Surfactant Depletion Combined with Injurious Ventilation Results in a Reproducible Model of the Acute Respiratory Distress Syndrome (ARDS)

The combination of surfactant wash-out with injurious ventilation reduces the recruitability of the lung injury as compared to models with exclusive surfactant wash-out. The model is reproducible and does not require additional techniques. Furthermore, a two-hit model closely mimics the realistic clinical situation.

The low recruitability of this model supports the experimental investigation of new ventilation strategies, paving the way for the translation of experimental lung research into clinical practice. To begin, set the mechanical ventilation parameters as described in the text manuscript, and target an end expiratory partial pressure of carbon dioxide of 35 to 40 millimeters of mercury and an oxygen saturation above 95%Use a continuous intravenous infusion of thiopentone and fentanyl to maintain the anesthesia, and administer a muscle relaxant if required. Cannulate the external jugular vein with a central venous catheter, and insert the introducer sheath of the pulmonary arterial catheter into the same vein.

Then, cannulate the femoral artery for invasive blood pressure monitoring. Calibrate the transducers against the atmosphere, which is zero millimeters of mercury and 200 millimeters of mercury for the arterial line, and 50 millimeters of mercury for the central venous line, and start monitoring by connecting them to the arterial catheter and the central venous line. Connect the pulmonary artery catheter to the pressure transducer system and calibrate the transducer against the atmosphere and 100 millimeters of mercury.

Then, introduce the pulmonary artery catheter through the introducer sheath with a deflated balloon for 10 to 15 centimeters, depending on the sheath length. Once the balloon has left the sheath, inflate it and advance the pulmonary artery catheter further while monitoring the pressure. Push the pulmonary artery catheter forward when the right atrium, the right ventricle, and the pulmonary artery pressure waves appear on the monitor, and stop when the pulmonary capillary wedge pressure wave is seen.

Then, record the pulmonary capillary wedge pressure at end expiration and deflate the balloon. Calculate the pressure parameters described in the text manuscript, and record the required respiratory settings and measurements to complete the dataset. Ventilate the animal with a fraction of inspired oxygen of one, then disconnect the animal from the ventilator.

Fill the lungs with pre-warmed saline using a funnel connected to the endotracheal tube. Stop if the mean arterial pressure decreases below 50 millimeters of mercury. Drain the lavage fluid by lowering the funnel to the ground level, and monitor the wave.

Reconnect to the animal to the ventilator for oxygenation and wait until the animal recuperates, then repeat lavages until the Horowitz index decreases below 100 millimeters of mercury for at least five minutes at a fraction of inspired oxygen of one, and a positive end expiratory pressure above five millibar. Take an arterial blood gas sample after five minutes following each lavage. Keep the fraction of inspired oxygen at one, and set the ventilator on the volume-guaranteed, pressure-controlled ventilation mode.

Increase the alarm threshold for peak inspiratory pressure to 60 millibar. Lower the respiratory rate, and set the inspiration-to-expiration ratio, then increase the tidal volume slowly up to 17 milliliters per kilogram body weight over at least two minutes. Do not increase the tidal volume further if an inspiratory pressure of 60 millibar is reached.

Reduce the positive end expository pressure to two millibar and ventilate the animal for up to two hours. The Horowitz index decreased during the surfactant washout in all animals, but the recruitment maneuver resulted in a notable increase in oxygenation after the surfactant wash-out. The injurious ventilation of two hours diminished lung recruitability with respect to gas exchange and the mean pulmonary arterial pressure.

The gas exchange parameters were improved with high tidal volumes due to the cyclic recruitment, while mean pulmonary arterial pressure was elevated due to high intrathoracic pressures and hypercapnia. Computer tomographic imaging of the lungs showed extensive atelectasis of the dependent areas of the lung during the ventilation, with a positive end expiratory pressure of six millibar, which resolved largely when the ventilation was escalated to a positive end expiratory pressure of 15 millibar. However, the substantial ubiquitous ground glass opacities did not resolve.

The alveolar opacities observed with a positive end expiratory pressure of 15 millibar indicated structural damage of the lungs. They were also observed in the post-mortem examination of the lungs. When attempting this protocol, it is important to adjust the duration of injurious ventilation because structural lung damage cannot be recruited, and an animal might die prematurely if the injury is too extensive.

The combination of surfactant depletion and injurious ventilation supports the investigation of therapies resulting in fast recruitment of atelectatic lung regions, such as ventilation modes with high ventilatory pressures.