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

Siriraj Hospital

Status: Enrolling

Conditions: Lung Injury; Respiratory Failure; Mechanical Ventilation Complication; Respiratory Distress Syndrome, Adult; Critical Illness

Treatments: Drug: Propofol; Procedure: Titrating sedation targeting both optimal P0.1 and appropriate arousal level; Drug: Cisatracurium; Drug: Dexmedetomidine; Drug: Midazolam; Drug: Fentanyl

Study type: Interventional

Funder types: Other

Identifiers

NCT06203405

SI915/2023

Details and patient eligibility

About

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.

Full 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)

Enrollment: 214 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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214 participants in 2 patient groups

Titrating sedation targeting both optimal P0.1 and appropriate arousal level

Experimental group

Description:

• Sedative drug adjustment to achieve the target of light sedation (RASS 0 to -2) and optimal respiratory drive measured by P0.1 of 1.5 - 3.5 cmH2O

Treatment:

Drug: Midazolam

Drug: Fentanyl

Drug: Cisatracurium

Drug: Dexmedetomidine

Procedure: Titrating sedation targeting both optimal P0.1 and appropriate arousal level

Drug: Propofol

Titrating sedation targeting appropriate arousal level alone

No Intervention group

Description:

• Sedative drug adjustment to achieve the target of light sedation (RASS 0 to -2) according to the standard clinical practice guidelines for managing pain and agitation for patients receiving mechanical ventilation in the ICU.