Validation of clinical applicable techniques for end inspiratory lung volume (Vei) measurement.

Chronic pulmonary obstructive disease (COPD) and asthma are characterized by
acute or chronic airflow obstruction due to dynamic airway collapse during
expiration (in COPD patients) or airway narrowing by bronchospasm or bronchial
wall edema. When on the ventilator, in these patients, lung emptying is slow
and in the case of a high ventilator respiratory rate or high tidal volume (Vt)
the next inspiration may occur before complete lung emptying. This will result
in pulmonary hyperinflation, which is defined as additional volume above the
relaxing lung volume (functional residual capacity (FRC)) at the end of
expiration. Accordingly, the next inspiration occurs at a higher lung volume.
This will result in high intrathoracic pressure, increasing the risk of
pulmonary barotrauma, in particular pneumothorax, and hemodynamic compromise.
Ultimately, respiratory arrest may develop. To limit the risks associated with
pulmonary hyperinflation, intensivists will determine the degree of pulmonary
hyperinflation by calculation of the pulmonary volume at the end of inspiration
(Vei). Previous studies have shown that maintaining Vei below 20 ml/kg
predicted bodyweight limits the risks associated with hyperinflation. Many
clinical protocols, including the protocol approved by the medical ICU staff of
the Radboudumc dictate a strategy to limit pulmonary hyperinflation based on
Vei.
The Vei can be determined in various ways. The first method to determine Vei is
to measure the actual expiratory volume (Vei_measurement). While the patient is
ventilated in controlled ventilator mode an inspiratory occlusion maneuver is
performed using the dedicated knob on the ventilator. Subsequently, the
endotracheal tube is occluded while the patient is disconnected from the
ventilator. The tube is connected to a dedicated set-up to measure expired
volume. This method is considered to be the gold standard to determine Vei.
However, a disadvantage is that this method is rather cumbersome to use in
clinical practice and requires specific disposables not always readily
available at the bedside.
A second method to determine Vei, which is commonly used in clinical practice,
is by using the following formula:

Vei = Vt x Pplateau / Pplateau - PEEPtotal (Vei_formula)

The pressures in this formula can be measured by performing occlusion maneuvers
as described above. The plateau pressure (Pplateau) is the airway pressure
measured during an inspiratory occlusion and the total amount of positive end
expiratory pressure (PEEPtotal) is the airway pressure measured during an
expiratory occlusion. PEEPtotal is the sum of externally applied PEEP plus the
amount of intrinsic PEEP, the latter represents dynamic hyperinflation. The
pressures measured are the mean pressures of the alveoli that are open during
an occlusion.
A third method to determine Vei is by measuring the expired volume using the
flowsensors of the ventilator. In this method, the patient is briefly (max 45
seconds) switched to another ventilation mode, that allows passive exhalation
for up to 45 seconds (pressure support ventilation (PSV)). The expired volume
is detected by the ventilator and allows calculation of Vei (Vei_ventilator).
This method is easy to use in clinical practice, there is no need for
additional equipment and there are no additional costs. However, this method
has not yet been clinically validated.
The aim of the study is to compare two clinically used methods for measurement
of Vei
against the gold standard.

The primary objective of this study is to validate two clinically applicable
techniques to measure pulmonary hyperinflation (Vei) in mechanically ventilated
patients with airflow obstruction. This will be done by assessing differences
between the two techniques and the gold standard.

This study is a single centre non-therapeutic observational study performed in
invasively ventilated patients on the intensive care unit (ICU) with airflow
obstruction. The gold standard will be compared with two clinically applicable
techniques to determine Vei in each patient. Measurements will take about 15
minutes, a second set of measurements will be performed if values are outside
the range dictated by our clinical protocol and after ventilator settings are
changed according to the clinical protocol.

The Vei is measured in patients to allow safe mechanical ventilation according
to the clinical protocol. In case the Vei is outside the range dictated by the
clinical protocol, ventilator settings will be modified according to the
protocol and Vei will again be measured in various ways. This could be a
potential benefit for patient care.

Occlusion manoeuvers:
Occlusion manoeuvers are frequently performed in clinical practice in this
patient population to determine the Vei_formula. In this study the time for
expiration (Te) will be slightly longer than according to the current clinical
protocol (maximum 45 seconds, instead of 20 seconds). However, in clinical
practice patients with airflow obstruction ventilated with volume control
ventilation (VCV), may be disconnected from mechanical ventilation several
times a day for a period up to 1 minute to avoid hyperinflation. So in fact,
the study procedures are not importantly different from clinical practice.
Risks are negligible and the burden can be considered minimal. For patient
safety, measurements will be terminated in case:
• arterial oxygen saturation < 90%
• heart rate > 140/minute or an increase or decrease in heart rate of more than
20%
• systolic blood pressure > 180 mmHg or < 90 mmHg

Blood withdrawal:
Blood will be withdrawn at least once, and in case ventilator settings are
changed, twice. Each sample requires 1.0 ml of blood. Blood will be withdrawn
from an indwelling arterial catheter already present as part of routine
clinical care. Therefore, no adverse events are anticipated from blood
withdrawal.

This study can only be performed in invasively ventilated ICU patients. The Vei
is already determined several times a day in this population to allow safe
mechanical ventilation. In healthy subjects with airflow obstruction dynamic
hyperinflation can also occur, but these subjects are not yet respiratory
insufficient and thus these subjects have different lung dynamics. Airway
collapse could perhaps be simulated, but this is obviously clinically less
relevant as it remains a model and cannot reflect the true in vivo situation.