Effects of Low Tidal Volume and Respiratory Rate Together with the Use of End-inspiratory on Alveolar Ventilation in ARDS Patients

Reduction of tidal volume (VT) to 6 mL/kg normalized to predicted body weight (PBW) and driving pressure limitation up to 15 cmH20 are essential ventilatory strategies that positively impact clinical outcomes of acute respiratory distress syndrome (ARDS) patients. Recently, mechanical power has also been linked to ventilator-induced lung injury (VILI) and associated with mortality, mainly due to its dynamic-elastic effects. However, despite using these low VT strategies, it is possible to develop VILI in moderate to severe ARDS patients, especially when driving pressure exceeds established safety limits for lung protection. In these situations, a VT less than 6 mL/kg-PBW is recommended, but an increase in respiratory rates (RR) is required to counteract the side effects of secondary hypercapnia (PaCO2 levels greater than 45 mmHg). In turn, the RR needed to achieve this target is at least 25 breaths/min, even if a mild degree of hypercapnia is often accepted. Yet, mechanical ventilator programming with higher RR per minute may promote lung tissue inflammation and could be associated with adverse outcomes in ARDS.

Thus, in ARDS is challenging to establish a combined strategy of tidal volume (VT) and respiratory rate RR reduction since its utmost problem is an increase in the partial pressure of carbon dioxide (PaCO2) and impairment of ventilatory efficiency, the magnitude of which is linked to the disease severity. For this reason, some non-invasive strategies are available to attenuate hypercapnia and improve the lung's ability to CO2 clearance. Among them, it is worth highlighting the end-inspiratory pause (EIP). This strategy has shown its usefulness in increasing CO2 clearance by improving the mean time given to inspired gas for distribution and diffusive mixing within the lungs. Nevertheless, the role of EIP as part of a protective ventilation strategy that combines the VT and RR reductions is unknown.

Therefore, we hypothesize that adding an end-inspiratory pause (EIP) improves CO2 expiration and that such an effect allows a decrease in the VT and RR for more lung-protective purposes. Thus, the main objective of this study is to evaluate the effects of an EIP on Bohr´s dead space (VDBohr/VT) and PaCO2 when combined with a VT and the RR reduction in ARDS. The secondary aim is to evaluate ventilatory strategy on air distribution and homogeneity by electrical impedance tomography.

Patient selection Patients ≥18 years of age with mild, moderate, and severe ARDS up to 5 days of mechanical ventilation. Patients must be under deep sedation and neuromuscular paralysis. Patients with hemodynamic instability, acute heart failure, previous chronic respiratory disease, and variations in oesophageal temperature higher than 0.5 °C in the last 2 hours will be excluded.

Baseline mechanical ventilation settings Mechanical ventilation at baseline will be programmed in volume-controlled mode with a Servo-i (Maquet, Solna, Sweden) and the following parameters: a VT of 7 ml/kg-PBW, an RR adjusted to ensure an arterial pH greater than 7.30 and no intrinsic positive end-expiratory pressure (PEEP), an inspiratory insufflation time of 0.6 seconds, an inspiratory: expiratory (I: E) ratio of 1:2, and no EIP. End-expiratory transpulmonary pressure will be set at the beginning of the study by electrical impedance tomography. The PBW was calculated as follows: 50+ [0.91 *(height in cm-152.4)] for men and 45.5+ [0.91* (height in cm-152.4)] for women. Active humidification will be used in all participants, and compressible volume compensation was performed in each mechanical ventilator used before starting the protocol.