Critical Illness, Lung Injury, Mechanical Ventilation Complication, Respiratory Distress Syndrome, Adult, Respiratory Failure
Conditions
Keywords
acute respiratory failure, sedation, respiratory drive monitoring, mechanical ventilation, intensive care unit
Brief 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.
Detailed 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)
Interventions
PROCEDURETitrating 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.
DRUGFentanyl
Continuous intravenous infusion of fentanyl 25-75 micrograms/hour
DRUGMidazolam
Continuous intravenous infusion of midazolam 0.02 - 0.1 milligrams/kilogram/hour
DRUGPropofol
Continuous intravenous infusion of propofol 5 - 50 micrograms/kilogram/minute
DRUGDexmedetomidine
Continuous intravenous infusion of dexmedetomidine 0.2 - 0.7 micrograms/kilogram/hour
DRUGCisatracurium
Continuous intravenous infusion of cisatracurium 5 - 20 milligrams/hour
Sponsors
Siriraj Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful extubation within 14 days after randomization | 14 days after randomization | Successful extubation within 14 days without reintubation within 28 days after ICU admission |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Successful extubation within 28 days after randomization | 28 days after randomization | Successful extubation without reintubation within 28 days after ICU admission |
| Duration of mechanical ventilation | 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 | Time from intubation to the last successful extubation |
| Ventilator-free days to day 28 after randomization | 28 days after randomization | Number of days alive without mechanical ventilation |
| Reintubation rate at 7 days after randomization | 7 days after randomization | Number of reintubation within 7 days after randomization |
| Self extubation rate at 7 days after extubation | 7 days after randomization | Number of self extubation (accidentally extubation without physician's order) within 7 days after randomization |
| Post-extubation respiratory failure | 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 | 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. |
| Tracheostomy | 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 | Number of tracheostomy performed |
| Lung injury score on day 3 after randomization | 3 days after randomization | Lung injury score on day 3 after randomization |
| Lung injury score on day 7 after randomization | 7 days after randomization | Lung injury score on day 7 after randomization |
| PaO2/FiO2 ratio on day 3 after randomization | 3 days after randomization | PaO2/FiO2 ratio on day 3 after randomization |
| PaO2/FiO2 ratio on day 7 after randomization | 7 days after randomization | PaO2/FiO2 ratio on day 7 after randomization |
| Rates of new diagnosis of ARDS according to the new Berlin criteria 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 | Number of ARDS diagnoses after randomization |
| Delirium 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 | Delirium assessed by positive CAM-ICU criteria during ICU admission |
| Successful extubation within 7 days after randomization | 7 days after randomization | Successful extubation within 7 days without reintubation within 28 days after ICU admission |
| ICU all-cause mortality | 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 | All-cause mortality during ICU admission |
| Hospital all-cause mortality | 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 | All-cause mortality during hospital admission |
| 28-day mortality after randomization | 28 days after randomization | All-cause mortality during 28-day after randomization |
| ICU length of stay | 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 | Time from ICU admission to ICU discharge |
| Hospital length of stay | 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 | Time from hospital admission to hospital discharge |
| Maximum infusion dose (per hour) of sedation | 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 | Maximum infusion dose (per hour) of sedation used during the study period |
| Duration (days) of sedation | 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 used during the study period |
| Ventilator-associated pneumonia | 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 | Number of ventilator-associated pneumonia diagnosed after randomization |
| Barotrauma | 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 | Number of barotrauma (pneumothorax, pneumomediastinum, subcutaneous emphysema) occurred after randomization |
| Serious adverse events | 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 | Number of serious adverse events (severe allergic reaction or anaphylaxis and propofol infusion syndrome defined as severe lactic acidosis and hypertriglyceridemia) occurred after randomization |
| Cardiac arrhythmia | 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 | Number of cardiac arrhythmia events occurred after randomization |
| Maximum infusion dose (per hour) of vasopressor | 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 | Maximum infusion dose (per hour) of vasopressor used during the study period |
| Duration (days) of vasopressor | 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 used during the study period |
| Glasgow Outcome Scale (GOS) at 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 | 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) |
Countries
Thailand
Contacts
Primary ContactNatdanai Ketdao, MD
Backup ContactTanuwong Viarasilpa, MD
Outcome results
None listed