Comparison of Weaning on Pressure Support vs. Proportional Assist Ventilation: A Pilot Study

Study Overview
=================
Brief Summary
-----------------
The study hypothesis is that reducing patient-ventilator asynchrony will reduce time required to wean from mechanical ventilation. The purpose of this pilot study is (1) to assess study feasibility in terms of recruitment, protocol adherence and efficacy of the intervention for reducing asynchrony, (2) to assess baseline rates of asynchrony and outcomes in the control arm in order to perform sample size calculations, if needed, for further, larger studies designed to detect differences in weaning time in specific, predefined populations and (3) to examine how often ineffective triggering (and therefore reduced ventilator respiratory rate) at higher levels of pressure support lead to a false conclusion that higher levels of support are needed to diminish respiratory distress.

Detailed Description
-----------------
Previous research has shown that approximately twenty-five percent of patients capable of triggering the ventilator in assisted modes have high rates of patient-ventilator asynchrony, and that such patients have a longer duration of mechanical ventilation. It is not known whether asynchrony is a cause of weaning failure or simply a marker of more severe respiratory failure. The most common type of asynchrony, ineffective triggering, may be both a marker of respiratory disease and a cause of delayed weaning. During ineffective triggering, the patient's inspiratory effort fails to trigger a ventilator breath, and thus the respiratory rate displayed on the ventilator underestimates the patient's true, intrinsic respiratory rate. Since ineffective triggering is more common at higher levels of pressure support than lower levels, an increase in respiratory rate during weaning of pressure support may indicate the development of respiratory distress or simply the abolition of ineffective triggering. Ineffective triggering may also cause delayed weaning because respiratory muscle energy is wasted on non-supported breaths. Proportional assist ventilation (PAV) is an FDA- and HPB-approved mode of ventilation in which the ventilator applies pressure in proportion to patient effort. Using PAV, patient-ventilator interaction may be optimized and ineffective triggering greatly reduced. Since the patient and ventilator respiratory rates are generally equivalent, a reduction in respiratory rate with increasing ventilatory support is less likely to be false positive indication of the need for greater assistance. In this study, patients with difficulty weaning from mechanical ventilation will be randomized to weaning with one of two weaning protocols: Proportional Assist Ventilation (PAV) weaning algorithm (intervention arm) vs. Pressure Support Ventilation (PSV) weaning algorithm (control arm).

Official Title
-----------------
Is Respiratory Rate an Adequate Indicator of Respiratory Distress During Weaning? A Comparison of Weaning on Pressure Support vs. Proportional Assist Ventilation.

Conditions
-----------------
Weaning From Mechanical Ventilation

Intervention / Treatment
-----------------
* Other: PSV
* Other: PAV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 years or greater Mechanically ventilated patients who are ready to begin weaning according to prespecified eligibility criteria, and tolerate thirty minutes of pressure support ventilation (PSV), but are not ready for extubation, defined as an frequency to tidal volume (f/Vt) greater-than (>) 105 after two minutes of constant positive airway pressure (CPAP) Reason for intubation partially or completely reversed Exclusion Criteria: Tolerating PSV 5 greater-than (>)2 hrs (Weaned) Plan to extubate today Extubated today Considering Withdrawal of life support (less-than (<)48hrs) Neurosurgical patient High SC injury/ progressive NMD Tracheostomy at time of ICU admission Has met all weaning eligibility and been on Pressure Support Ventilation (PSV) >36 hours

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Proportional Assist Ventilation (PAV)<br>Proportional Assist Ventilation (PAV+ on the PB840 ventilator) will be used according to a weaning algorithm. If patients develop distress despite maximum levels of support on PAV+, they will be temporarily switched to assist control mode. | Other: PAV<br>* Proportional Assist Ventilation will be used until patient is extubated.<br>|
| Active Comparator: Pressure Support Ventilation (PSV)<br>Pressure Support Ventilation on the PV840 ventilator will be used according to a weaning algorithm. If patients develop distress despite maximal level of support on PSV, they will be temporarily switched to assist-control mode. | Other: PSV<br>* Pressure Support Ventilation will be used until patient is extubated<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of weaning | Duration of weaning will be assessed as (a) the time elapsed from study randomization until the patient successfully passes a spontaneous breathing trial, (b) time from randomization to successful extubation, and (c) number of ventilator-free days, defined as the number of days alive and free of mechanical ventilation during the 28 days post randomization. All patients enrolled in the study will be followed until discharge from ICU. A prior subgroup analysis is planned for patients with a high asynchrony index at baseline. | From time of randomization up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in asynchrony index from baseline | Asynchrony index (percent (%) of asynchronous breaths) measured by visual inspection of flow and airway pressure tracings at baseline (just prior to randomization) and at high and low levels of support in both Proportional Assist Ventilation (PAV) and Pressure Support Ventilation (PSV) weaning algorithms. These measurements are recorded during the first seven days post randomization. | Measurement of flow, airway pressure, and estimate of respiratory muscle pressure recorded at baseline then again, at high and at low levels of support during the first seven days of the weaning protocol | 
| Change in sedative drug administration from baseline | Total dose of sedative and narcotic drugs (converted into lorazepam and morphine equivalents) administered on day 0 (baseline) and day 1, 3 and 7 of study protocol, as percentage of baseline dose | Daily dose of sedative drugs administered at baseline and day 1, 3, and 7 of study protocol | 
| Delirium | Incidence of a positive delirium screening assessment (using Confusion Assessment Method - Intensive Care Unit (CAM-ICU) or Intensive Care Delirium Screening Checklist (ICDSC)) at baseline, and duration of delirium as a percentage of time in ICU post randomization. | Up to 28 days post randomization | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Weaning, mechanical ventilation, Proportional Assist Ventilation