedation;, ARDS;, Mechanical ventilation, Hypnotics, Antianxiety Drugs, Causing, Adverse Effects, Therapeutic Use