Invasive Mechanical Ventilation in COVID-19

Patients with severe COVID-19 pneumonia present with severe hypoxemic respiratory failure, typically meet the clinical criteria for acute respiratory distress syndrome (ARDS) and often require invasive mechanical ventilation. While peculiar pathophysiological aspects deserve discussion to better tailor the mechanical ventilation settings in these patients, most recommendations on the ventilatory management of these patients are derived from studies in patients with ARDS from causes other than COVID-19. Protective ventilation is recommended in most COVID-19 patients, tidal volume should be kept around 6 mL per kg of predicted body weight, positive end-expiratory pressure (PEEP) should be titrated individually considering that in many patients with COVID-19 improvement of oxygenation at higher PEEP is often accompanied by worsening of respiratory system compliance. Therefore, attention should be paid in limiting plateau and driving pressures to avoid excessive strain potentially resulting in ventilator-induced lung injury. Prone positioning has been used extensively in COVID-19 patients, but its impact on mortality is uncertain. Inhaled nitric oxide, extracorporeal CO2 removal (ECCO2R), and extracorporeal membrane oxygenation (ECMO) should be considered in selected patients as rescue measures. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.

Patient Self-Inflicted Lung Injury-A Narrative Review of Pathophysiology, Early Recognition, and Management Options.

Patient self-inflicted lung injury (P-SILI) is a life-threatening condition arising from excessive respiratory effort and work of breathing in patients with lung injury. The pathophysiology of P-SILI involves factors related to the underlying lung pathology and vigorous respiratory effort. P-SILI might develop both during spontaneous breathing and mechanical ventilation with preserved spontaneous respiratory activity. In spontaneously breathing patients, clinical signs of increased work of breathing and scales developed for early detection of potentially harmful effort might help clinicians prevent unnecessary intubation, while, on the contrary, identifying patients who would benefit from early intubation. In mechanically ventilated patients, several simple non-invasive methods for assessing the inspiratory effort exerted by the respiratory muscles were correlated with respiratory muscle pressure. In patients with signs of injurious respiratory effort, therapy aimed to minimize this problem has been demonstrated to prevent aggravation of lung injury and, therefore, improve the outcome of such patients. In this narrative review, we accumulated the current information on pathophysiology and early detection of vigorous respiratory effort. In addition, we proposed a simple algorithm for prevention and treatment of P-SILI that is easily applicable in clinical practice.

Mechanical power of ventilation and driving pressure: two undervalued parameters for pre extracorporeal membrane oxygenation ventilation and during daily management?

The current ARDS guidelines highly recommend lung protective ventilation which include plateau pressure (Pplat < 30 cm H2O), positive end expiratory pressure (PEEP > 5 cm H2O) and tidal volume (Vt of 6 ml/kg) of predicted body weight. In contrast, the ELSO guidelines suggest the evaluation of an indication of veno-venous extracorporeal membrane oxygenation (ECMO) due to hypoxemic or hypercapnic respiratory failure or as bridge to lung transplantation. Finally, these recommendations remain a wide range of scope of interpretation. However, particularly patients with moderate-severe to severe ARDS might benefit from strict adherence to lung protective ventilation strategies. Subsequently, we discuss whether extended physiological ventilation parameter analysis might be relevant for indication of ECMO support and can be implemented during the daily routine evaluation of ARDS patients. Particularly, this viewpoint focus on driving pressure and mechanical power.

Relationship of Extravascular Lung Water and Pulmonary Vascular Permeability to Respiratory Mechanics in Patients with COVID-19-Induced ARDS.

During acute respiratory distress syndrome (ARDS), the increase in pulmonary vascular permeability and lung water induced by pulmonary inflammation may be related to altered lung compliance. A better understanding of the interactions between respiratory mechanics variables and lung water or capillary permeability would allow a more personalized monitoring and adaptation of therapies for patients with ARDS. Therefore, our main objective was to investigate the relationship between extravascular lung water (EVLW) and/or pulmonary vascular permeability index (PVPI) and respiratory mechanic variables in patients with COVID-19-induced ARDS. This is a retrospective observational study from prospectively collected data in a cohort of 107 critically ill patients with COVID-19-induced ARDS from March 2020 to May 2021. We analyzed relationships between variables using repeated measurements correlations. We found no clinically relevant correlations between EVLW and the respiratory mechanics variables (driving pressure (correlation coefficient [CI 95%]: 0.017 [-0.064; 0.098]), plateau pressure (0.123 [0.043; 0.202]), respiratory system compliance (-0.003 [-0.084; 0.079]) or positive end-expiratory pressure (0.203 [0.126; 0.278])). Similarly, there were no relevant correlations between PVPI and these same respiratory mechanics variables (0.051 [-0.131; 0.035], 0.059 [-0.022; 0.140], 0.072 [-0.090; 0.153] and 0.22 [0.141; 0.293], respectively). In a cohort of patients with COVID-19-induced ARDS, EVLW and PVPI values are independent from respiratory system compliance and driving pressure. Optimal monitoring of these patients should combine both respiratory and TPTD variables.

Very Low Driving-Pressure Ventilation in Patients With COVID-19 Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation: A Physiologic Study.

OBJECTIVES: To determine in patients with acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) whether reducing driving pressure (ΔP) would decrease plasma biomarkers of inflammation and lung injury (interleukin-6 [IL-6], IL-8, and the soluble receptor for advanced glycation end-products sRAGE). DESIGN: A single-center prospective physiologic study. SETTING: At a single university medical center. PARTICIPANTS: Adult patients with severe COVID-19 ARDS on VV ECMO. INTERVENTIONS: Participants on VV ECMO had the following biomarkers measured: (1) pre-ECMO with low-tidal-volume ventilation (LTVV), (2) post-ECMO with LTVV, (3) during low-driving-pressure ventilation (LDPV), (4) after 2 hours of very low driving-pressure ventilation (V-LDPV, main intervention ΔP = 1 cmH2O), and (5) 2 hours after returning to LDPV. MAIN MEASUREMENTS AND RESULTS: Twenty-six participants were enrolled; 21 underwent V-LDPV. There was no significant change in IL-6, IL-8, and sRAGE from LDPV to V-LDPV and from V-LDPV to LDPV. Only participants (9 of 21) with nonspontaneous breaths had significant change (p < 0.001) in their tidal volumes (Vt) (mean ± SD), 1.9 ± 0.5, 0.1 ± 0.2, and 2.0 ± 0.7 mL/kg predicted body weight (PBW). Participants with spontaneous breathing, Vt were unchanged-4.5 ± 3.1, 4.7 ± 3.1, and 5.6 ± 2.9 mL/kg PBW (p = 0.481 and p = 0.065, respectively). There was no relationship found when accounting for Vt changes and biomarkers. CONCLUSIONS: Biomarkers did not significantly change with decreased ΔPs or Vt changes during the first 24 hours post-ECMO. Despite deep sedation, reductions in Vt during V-LDPV were not reliably achieved due to spontaneous breaths. Thus, patients on VV ECMO for ARDS may have higher Vt (ie, transpulmonary pressure) than desired despite low ΔPs or Vt.

Adherence to protective mechanical ventilation in COVID-19 versus non-COVID-19-associated acute respiratory distress syndrome: Comparison between two prospective cohorts.

OBJECTIVE: To compare adherence to protective mechanical ventilation (MV) parameters in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 with patients with ARDS from other etiologies. DESIGN: Multiple prospective cohort study. SETTING: Two Brazilian cohorts of ARDS patients were evaluated. One with COVID-19 patients admitted to two Brazilian intensive care units (ICUs) in 2020 and 2021 (C-ARDS, n=282), the other with ARDS-patients from other etiologies admitted to 37 Brazilian ICUs in 2016 (NC-ARDS, n=120). PATIENTS: ARDS patients under MV. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Adherence to protective MV (tidal volume ≤8mL/kg PBW; plateau pressure ≤30cmH2O; and driving pressure ≤15cmH2O), adherence to each individual component of the protective MV, and the association between protective MV and mortality. RESULTS: Adherence to protective MV was higher in C-ARDS than in NC-ARDS patients (65.8% vs. 50.0%, p=0.005), mainly due to a higher adherence to driving pressure ≤15cmH2O (75.0% vs. 62.4%, p=0.02). Multivariable logistic regression showed that the C-ARDS cohort was independently associated with adherence to protective MV. Among the components of the protective MV, only limiting driving pressure was independently associated with lower ICU mortality. CONCLUSIONS: Higher adherence to protective MV in patients with C-ARDS was secondary to higher adherence to limiting driving pressure. Additionally, lower driving pressure was independently associated with lower ICU mortality, which suggests that limiting exposure to driving pressure may improve survival in these patients.

Use of the Prone Position in Critically Ill COVID-19 Patients: Can the Response Be Predicted?

Background: Coronavirus disease 2019 (COVID-19) can cause acute respiratory failure and acute respiratory distress syndrome (ARDS). The prone position (PP) is widely used in patients with severe hypoxemia due to ARDS as it improves oxygenation. The aim of this study was to investigate whether improvements in gas exchange and lung mechanics with the PP were associated with survival in ventilated COVID-19 patients. Methods: Fourteen ventilated patients who were placed in the PP were included from May to June 2021. Clinical manifestations and lung mechanics parameters were collected. Results: The overall intensive care unit (ICU) mortality rate was 42.9%. Nonsurvivors were older (p = 0.014) and had higher Charlson comorbidity index (2.1 +/- 1.5 vs. 4.8 +/- 2.4, p = 0.035) and Sepsis-related Organ Failure Assessment (SOFA) (3.3 +/- 1.0 vs. 7.3 +/- 3.5, p = 0.019) scores compared to survivors. There was no difference in PaO2/FiO(2) (P/F ratio) at baseline between the survivors and nonsurvivors. The improvement in P/F ratio (p = 0.0037) and reduction in driving pressure (Pdrive) (p = 0.046) on the second day after first PP were correlated with lower mortality. Significant predictors of successfully stopping prone treatment included a reduction in Pdrive at the first hour, lower tidal volume (Vt) at the fourth hour, and P/F ratio improvement on the second day after PP. Conclusion: Improvement in P/F ratio and reduction in driving pressure on the second day after PP were correlated with reduced mortality. Three parameters could predict successful resumption of the supine position. Copyright (c) 2022, Taiwan Society of Geriatric Emergency & Critical Care Medicine.

Driving pressure-guided ventilation decreases the mechanical power compared to predicted body weight-guided ventilation in the Acute Respiratory Distress Syndrome.

BACKGROUND: Whether targeting the driving pressure (∆P) when adjusting the tidal volume in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS) may decrease the risk of ventilator-induced lung injury remains a matter of research. In this study, we assessed the effect of a ∆P-guided ventilation on the mechanical power. METHODS: We prospectively included adult patients with moderate-to-severe ARDS. Positive end expiratory pressure was set by the attending physician and kept constant during the study. Tidal volume was first adjusted to target 6 ml/kg of predicted body weight (PBW-guided ventilation) and subsequently modified within a range from 4 to 10 ml/kg PBW to target a ∆P between 12 and 14 cm H2O. The respiratory rate was then re-adjusted within a range from 12 to 40 breaths/min until EtCO2 returned to its baseline value (∆P-guided ventilation). Mechanical power was computed at each step. RESULTS: Fifty-one patients were included between December 2019 and May 2021. ∆P-guided ventilation was feasible in all but one patient. The ∆P during PBW-guided ventilation was already within the target range of ∆P-guided ventilation in five (10%) patients, above in nine (18%) and below in 36 (72%). The change from PBW- to ∆P-guided ventilation was thus accompanied by an overall increase in tidal volume from 6.1 mL/kg PBW [5.9-6.2] to 7.7 ml/kg PBW [6.2-8.7], while respiratory rate was decreased from 29 breaths/min [26-32] to 21 breaths/min [16-28] (p < 0.001 for all comparisons). ∆P-guided ventilation was accompanied by a significant decrease in mechanical power from 31.5 J/min [28-35.7] to 28.8 J/min [24.6-32.6] (p < 0.001), representing a relative decrease of 7% [0-16]. With ∆P-guided ventilation, the PaO2/FiO2 ratio increased and the ventilatory ratio decreased. CONCLUSION: As compared to a conventional PBW-guided ventilation, a ∆P-guided ventilation strategy targeting a ∆P between 12 and 14 cm H2O required to change the tidal volume in 90% of the patients. Such ∆P-guided ventilation significantly reduced the mechanical power. Whether this physiological observation could be associated with clinical benefit should be assessed in clinical trials.

Venovenous extracorporeal CO2 removal to support ultraprotective ventilation in moderate-severe acute respiratory distress syndrome: A systematic review and meta-analysis of the literature.

BACKGROUND: A strategy that limits tidal volumes and inspiratory pressures, improves outcomes in patients with the acute respiratory distress syndrome (ARDS). Extracorporeal carbon dioxide removal (ECCO2R) may facilitate ultra-protective ventilation. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of venovenous ECCO2R in supporting ultra-protective ventilation in moderate-to-severe ARDS. METHODS: MEDLINE and EMBASE were interrogated for studies (2000-2021) reporting venovenous ECCO2R use in patients with moderate-to-severe ARDS. Studies reporting ≥10 adult patients in English language journals were included. Ventilatory parameters after 24 h of initiating ECCO2R, device characteristics, and safety outcomes were collected. The primary outcome measure was the change in driving pressure at 24 h of ECCO2R therapy in relation to baseline. Secondary outcomes included change in tidal volume, gas exchange, and safety data. RESULTS: Ten studies reporting 421 patients (PaO2:FiO2 141.03 mmHg) were included. Extracorporeal blood flow rates ranged from 0.35-1.5 L/min. Random effects modelling indicated a 3.56 cmH2O reduction (95%-CI: 3.22-3.91) in driving pressure from baseline (p < .001) and a 1.89 mL/kg (95%-CI: 1.75-2.02, p < .001) reduction in tidal volume. Oxygenation, respiratory rate and PEEP remained unchanged. No significant interactions between driving pressure reduction and baseline driving pressure, partial pressure of arterial carbon dioxide or PaO2:FiO2 ratio were identified in metaregression analysis. Bleeding and haemolysis were the commonest complications of therapy. CONCLUSIONS: Venovenous ECCO2R permitted significant reductions in ∆P in patients with moderate-to-severe ARDS. Heterogeneity amongst studies and devices, a paucity of randomised controlled trials, and variable safety reporting calls for standardisation of outcome reporting. Prospective evaluation of optimal device operation and anticoagulation in high quality studies is required before further recommendations can be made.

Validation of at-the-bedside formulae for estimating ventilator driving pressure during airway pressure release ventilation using computer simulation.

BACKGROUND: Airway pressure release ventilation (APRV) is widely available on mechanical ventilators and has been proposed as an early intervention to prevent lung injury or as a rescue therapy in the management of refractory hypoxemia. Driving pressure ([Formula: see text]) has been identified in numerous studies as a key indicator of ventilator-induced-lung-injury that needs to be carefully controlled. [Formula: see text] delivered by the ventilator in APRV is not directly measurable in dynamic conditions, and there is no "gold standard" method for its estimation. METHODS: We used a computational simulator matched to data from 90 patients with acute respiratory distress syndrome (ARDS) to evaluate the accuracy of three "at-the-bedside" methods for estimating ventilator [Formula: see text] during APRV. RESULTS: Levels of [Formula: see text] delivered by the ventilator in APRV were generally within safe limits, but in some cases exceeded levels specified by protective ventilation strategies. A formula based on estimating the intrinsic positive end expiratory pressure present at the end of the APRV release provided the most accurate estimates of [Formula: see text]. A second formula based on assuming that expiratory flow, volume and pressure decay mono-exponentially, and a third method that requires temporarily switching to volume-controlled ventilation, also provided accurate estimates of true [Formula: see text]. CONCLUSIONS: Levels of [Formula: see text] delivered by the ventilator during APRV can potentially exceed levels specified by standard protective ventilation strategies, highlighting the need for careful monitoring. Our results show that [Formula: see text] delivered by the ventilator during APRV can be accurately estimated at the bedside using simple formulae that are based on readily available measurements.

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.

Association of Time-Varying Intensity of Ventilation With Mortality in Patients With COVID-19 ARDS: Secondary Analysis of the PRoVENT-COVID Study.

Background: High intensity of ventilation has an association with mortality in patients with acute respiratory failure. It is uncertain whether similar associations exist in patients with acute respiratory distress syndrome (ARDS) patients due to coronavirus disease 2019 (COVID-19). We investigated the association of exposure to different levels of driving pressure (ΔP) and mechanical power (MP) with mortality in these patients. Methods: PRoVENT-COVID is a national, retrospective observational study, performed at 22 ICUs in the Netherlands, including COVID-19 patients under invasive ventilation for ARDS. Dynamic ΔP and MP were calculated at fixed time points during the first 4 calendar days of ventilation. The primary endpoint was 28-day mortality. To assess the effects of time-varying exposure, Bayesian joint models adjusted for confounders were used. Results: Of 1,122 patients included in the PRoVENT-COVID study, 734 were eligible for this analysis. In the first 28 days, 29.2% of patients died. A significant increase in the hazard of death was found to be associated with each increment in ΔP (HR 1.04, 95% CrI 1.01-1.07) and in MP (HR 1.12, 95% CrI 1.01-1.36). In sensitivity analyses, cumulative exposure to higher levels of ΔP or MP resulted in increased risks for 28-day mortality. Conclusion: Cumulative exposure to higher intensities of ventilation in COVID-19 patients with ARDS have an association with increased risk of 28-day mortality. Limiting exposure to high ΔP or MP has the potential to improve survival in these patients. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04346342.

Lower Driving Pressure and Neuromuscular Blocker Use Are Associated With Decreased Mortality in Patients With COVID-19 ARDS.

BACKGROUND: The impact of mechanical ventilation parameters and management on outcomes of patients with coronavirus disease 2019 (COVID-19) ARDS is unclear. METHODS: This multi-center observational study enrolled consecutive mechanically ventilated patients with COVID-19 ARDS admitted to one of 7 Korean ICUs between February 1, 2020-February 28, 2021. Patients who were age < 17 y or had missing ventilation parameters for the first 4 d of mechanical ventilation were excluded. Multivariate logistic regression was used to identify which strategies or ventilation parameters that were independently associated with ICU mortality. RESULTS: Overall, 129 subjects (males, 60%) with a median (interquartile range) age of 69 (62-78) y were included. Neuromuscular blocker (NMB) use and prone positioning were applied to 76% and 16% of subjects, respectively. The ICU mortality rate was 37%. In the multivariate analysis, higher dynamic driving pressure (ΔP) values during the first 4 d of mechanical ventilation were associated with increased mortality (adjusted odds ratio 1.16 [95% CI 1.00-1.33], P = .046). NMB use was associated with decreased mortality (adjusted odds ratio 0.27 [95% CI 0.09-0.81], P = .02). The median tidal volume values during the first 4 d of mechanical ventilation and the ICU mortality rate were significantly lower in the NMB group than in the no NMB group. However, subjects who received NMB for ≥ 6 d (vs < 6 d) had higher ICU mortality rate. CONCLUSIONS: In subjects with COVID-19 ARDS receiving mechanical ventilation, ΔP during the first 4 d of mechanical ventilation was independently associated with mortality. The short-term use of NMB facilitated lung-protective ventilation and was independently associated with decreased mortality.

Effect of INTELLiVENT-ASV versus Conventional Ventilation on Ventilation Intensity in Patients with COVID-19 ARDS-An Observational Study.

Driving pressure (ΔP) and mechanical power (MP) are associated with outcomes in critically ill patients, irrespective of the presence of Acute Respiratory Distress Syndrome (ARDS). INTELLiVENT-ASV, a fully automated ventilatory mode, controls the settings that affect ΔP and MP. This study compared the intensity of ventilation (ΔP and MP) with INTELLiVENT-ASV versus conventional ventilation in a cohort of COVID-19 ARDS patients in two intensive care units in the Netherlands. The coprimary endpoints were ΔP and MP before and after converting from conventional ventilation to INTELLiVENT-ASV. Compared to conventional ventilation, INTELLiVENT-ASV delivered ventilation with a lower ΔP and less MP. With conventional ventilation, ΔP was 13 cmH2O, and MP was 21.5 and 24.8 J/min, whereas with INTELLiVENT-ASV, ΔP was 11 and 10 cmH2O (mean difference -2 cm H2O (95 %CI -2.5 to -1.2 cm H2O), p < 0.001) and MP was 18.8 and 17.5 J/min (mean difference -7.3 J/Min (95% CI -8.8 to -5.8 J/min), p < 0.001). Conversion from conventional ventilation to INTELLiVENT-ASV resulted in a lower intensity of ventilation. These findings may favor the use of INTELLiVENT-ASV in COVID-19 ARDS patients, but future studies remain needed to see if the reduction in the intensity of ventilation translates into clinical benefits.

Association of intensity of ventilation with 28-day mortality in COVID-19 patients with acute respiratory failure: insights from the PRoVENT-COVID study.

BACKGROUND: The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure. METHODS: We aimed to investigate the impact of intensity of ventilation on patient outcome. The PRoVENT-COVID study is a national multicenter observational study in COVID-19 patients receiving invasive ventilation. Ventilator parameters were collected a fixed time points on the first calendar day of invasive ventilation. Mean dynamic ΔP and MP were calculated for individual patients at time points without evidence of spontaneous breathing. A Cox proportional hazard model, and a double stratification analysis adjusted for confounders were used to estimate the independent associations of ΔP and MP with outcome. The primary endpoint was 28-day mortality. RESULTS: In 825 patients included in this analysis, 28-day mortality was 27.5%. ΔP was not independently associated with mortality (HR 1.02 [95% confidence interval 0.88-1.18]; P = 0.750). MP, however, was independently associated with 28-day mortality (HR 1.17 [95% CI 1.01-1.36]; P = 0.031), and increasing quartiles of MP, stratified on comparable levels of ΔP, had higher risks of 28-day mortality (HR 1.15 [95% CI 1.01-1.30]; P = 0.028). CONCLUSIONS: In this cohort of critically ill invasively ventilated COVID-19 patients with acute respiratory failure, we show an independent association of MP, but not ΔP with 28-day mortality. MP could serve as one prognostic biomarker in addition to ΔP in these patients. Efforts aiming at limiting both ΔP and MP could translate in a better outcome. Trial registration Clinicaltrials.gov (study identifier NCT04346342).

The effect of driving pressures in COVID-19 ARDS: Lower may still be better as in classic ARDS.

BACKGROUND: The respiratory dynamics of coronavirus disease 2019 (COVID-19) patients under invasive ventilation are still not well known. In this prospective cohort, we aimed to assess the characteristics of the respiratory system in COVID-19 patients under invasive mechanical ventilation and evaluate their relationship with mortality. METHODS: Fifty-eight COVID-19 patients who underwent invasive mechanical ventilation between March 11, 2020 and September 1, 2020 were enrolled for the present study. Demographics and laboratory values at baseline were recorded. Respiratory variables such as tidal volume, plateau pressure, positive end expiratory pressure, static compliance, and driving pressure were recorded daily under passive conditions. Further, the median values were analyzed. RESULTS: Median age of the patients was 64 years (58-72). Mortality was 60% on day 28. Plateau pressure, driving pressure, and static compliance significantly differ between the survivors and non-survivors. When patients were categorized into two groups based on the median driving pressure (Pdrive) of ≤15 cmH2O or >15 cmH2O during their invasive mechanical ventilation period, there was significantly better survival on day 28 in patients having a Pdrive ≤ 15 cmH2O [28 days (95% CI = 19-28) vs 16 days (95% CI = 6-25), (log-rank p = 0.026). CONCLUSION: COVID-19 related acute respiratory distress syndrome (ARDS) seemed to have similar characteristics as other forms of ARDS. Lung protective ventilation with low plateau and driving pressures might be related to lower mortality.

Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS.

BACKGROUND: Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. METHODS: Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. RESULTS: A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH2O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH2O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. CONCLUSIONS: Crs < 48 ml/cmH2O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death.

ECCO2R in 12 COVID-19 ARDS Patients With Extremely Low Compliance and Refractory Hypercapnia.

Purpose: A phenotype of COVID-19 ARDS patients with extremely low compliance and refractory hypercapnia was found in our ICU. In the context of limited number of ECMO machines, feasibility of a low-flow extracorporeal carbon dioxide removal (ECCO2R) based on the renal replacement therapy (RRT) platform in these patients was assessed. Methods: Single-center, prospective study. Refractory hypercapnia patients with COVID-19-associated ARDS were included and divided into the adjusted group and unadjusted group according to the level of PaCO2 after the application of the ECCO2R system. Ventilation parameters [tidal volume (VT), respiratory rate, and PEEP], platform pressure (Pplat) and driving pressure (DP), respiratory system compliance, arterial blood gases, and ECCO2R system characteristics were collected. Results: Twelve patients with refractory hypercapnia were enrolled, and the PaCO2 was 64.5 [56-88.75] mmHg. In the adjusted group, VT was significantly reduced from 5.90 ± 0.16 to 5.08 ± 0.43 ml/kg PBW; DP and Pplat were also significantly reduced from 23.5 ± 2.72 mmHg and 29.88 ± 3.04 mmHg to 18.5 ± 2.62 mmHg and 24.75 ± 3.41 mmHg, respectively. In the unadjusted group, PaCO2 decreased from 94 [86.25, 100.3] mmHg to 80 [67.50, 85.25] mmHg but with no significant difference, and the DP and Pplat were not decreased after weighing the pros and cons. Conclusions: A low-flow ECCO2R system based on the RRT platform enabled CO2 removal and could also decrease the DP and Pplat significantly, which provided a new way to treat these COVID-19 ARDS patients with refractory hypercapnia and extremely low compliance. Clinical Trial Registration: https://www.clinicaltrials.gov/, identifier NCT04340414.

Personalized mechanical ventilation in acute respiratory distress syndrome.

A personalized mechanical ventilation approach for patients with adult respiratory distress syndrome (ARDS) based on lung physiology and morphology, ARDS etiology, lung imaging, and biological phenotypes may improve ventilation practice and outcome. However, additional research is warranted before personalized mechanical ventilation strategies can be applied at the bedside. Ventilatory parameters should be titrated based on close monitoring of targeted physiologic variables and individualized goals. Although low tidal volume (VT) is a standard of care, further individualization of VT may necessitate the evaluation of lung volume reserve (e.g., inspiratory capacity). Low driving pressures provide a target for clinicians to adjust VT and possibly to optimize positive end-expiratory pressure (PEEP), while maintaining plateau pressures below safety thresholds. Esophageal pressure monitoring allows estimation of transpulmonary pressure, but its use requires technical skill and correct physiologic interpretation for clinical application at the bedside. Mechanical power considers ventilatory parameters as a whole in the optimization of ventilation setting, but further studies are necessary to assess its clinical relevance. The identification of recruitability in patients with ARDS is essential to titrate and individualize PEEP. To define gas-exchange targets for individual patients, clinicians should consider issues related to oxygen transport and dead space. In this review, we discuss the rationale for personalized approaches to mechanical ventilation for patients with ARDS, the role of lung imaging, phenotype identification, physiologically based individualized approaches to ventilation, and a future research agenda.

Acute Respiratory Distress Syndrome: Ventilator Management and Rescue Therapies.

This review describes the management of mechanical ventilation in patients with acute respiratory distress syndrome, including in those with coronavirus disease 2019. Low tidal volume ventilation with a moderate to high positive end-expiratory pressure remains the foundation of an evidence-based approach. We consider strategies for setting positive end-expiratory pressure levels, the use of recruitment maneuvers, and the potential role of driving pressure. Rescue therapies including prone positioning and extracorporeal membrane oxygenation are also discussed.