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

N/ARecruitingNCT06203405

Siriraj Hospital214 enrolled

Overview

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.

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Interventions

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

* 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.

FentanylDRUG

Continuous intravenous infusion of fentanyl 25-75 micrograms/hour

MidazolamDRUG

Continuous intravenous infusion of midazolam 0.02 - 0.1 milligrams/kilogram/hour

PropofolDRUG

Continuous intravenous infusion of propofol 5 - 50 micrograms/kilogram/minute

DexmedetomidineDRUG

Continuous intravenous infusion of dexmedetomidine 0.2 - 0.7 micrograms/kilogram/hour

CisatracuriumDRUG

Continuous intravenous infusion of cisatracurium 5 - 20 milligrams/hour

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Successful extubation within 14 days after randomization

Successful extubation within 14 days without reintubation within 28 days after ICU admission

Time frame: 14 days after randomization

Secondary Outcomes

Successful extubation within 7 days after randomization

Successful extubation within 7 days without reintubation within 28 days after ICU admission

Time frame: 7 days after randomization

Successful extubation within 28 days after randomization

Successful extubation without reintubation within 28 days after ICU admission

Time frame: 28 days after randomization

Duration of mechanical ventilation

Time from intubation to the last successful extubation

Time frame: 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

Ventilator-free days to day 28 after randomization

Number of days alive without mechanical ventilation

Time frame: 28 days after randomization

Reintubation rate at 7 days after randomization

Number of reintubation within 7 days after randomization

Time frame: 7 days after randomization

Self extubation rate at 7 days after extubation

Number of self extubation (accidentally extubation without physician's order) within 7 days after randomization

Time frame: 7 days after randomization

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.

Time frame: 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

Tracheostomy

Number of tracheostomy performed

Time frame: 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

Lung injury score on day 3 after randomization

Time frame: 3 days after randomization

Lung injury score on day 7 after randomization

Time frame: 7 days after randomization

PaO2/FiO2 ratio on day 3 after randomization

Time frame: 3 days after randomization

PaO2/FiO2 ratio on day 7 after randomization

Time frame: 7 days after randomization

Rates of new diagnosis of ARDS according to the new Berlin criteria after randomization

Number of ARDS diagnoses after randomization

Time frame: 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

Delirium during ICU admission

Delirium assessed by positive CAM-ICU criteria during ICU admission

Time frame: 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

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)

Time frame: 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

ICU all-cause mortality

All-cause mortality during ICU admission

Time frame: 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

Hospital all-cause mortality

All-cause mortality during hospital admission

Time frame: 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

28-day mortality after randomization

All-cause mortality during 28-day after randomization

Time frame: 28 days after randomization

ICU length of stay

Time from ICU admission to ICU discharge

Time frame: 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

Hospital length of stay

Time from hospital admission to hospital discharge

Time frame: 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

Maximum infusion dose (per hour) of sedation

Maximum infusion dose (per hour) of sedation used during the study period

Time frame: 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

Duration (days) of sedation

Duration (days) of sedation used during the study period

Time frame: 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

Ventilator-associated pneumonia

Number of ventilator-associated pneumonia diagnosed after randomization

Time frame: 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

Barotrauma

Number of barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema) occurred after randomization

Time frame: 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

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

Time frame: 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

Cardiac arrhythmia

Number of cardiac arrhythmia events occurred after randomization

Time frame: 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

Maximum infusion dose (per hour) of vasopressor

Maximum infusion dose (per hour) of vasopressor used during the study period

Time frame: 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

Duration (days) of vasopressor

Duration (days) of vasopressor used during the study period

Time frame: 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

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts