We conducted a lung simulation study using a high-end lung simulator to investigate the effect of reductions in PS and increase in the respiratory rate on SBTs.

### Devices

We used an IngMar ASL 5000™ artificial lung simulator (version 3.4, 3.5; IngMar Medical, Pittsburgh, PA) with a built-in cylinder with a 17.8-cm diameter. The ASL 5000™ is a popular lung stimulator, which can imitate different breathing conditions and can measure various ventilation parameters including WOB, trigger work (TW), pressure of effort (pressure of muscle [Pmus]), maximum pressure drop during trigger, and positive end-expiratory pressure (PEEP). Respiratory parameters are automatically displayed on the control panel. We regarded the ASL 5000™ as a model of the lower respiratory tract (i.e., the upper respiratory tract was not included). We set the ASL 5000™ to reflect a 3-kg neonate after cardiac surgery to simulate SBTs with compliance at 0.5 mL/cmH_{2}O/kg [5] and resistance at 40 cmH_{2}O/L/s. The reference values for healthy neonate compliance and resistance are 1.5–2.0 mL/cmH_{2}O/kg and 20–40 cmH_{2}O/L/s, respectively [13, 14]. The ASL 5000™ was set to the constant VT mode under computer control, with a tidal volume of 30 mL (10 mL/kg) and a minute volume of 720–1080 mL/min, which corresponds to a respiratory rate (f) of 24–36/min. Endotracheal tubes with an inside diameter of 3.0 and 3.5 (Mallinckrodt™; Hi-Contour Oral/Nasal Tracheal Tube Cuffed Murphy Eye, Dublin, Ireland) were clinically curved and cuffed to prevent gas leakage. A 22/19-mm adapter with a built-in duct (diameter, 9 mm) was attached because the port of the ASL 5000™ was too large to attach an endotracheal tube. A ventilator (SERVO-i Universal™, version 3.0.1; Maquet, Danvers, MA) was set at PSV: PEEP, 4 cmH_{2}O; FIO_{2}, 0.4; inspiration time was set at 45% of respiration; and bias flow of 0.5 L/min was continuously delivered to the respiratory circuit. Trigger sensitivity was set to 5 to detect bias flow deviation of 0.25 L/min at the expiratory channel. The ventilator was connected to the artificial lung by means of a respiratory circuit (Smooth-Bor™; Smooth-Bor Plastics, Laguna Hills, CA). No respiratory humidifier or heat/moisture exchanger was used.

### Study

The following work and pressure parameters were measured under three breathing settings: (1) ASL 5000™ alone, (2) T-piece breathing, and (3) PSV. The parameters were measured under two control settings: the respiratory rate control setting and the PS control setting. At first, the parameters of all three breathing settings were measured in the respiratory rate control setting. In the respiratory rate control setting, the respiratory rate was increased from 24 to 36/min. The parameters under PSV were measured with a fixed PS of 10 cmH_{2}O and 8 cmH_{2}O in the respiratory rate control setting. Then, the PS control setting was used under PSV alone. The parameters were measured under the PS control setting with a fixed respiratory rate of 24 and 36/min. Under the PS control setting, PS was decreased from 14 to 0 cmH_{2}O.

### Definition of respiratory variables

WOB measurement was started at 0.5 mL of gas inhaled and ended at 0.5 mL gas exhaled. TW was defined as the WOB between the start of the WOB measurement and the point in time at which airway pressure returned to baseline (PEEP), after a downward deflection. WOB and TW were calculated using Eq. (1) (below). Patient effort was defined as the negative of muscle pressure [− Pmus], which resembles an esophageal pressure tracing. We specified that the WOB of the ASL 5000™ alone must be lower than the WOB after extubation, because the ASL 5000™ did not include the upper respiratory tract.

$$ \mathrm{WOB}\left(\mathrm{mJ}/\mathrm{Breath}\right)=\int \mathrm{Pmus}\left({\mathrm{cmH}}_2\mathrm{O}\right)\ \mathrm{dV} $$

(1)

WOB was measured at a stable tidal volume, and the mean and standard deviation values were determined from 10 breaths to account for instability.

Dynamic distending pressure was calculated using Eq. (2):

$$ \mathrm{Dynamic}\ \mathrm{distending}\ \mathrm{pressure}\left({\mathrm{cmH}}_2\mathrm{O}\right)=\mathrm{PIP}\ \left({\mathrm{cmH}}_2\mathrm{O}\right)-\mathrm{Pmus}\left({\mathrm{cmH}}_2\mathrm{O}\right) $$

(2)

Peak inspiratory pressure (PIP) is the pressure which is delivered by ventilator. Dynamic distending pressure of T-piece breathing is equivalent of Pmus of T-piece breathing, because T-piece breathing is not under pressure support.

The Reynolds number was calculated from the mean and peak flow using Eq. (3) [15].

$$ \operatorname{Re}=\left[2\rho \left(\mathrm{g}/{\mathrm{cm}}^3\right)\times \dot{V} \left({\mathrm{cm}}^3/\mathrm{s}\right)\right]\div \left[\pi \times r\left(\mathrm{cm}\right)\times \eta \left(\mathrm{poise}\right)\right] $$

(3)

where we used the following constants: 20 °C; dry gas, FiO_{2}, 0.4, viscosity *η* (poise = 0.1 Pa s = kg/m s), 18.72 × 10^{−6}, and density *ρ* (g/cm^{3}), 1.231 × 10^{3} [16, 17]. *V̇* is the mean flow rate (cm^{3}/s), *r* is the inner radius of the tube (cm), and *π* is the ratio of the circumference of the circle to its diameter.

### Statistical analysis

Ten successive breaths per condition were measured. We used two-way analysis of variance (ANOVA) with Tukey’s multiple-comparison test for statistical analyses. WOB and TW were analyzed by linear or non-linear regression analysis as appropriately. All statistical analyses were performed using GraphPad Prism (GraphPad Software, Inc., La Jolla, CA). A *p* value < 0.05 was considered statistically significant.