Sequential Use of Propofol/Midazolam and Dexmedetomidine for Sedation in Mechenical Ventialtion Patients in ICU.

Sequential Use of Propofol/Midazolam and Dexmedetomidine for Sedation in Mechenical Ventialtion Patients in ICU, A Randomized Controlled Study.

For the patient who passed the screen of weaning from ventilation, the traditional sedation drug such as propofol and midazolam should be decreased or stopped, then it would induce the stress response and agitation, such as hypertension,tachycardia etc. In order to resolve that problem, the sedation should be given again. but if renewed to sedation, it would cause prolonged sedation and ventilation duration.

So as to resolve above issues, after the patient passed the screen of weaning, sedation is changed to Dexmedetomidine, a new sedation drug, that could wake up at any time. So our study to compare the efficacy and safety of sequential sedation of propofol or midazolam and dexmedetomidine in mechanical ventilated ICU patients.

Study Overview

• Status: Unknown
• Conditions: Mechanical Ventilation Complication
• Intervention / Treatment: Drug: Fentanyl; Procedure: Sedation assessment; Procedure: Screen of weaning; Drug: Propofol; Drug: Dexmedetomidine; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Written Informed Consent
2. Anticipated Ventilation and sedation duration of at least 48 hours
3. Age≥18 years old
4. Weight is in the range of ±20% of standard weight.[Standard weight= (Height(cm)-80)×70﹪ for male and (Height(cm)-70)×60﹪for female] -

Exclusion Criteria:

1. Extremely unstable of circulatory system, such as systolic blood pressure less than 90 mm Hg despite continuous infusions of vasopressors before the start of study drug infusion or shock；
2. Heart rate less than 50 bpm
3. Second or third degree heart block
4. Serious central nervous system pathology(acute stroke, uncontrolled seizures,severe dementia)
5. Acute hepatitis or severe liver disease (Child-Pugh class C)
6. Dialysis of all types 7）History of neuromuscular disease

8) Unstable mental status and metal illness 9) Sure or suspected abuse of narcotics and alcohol independence 10) Allergy to experimental drug and other contraindication 11) Advanced tumor patients 12) Neuromuscular blockade other than for intubation 13) Pregnancy or lactation 14) Patient that participate other trial at past 30 days -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Propofol/Dexmedetomidine; Propofol is started with dosage of 0.3 mg/kg/h, observe the patient's response, increase 0.3 mg/kg/h propofol every 10 minutes until target sedation level is obtained(Riker Sedation Agitation Score(SAS) 3-4),then 0.3-3 mg/kg/h propofol is maintained.; After the screen of the weaning is passed, change to Dexmedetomidine sedation, the dose is 0.2-0.7 mg/kg/h and continuously pumped, increase the dose 0.1-0.2 mg/kg/h every 30 minutes, titrate to Riker Sedation Agitation Score(SAS) 3-4，the maximum dose is 1 mg/kg/h maintained，and prepare for weaning.	Drug: Fentanyl; Fentanyl 0.7-1μg/kg，prn pain assessment is done every 4 hours，maintain Behavioral Pain Scale（BPS） 0-2.; Procedure: Sedation assessment; Sedation assessment is done every 4 hours,maintain the Riker Sedation Agitation Score(SAS) 3-4.; Procedure: Screen of weaning; 1. Screen of weaning is done at 8:00 every morning. 2 If the patient is successful to wean, stop the Dexmedetomidine sedation. 3. If failed to wean, the patient is ventilated again and try to wean after 24 hours, until it is successful to wean and stop sedation，; Drug: Propofol; Propofol is started with dosage of 0.3 mg/kg/h, observe the patient's response, increase 0.3 mg/kg/h propofol every 10 minutes until target sedation level is obtained(Riker Sedation Agitation Score(SAS) 3-4),then 0.3-3 mg/kg/h propofol is maintained.; Drug: Dexmedetomidine; After the screen of the weaning is passed, change to Dexmedetomidine sedation, the dose is 0.2-0.7 mg/kg/h and continuously pumped, increase the dose 0.1-0.2 mg/kg/h every 30 minutes, titrate to Riker Sedation Agitation Score(SAS) 3-4，the maximum dose is 1 mg/kg/h maintained，and prepare for weaning.; Other Names: Yisi
Experimental: Midazolam/Dexmedetomidine; Midazolam 2 mg is slowly titrated to Riker Sedation Agitation Score(SAS) 3-4 every 10 minutes, then Midazolam 0.02-0.1 mg/kg/h is maintained.; After the screen of the weaning is passed, change to Dexmedetomidine sedation, the dose is 0.2-0.7 mg/kg/h and continuously pumped, increase the dose 0.1-0.2 mg/kg/h every 30 minutes, titrate to Riker Sedation Agitation Score(SAS) 3-4，the maximum dose is 1 mg/kg/h maintained，and prepare for weaning.	Drug: Fentanyl; Fentanyl 0.7-1μg/kg，prn pain assessment is done every 4 hours，maintain Behavioral Pain Scale（BPS） 0-2.; Procedure: Sedation assessment; Sedation assessment is done every 4 hours,maintain the Riker Sedation Agitation Score(SAS) 3-4.; Procedure: Screen of weaning; 1. Screen of weaning is done at 8:00 every morning. 2 If the patient is successful to wean, stop the Dexmedetomidine sedation. 3. If failed to wean, the patient is ventilated again and try to wean after 24 hours, until it is successful to wean and stop sedation，; Drug: Dexmedetomidine; After the screen of the weaning is passed, change to Dexmedetomidine sedation, the dose is 0.2-0.7 mg/kg/h and continuously pumped, increase the dose 0.1-0.2 mg/kg/h every 30 minutes, titrate to Riker Sedation Agitation Score(SAS) 3-4，the maximum dose is 1 mg/kg/h maintained，and prepare for weaning.; Other Names: Yisi; Drug: Midazolam; Midazolam 2 mg is slowly titrated to Riker Sedation Agitation Score(SAS) 3-4 every 10 minutes, then Midazolam 0.02-0.1 mg/kg/h is maintained.; Other Names: Liyuexi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilation duration	The time of intubation and the time of weaning from mechanical ventilation are recorded.	From intubation to weaning from mechanical ventilation, up to 7 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium	Using the Mini-mental State Examination(MMSE) to examine the delirium.	From the beginning of sedation to discharge from ICU, up to 28 days.
Blood pressure	blood pressure is recorded.	From the beginning to weaning of sedation, up to 7 days.
Cost of sedation drug	The cost of sedation drug is calculated.	From the admition to discharge from ICU,up to 28 days.
Cost of narcotics	Cost of narcotics is calculated.	From the admition to discharge from ICU,up to 28 days.
Cost of ICU stay		From the beginning to weaning of sedation, up to 7 days.
Heart rate		From the beginning to weaning of sedation, up to 7 days.
Respiration Rate		From the beginning to weaning of sedation, up to 7 days.
Pulse blood oxygen saturation		From the beginning to weaning of sedation, up to 7 days.

Collaborators and Investigators

• Sponsor: Tianjin Third Central Hospital
• Collaborators: Chinese Medical Association
• Investigators: Principal Investigator: Jun Li, Professor, Tianjin Third Central Hospital

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): April 1, 2015
• Study Completion (Anticipated): April 1, 2015

Study Registration Dates

• First Submitted: April 21, 2014
• First Submitted That Met QC Criteria: April 22, 2014
• First Posted (Estimate): April 24, 2014

Study Record Updates

• Last Update Posted (Estimate): April 24, 2014
• Last Update Submitted That Met QC Criteria: April 22, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: combined sedation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Fentanyl; Midazolam; Propofol; Dexmedetomidine
• Other Study ID Numbers: CMATJHICU