Midazolam Used Alone or Sequential Use of Midazolam and Propofol/Dexmedetomidine in Mechanically Ventilated Patients

Sponsor

West China Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02528513

Collaborator

(none)

240

Enrollment

Location

Arms

14.1

Duration (Months)

17.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate effects, safety and cost of midazolam used alone or sequential use of midazolam and propofol/dexmedetomidine for long-term sedation in critically ill, mechanically ventilated patients.

Condition or Disease	Intervention/Treatment	Phase
Mechanical Ventilation Complication Delirium	Drug: midazolam Drug: Fentanyl Drug: propofol Drug: Dexmedetomidine Procedure: Procedure:sedation assessment Procedure: Procedure:Weaning Drug: midazolam(used for passing the SBT safety screen)	Phase 4

Detailed Description

It is well known that sedation is frequently required as a component of compassionate care in critically ill patients. Until now, there is no ideal sedation drug and every sedation drug has its advantage and disadvantage for long-term sedation in critically ill, mechanically ventilated patients. The sequential use of midazolam and propofol for long-term sedation was associated with a faster recovery, earlier extubation, shorter mechanical ventilation time and less cost of total ICU treatment compared with midazolam alone, The protocol was associated with less cost of pharmaceutical sedation compared with propofol alone. But, propofol and midazolam may cause respiratory depression and delirium. Both drugs should be stopped after the patient passed the screen of weaning from mechanical ventilation, then it would induce the stress response and agitation, it would cause prolonged sedation and delay extubation.

Dexmedetomidine is a centrally acting a2-receptor agonist, has less effect on arousability and respiratory depression. The purpose of this study was to evaluate effects, safety and cost of midazolam used alone or sequential use of midazolam and propofol/dexmedetomidine for long-term sedation in critically ill, mechanically ventilated patients.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Midazolam Used Alone or Sequential Use of Midazolam and Propofol/Dexmedetomidine for Long-Term Sedation in Critically Ill, Mechanically Ventilated Patients: a Prospective, Randomized Study

Study Start Date :

Dec 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2016

Anticipated Study Completion Date :

Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: midazolam Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to achieve the desired level of sedation. After the spontaneous breathing trial safety screen is passed, midazolam will continue to be used for sedation, with the dosage adjusted to achieve the desired level of sedation.	Drug: midazolam Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to RASS score (-3 to 0). Other Names: Liyuxi Drug: Fentanyl Fentanyl is used with bolus dosage of 1-2ug/kg and maintenance dosage of 1-2ug/kg/h, with the dosage adjusted to critical care pain observation tool（CPOT）score(0-1). Procedure: Procedure:sedation assessment The nursing staff continuously monitored the sedation depth and adjusted the dosages of sedative and analgesic drugs to maintain the sedation target level. The sedation depth were assessed and recorded every 4 h (or more frequently when indicated). Procedure: Procedure:Weaning the respiratory therapists managed patients with a daily interruption of continuous sedation and the spontaneous breathing trial (SBT) protocols daily. Drug: midazolam(used for passing the SBT safety screen) After the spontaneous breathing trial safety screen is passed,in the midazolam group, midazolam will continue to be used for sedation, with the dosage adjusted to RASS score (-2 to 0). Other Names: Liyuxi
Experimental: midazolam/propofol Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to achieve the desired level of sedation. After the spontaneous breathing trial safety screen is passed, midazolam is switched to propofol, which is administered at the maintenance dosage of 0.50-3.00mg/kg/h, with the dosage adjusted to achieve the desired level of sedation.	Drug: midazolam Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to RASS score (-3 to 0). Other Names: Liyuxi Drug: Fentanyl Fentanyl is used with bolus dosage of 1-2ug/kg and maintenance dosage of 1-2ug/kg/h, with the dosage adjusted to critical care pain observation tool（CPOT）score(0-1). Drug: propofol After the spontaneous breathing trial safety screen is passed, midazolam is switched to propofol, which is administered at the maintenance dosage of 0.50-3.00mg/kg/h, with the dosage adjusted to RASS score (-2 to 0). Procedure: Procedure:sedation assessment The nursing staff continuously monitored the sedation depth and adjusted the dosages of sedative and analgesic drugs to maintain the sedation target level. The sedation depth were assessed and recorded every 4 h (or more frequently when indicated). Procedure: Procedure:Weaning the respiratory therapists managed patients with a daily interruption of continuous sedation and the spontaneous breathing trial (SBT) protocols daily.
Experimental: midazolam/dexmedetomidine Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to achieve the desired level of sedation. After the spontaneous breathing trial safety screen is passed, midazolam is switched to dexmedetomidine, which is administered at an infusion bolus of 0.5 μg/kg over 10 min (given or not according to patients' condition) and the maintenance dosage of 0.2-0.7ug/kg/h, with the dosage adjusted to achieve the desired level of sedation.	Drug: midazolam Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to RASS score (-3 to 0). Other Names: Liyuxi Drug: Fentanyl Fentanyl is used with bolus dosage of 1-2ug/kg and maintenance dosage of 1-2ug/kg/h, with the dosage adjusted to critical care pain observation tool（CPOT）score(0-1). Drug: Dexmedetomidine After the spontaneous breathing trial safety screen is passed, midazolam is switched to dexmedetomidine, which is administered at an infusion bolus of 0.5μg/kg over 10 min (given or not according to patients' condition) and the maintenance dosage of 0.2-0.7ug/kg/h, with the dosage adjusted to RASS score (-2 to 0). Procedure: Procedure:sedation assessment The nursing staff continuously monitored the sedation depth and adjusted the dosages of sedative and analgesic drugs to maintain the sedation target level. The sedation depth were assessed and recorded every 4 h (or more frequently when indicated). Procedure: Procedure:Weaning the respiratory therapists managed patients with a daily interruption of continuous sedation and the spontaneous breathing trial (SBT) protocols daily.

Arm

Intervention/Treatment

Experimental: midazolam

Drug: midazolam

Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to RASS score (-3 to 0).

Other Names:

Liyuxi

Drug: Fentanyl

Fentanyl is used with bolus dosage of 1-2ug/kg and maintenance dosage of 1-2ug/kg/h, with the dosage adjusted to critical care pain observation tool（CPOT）score(0-1).

Procedure: Procedure:sedation assessment

The nursing staff continuously monitored the sedation depth and adjusted the dosages of sedative and analgesic drugs to maintain the sedation target level. The sedation depth were assessed and recorded every 4 h (or more frequently when indicated).

Procedure: Procedure:Weaning

the respiratory therapists managed patients with a daily interruption of continuous sedation and the spontaneous breathing trial (SBT) protocols daily.

Drug: midazolam(used for passing the SBT safety screen)

After the spontaneous breathing trial safety screen is passed,in the midazolam group, midazolam will continue to be used for sedation, with the dosage adjusted to RASS score (-2 to 0).

Other Names:

Liyuxi

Experimental: midazolam/propofol

Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to achieve the desired level of sedation. After the spontaneous breathing trial safety screen is passed, midazolam is switched to propofol, which is administered at the maintenance dosage of 0.50-3.00mg/kg/h, with the dosage adjusted to achieve the desired level of sedation.

Drug: midazolam

Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to RASS score (-3 to 0).

Other Names:

Liyuxi

Drug: Fentanyl

Fentanyl is used with bolus dosage of 1-2ug/kg and maintenance dosage of 1-2ug/kg/h, with the dosage adjusted to critical care pain observation tool（CPOT）score(0-1).

Drug: propofol

After the spontaneous breathing trial safety screen is passed, midazolam is switched to propofol, which is administered at the maintenance dosage of 0.50-3.00mg/kg/h, with the dosage adjusted to RASS score (-2 to 0).

Procedure: Procedure:sedation assessment

Procedure: Procedure:Weaning

the respiratory therapists managed patients with a daily interruption of continuous sedation and the spontaneous breathing trial (SBT) protocols daily.

Experimental: midazolam/dexmedetomidine

Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to achieve the desired level of sedation. After the spontaneous breathing trial safety screen is passed, midazolam is switched to dexmedetomidine, which is administered at an infusion bolus of 0.5 μg/kg over 10 min (given or not according to patients' condition) and the maintenance dosage of 0.2-0.7ug/kg/h, with the dosage adjusted to achieve the desired level of sedation.

Drug: midazolam

Midazolam is started with an infusion bolus of 0.03-0.30 mg/kg and continuous infusion of 0.03-0.20 mg/kg/h, with the dosage adjusted to RASS score (-3 to 0).

Other Names:

Liyuxi

Drug: Fentanyl

Fentanyl is used with bolus dosage of 1-2ug/kg and maintenance dosage of 1-2ug/kg/h, with the dosage adjusted to critical care pain observation tool（CPOT）score(0-1).

Drug: Dexmedetomidine

After the spontaneous breathing trial safety screen is passed, midazolam is switched to dexmedetomidine, which is administered at an infusion bolus of 0.5μg/kg over 10 min (given or not according to patients' condition) and the maintenance dosage of 0.2-0.7ug/kg/h, with the dosage adjusted to RASS score (-2 to 0).

Procedure: Procedure:sedation assessment

Procedure: Procedure:Weaning

the respiratory therapists managed patients with a daily interruption of continuous sedation and the spontaneous breathing trial (SBT) protocols daily.

Outcome Measures

Primary Outcome Measures

Weaning time [From sedation sequential criteria to extubation, up to 28 days]

Secondary Outcome Measures

The pharmaceutical costs of sedation [From sedation drug is used to cessation of sedation up to 28 days.]
The total ICU costs [From admitted to ICU until ventilation and participants discharged from ICU, up to 28 days.]
The incidence of delirium (patients with diagnosis of delirium/ total patients in each group × 100% ) [From sedation drug is used to cessation of sedation, up to 28 days.]
After the daily interruption of continuous sedation,delirium is assessed by the the confusion assessment method for the diagnosis of delirium in ICU(CAM-ICU). If the patient has the clinical features of 1 and 2, or 3,or 4 in the CAM-ICU, delirium can be diagnosed.
Sedation satisfaction degree (The total time within target sedation level/total evaluation times ×100% ) [From sedation drug is used to cessation of sedation up to 28 days.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Intubated patients;
Age≥18 years old;
Anticipated Ventilation and sedation duration of at least 72 hours.

Exclusion Criteria:

Allergy to the study drug;
suspected pregnancy;
gross obesity;
Extremely unstable of circulatory system, such as systolic blood pressure less than 90 mm Hg despite plasma volume expansion and continuous infusions of vasopressors before the start of study drug infusion;
Uncontrolled abnormal hypertension, such as systolic blood pressure more than 180 mmHg or diastolic more than105 mmHg;
Heart rate less than 50 bpm;
Second or third degree heart block;
moribund state;
history of alcoholism or intake of anti-anxiety drugs or hypnotics;
chronic renal failure;
coma by cranial trauma or neurosurgery or unknown etiology or epileptic state;
History of neuromuscular disease;
unwillingness to provide informed consent by patients or their authorized surrogates following ICU admission.