The Effect of Analgesia Based Sedation Protocol on Brain Function of Critical Care Patients

Study Overview
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Brief Summary
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Benzodiazepines is a commonly uesd sedative medication,there are many reports that Benzodiazepines is associated with delirium ,but using of analgesia reduces benzodiazepines requirements .The purpose of this study is to determine whether analgesia based sedation protocol reduces the incident of delirium.

Conditions
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Delirium

Intervention / Treatment
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* Drug: Fentanyl
* Drug: Remifentanil
* Drug: Normal saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signing a consent form postoperative patient Requirement for mechanical ventilation and anticipate time of mechanical ventilation more than 24 hours Requirement for sedation Age more than 18 and less than 85 years old Exclusion Criteria: Unstable blood circulation Heart rate less than 50 beats per minute II ° ～ III ° atrioventricular conduct block Intracranial lesions 、neurosurgical intervention and mental disability inability to cooperate; Receipt of antipsychotics 、hypnotic drugs before surgery ; Alcohol abuse; Liver failure class Child-Pugh C; Acute Respiratory Distress Syndrome; Acute or chronic renal failure; Other severe diseases ,septic shock; Receipt of neuromuscular blocking drug; Pregnancy and nursing woman; Allergy to investigational drug or other contraindication.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remifentanil，midazolam<br>Remifentanil 1µg/kg/hr intravenous pump and Midazolam loading dose 0.05mg/kg followed by 0.02 0.1mg/kg/h continuous intravenous pump for 7days or extubation | Drug: Remifentanil<br> <br> |
| Experimental: Fentanyl，midazolam<br>Fentanyl 1µg/kg/hr intravenous pump and Midazolam loading dose 0.05mg/kg followed by 0.02 0.1mg/kg/h continuous intravenous pump for 7days or extubation | Drug: Fentanyl<br> <br> |
| Placebo Comparator: Normal saline<br>Normal saline1µg/kg/hr intravenous pump and Midazolam loading dose 0.05mg/kg followed by 0.02 0.1mg/kg/h continuous intravenous pump for 7days or extubation | Drug: Normal saline<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and duration of delirium in patients with different regimens |  | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality |  | 28 days | 
| Ventilator-free days |  | an expected average of 7 days | 
| Mean days of mechanical ventilation |  | an expected average of 7 days | 
| Length of ICU stay |  | an expected average of 7 days | 
| Index of anesthesia depth monitoring | Analgesic level、sedation level、brain function、 blood perfusion for peripheral and brain circulation、sleep stages and variation of blood volume | From admission to ICU to weaning,about 7 days | 
| Infusion velocity and total dose of sedative drugs in different groups |  | From admission to ICU to extubation or drug withdrawal,about 7 days | 
| Plasma melatonin level |  | Every 6 hours during the next ICU day | 
| Total rescue dose of midazolam |  | Seven days after giving midazolam to patient | 
| Variations of HR、RR、BP、SpO2 |  | an expected average of 7 days |