Clinical trial NCT02528513: Midazolam Used Alone or Sequential Use of Midazolam and Propofol/Dexmedetomidine in Mechanically Ventilated Patients
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Mechanical Ventilation
Complication
Delirium
Keywords: sedation
Midazolam
Propofol
Dexmedetomidine
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2015-08-19
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Weaning time
timeFrame: From sedation sequential criteria to extubation, up to 28 days
Secondary outcomes:
measure: The pharmaceutical costs of sedation
timeFrame: From sedation drug is used to cessation of sedation up to 28 days.
measure: The total ICU costs
timeFrame: From admitted to ICU until ventilation and participants discharged from ICU, up to 28 days.
measure: The incidence of delirium (patients with diagnosis of delirium/ total patients in each group × 100% )
timeFrame: From sedation drug is used to cessation of sedation, up to 28 days.
measure: Sedation satisfaction degree (The total time within target sedation level/total evaluation times ×100% )
timeFrame: From sedation drug is used to cessation of sedation up to 28 days.
Other outcomes:
Locations:
city: Chengdu
country: China
facility: Department of Critical care medicine of West China Hospital
state: Sichuan
Study officials:
affiliation: Critical Medicine Department,West China Hospital of Sichuan University
name: Y Kang, Dr
role: STUDY_CHAIR
References:
citation: 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.