ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12614001069640

Ethics application status

Approved

Date submitted

22/09/2014

Date registered

7/10/2014

Date last updated

22/11/2022

Date data sharing statement initially provided

4/03/2019

Type of registration

Prospectively registered

Titles & IDs

Public title

Optimising mechanical ventilation in Intensive Care Unit (ICU)

Scientific title

The effect of Model-based positive end expiratory pressure (PEEP) selection compared to standard practice PEEP selection in the length of mechanical ventilation of respiratory failure patients.

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1161-1833

Trial acronym

Clinical Utilisation of Respiratory Elastance: the 'CURE' Study - Optimising PEEP in people on mechanical ventilation

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Acute respiratory distress syndrome (mild, moderate, severe)

Respiratory failure patients requiring mechanical ventilation

Condition category

Condition code

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Clinical Protocol
Patients who meet the inclusion criteria will be randomised to intervention or control Patients’ data on both arms will be monitored.

Patients on the intervention will have their ventilation PEEP setting being guided by the bedside computer using the pulmonary elastance model. Patients will undergo Maximum Recruitment Manoeuvre (MaxRM) or PEEP adjustment and Monitoring Procedure (PUMP). MaxRM and PUMP are step-wise PEEP change recruitment manoeuvres (RM). During the RM, PEEP will be adjusted by steps of increase and decrease and the pulmonary elastance of the patient at each PEEP is calculated using the bedside computer.

The protocol will ideally be run for at least 48 hours, and discontinued at the discretion of the clinician when patient lung condition has significantly improved. Data collection will continue until patient is discontinued from mechanical ventilation.

Patient Preparation
1. For the length of mechanical ventilation, patients will be randomised to Control or Intervention using a block randomisation software.

2. For patients randomised for control, they will receive current standard of care of the participating centre.

3. For patients included for intervention, the PEEP and MV will be guided by clinicians using bedside computers.
(i) All patients in the intervention are ventilated using (i) Puritan Bennett PB840 ventilator (Covidien, Boulder, CO, USA) or (ii) Draeger V500 ventilator (Dragerwerk AG & Co. Lubeck, Germany) or (iii) Hamilton Medical G5 ventilator (Bonaduz, Switzerland) using synchronized intermittent mandatory ventilation (SIMV) with volume control while maintaining tidal volume and FiO2 similar to the control group.
(ii) Before the RM, patients may be sedated and paralyzed with muscle relaxants to prevent spontaneous breathing efforts.
(iii) The first RM when the patient is included in the study is a maximum recruitment manoeuvre (MaxRM). This is done at the beginning of the trial by clinicians and only repeated if clinically indicated. Other PEEP adjustments will be a modification of the MaxRM. The PEEP Adjustment and Monitoring Procedure is referred to as a ‘PUMP’, where the change of PEEP is -2 cmH2O to 6 cmH2O of the current PEEP setting The PUMP may be performed by either medical or nursing staff trained in the technique.
(iv) The PEEP adjustment will stop
a. When weaning from mechanical ventilation is considered appropriate, and
b. The patient has transitioned to spontaneous breathing; defined as when the respiratory rate is set to equal or less than 10 breaths per minute and
c. Patient's FiO2 equal or less than 35% and
d. Arterial blood oxygen, PaO2 equal or more than 60mmHg at FiO2 equal or less than 35% for the last 24 hours.
e. After 10 days from study enrolment.
f. At the discretion of the clinician when the patient's lung injury is no longer thought to be delaying their recovery.

4. Data will be collected continuously until the patient is disconnected from the ventilator.

Maximum Recruitment Manoeuvre (MaxRM)
Patients randomised into intervention will immediately receive the following intervention:
1. Patient airway cuff pressure will be increased to 50 cmH2O to prevent leaks during maximum recruitment manoeuvre (MaxRM).
2. The peak airway pressure alarm on the ventilator is set to 55 cmH2O.
3. Prior to the MaxRM, a muscle relaxant with appropriate sedation (eg. fentanyl and/ or propofol) are co-administered.
4. During the MaxRM, PEEP is initially increased in steps of 4 cmH2O above the baseline PEEP level (selected by clinicians) until Peak airway pressure reaches (PIP) equal or more than 45 cmH2O and thereafter, in 2 cmH2O until PIP equal or more than 50 cmH2O.
5. Each PEEP is maintained for 10-15 breathing cycles for calculation of Elastance before a subsequent PEEP increase.
6. After reaching PIP of equal or more than 50 cmH2O, PEEP is reduced by 4 cmH2O steps until initial PEEP setting.
7. Once PEEP has returned to the initial setting, a second RM is performed with PEEP increase steps of 4 cmH2O to the same PIP used in the first RM. PEEP is then decreased by steps of 2 cmH2O until the optimal PEEP level has been obtained. This PEEP will be recommended by bedside computer when the elastance decrement is e equal or less than 5% of the previous value.
8. If the intensive care clinicians do not feel the recommended PEEP level is appropriate, they will have the discretion to select a PEEP of their choice. The clinician will be prompted to record the reasons they have not followed the recommendation.
9. This process will be performed at the beginning of the trial, and only repeated at the clinician’s discretion, e.g. if there has been a possible loss of recruitment following a disconnection from the ventilator.
10. At the end of the MaxRM, the cuff pressure is reduced back to ~30 cmH2O and the ventilator high pressure alarm is set to back to initial setting.

PEEP adjustment and Monitoring Procedure (PUMP)
This procedure is performed when:
i. The patient is turned to supine position or
ii. Every subsequent 6 hours after the first RM or
iii. If the FiO2 is increased by equal or more than 10% or
iv. Anytime at the clinician's discretion
Whichever of (i) –(iv) occurs first triggers a PUMP procedure.
*Usual clinical practice is to turn patients left side to supine to right side every three hours

The procedure for the above PEEP adjustment and monitoring manoeuvres (PUMPs) are as follows:
1. PEEP is first decreased by 2 cmH2O and increased in 2 steps of 4 cmH2O with 10-15 breathing cycles at each step before decreasing back in 4 cmH2O decrements to -2 cmH2O of baseline PEEP.
2. Step 1 is immediately repeated, except the PEEP is reduced in 2 cm decrements.
3. The Bedside computer will recommend the optimal PEEP, at a PEEP higher than minimal elastance at the end of the second PUMP Recruitment Manoeuvre.
4. If the intensive care clinicians do not feel the recommended PEEP level is appropriate, they will have the discretion to select a PEEP of their choice. The clinician will be prompted to record the reasons they have not followed the recommendation.

Intervention code [1]

Treatment: Devices

Comparator / control treatment

Patients on standard ventilation practice based on clinicians and hospital practice.

The patients will receive current standard of care, which limits plateau pressure less than or equal to 30 cmH2O while maximising tidal volume, Vt = 4 to 8ml/kg based on predicted body weight using arm demispan.

Positive end expiratory pressure (PEEP) and MV will be selected by clinicians as per standard practice.

FiO2 (fraction of inspired oxygen) will be adjusted as follows: The pulse oximetry recording (SpO2) will be maintained
(i) equal or more than 96% if the FiO2 is equal or more than 30% but less than 40%;
(ii) equal or more than 94% if the FiO2 is equal or more than 40%, but less than 60% and
(iii) 88% - 92% if the FiO2 is equal or more than 60%.

It is very important to standardise oxygen titration to pulse oximetry recordings to ensure robustness of outcomes. Upper and lower SpO2 alarm limits will be set to ensure these guidelines are followed. There is no upper SpO2 limit if the FiO2 is less than 30%.

Control group

Active

Outcomes

Primary outcome [1]

Length of mechanical ventilation (LoMV)

Timepoint [1]