Flow-Controlled Ventilation May Reduce Mechanical Power and Increase Ventilatory Efficiency in Severe Coronavirus Disease-19 Acute Respiratory Distress Syndrome (preprint)

Background: . The prevention of ventilator-induced lung injury is the mainstay of the management of mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). Reducing mechanical power during invasive mechanical ventilation may be beneficial. Flow-controlled ventilation (FCV) (Evone ® , Ventinova Medical, Eindhoven, The Netherlands) is a ventilatory mode providing low and controlled flow rates throughout both inspiration and expiration. We hypothesize that FCV would reduce mechanical power and ventilatory ratio, by allowing the reduction of minute ventilation, in coronavirus disease (COVID)-19 patients developing refractory hypoxemia despite optimization of conventional constant-flow volume-targeted mechanical ventilation (CMV) and prone positioning. Methods: . The study was performed in the intensive care unit of the Vittorio Veneto Hospital (Italy). We included 10 sedated and paralyzed patients with ARDS secondary to COVID-19, with arterial partial pressure of oxygen to inspired oxygen fraction ratio (PaO2/FiO2) < 150 mmHg during CMV while in prone position for at least 12 consecutive hours. All measurements were obtained in CMV prior to switching to FCV (CMV1), after 4 hours of FCV, and then again after 4 hours of CMV (CMV2). Results: . During FCV inspiratory flow rate, respiratory rate, and minute ventilation were significantly lower than with both CMV1 and CMV2. Mechanical power was 10.8 (9.9-13.4) J/min, as opposed to CMV1 [22.7 (20.3-25.6) J/min (p=0.006)] and CMV2 [20.1 (19.0-24.0) J/min (p=0.006)]. Ventilatory ratio also significantly decreased to 1.40 (1.28-1.44) from CMV1 [2.22 (1.90-2.56) (p=0.006)] and then increased again during CMV2 [2.20 (1.79-2.57) (p=0.006)]. Arterial partial pressure of carbon dioxide, pH, and PaO2/FiO2 were not significantly different among the three conditions. Conclusions: . FCV reduced mechanical power and increased ventilatory efficiency in severely hypoxemic COVID-19 patients receiving CMV and prone positioning.

Outcomes of COVID-19 Patients Intubated After Failure of Non-Invasive Ventilation: A Multicenter Observational Study. (preprint)

IntroductionThe efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the Intensive Care Unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: 1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and 2) assessing whether the length of NIV application affects patient survival. MethodsThis observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. ResultsAmong the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06 - 4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04 - 1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. ConclusionsIn-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality. 

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

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. 

Lung Ultrasound to Predict COVID-19 Pneumonia: A Multicenter Descriptive Study (preprint)

Background: The pandemic surge of Coronavirus disease 2019 (COVID-19) is posing the unprecedent challenge of rapidly identifying and isolating probable cases and diagnosing the main respiratory complications. We aimed to describe the application of a lung ultrasound (LUS)-based diagnostic approach, combining the LUS likelihood of COVID-19 pneumonia with patient’s symptoms and clinical history.Methods: This is an international multicenter prospective observational study on patients suspected for COVID-19, presenting to 22 different US and European hospitals. Patients underwent LUS and reverse transcription-polymerase chain reaction (RT-PCR) swab test. We identified 3 different clinical phenotypes based on pre-existing chronic cardiac or respiratory diseases (mixed phenotype), and on the presence (severe phenotype) or absence (mild phenotype) of signs and/or symptoms of respiratory failure at presentation. We defined the LUS likelihood of COVID-19 pneumonia according to 4 different patterns, characterized by the presence and distribution of typical and atypical LUS signs: high (HPLUS), intermediate (IPLUS), alternative (APLUS) and low (LPLUS) probability patterns. The association between the combination of patterns and phenotypes with RT-PCR results was described and analyzed.Findings: We studied 1462 patients, classified in mild (n=400), severe (n=727) and mixed (n=335) phenotypes. In the overall population, the HPLUS corresponded to a positive RT-PCR in 92.6% of cases, with similarly high percentages in all clinical phenotypes ranging from 87.5% (mild) to 90.3% (mixed) and 96.5% (severe). The IPLUS yielded a lower match with positive RT-PCR (65.7%). In patients with respiratory failure, the LPLUS predicted a negative RT-PCR in 100% of cases. In the overall population, the APLUS indicated an alternative pulmonary condition in 81.1% of patients. At multivariate analysis the HPLUS strongly predicted RT-PCR positivity (odds ratio 4.173, interquartile range 2.595-6.712, p<0.0001), independently from age, low oxygen saturation and dyspnea.Interpretation: Combining LUS patterns of probability for interstitial pneumonia with clinical phenotypes at presentation could facilitate the early diagnosis of COVID-19 or suggest an alternative pulmonary condition. This approach may be useful to rapidly guide and support patient’s allocation for a wiser use of hospital resources during a pandemic surge.Funding: None.Conflict of Interest: The authors declare no conflicts of interest. Ethical Approval: The local Ethical Committee Boards of each center approved the study, and the study was conducted following the ethical standards of the 1964 Helsinki declaration and its later amendments and with local guidelines for good clinical practice.