Positive end-expiratory pressure in COVID-19 acute respiratory distress syndrome: the heterogeneous effects

Background We hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5–15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients. Methods Sixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54–67] years, PaO2/FiO2 113 [79–158] mmHg and PEEP 10 [10–10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected. Results At 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial–venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP. Conclusions In COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.

Lung and chest wall mechanics in patients with acute respiratory distress syndrome, expiratory flow limitation, and airway closure

Expiratory flow limitation (EFL) and airway closure (AC) were observed in 32% and 52%, respectively, of 25 patients with ARDS investigated during mechanical ventilation in supine position with a positive end-expiratory pressure of 5 cmH2O. The performance of dynamic lung elastance to detect expiratory flow limitation was good and better than that to detect airway closure. The vast majority of patients with EFL also had AC; however, AC can occur in the absence of EFL.

Distinguishing L and H phenotypes of COVID-19 using a single x-ray image

Recent observations have shown that there are two types of COVID-19 response: an H phenotype with high lung elastance and weight, and an L phenotype with low measures1. H-type patients have pneumonia-like thickening of the lungs and require ventilation to survive; L-type patients have clearer lungs that may be injured by mechanical assistance2,3. As treatment protocols differ between the two types, and the number of ventilators is limited, it is vital to classify patients appropriately. To date, the only way to confirm phenotypes is through high-resolution computed tomography2. Here, we identify L- and H-type patients from their frontal chest x-rays using feature-embedded machine learning. We then apply the categorization to multiple images from the same patient, extending it to detect and monitor disease progression and recovery. The results give an immediate criterion for coronavirus triage and provide a methodology for respiratory diseases beyond COVID-19.

Lung Recruitment in Obese Patients with Acute Respiratory Distress Syndrome

Editor’s Perspective What We Already Know about This Topic Obesity increases the propensity to atelectasis in acute respiratory distress syndrome, but the optimal approach to reversing this atelectasis is uncertain What This Article Tells Us That Is New A clinical crossover study comparing three approaches to titrate positive end-expiratory pressure (PEEP; according to a fixed table, according to end-expiratory esophageal pressure, and targeting the best compliance during a decremental PEEP trial) found that a recruitment maneuver followed by decremental PEEP minimized atelectasis and overdistension, and best restored compliance and oxygenation without causing hemodynamic impairment Background Obese patients are characterized by normal chest-wall elastance and high pleural pressure and have been excluded from trials assessing best strategies to set positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). The authors hypothesized that severely obese patients with ARDS present with a high degree of lung collapse, reversible by titrated PEEP preceded by a lung recruitment maneuver. Methods Severely obese ARDS patients were enrolled in a physiologic crossover study evaluating the effects of three PEEP titration strategies applied in the following order: (1) PEEPARDSNET: the low PEEP/Fio2 ARDSnet table; (2) PEEPINCREMENTAL: PEEP levels set to determine a positive end-expiratory transpulmonary pressure; and (3) PEEPDECREMENTAL: PEEP levels set to determine the lowest respiratory system elastance during a decremental PEEP trial following a recruitment maneuver on respiratory mechanics, regional lung collapse, and overdistension according to electrical impedance tomography and gas exchange. Results Fourteen patients underwent the study procedures. At PEEPARDSNET (13 ± 1 cm H2O) end-expiratory transpulmonary pressure was negative (−5 ± 5 cm H2O), lung elastance was 27 ± 12 cm H2O/L, and PaO2/Fio2 was 194 ± 111 mmHg. Compared to PEEPARDSNET, at PEEPINCREMENTAL level (22 ± 3 cm H2O) lung volume increased (977 ± 708 ml), lung elastance decreased (23 ± 7 cm H2O/l), lung collapse decreased (18 ± 10%), and ventilation homogeneity increased thus rising oxygenation (251 ± 105 mmHg), despite higher overdistension levels (16 ± 12%), all values P < 0.05 versus PEEPARDSnet. Setting PEEP according to a PEEPDECREMENTAL trial after a recruitment maneuver (21 ± 4 cm H2O, P = 0.99 vs. PEEPINCREMENTAL) further lowered lung elastance (19 ± 6 cm H2O/l) and increased oxygenation (329 ± 82 mmHg) while reducing lung collapse (9 ± 2%) and overdistension (11 ± 2%), all values P < 0.05 versus PEEPARDSnet and PEEPINCREMENTAL. All patients were maintained on titrated PEEP levels up to 24 h without hemodynamic or ventilation related complications. Conclusions Among the PEEP titration strategies tested, setting PEEP according to a PEEPDECREMENTAL trial preceded by a recruitment maneuver obtained the best lung function by decreasing lung overdistension and collapse, restoring lung elastance, and oxygenation suggesting lung tissue recruitment.

Role of Chymotrypsin-like Elastase 1 in Lung Physiology and in α1-Antitrypsin Deficiency

Abstractα1-antitrypsin related lung disease (AAT-RLD) is the fourth leading indication for lung transplantation and is characterized by protease-mediated progressive emphysema that manifests in the 4th or 5th decade of life. Chymotrypsin-like elastase 1 (Cela1) is a digestive enzyme that binds to elastin in a stretch-dependent manner and is covalently neutralized by AAT. We hypothesized a role for Cela1 in AAT-RLD. Cela1-/- mice where phenotypically similar to wild type but had higher lung elastance and lacked stretch-inducible elastase activity. Wild-type mice administered anti-AAT oligo had reduced amounts of lung Cela1-AAT fusion protein in lung homogenate and spontaneously developed emphysema after 6 weeks. Cela1-/- mice administered anti-AAT oligo were completely protected from these emphysematous changes. Cela1 recombinant protein did not require propeptide cleavage for elastolysis, and its elastolytic profile was similar to that of other pancreatic elastases. Phylogenetic analysis of vertebrate Cela promoter and protein sequences showed that placental mammal Cela1 was distinct from other Cela’s, and that the placental mammal the Cela1 gene was invariantly conserved despite variable loss of other Cela genes in non-carnivores. These data demonstrate that the pancreatic enzyme Cela1 has been evolutionarily co-opted for a role in reducing lung elastance in the placental mammal lineage and that its stretch-regulated expression and elastolytic activity is responsible for emphysema in the absence of its anti-protease: AAT.