A Retrospective Analysis of the Effects of TIME on Compliance and Driving Pressures in Acute Respiratory Distress Syndrome: The TIMED Study

Background:The evolution of compliance and driving pressure in acute respiratory distress syndrome (ARDS) and the effects of time spent on noninvasive respiratory support prior to intubation has not been well studied. We conducted this study to assess the effect of the duration of noninvasive respiratory support prior to intubation (i.e., Noninvasive ventilation (NIV), High flow nasal cannula (HFNC), or a combination of NIV and HFNC) on static compliance and driving pressure and retrospectively describe its trajectory over time for COVID-19 and non-COVID-19 ARDS while on mechanical ventilation. Methods: Retrospective analysis of prospectively collected data from one university-affiliated academic medical center, one a rural magnet hospital, and three suburban community facilities. A total of 589 patients were included: 55 COVID-19 positive, 137 culture positive, and 397 culture negative patients. Static compliance and driving pressure were calculated at each 8-hour ventilator check. Results:Days of pre-intubation noninvasive respiratory support was associated with worse compliance and driving pressure but did not moderate any trajectory. COVID-19 positive patients showed non-statistically significant worsening compliance by 0.08-units per ventilator check (p = .241), whereas COVID-19 negative patients who were either culture positive or negative patients showed statistically significant improvement (0.12 and 0.18, respectively; both p < .05); a statistically similar but inverse pattern was observed for driving pressure. ConclusionIn contrast to non-COVID-19 ARDS, COVID-19 ARDS was associated with a more ominous trajectory with no improvement in static lung compliance or driving pressures. Though there was no association between days of pre-intubation noninvasive respiratory support and mortality, its use was associated with worse overall compliance and driving pressure.

Synergistic Effect of Static Compliance and D-dimers to Predict Outcome of Patients with COVID-19-ARDS: A Prospective Multicenter Study

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A “training sample” (March–June 2020) and a “testing sample” (September 2020–January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). “Training” and “testing” samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.

Quasi-Static Compliance Calibration of Serial Articulated Industrial Manipulators

This article presents a procedure for the quasi-static compliance calibration of serial articulated industrial manipulators. Quasi-static compliance refers to the apparent stiffness displayed by manipulators at low-velocity movements, i.e., from 50 to 250 mm/s. The novelty of the quasi-static compliance calibration procedure lies in the measurement phase, in which the quasi-static deflections of the manipulator’s end effector are measured under movement along a circular trajectory. The quasi-static stiffness might be a more applicable model parameter, i.e., representing the actual manipulator more accurately, for manipulators at low-velocity movements. This indicates that the quasi-static robot model may yield more accurate estimates for the trajectory optimization compared with static stiffness in the implementation phase. This study compares the static and apparent quasi-static compliance. The static deflections were measured at discretized static configurations along circular trajectories, whereas the quasi-static deflections were measured under circular motion along the same trajectories. Loads of different magnitudes were induced using the Loaded Double Ball Bar. The static and quasi-static displacements were measured using a linear variable differential transformer embedded in the Loaded Double Ball Bar and a Leica AT901 laser tracker. These measurement procedures are implemented in a case study on a large serial articulated industrial manipulator in five different positions of its workspace. This study shows that the measured quasi-static deflections are bigger than the measured static deflections. This, in turn, indicates a significant difference between the static and apparent quasi-static compliance. Finally, the implementation of the model parameters to improve the accuracy of robots and the challenges in realizing cost-efficient compliance calibration are discussed.

Exogenous pulmonary surfactant in COVID-19 ARDS. The similarities to neonatal RDS suggest a new scenario for an ‘old’ strategy

Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 infection has some unusual characteristics that differentiate it from the pathophysiology described in the more ‘typical’ ARDS. Among multiple hypotheses, a close similarity has been suggested between COVID-19 ARDS and neonatal respiratory distress syndrome (RDS). With this opinion paper, we investigated the pathophysiological similarities between infant respiratory diseases (RDS and direct neonatal ARDS (NARDS)) and COVID-19 in adults. We also analysed, for the first time, similarities in the response to exogenous surfactant administration in terms of improved static compliance in RDS and direct NARDS, and adult COVID-19 ARDS. In conclusion, we believe that if the pathological processes are similar both from the pathophysiological point of view and from the response in respiratory mechanics to a recruitment treatment such as surfactant, perhaps the latter could be considered a plausible option and lead to recruitment in clinical trials currently ongoing on patients with COVID-19.

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.

The influence of the post-pulmonary septum and submersion on the pulmonary mechanics of Trachemys scripta (Cryptodira: Emydidae)

The respiratory system of chelonians needs to function within a mostly solid carapace, with ventilation depending on movements of the flanks. When submerged, inspiration has to work against a hydrostatic pressure and we examined breathing mechanics in Trachemys scripta while underwater. Furthermore, the respiratory system of T. scripta possesses a well-developed post-pulmonary septum (PPS), and we investigated its role on breathing mechanics of lungs with and without their PPS attached. Static compliance was significantly increased in submerged animals and in animals with and without their PPS, while the removal of the PPS did not result in a significantly different static compliance. Dynamic compliance was significantly affected by changes in volume and frequency in every treatment, with submergence significantly decreasing dynamic compliance. The presence of the PPS significantly increased dynamic compliance. Submersion did not alter significantly work per ventilation, but caused minute work of breathing to be much greater at any frequency and ventilation level analyzed. Lungs with or without their PPS did not show significantly different work per ventilation when compared to intact animal. Our results demonstrate that submersion results in significantly altered breathing mechanics, increasing minute work of breathing greatly. The PPS was shown to maintain a constant volume within the animal's body cavity, wherein the lungs can be ventilated more easily, highlighting the importance of this coelomic subdivision in the chelonian body cavity.

Static Compliance and Driving Pressure are Associated with ICU Mortality in Intubated COVID-19 ARDS

Background: 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 (CMV) are associated with intensive care unit (ICU) mortality in COVID-19 acute respiratory distress syndrome (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 CMV, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of CMV were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients.Results: 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: i) Crs was not linearly associated with ICU mortality (p-value for non-linearity=0.01), with a greater risk of death for values <48 ml/cmH2O; ii) the association between DP and ICU mortality was linear (p-value for non-linearity=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); iii) 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.

Static compliance of the respiratory system in COVID-19 related ARDS: an international multicenter study

Background Controversies exist on the nature of COVID-19 related acute respiratory distress syndrome (ARDS) in particular on the static compliance of the respiratory system (Crs). We aimed to analyze the association of Crs with outcome in COVID-19-associated ARDS, to ascertain its determinants and to describe its evolution at day-14. Methods In this observational multicenter cohort of patients with moderate to severe Covid-19 ARDS, Crs was measured at day-1 and day-14. Association between Crs or Crs/ideal body weight (IBW) and breathing without assistance at day-28 was analyzed with multivariable logistic regression. Determinants were ascertained by multivariable linear regression. Day-14 Crs was compared to day-1 Crs with paired t-test in patients still under controlled mechanical ventilation. Results The mean Crs in 372 patients was 37.6 ± 13 mL/cmH2O, similar to as in ARDS of other causes. Multivariate linear regression identified chronic hypertension, low PaO2/FiO2 ratio, low PEEP, and low tidal volume as associated with lower Crs/IBW. After adjustment on confounders, nor Crs [OR 1.0 (CI 95% 0.98–1.02)] neither Crs/IBW [OR 0.63 (CI 95% 0.13–3.1)] were associated with the chance of breathing without assistance at day-28 whereas plateau pressure was [OR 0.93 (CI 95% 0.88–0.99)]. In a subset of 108 patients, day-14 Crs decreased compared to day-1 Crs (31.2 ± 14.4 mL/cmH2O vs 37.8 ± 11.4 mL/cmH2O, p < 0.001). The decrease in Crs was not associated with day-28 outcome. Conclusion In a large multicenter cohort of moderate to severe COVID-19 ARDS, mean Crs was decreased below 40 mL/cmH2O and was not associated with day-28 outcome. Crs decreased between day-1 and day-14 but the decrease was not associated with day-28 outcome.

Prone positioning improves oxygenation and lung recruitment in patients with SARS-CoV-2 acute respiratory distress syndrome; a single centre cohort study of 20 consecutive patients

Objective We aimed to characterize the effects of prone positioning on respiratory mechanics and oxygenation in invasively ventilated patients with SARS-CoV-2 ARDS. Results This was a prospective cohort study in the Intensive Care Unit (ICU) of a tertiary referral centre. We included 20 consecutive, invasively ventilated patients with laboratory confirmed SARS-CoV-2 related ARDS who underwent prone positioning in ICU as part of their management. The main outcome was the effect of prone positioning on gas exchange and respiratory mechanics. There was a median improvement in the PaO2/FiO2 ratio of 132 in the prone position compared to the supine position (IQR 67–228). We observed lower PaO2/FiO2 ratios in those with low (< median) baseline respiratory system static compliance, compared to those with higher (> median) static compliance (P < 0.05). There was no significant difference in respiratory system static compliance with prone positioning. Prone positioning was effective in improving oxygenation in SARS-CoV-2 ARDS. Furthermore, poor respiratory system static compliance was common and was associated with disease severity. Improvements in oxygenation were partly due to lung recruitment. Prone positioning should be considered in patients with SARS-CoV-2 ARDS.