Proportional Assist Ventilation for Minimizing the Duration of Mechanical Ventilation: The PROMIZING Study

A staged enrolment process will be used to identify patients eligible to be enrolled and randomized in the study. At each stage of the enrolment process, a patient must meet inclusion criteria and not meet exclusion criteria in order to pass. To progress to the next stage, patients must continue to pass criteria from the prior stages. After enrolment, there are also specific tests to perform (with pass/fail criteria) to determine eligibility to be randomized.

A. SCREENING INCLUSION CRITERIA:

• A1. Age 18 years or older
• A2. Intubated and receiving any mode of invasive mechanical ventilation ≥ 24 hours

A. SCREENING EXCLUSION CRITERIA:

• A3. Anticipating withdrawal of life support and/or shift to palliation as the goal of care
• A4. Severe central neurologic disorder (eg. Hemorrhage, stroke, tumour) causing elevated intracranial pressure, or impaired control of breathing, or requiring specific ventilator adjustments (i.e. To attain specific CO2 target) or requiring neurosurgical intervention
• A5. Known or suspected severe or progressive neuromuscular disorder likely to result in prolonged or chronic ventilator dependence (eg. Guillain-Barré syndrome, Myasthenia Gravis, ALS, MS, high spinal cord injury, kyphoscoliosis or other restrictive disorder) (Note that obesity hypoventilation syndrome that may be managed with nocturnal non-invasive ventilation is NOT an exclusion under A5)
• A6. Severe COPD: Baseline daytime hypercapnia (pCO2> 50 mmHg) OR GOLD 4 airflow limitation (FEV1\<30% predicted) OR MRC class 4 symptoms ("I am too breathless to leave the house" OR "I am breathless when dressing")
• A7. Broncho-pleural fistula
• A8. Tracheostomy present at ICU admission for the purpose of chronic or prolonged mechanical ventilation (>21 days). (Note that a patient who was endotracheally intubated for acute respiratory failure and received a tracheostomy during their ICU admission, prior to enrolment, is not excluded under A8).
• A9. Current enrolment in a confounding study, as assessed by the steering committee
• A10. Previous randomization in the PROMIZING Study
• A11. Severe, end-stage, irreversible respiratory or cardiac disease (e.g. interstitial lung disease, pulmonary fibrosis, cardiomyopathy, valvulopathy) likely to result in prolonged or chronic ventilator dependence /unlikely to wean from mechanical ventilation [Note: patients who are candidates for intervention to treat the underlying respiratory/cardiac disease (e.g. lung transplant, heart transplant, cardiac surgery) may be re-evaluated once intervention is complete and they no longer meet criteria A11.]

B. ENROLMENT INCLUSION CRITERIA:

• B1. Ability or potential ability to trigger ventilator breaths (i.e. not receiving neuromuscular blockade).
• B2. On Assist/Control volume-cycled ventilation: Technically satisfactory plateau pressure ≤ 30 cm H2O (see Operations Manual) OR On Assist/Control pressure-controlled ventilation or similar mode: Pressure control plus PEEP ≤ 30 cm H2O OR On Pressure Support ventilation: Pressure support plus PEEP ≤ 30 cm H2O OR On Proportional Assist ventilation: PAV gain \<85%
• B3. PaO2 ≥ 60 mmHg or SpO2 ≥ 90% on FiO2 ≤ 0.60 and PEEP ≤ 15 cm H2O
• B4. Metabolic disorders corrected: pH ≥7.32
• B5. Stable hemodynamic status: stable or decreasing doses of vasopressors for ≥6 hours
• B6. Anticipate ongoing need for ventilation >24 hours

B. ENROLMENT EXCLUSION CRITERIA:

• B7. Extubated
• B8. Died
• B9. Patient has met enrolment inclusion criteria B1-B5 AND has tolerated pressure support of 0-20 cm H2O or proportional assist ventilation of 0-85% for ≥24 consecutive hours (including time on CPAP, t-piece, or tracheostomy mask). (Note (1): that it is acceptable to include a patient who has been tried on pressure support or proportional assist ventilation but has required pressures >20 cmH2O or assistance >85% or has required return to A/C ventilation within the 24 hour time window; Note (2): B9 does not apply to patients on ECMO.)
• B10. Patient transferred to a non-participating centre

B. ENROLMENT DEFERRAL CRITERIA:

• B11. Plan to extubate/discontinue mechanical ventilation within \<24 hours (Reassess within 24 hours)
• B12. Patient currently on ECMO (Reassess patient once off ECMO)
• C9: Plan for surgery or complex procedure that will require full ventilation to be done prior to attempting extubation (e.g. Procedure requiring neuromuscular blockade and/or heavy sedation, such that patient would be apneic, or not be able to trigger ventilator) (Reassess after surgery/procedure complete)

C. PRESSURE SUPPORT TRIAL INCLUSION CRITEIRA:

• C2. Upon review of Screening and Enrolment criteria (A and B), the patient still passes.
• C3. Treating physician has provided verbal consent to proceed with standardized tests and randomization if eligibility criteria are met.

C. PRESSURE SUPPORT TRIAL DEFERRAL CRITERIA:

• C6. High dose vasopressor requirements (i.e. epinephrine or norepinephrine >0.5 ug/kg/min or equivalent) OR patient requiring an increase in dose of vasopressor within 6 hrs
• C7. Active cardiac ischemia (dynamic ST changes on monitor or ECG within 6 hours)
• C8. Unstable arrhythmias (HR>140 or \<50) with clinical signs of low cardiac output or or SBP\<80 mmHg
• C10. Receiving a "strict lung protective" ventilation strategy for ARDS (eg. Order on chart to keep Vt ≤6 mL/kg PBW)

C. PRESSURE SUPPORT TRIAL EXCLUSION CRITERIA:

• C12. Treating physician has declined consent

D. WEANING CRITERIA:

• D1. SpO2≥ 90% on FiO2 ≤0.40 and PEEP ≤8 cmH2O
• D2. pH ≥7.32
• D3. Vasopressor requirements no higher than norepinephrine 0.1 ug/kg/min or equivalent.

In the final stage (E), patients will be considered eligible for randomization if the following criteria are met.

E. RANDOMIZATION INCLUSION CRITERIA:

• C1. Patient/SDM has provided consent OR Plan to obtain deferred consent as Patient incapable and no SDM available to provide consent within the randomization window
• E1. Upon review of Criteria A, B, and C, the patient still passes and the patient has passed the PST.
• E2. Does not meet Weaning Criteria OR Fails the ZERO CPAP Trial OR Fails the SBT

E. RANDOMIZATION EXCLUSION CRITERIA:

• B9. Patient has met enrolment inclusion criteria B1-B5 AND has tolerated pressure support of 0-20 cm H2O or proportional assist ventilation of 0-85% ≥24 consecutive hours (including time on CPAP, t-piece, or tracheostomy mask). Note (1): It is acceptable to include a patient who has been tried on pressure support or proportional assist ventilation but has required pressures >20 cmH2O or assistance >85% or has required return to A/C ventilation within the 24 hour time window; Note (2): B9 does not apply to patients while on ECMO
• C4. Patient/SDM has declined consent
• C5. Patient incapable and no SDM available to provide consent (not applicable if plan to obtain deferred consent)
• E3. Passed SBT on t-piece, FiO2 0.40 for 30-120 minutes
• E4. Approval withdrawn (by physician or patient/SDM)