Mechanical Insufflation-Exsufflation (Cough Assist) in Critically Ill Adults

Study Overview
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Brief Summary
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The goal of this randomized feasibility trial is to evaluate the feasibility of Mechanical Insufflation-Exsufflation (MI-E) in invasively ventilated critically ill patients. The main question[s] it aims to answer are: Is MI-E feasible? Is MI-E safe? Participants in the intervention group will receive: MI-E Airway secretions will be removed by endotracheal suctioning, as part of routine airway care. Manual hyperinflation will only be used when necessary in an emergency situation. Patients in the control group will receive endotracheal suctioning and manual hyperinflation when clinically indicated. The primary outcome is the proportion of delivered MI-E sessions (2 times per calendar day a MI-E session of 3 x 3 cycles of an in- and exsufflation) per patient according to study protocol (feasibility). Secondary outcomes are the total number of serious adverse events in relation to MI-E (safety) and preliminary exploratory data on the need for airway care interventions and clinical outcomes including duration of invasive ventilation, length of stay in ICU and mortality (efficacy).

Detailed Description
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Bedside nurses, trained in using the MI-E device, will apply MI-E sessions at two moments per calendar day (morning and afternoon) for a maximum of 7 days while a patient is invasively ventilated. MI-E settings are a 2-second insufflation and an immediate 2-second exsufflation. The cycles of the MI-E session will be performed with a positive and negative pressure of 40 cmH2O. The program is set up with the possibility of auto-triggering by the patient.

Official Title
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Mechanical Insufflation-Exsufflation (Cough Assist) in Critically Ill Adults (ACACIA)-a Randomized Clinical Feasibility Trial

Conditions
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Critically Ill

Intervention / Treatment
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* Device: Mechanical Insufflation-Exsufflation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: admission to one of the participating ICUs; receiving invasive mechanical ventilation via an endotracheal tube; and expected to need invasive ventilation for more than 48 hours from consideration for inclusion. Exclusion Criteria: use of MI-E before hospital admission, i.e., at home; known presence of bullous emphysema; known bronchopleural fistula; known pneumothorax or pneumomediastinum; known rib fractures; known barotrauma; known unstable spinal fractures; unsecured subarachnoidal haemorrhage; uncontrollable intracranial pressures; and any infection, or colonization with pathogens that requires strict aerogenic isolation. With an exception for patients in cohort isolation due to COVID-19.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mechanical Insufflation-Exsufflation<br>Invasively ventilated patients will receive MI-E until successful extubation or for a maximum of 7 days. MI-E will be given in the morning and afternoon each calendar day. Patients will be pre-oxygenated with FiO2 100% prior to disconnection from the ventilator; additional 15 litres oxygen can be added; A pre-set program is used: three times three cycles with a 2-second insufflation and an immediate 2-second exsufflation. The cycles of the MI-E session will be performed with a positive and negative pressure of 40 cmH2O. The program is set up with the possibility of auto-triggering by the patient. | Device: Mechanical Insufflation-Exsufflation<br>* MI-E will be applied twice a day in invasively ventilated patients. Since the severity of illness can change in the ICU, each day the attending nurse will check for clinical reasons to not apply MI-E with regard to safety. The following clinical criteria are predefined as a reason to refrain from MI-E at that day: severe ventilator instability (requiring > 12 cm H2O PEEP and dependency of > 60% FiO2); severe hemodynamic instability (a need for large and sustained increase in continuous administration of intravenous vasopressive medication that are adjusted on a frequent basis in each nursing shift); extra corporal membrane oxygenation (ECMO); and deeply sedated patient (RASS score ≤ -4).<br>* Other names: Cough assist;|
| No Intervention: Standard airway care<br>Patients in the control group will receive usual airway care which includes endotracheal suctioning and manual hyperinflation used when indicated based on clinical signs as part of regular airway care. Care protocols for endotracheal suctioning and manual hyperinflation are predefined. As with the intervention arm, there will be no use of saline instillation during suctioning. Manual hyperinflation technique is described in the care protocol of the intensive care unit and ICU nurses are trained to perform this technique. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| intervention delivery | the proportion of complete sessions of MI-E every calender day (i.e. two MI-E sessions with 3 x 3 cycles of an in- and exsufflation) for all patients with a maximum of seven days of invasive ventilation | max. 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of pneumothorax (safety) | incidence of pneumothorax for which drainage is needed attributed to MI-E or to routine airway care procedures (i.e., manual hyperinflation) | max 7 days | 
| incidence of endotracheal tube obstruction (safety) | incidence of endotracheal tube obstruction due to mucus plugging attributed to MI-E or regular airway care | max 7 days | 
| incidence of severe hypoxemia (safety) | incidence of severe hypoxemia | max 7 days | 
| incidence of severe hypotension (safety) | incidence of severe hypotension | max 7 days | 
| incidence of severe hypertension (safety) | incidence of severe hypertension | max 7 days | 
| Acceptability of Intervention Measure (AIM) | 1 = Completely disagree, 2 = Disagree, 3 = Neither agree nor disagree, 4 = Agree, 5 = Response scale 1 (completely disagree) - 5 (completely agree) | through study completion, estimated one year | 
| Intervention Appropriateness Measure (IAM) | 1 = Completely disagree, 2 = Disagree, 3 = Neither agree nor disagree, 4 = Agree, 5 = Response scale 1 (completely disagree) - 5 (completely agree) | through study completion, estimated one year | 
| Feasibility of Intervention Measure (FIM) | 1 = Completely disagree, 2 = Disagree, 3 = Neither agree nor disagree, 4 = Agree, 5 = Response scale 1 (completely disagree) - 5 (completely agree) | through study completion, estimated one year | 
| amount of time needed for MI-E (feasibility) | time needed to deliver the MI-E intervention | maximum of 1 hour per session | 
| endotracheal suctioning (feasibility) | frequency of endotracheal suctioning per ventilation day | max. 7 days | 
| MH (feasibility of MI-E) | frequency of manual hyperinflation | max. 7 days | 
| VAP (efficacy MI-E sample size calculation) | incidence of ventilator associated pneumonia (VAP) | 28 days after inclusion | 
| duration MV (efficacy MI-E sample size calculation) | duration of invasive ventilation | 28 days after inclusion | 
| Mortality day 28 (efficacy MI-E sample size calculation) | mortality at day 28 | up to day 28 from ICU admission | 
| VFD-28 (efficacy MI-E sample size calculation) | ventilator-free days at day 28 | 28 days after inclusion | 
| ICU mortality (efficacy MI-E sample size calculation) | ICU mortality | 28 days after inclusion | 
| hospital mortality (efficacy MI-E sample size calculation) | hospital mortality | 28 days after inclusion | 
| supplemental oxygen (efficacy MI-E sample size calculation) | use of supplemental oxygen on ICU delivery after detubation | 28 days after inclusion | 
| LOS ICU (efficacy MI-E sample size calculation) | length of stay in ICU | 28 days after inclusion | 
| LOS hospital (efficacy MI-E sample size calculation) | length of stay in hospital | 28 days after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mechanical insufflation-exsufflation, Cough Assist