The Efficacy of P0.1-guided Sedation Protocol in Critically Ill Patients Receiving Invasive Mechanical Ventilation: A Randomized Controlled Trial

Critical Illness Clinical Trial

Official title:

The Efficacy of P0.1-guided Sedation Protocol in Critically Ill Patients Receiving Invasive Mechanical Ventilation: A Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06203405
• Other study ID #: SI915/2023
• Status: Recruiting
• Phase: N/A
• Start date: December 22, 2023
• Est. completion date: June 30, 2025

Study information

• Verified date: January 2024
• Source: Siriraj Hospital
• Contact: Natdanai Ketdao, MD
• Phone: +66880684998
• Email: natdke[@]kku.ac.th
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial aims to assess the efficacy of sedation protocol targeting optimal respiratory drive using P0.1 and arousal level compared with conventional sedation strategy (targeting arousal level alone) in patients requiring mechanical ventilation in the medical intensive care unit.

Description:

Objective: to assess the efficacy of sedation protocol targeting optimal respiratory drive using P0.1 and RASS score compared with conventional sedation strategy (targeting RASS score alone) in patients requiring mechanical ventilation in the medical intensive care unit

The main questions it aims to answer are:

• Will titration of sedation targeting optimal respiratory drive assessed by P0.1 and arousal level improve outcomes in patients requiring mechanical ventilation in the medical ICU?

Study protocol Mechanically ventilated patients admitted to the medical ICU will be screened daily by the investigators. If the patients meet the eligibility criteria, they will be informed about the study protocol and potential risks and undergo informed consent. Then patients will be randomized in a 1:1 ratio and allocated to each study group (intervention and control group).

• After allocation, patients will be monitored for arousal level using RASS score and respiratory drive by P0.1 measured automatically from mechanical ventilators during the study period.

• Sedation and neuromuscular blocking agents used will be adjusted according to the group to which patients are allocated.

• Intervention group: Adjustment of sedation and neuromuscular blocking agents to achieve the target of light sedation (RASS 0 to -2) and optimal P0.1 (1.5 to 3.5 cmH2O) for 48 hours

• Control group: Adjustment of sedation to achieve the target of light sedation (RASS 0 to -2) alone for 48 hours

Researchers will compare the outcomes (rate of successful extubation, ICU and hospital mortality, ICU and hospital length of stay, duration of mechanical ventilation, amount and duration of sedation used during the study period) between the above sedation protocol (interventional group) and conventional sedation strategy (control group)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 214
• Est. completion date: June 30, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients admitted to the medical intensive care unit at Department of Medicine, Siriraj Hospital

2. Age =18 years old

3. Receiving mechanical ventilation due to acute respiratory failure within 72 hours before enrollment (including patients receiving mechanical ventilation before ICU admission)

Exclusion Criteria:

1. Patients receiving mechanical ventilation due to indications other than acute respiratory failure, such as postoperative procedures or airway protection in comatose patients

2. Patients receiving mechanical ventilation for >72 hours before enrollment

3. Patients receiving neuromuscular blocking agents prior to randomization

4. Patients with impaired secretion clearance or upper airway obstruction anticipating a tracheostomy

5. Patients with severe metabolic acidosis (arterial pH <7.2) who do not have a plan for renal replacement therapy

6. Patients intubated for neurological conditions, including intracranial hypertension, intracranial hemorrhage, large cerebral infarction, status epilepticus, or neuromuscular diseases

7. Post-cardiac arrest patients

8. Patients with severe liver dysfunction, including acute fulminant liver failure or cirrhosis with the Child-Pugh score B or C

9. Patients who have a previous allergy to any of the opioid, sedation, or neuromuscular blocking drugs

10. Pregnancy

11. Patients with do-not-resuscitate (DNR) orders or decisions to withhold life-sustaining treatments

12. Patients who refuse to participate in the study or cannot identify legally authorized representatives (LAR) within 24 hours after enrollment

Related Conditions & MeSH terms

• Acute Lung Injury
• Critical Illness
• Lung Injury
• Mechanical Ventilation Complication
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Failure
• Respiratory Insufficiency

Intervention

Procedure:
• Titrating sedation targeting both optimal P0.1 and appropriate arousal level
Sedation will be adjusted initially to target light sedation (RASS 0 to -2). Sedative drugs include IV fentanyl (25-75 mcg/h), midazolam (0.02- 0.1 mg/kg/h), propofol (5-50 mcg/kg/min), dexmedetomidine (0.2-0.7 mcg/kg/h). Deep sedation and neuromuscular blocking agents are allowed to facilitate mechanical ventilation adjustment in patients with refractory hypoxemia. Dose of cisatracurium is 0.15-0.2 mg/kg intravenous bolus, then continuous infusion at 5 -20 mg/h. Then sedation adjustment will be guided by P0.1 measurement. If P0.1 value of 1.5-3.5 cmH2O is achieved, no further adjustment is required. If P0.1 value <1.5, sedation will be reduced. If P0.1 value >3.5, sedation will be increased. If P0.1 value is still >3.5 with deep sedation, cisatracurium will be allowed and titrated until P0.1 value <3.5 cmH2O. The study protocol will be continued for 48 hours or until the patients are considered ready for weaning.

Drug:
• Fentanyl
Continuous intravenous infusion of fentanyl 25-75 micrograms/hour
• Midazolam
Continuous intravenous infusion of midazolam 0.02 - 0.1 milligrams/kilogram/hour
• Propofol
Continuous intravenous infusion of propofol 5 - 50 micrograms/kilogram/minute
• Dexmedetomidine
Continuous intravenous infusion of dexmedetomidine 0.2 - 0.7 micrograms/kilogram/hour
• Cisatracurium
Continuous intravenous infusion of cisatracurium 5 - 20 milligrams/hour

Locations

Country	Name	City	State
Thailand	Siriraj Hospital	Bangkok

Sponsors (1)

Lead Sponsor	Collaborator
Siriraj Hospital

Country where clinical trial is conducted

Thailand, 

References & Publications (37)

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* Note: There are 37 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Successful extubation within 14 days after randomization	Successful extubation within 14 days without reintubation within 28 days after ICU admission	14 days after randomization
Secondary	Successful extubation within 7 days after randomization	Successful extubation within 7 days without reintubation within 28 days after ICU admission	7 days after randomization
Secondary	Successful extubation within 28 days after randomization	Successful extubation without reintubation within 28 days after ICU admission	28 days after randomization
Secondary	Duration of mechanical ventilation	Time from intubation to the last successful extubation	From date of intubation until the date of last successful extubation or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Ventilator-free days to day 28 after randomization	Number of days alive without mechanical ventilation	28 days after randomization
Secondary	Reintubation rate at 7 days after randomization	Number of reintubation within 7 days after randomization	7 days after randomization
Secondary	Self extubation rate at 7 days after extubation	Number of self extubation (accidentally extubation without physician's order) within 7 days after randomization	7 days after randomization
Secondary	Post-extubation respiratory failure	Patients who meet at least one of the following criteria within 72 hours after extubation: respiratory rate more than 35 breaths/minute, oxygen saturation less than 90% or PaO2 less than 80 mmHg despite receiving FiO2 >50%, respiratory acidosis with pH <7.35 or PaCO2 >50 mmHg or increase of 20% from baseline.	From date of randomization until the date of the first event of post-extubation respiratory failure or date of death from any cause or ICU discharge, whichever came first, assessed up to 28 days
Secondary	Tracheostomy	Number of tracheostomy performed	From date of randomization until the date of tracheostomy or date of death from any cause or ICU discharge, whichever came first, assessed up to 28 days
Secondary	Lung injury score on day 3 after randomization	Lung injury score on day 3 after randomization	3 days after randomization
Secondary	Lung injury score on day 7 after randomization	Lung injury score on day 7 after randomization	7 days after randomization
Secondary	PaO2/FiO2 ratio on day 3 after randomization	PaO2/FiO2 ratio on day 3 after randomization	3 days after randomization
Secondary	PaO2/FiO2 ratio on day 7 after randomization	PaO2/FiO2 ratio on day 7 after randomization	7 days after randomization
Secondary	Rates of new diagnosis of ARDS according to the new Berlin criteria after randomization	Number of ARDS diagnoses after randomization	From date of randomization until the date of new onset ARDS diagnosis after randomization or date of death from any cause or ICU discharge, whichever came first, assessed up to 28 days
Secondary	Delirium during ICU admission	Delirium assessed by positive CAM-ICU criteria during ICU admission	From date of randomization until the date of diagnosis of delirium diagnosis or date of death from any cause or ICU discharge, whichever came first, assessed up to 28 days
Secondary	Glasgow Outcome Scale (GOS) at hospital discharge	Functional status assessed by Glasgow Outcome Scale (GOS) at hospital discharge; Unabbreviated title: Glasgow Outcome Scale; Maximum score: 5 = good recovery; 4 = Moderate disability, 3 = Severe disability, 2 = Vegetative state; Minimum score: 1 = death (Higher scores mean better outcome)	From date of randomization until the date of hospital discharge or date of death from any cause , whichever came first, assessed up to 28 days
Secondary	ICU all-cause mortality	All-cause mortality during ICU admission	From date of randomization until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Hospital all-cause mortality	All-cause mortality during hospital admission	From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	28-day mortality after randomization	All-cause mortality during 28-day after randomization	28 days after randomization
Secondary	ICU length of stay	Time from ICU admission to ICU discharge	From date of randomization until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Hospital length of stay	Time from hospital admission to hospital discharge	From date of randomization until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Maximum infusion dose (per hour) of sedation	Maximum infusion dose (per hour) of sedation used during the study period	From date of sedation initiation until the date of sedation discontinuation or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Duration (days) of sedation	Duration (days) of sedation used during the study period	From date of sedation initiation until the date of sedation discontinuation or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Ventilator-associated pneumonia	Number of ventilator-associated pneumonia diagnosed after randomization	From date of randomization until the date of first diagnosed ventilator-associated pneumonia or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Barotrauma	Number of barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema) occurred after randomization	From date of randomization until the date of first documented barotrauma or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Serious adverse events	Number of serious adverse events (severe allergic reaction or anaphylaxis and propofol infusion syndrome defined as severe lactic acidosis and hypertriglyceridemia) occurred after randomization	From date of randomization until the date of first documented serious adverse events or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Cardiac arrhythmia	Number of cardiac arrhythmia events occurred after randomization	From date of randomization until the date of first documented cardiac arrhythmia events or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Maximum infusion dose (per hour) of vasopressor	Maximum infusion dose (per hour) of vasopressor used during the study period	From date of vasopressor initiation until the date of vasopressor discontinuation or date of death from any cause, whichever came first, assessed up to 28 days
Secondary	Duration (days) of vasopressor	Duration (days) of vasopressor used during the study period	From date of vasopressor initiation until the date of vasopressor discontinuation or date of death from any cause, whichever came first, assessed up to 28 days