Safety and Efficacy of Combined Sedation With Midazolam and Dexmedetomidine in ICU Patients

It is well known that ICU patients need sedation. Now no ideal sedation drug existed and every sedation drug has its advantage and disadvantage,so combined sedation may use the advantage and avoid the disadvantage of the sedation drug according to the patients'condition. Until now, there is rare study about the combined sedation or sequenced sedation of different sedation drug.The purpose of the study is to explore the value of combined sedation with midazolam and dexmedetomidine compared to single drug sedation in ICU, so as to seek an ideal sedation protocol that could reduce the cost of treatment,obtain the appropriate sedation not under sedation or over sedation,reduce the incidence of delirium, reduce the adverse event of sedation.

Study Overview

• Status: Unknown
• Conditions: Delirium
• Intervention / Treatment: Drug: midazolam; Drug: Fentanyl; Drug: Dexmedetomidine

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Department ICU, Shandong university affiliated Qilu Hospital.
      • Contact: Da W Wu, Doctor; Phone Number: 13791122767; Email: wdw.55@163.com
      • Principal Investigator: Qian Zhai, Doctor

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. ICU patients needing sedation
2. 18 years or older
3. mechanically ventilated for less than 96 hours prior to start of study drug.

Exclusion Criteria:

1. Trauma and burn patients as admitting diagnosis.
2. Dialysis of all types.
3. Pregnant or lactation.
4. Neuromuscular blockade other than for intubation.
5. Epidural or spinal analgesia.
6. General anesthesia prior to or planned after the start of study drug infusion
7. Serious central nervous system pathology(acute stroke, uncontrolled seizures,severe dementia).
8. Acute hepatitis or severe liver disease (Child-Pugh class C).
9. Unstable angina or acute myocardial infarction.
10. Left ventricular ejection fraction less than 30%,heart rate less than 50/min. 11.Second or third degree heart block.

12.Allergy to the study drug. 13.Systolic blood pressure less than 90 mm Hg despite continuous infusions of 2 vasopressors before the start of study drug infusion.

14. Patients with renal insufficiency were randomized and treated; however, patients were discontinued if they required dialysis.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: midazolam; Initiative dosage of midazolam is 0.05 mg/kg given intravenously, the maintenance dosage is 0.01-0.05 mg/kg/h, drug dosage is adjusted by target sedation level.	Drug: midazolam; If the target sedation level is not obtained using the above recommended dosage, midazolam 0.01-0.05 mg/kg is added every 10-15min, until the target sedation level is obtained. If it is over sedation (RASS -3 to -5), and reduction of the dosage of the sedation drug could not ease the situation, and then stop the sedation until the target sedation level is obtained.; Other Names: Liyuxi; Drug: Fentanyl; Fentanyl is used as analgesic drug in order to obtain the VAS <3.
Experimental: Dexmedetomidine; The loading dose of dexmedetomidine is 0.5-0.8 μg/kg given intravenously more than 10 min, the maintenance dosage is 0.2-0.7 μg/kg/h,the drug dosage is adjusted by target sedation level.	Drug: Fentanyl; Fentanyl is used as analgesic drug in order to obtain the VAS <3.; Drug: Dexmedetomidine; If the target sedation level is not obtained using the above recommended dosage, midazolam 0.01-0.05 mg/kg is added every 10-15min, until the target sedation level is obtained. If it is over sedation (RASS -3 to -5), and reduction of the dosage of the sedation drug could not ease the situation, and then stop the sedation until the target sedation level is obtained.; Other Names: Yisi
Experimental: midazolam & dexmedetomidine; Initiative dosage of midazolam is 0.05 mg/kg given intravenously, The loading dose of dexmedetomidine is 0.5-0.8 μg/kg given intravenously more than 10 min(given or not according to patients' condition),. The maintenance dosage of midazolam is 0.01-0.05 mg/kg/h, the maintenance dosage of dexmedetomidine is 0.2-0.7 μg/kg/h,the drug dosage is adjusted by target sedation level.	Drug: midazolam; If the target sedation level is not obtained using the above recommended dosage, midazolam 0.01-0.05 mg/kg is added every 10-15min, until the target sedation level is obtained. If it is over sedation (RASS -3 to -5), and reduction of the dosage of the sedation drug could not ease the situation, and then stop the sedation until the target sedation level is obtained.; Other Names: Liyuxi; Drug: Fentanyl; Fentanyl is used as analgesic drug in order to obtain the VAS <3.; Drug: Dexmedetomidine; If the target sedation level is not obtained using the above recommended dosage, midazolam 0.01-0.05 mg/kg is added every 10-15min, until the target sedation level is obtained. If it is over sedation (RASS -3 to -5), and reduction of the dosage of the sedation drug could not ease the situation, and then stop the sedation until the target sedation level is obtained.; Other Names: Yisi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The total time within target sedation level	Sedation level with RASS score is recorded every 4 hours during sedation.; When target sedation was not obtained, sedation drug dosage changed and when adverse event needed to be treated, the sedation level is also recorded.; The adjustment of sedation drug is recorded.	From sedation drug is used to weaning from sedation up to 28 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The dosage of sedation/analgesic drug	Record the induced and maintained dosage of sedation/opioid analgesic drug. The total dosage of sedation/opioid analgesic drug. The added dosage of midazolam.	From sedation/analgesic drug is used to weaning from sedation/analgesic up to 28 days.
Duration of mechanical ventilation	The duration of mechanical ventilation is recorded.	From beginning to weaning from ventilation up to 28 days..
Economic outcome	The cost of sedation drug used is recorded. The cost of mechanical ventilation is recorded. The cost of ICU residency is recorded.	From admitted to ICU until ventilation and sedation stopped and participants discharged from ICU up to 28 days.
Satisfactory of patients to ICU stay from admitted until discharged from ICU	Evaluated the satisfactory of patients to ICU. Using scores including 0 to 10. 0 presents extremely dissatisfied and 10 presents extremely satisfied.	Assessed at time of 1 week participants discharged from ICU.
Delirium	Delirium is evaluated when daily sedation interruption is done during sedation. Delirium incidence is recorded using CAM-ICU. Treatment of delirium is recorded including drug,dosage and method of administration.	From sedation drug is used to weaning from sedation, up to 28 days.
Vital signs	Heart rate(HR),main arterial pressure(MAP),respiratory rate(RR),pulse saturate of oxygen(SPO2) are recorded every 4 hours. When sedation drug dosage changed and adverse events treated,the vital signs is also recorded. Gas blood analysis index is recorded when the daily interruption is done and when the SPO2 is less 90% or 10% decrease than normal.	From sedation drug is used to weaning from sedation, up to 28 days.
Duration of ICU stay	Record when participants discharged form ICU.	From date of admission until participants discharged from ICU up to 28 days.

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University
• Collaborators: Chinese Medical Association
• Investigators: Study Director: Da W Wu, Doctor., Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Anticipated): December 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: February 25, 2014
• First Submitted That Met QC Criteria: March 5, 2014
• First Posted (Estimate): March 6, 2014

Study Record Updates

• Last Update Posted (Estimate): March 6, 2014
• Last Update Submitted That Met QC Criteria: March 5, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Intensive care unit; Mechanical ventilation; Combined sedation
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; 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; Dexmedetomidine
• Other Study ID Numbers: CMAqiluICU