Tidal lung hysteresis to interpret PEEP-induced changes in compliance in ARDS patients.

BACKGROUND: In ARDS, the PEEP level associated with the best respiratory system compliance is often selected; however, intra-tidal recruitment can increase compliance, falsely suggesting improvement in baseline mechanics. Tidal lung hysteresis increases with intra-tidal recruitment and can help interpreting changes in compliance. This study aims to assess tidal recruitment in ARDS patients and to test a combined approach, based on tidal hysteresis and compliance, to interpret decremental PEEP trials. METHODS: A decremental PEEP trial was performed in 38 COVID-19 moderate to severe ARDS patients. At each step, we performed a low-flow inflation-deflation manoeuvre between PEEP and a constant plateau pressure, to measure tidal hysteresis and compliance. RESULTS: According to changes of tidal hysteresis, three typical patterns were observed: 10 (26%) patients showed consistently high tidal-recruitment, 12 (32%) consistently low tidal-recruitment and 16 (42%) displayed a biphasic pattern moving from low to high tidal-recruitment below a certain PEEP. Compliance increased after 82% of PEEP step decreases and this was associated to a large increase of tidal hysteresis in 44% of cases. Agreement between best compliance and combined approaches was accordingly poor (K = 0.024). The combined approach suggested to increase PEEP in high tidal-recruiters, mainly to keep PEEP constant in biphasic pattern and to decrease PEEP in low tidal-recruiters. PEEP based on the combined approach was associated with lower tidal hysteresis (92.7 ± 20.9 vs. 204.7 ± 110.0 mL; p < 0.001) and lower dissipated energy per breath (0.1 ± 0.1 vs. 0.4 ± 0.2 J; p < 0.001) compared to the best compliance approach. Tidal hysteresis ≥ 100 mL was highly predictive of tidal recruitment at next PEEP step reduction (AUC 0.97; p < 0.001). CONCLUSIONS: Assessment of tidal hysteresis improves the interpretation of decremental PEEP trials and may help limiting tidal recruitment and energy dissipated into the respiratory system during mechanical ventilation of ARDS patients.

Association of lung recruitment and change in recruitment-to-inflation ratio from supine to prone position in acute respiratory distress syndrome.

Prone positioning is an evidence-based treatment for patients with moderate-to-severe acute respiratory distress syndrome. Lung recruitment has been proposed as one of the mechanisms by which prone positioning reduces mortality in this group of patients. Recruitment-to-inflation ratio (R/I) is a method to measure potential for lung recruitment induced by a change in positive end-expiratory pressure (PEEP) on the ventilator. The association between R/I and potential for lung recruitment in supine and prone position has not been studied with computed tomography (CT) scan imaging. In this secondary analysis, we sought to investigate the correlation between R/I measured in supine and prone position with CT and the potential for lung recruitment as measured by CT scan. Among 23 patients, the median R/I did not significantly change from supine (1.9 IQR 1.6-2.6) to prone position (1.7 IQR 1.3-2.8) (paired t test p = 0.051) but the individual changes correlated with the different response to PEEP. In supine and in prone position, R/I significantly correlated with the proportion of lung tissue recruitment induced by the change of PEEP. Lung tissue recruitment induced by a change of PEEP from 5 to 15 cmH2O was 16% (IQR 11-24%) in supine and 14.3% (IQR 8.4-22.6%) in prone position, as measured by CT scan analysis (paired t test p = 0.56). In this analysis, PEEP-induced recruitability as measured by R/I correlated with PEEP-induced lung recruitment as measured by CT scan, and could help to readjust PEEP in prone position.

Lung Recruitment Assessed by Electrical Impedance Tomography (RECRUIT): A Multicenter Study of COVID-19 Acute Respiratory Distress Syndrome.

Rationale: Defining lung recruitability is needed for safe positive end-expiratory pressure (PEEP) selection in mechanically ventilated patients. However, there is no simple bedside method including both assessment of recruitability and risks of overdistension as well as personalized PEEP titration. Objectives: To describe the range of recruitability using electrical impedance tomography (EIT), effects of PEEP on recruitability, respiratory mechanics and gas exchange, and a method to select optimal EIT-based PEEP. Methods: This is the analysis of patients with coronavirus disease (COVID-19) from an ongoing multicenter prospective physiological study including patients with moderate-severe acute respiratory distress syndrome of different causes. EIT, ventilator data, hemodynamics, and arterial blood gases were obtained during PEEP titration maneuvers. EIT-based optimal PEEP was defined as the crossing point of the overdistension and collapse curves during a decremental PEEP trial. Recruitability was defined as the amount of modifiable collapse when increasing PEEP from 6 to 24 cm H2O (ΔCollapse24-6). Patients were classified as low, medium, or high recruiters on the basis of tertiles of ΔCollapse24-6. Measurements and Main Results: In 108 patients with COVID-19, recruitability varied from 0.3% to 66.9% and was unrelated to acute respiratory distress syndrome severity. Median EIT-based PEEP differed between groups: 10 versus 13.5 versus 15.5 cm H2O for low versus medium versus high recruitability (P < 0.05). This approach assigned a different PEEP level from the highest compliance approach in 81% of patients. The protocol was well tolerated; in four patients, the PEEP level did not reach 24 cm H2O because of hemodynamic instability. Conclusions: Recruitability varies widely among patients with COVID-19. EIT allows personalizing PEEP setting as a compromise between recruitability and overdistension. Clinical trial registered with www.clinicaltrials.gov (NCT04460859).

Prognostic factors associated with mortality among patients receiving venovenous extracorporeal membrane oxygenation for COVID-19: a systematic review and meta-analysis.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (ECMO) can be considered for patients with COVID-19-associated acute respiratory distress syndrome (ARDS) who continue to deteriorate despite evidence-based therapies and lung-protective ventilation. The Extracorporeal Life Support Organization has emphasised the importance of patient selection; however, to better inform these decisions, a comprehensive and evidence-based understanding of the risk factors associated with poor outcomes is necessary. We aimed to summarise the association between pre-cannulation prognostic factors and risk of mortality in adult patients requiring venovenous ECMO for the treatment of COVID-19. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and Embase from Dec 1, 2019, to April 14, 2022, for randomised controlled trials and observational studies involving adult patients who required ECMO for COVID-19-associated ARDS and for whom pre-cannulation prognostic factors associated with in-hospital mortality were evaluated. We conducted separate meta-analyses of unadjusted and adjusted odds ratios (uORs), adjusted hazard ratios (aHRs), and mean differences, and excluded studies if these data could not be extracted. We assessed the risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Our protocol was registered with the Open Science Framework registry, osf.io/6gcy2. FINDINGS: Our search identified 2888 studies, of which 42 observational cohort studies involving 17 449 patients were included. Factors that had moderate or high certainty of association with increased mortality included patient factors, such as older age (adjusted hazard ratio [aHR] 2·27 [95% CI 1·63-3·16]), male sex (unadjusted odds ratio [uOR] 1·34 [1·20-1·49]), and chronic lung disease (aHR 1·55 [1·20-2·00]); pre-cannulation disease factors, such as longer duration of symptoms (mean difference 1·51 days [95% CI 0·36-2·65]), longer duration of invasive mechanical ventilation (uOR 1·94 [1·40-2·67]), higher partial pressure of arterial carbon dioxide (mean difference 4·04 mm Hg [1·64-6·44]), and higher driving pressure (aHR 2·36 [1·40-3·97]); and centre factors, such as less previous experience with ECMO (aOR 2·27 [1·28-4·05]. INTERPRETATION: The prognostic factors identified highlight the importance of patient selection, the effect of injurious lung ventilation, and the potential opportunity for greater centralisation and collaboration in the use of ECMO for the treatment of COVID-19-associated ARDS. These factors should be carefully considered as part of a risk stratification framework when evaluating a patient for potential treatment with venovenous ECMO. FUNDING: None.

Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis.

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60-0.96, high certainty), the posterior probability of benefit of the esophageal pressure-guided strategy was 87% (RR, 0.77; 95% CrI, 0.48-1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67-1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89-1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04-1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

Driving pressure monitoring during acute respiratory failure in 2020.

PURPOSE OF REVIEW: Assess the most recent studies using driving pressure (DP) as a monitoring technique under mechanical ventilation and describe the technical challenges associated with its measurement. RECENT FINDINGS: DP is consistently associated with survival in acute respiratory failure and acute respiratory distress syndrome (ARDS) and can detect patients at higher risk of ventilator-induced lung injury. Its measurement can be challenged by leaks and ventilator dyssynchrony, but is also feasible under pressure support ventilation. Interestingly, an aggregated summary of published results suggests that its level is on average slightly lower in patients with coronavirus disease-19 induced ARDS than in classical ARDS. SUMMARY: The DP is easy to obtain and should be incorporated as a minimal monitoring technique under mechanical ventilation.

Personalized Ventilation to Multiple Patients Using a Single Ventilator: Description and Proof of Concept.

OBJECTIVES: To design and test a ventilator circuit that can be used for ventilation of two or more patients with a single ventilator, while allowing individualization of tidal volume, fractional concentration of oxygen, and positive end-expiratory pressure to each patient, irrespective of the other patient's respiratory system mechanics. DESIGN: Description and proof of concept studies. SETTINGS: Respiratory therapy laboratory. SUBJECTS: Ventilation of mechanical test lungs. INTERVENTIONS: Following a previously advocated design, we used components readily available in our hospital to assemble two "bag-in-a-box" breathing circuits. Each patient circuit consisted of a flexible bag in a rigid container connected via one-way valve to a test lung, along with an inline positive end-expiratory pressure valve, connected to the ventilator's expiratory limb. Compressed gas fills the bags during "patient" exhalation. During inspiration, gas from the ventilator, in pressure control mode, enters the containers and displaces gas from the bags to the test lungs. We varied tidal volume, "respiratory system" compliance, and positive end-expiratory pressure in one lung and observed the effect on the tidal volume of the other. MEASUREMENTS AND MAIN RESULTS: We were able to obtain different tidal volume, dynamic driving pressure, and positive end-expiratory pressure in the two lungs under widely different compliances in both lungs. Complete obstruction, or disconnection at the circuit connection to one test lung, had minimal effect (< 5% on average) on the ventilation to the co-ventilated lung. CONCLUSIONS: A secondary circuit "bag-in-the-box" system enables individualized ventilation of two lungs overcoming many of the concerns of ventilating more than one patient with a single ventilator.

External chest-wall compression in prolonged COVID-19 ARDS with low-compliance: a physiological study.

BACKGROUND: External chest-wall compression (ECC) is sometimes used in ARDS patients despite lack of evidence. It is currently unknown whether this practice has any clinical benefit in patients with COVID-19 ARDS (C-ARDS) characterized by a respiratory system compliance (Crs) < 35 mL/cmH2O. OBJECTIVES: To test if an ECC with a 5 L-bag in low-compliance C-ARDS can lead to a reduction in driving pressure (DP) and improve gas exchange, and to understand the underlying mechanisms. METHODS: Eleven patients with low-compliance C-ARDS were enrolled and underwent 4 steps: baseline, ECC for 60 min, ECC discontinuation and PEEP reduction. Respiratory mechanics, gas exchange, hemodynamics and electrical impedance tomography were recorded. Four pigs with acute ARDS were studied with ECC to understand the effect of ECC on pleural pressure gradient using pleural pressure transducers in both non-dependent and dependent lung regions. RESULTS: Five minutes of ECC reduced DP from baseline 14.2 ± 1.3 to 12.3 ± 1.3 cmH2O (P < 0.001), explained by an improved lung compliance. Changes in DP by ECC were strongly correlated with changes in DP obtained with PEEP reduction (R2 = 0.82, P < 0.001). The initial benefit of ECC decreased over time (DP = 13.3 ± 1.5 cmH2O at 60 min, P = 0.03 vs. baseline). Gas exchange and hemodynamics were unaffected by ECC. In four pigs with lung injury, ECC led to a decrease in the pleural pressure gradient at end-inspiration [2.2 (1.1-3) vs. 3.0 (2.2-4.1) cmH2O, P = 0.035]. CONCLUSIONS: In C-ARDS patients with Crs < 35 mL/cmH2O, ECC acutely reduces DP. ECC does not improve oxygenation but it can be used as a simple tool to detect hyperinflation as it improves Crs and reduces Ppl gradient. ECC benefits seem to partially fade over time. ECC produces similar changes compared to PEEP reduction.

Mortality and Pulmonary Embolism in Acute Respiratory Distress Syndrome From COVID-19 vs. Non-COVID-19.

Purpose: There may be a difference in respiratory mechanics, inflammatory markers, and pulmonary emboli in COVID-19 associated ARDS vs. ARDS from other etiologies. Our purpose was to determine differences in respiratory mechanics, inflammatory markers, and incidence of pulmonary embolism in patients with and without COVID-19 associated ARDS admitted in the same period and treated with a similar ventilation strategy. Methods: A cohort study of COVID-19 associated ARDS and non COVID-19 patients in a Saudi Arabian center between June 1 and 15, 2020. We measured respiratory mechanics (ventilatory ratio (VR), recruitability index (RI), markers of inflammation, and computed tomography pulmonary angiograms. Results: Forty-two patients with COVID-19 and 43 non-COVID patients with ARDS comprised the cohort. The incidence of "recruitable" patients using the recruitment/inflation ratio was slightly lower in COVID-19 patients (62 vs. 86%; p = 0.01). Fifteen COVID-19 ARDS patients (35.7%) developed a pulmonary embolism as compared to 4 (9.3%) in other ARDS patients (p = 0.003). In COVID-19 patients, a D-Dimer ≥ 5.0 mcg/ml had a 73% (95% CI 45-92%) sensitivity and 89% (95% CI 71-98%) specificity for predicting pulmonary embolism. Crude 60-day mortality was higher in COVID-19 patients (35 vs. 15%; p = 0.039) but three multivariate analysis showed that independent predictors of 60-day mortality included the ventilatory ratio (OR 3.67, 95% CI 1.61-8.35), PaO2/FIO2 ratio (OR 0.93; 95% CI 0.87-0.99), IL-6 (OR 1.02, 95% CI 1.00-1.03), and D-dimer (OR 7.26, 95% CI 1.11-47.30) but not COVID-19 infection. Conclusion: COVID-19 patients were slightly less recruitable and had a higher incidence of pulmonary embolism than those with ARDS from other etiologies. A high D-dimer was predictive of pulmonary embolism in COVID-19 patients. COVID-19 infection was not an independent predictor of 60-day mortality in the presence of ARDS.

Do ventilatory parameters influence outcome in patients with severe acute respiratory infection? Secondary analysis of an international, multicentre14-day inception cohort study.

PURPOSE: To investigate the possible association between ventilatory settings on the first day of invasive mechanical ventilation (IMV) and mortality in patients admitted to the intensive care unit (ICU) with severe acute respiratory infection (SARI). MATERIALS AND METHODS: In this pre-planned sub-study of a prospective, multicentre observational study, 441 patients with SARI who received controlled IMV during the ICU stay were included in the analysis. RESULTS: ICU and hospital mortality rates were 23.1 and 28.1%, respectively. In multivariable analysis, tidal volume and respiratory rate on the first day of IMV were not associated with an increased risk of death; however, higher driving pressure (DP: odds ratio (OR) 1.05; 95% confidence interval (CI): 1.01-1.1, p = 0.011), plateau pressure (Pplat) (OR 1.08; 95% CI: 1.04-1.13, p < 0.001) and positive end-expiratory pressure (PEEP) (OR 1.13; 95% CI: 1.03-1.24, p = 0.006) were independently associated with in-hospital mortality. In subgroup analysis, in hypoxemic patients and in patients with acute respiratory distress syndrome (ARDS), higher DP, Pplat, and PEEP were associated with increased risk of in-hospital death. CONCLUSIONS: In patients with SARI receiving IMV, higher DP, Pplat and PEEP, and not tidal volume, were associated with a higher risk of in-hospital death, especially in those with hypoxemia or ARDS.

The central nervous system during lung injury and mechanical ventilation: a narrative review.

Mechanical ventilation induces a number of systemic responses for which the brain plays an essential role. During the last decade, substantial evidence has emerged showing that the brain modifies pulmonary responses to physical and biological stimuli by various mechanisms, including the modulation of neuroinflammatory reflexes and the onset of abnormal breathing patterns. Afferent signals and circulating factors from injured peripheral tissues, including the lung, can induce neuronal reprogramming, potentially contributing to neurocognitive dysfunction and psychological alterations seen in critically ill patients. These impairments are ubiquitous in the presence of positive pressure ventilation. This narrative review summarises current evidence of lung-brain crosstalk in patients receiving mechanical ventilation and describes the clinical implications of this crosstalk. Further, it proposes directions for future research ranging from identifying mechanisms of multiorgan failure to mitigating long-term sequelae after critical illness.

A rational approach on the use of extracorporeal membrane oxygenation in severe hypoxemia: advanced technology is not a panacea.

Veno-venous extracorporeal membrane oxygenation (ECMO) is a helpful intervention in patients with severe refractory hypoxemia either because mechanical ventilation cannot ensure adequate oxygenation or because lung protective ventilation is not feasible. Since ECMO is a highly invasive procedure with several, potentially devastating complications and its implementation is complex and expensive, simpler and less invasive therapeutic options should be first exploited. Low tidal volume and driving pressure ventilation, prone position, neuromuscular blocking agents and individualized ventilation based on transpulmonary pressure measurements have been demonstrated to successfully treat the vast majority of mechanically ventilated patients with severe hypoxemia. Veno-venous ECMO has a place in the small portion of severely hypoxemic patients in whom these strategies fail. A combined analysis of recent ARDS trials revealed that ECMO was used in only 2.15% of patients (n = 145/6736). Nevertheless, ECMO use has sharply increased in the last decade, raising questions regarding its thoughtful use. Such a policy could be harmful both for patients as well as for the ECMO technique itself. This narrative review attempts to describe together the practical approaches that can be offered to the sickest patients before going to ECMO, as well as the rationale and the limitations of ECMO. The benefit and the drawbacks associated with ECMO use along with a direct comparison with less invasive therapeutic strategies will be analyzed.

Longitudinal changes in compliance, oxygenation and ventilatory ratio in COVID-19 versus non-COVID-19 pulmonary acute respiratory distress syndrome.

BACKGROUND: Differences in physiology of ARDS have been described between COVID-19 and non-COVID-19 patients. This study aimed to compare initial values and longitudinal changes in respiratory system compliance (CRS), oxygenation parameters and ventilatory ratio (VR) in patients with COVID-19 and non-COVID-19 pulmonary ARDS matched on oxygenation. METHODS: 135 patients with COVID-19 ARDS from two centers were included in a physiological study; 767 non-COVID-19 ARDS from a clinical trial were used for the purpose of at least 1:2 matching. A propensity-matching was based on age, severity score, oxygenation, positive end-expiratory pressure (PEEP) and pulmonary cause of ARDS and allowed to include 112 COVID-19 and 198 non-COVID pulmonary ARDS. RESULTS: The two groups were similar on initial oxygenation. COVID-19 patients had a higher body mass index, higher CRS at day 1 (median [IQR], 35 [28-44] vs 32 [26-38] ml cmH2O-1, p = 0.037). At day 1, CRS was correlated with oxygenation only in non-COVID-19 patients; 61.6% and 68.2% of COVID-19 and non-COVID-19 pulmonary ARDS were still ventilated at day 7 (p = 0.241). Oxygenation became lower in COVID-19 than in non-COVID-19 patients at days 3 and 7, while CRS became similar. VR was lower at day 1 in COVID-19 than in non-COVID-19 patients but increased from day 1 to 7 only in COVID-19 patients. VR was higher at days 1, 3 and 7 in the COVID-19 patients ventilated using heat and moisture exchangers compared to heated humidifiers. After adjustment on PaO2/FiO2, PEEP and humidification device, CRS and VR were found not different between COVID-19 and non-COVID-19 patients at day 7. Day-28 mortality did not differ between COVID-19 and non-COVID-19 patients (25.9% and 23.7%, respectively, p = 0.666). CONCLUSIONS: For a similar initial oxygenation, COVID-19 ARDS initially differs from classical ARDS by a higher CRS, dissociated from oxygenation. CRS become similar for patients remaining on mechanical ventilation during the first week of evolution, but oxygenation becomes lower in COVID-19 patients. TRIAL REGISTRATION: clinicaltrials.gov NCT04385004.