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

NCT ID: NCT02528513

Last Updated: 2016-04-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2017-02-28

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.

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.

Conditions

Mechanical Ventilation; Complication; Delirium

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

midazolam

1. 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.

2. 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.

Group Type: EXPERIMENTAL

midazolam

Intervention Type: DRUG

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).

Fentanyl

Intervention Type: DRUG

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:sedation assessment

Intervention Type: PROCEDURE

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:Weaning

Intervention Type: PROCEDURE

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

midazolam(used for passing the SBT safety screen)

Intervention Type: DRUG

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).

midazolam/propofol

1. 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.

2. 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.

Group Type: EXPERIMENTAL

midazolam

Intervention Type: DRUG

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).

Fentanyl

Intervention Type: DRUG

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).

propofol

Intervention Type: DRUG

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:sedation assessment

Intervention Type: PROCEDURE

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:Weaning

Intervention Type: PROCEDURE

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

midazolam/dexmedetomidine

1. 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.

2. 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.

Group Type: EXPERIMENTAL

midazolam

Intervention Type: DRUG

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).

Fentanyl

Intervention Type: DRUG

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).

Dexmedetomidine

Intervention Type: DRUG

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:sedation assessment

Intervention Type: PROCEDURE

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:Weaning

Intervention Type: PROCEDURE

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

Interventions

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).

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: 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).

Intervention Type: DRUG

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).

Intervention Type: PROCEDURE

Procedure:Weaning

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

Intervention Type: PROCEDURE

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).

Intervention Type: DRUG

Other Intervention Names

Liyuxi; Liyuxi

Eligibility Criteria

Inclusion Criteria

1. Intubated patients;

2. Age≥18 years old;

3. Anticipated Ventilation and sedation duration of at least 72 hours.

Exclusion Criteria

1. Allergy to the study drug;

2. suspected pregnancy;

3. gross obesity;

4. 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;

5. Uncontrolled abnormal hypertension, such as systolic blood pressure more than 180 mmHg or diastolic more than105 mmHg;

6. Heart rate less than 50 bpm;

7. Second or third degree heart block;

8. moribund state;

9. history of alcoholism or intake of anti-anxiety drugs or hypnotics;

10. chronic renal failure;

11. coma by cranial trauma or neurosurgery or unknown etiology or epileptic state;

12. History of neuromuscular disease;

13. unwillingness to provide informed consent by patients or their authorized surrogates following ICU admission.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

West China Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhou Yongfang

Zhou Yongfang

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Y Kang, Dr

Role: STUDY_CHAIR

Critical Medicine Department,West China Hospital of Sichuan University

Locations

Department of Critical care medicine of West China Hospital

Chengdu, Sichuan, China

Countries

China

References

Zhou Y, Yang J, Wang B, Wang P, Wang Z, Yang Y, Liang G, Jing X, Jin X, Zhang Z, Deng Y, Hu C, Liao X, Yin W, Tang Z, Tian Y, Tao L, Kang Y. Sequential use of midazolam and dexmedetomidine for long-term sedation may reduce weaning time in selected critically ill, mechanically ventilated patients: a randomized controlled study. Crit Care. 2022 May 3;26(1):122. doi: 10.1186/s13054-022-03967-5.

Reference Type: DERIVED

PMID: 35505432 (View on PubMed)

Other Identifiers

HaxiICU

Identifier Type: -

Identifier Source: org_study_id