Role of cardiopulmonary interactions in development of ventilator-induced lung injury-Experimental evidence and clinical implications

Ventilator-induced lung injury (VILI) impacts outcomes in ARDS and optimization of ventilatory strategies improves survival. Decades of research has identified various mechanisms of VILI, largely focusing on airspace forces of plateau pressure, tidal volume and driving pressure. Experimental evidence indicates the role of adverse cardiopulmonary interaction during mechanical ventilation, contributing to VILI genesis mostly by modulating pulmonary vascular dynamics. Under passive mechanical ventilation, high transpulmonary pressure increases afterload on right heart while high pleural pressure reduces the RV preload. Together, they can result in swings of pulmonary vascular flow and pressure. Altered vascular flow and pressure result in increased vascular shearing and wall tension, in turn causing direct microvascular injury accompanied with permeability to water, proteins and cells. Moreover, abrupt decreases in airway pressure, may result in sudden overperfusion of the lung and result in similar microvascular injury, especially when the endothelium is stretched or primed at high positive end-expiratory pressure. Microvascular injury is universal in VILI models and presumed in the diagnosis of ARDS; preventing such microvascular injury can reduce VILI and impact outcomes in ARDS. Consequently, developing cardiovascular targets to reduce macro and microvascular stressors in the pulmonary circulation can potentially reduce VILI. This paper reviews the role of cardiopulmonary interaction in VILI genesis

Understanding clinical and biological heterogeneity to advance precision medicine in paediatric acute respiratory distress syndrome

Paediatric acute respiratory distress syndrome (PARDS) is a heterogeneous clinical syndrome that is associated with high rates of mortality and long-term morbidity. Factors that distinguish PARDS from adult acute respiratory distress syndrome (ARDS) include changes in developmental stage and lung maturation with age, precipitating factors, and comorbidities. No specific treatment is available for PARDS and management is largely supportive, but methods to identify patients who would benefit from specific ventilation strategies or ancillary treatments, such as prone positioning, are needed. Understanding of the clinical and biological heterogeneity of PARDS, and of differences in clinical features and clinical course, pathobiology, response to treatment, and outcomes between PARDS and adult ARDS, will be key to the development of novel preventive and therapeutic strategies and a precision medicine approach to care. Studies in which clinical, biomarker, and transcriptomic data, as well as informatics, are used to unpack the biological and phenotypic heterogeneity of PARDS, and implementation of methods to better identify patients with PARDS, including methods to rapidly identify subphenotypes and endotypes at the point of care, will drive progress on the path to precision medicine.</p

A Gas-Powered, Patient-Responsive Automatic Resuscitator For Use In Acute Respiratory Failure: A Bench And Experimental Study

BACKGROUND: During the COVID-19 pandemic, a need for innovative, inexpensive, and simple ventilator devices for mass use has emerged. The Oxylator (CPR Medical Devices, Markham, Ontario, Canada) is an FDA-approved, fist-size, portable ventilation device developed for out-of-hospital emergency ventilation. It has not been tested in conditions of severe lung injury or with added PEEP. We aimed to assess the performance and reliability of the device in simulated and experimental conditions of severe lung injury, and to derive monitoring methods to allow the delivery of safe, individualized ventilation during situations of surge. METHODS: We bench-tested the functioning of the device with an added PEEP valve extensively, mimicking adult patients with various respiratory mechanics during controlled ventilation, spontaneous breathing, and prolonged unstable conditions where mechanics or breathing effort was changed at every breath. The device was further tested on a porcine model (4 animals) after inducing lung injury, and these results were compared with conventional ventilation modes. RESULTS: The device was stable and predictable, delivering a constant flow (30 L/min) and cycling automatically at the inspiratory pressure set (minimum of 20 cm H2O) above auto-PEEP. Changes in respiratory mechanics manifested as changes in respiratory timing, allowing prediction of tidal volumes from breathing frequency. Simulating lung injury resulted in relatively low tidal volumes (330 mL with compliance of 20 mL/cm H2O). In the porcine model, arterial oxygenation, CO2, and pH were comparable to conventional modes of ventilation. CONCLUSIONS: The Oxylator is a simple device that delivered stable ventilation with tidal volumes within a clinically acceptable range in bench and porcine lung models with low compliance. External monitoring of respiratory timing is advisable, allowing tidal volume estimation and recognition of changes in respiratory mechanics. The device can be an efficient, low-cost, and practical rescue solution for providing ventilatory support as a temporary bridge, but it requires a caregiver at the bedside

Mechanical Ventilation in ARDS With an Automatic Resuscitator

BACKGROUND: The Oxylator is an automatic resuscitator, powered only by an oxygen cylinder with no electricity required, that could be used in acute respiratory failure in situations in which standard mechanical ventilation is not available or feasible. We aimed to assess the feasibility and safety of mechanical ventilation by using this automatic resuscitator in an animal model of ARDS. METHODS: A randomized experimental study in a porcine ARDS model with 12 pigs randomized to the Oxylator group or the control group (6 per group) and ventilated for 4 h. In the Oxylator group, peak pressure was set at 20 cm H2O and PEEP was set at the lowest observed breathing frequency during a decremental PEEP titration. The control pigs were ventilated with a conventional ventilator by using protective settings and PEEP at the crossing point of collapse and overdistention, as indicated by electrical impedance tomography. Our end points were feasibility and safety as well as respiratory mechanics, gas exchange, and hemodynamics. RESULTS: After lung injury, the mean ± SD respiratory system compliance and PaO2 /FIO2 were 13 ± 2 mL/cm H2O and 61 ± 17 mm Hg, respectively. The mean ± SD total PEEP was 10 ± 2 cm H2O and 13 ± 2 cm H2O in the control and Oxylator groups, respectively (P = .046). The mean plateau pressure was kept to 8 mL/kg but was 6 ± 0.4 mL/kg at 4 h, whereas the breathing frequency increased from 38 ± 4 to 48 ± 3 breaths/min (P < .001). There was no difference in driving pressure, compliance, PaO2 /FIO2 , and pulmonary shunt between the groups. The mean ± SD PaCO2 was higher in the Oxylator group after 4 h, 74 ± 9 mm Hg versus 58 ± 6 mm Hg (P < .001). There were no differences in hemodynamics between the groups, including blood pressure and cardiac output. CONCLUSIONS: Short-term mechanical ventilation by using an automatic resuscitator and a fixed pressure setting in an ARDS animal model was feasible and safe