Ventilator-induced Lung Injury Vortex in Patients With SARS-CoV-2
Conditions: ARDS, Mechanical Ventilation Complication, Ventilator-Induced Lung Injury
Sponsor: Hospital El Cruce

VENTILATOR-IDUCED LUNG VORTEX IN 
PATIENTS WITH SARS-CoV-2 
 
NCT04174313 
 
MARCH 25, 2020 
 
 

 
 
Materials and method  
 
This study was conducted in the ICU dedicated to COVID-19 patients of an intensive 
care unit at a university hospital in Argentina. Approval was obtained from local 
institutional review board (resolution number: 68/2019) and informed consent followed 
the ethical committee’s recommendations.  
 
Inclusion criteria: This single-center prospective observational study evaluated 
consecutively admitted adult patients who were suffering from ARDS secondary to 
COVID-19 and needed volume-controlled ventilation (VCV) for at least 7 days. These 
eligibility criteria were decided in order to allow a minimum monitoring of the 
mechanical variables. Those who did not meet such requirement were excluded. 
ARDS was defined according to the Berlin criteria (19) while the diagnosis of COVID-
19 pneumonia was established based on CT images showing such condition and on real-
time polymerase chain reaction (RT-PCR) test for coronavirus disease-2019. 
 
Exclusion criteria: Patients with do-not-resuscitate (DNR) orders and pregnant women. 
Cardiac arrest before ICU admission. Extra corporeal membrane oxygenation (ECMO) 
requirement within the first 24 h of ICU admission and chronic obstructive pulmonary 
disease with gold class 3 or 4, or home oxygen therapy (20). 
 
Procedure: Patients were administered sedatives and analgesics (propofol and fentanyl) 
to obtain a score of -5 on the RASS scale. The protective ventilatory strategy included: 
low tidal volume ventilation (6 ml/kg/PBW), plateau pressure limitation (PPlat: <30 
cmH2O) and prone positioning for severe hypoxemia (21). FiO2 and PaCO2 were 
adjusted to achieve SaO2 between 92 and 96% and pH >7.20, respectively. PEEP was 
titrated according to the best compliance of the respiratory system (CRS), without 
exceeding the PPlat limit set. Neuromuscular blockers were administered to patients 
suffering from severe ARDS (PaO2/FiO2 <100) and to the ones with hypoxemia 
associated with asynchronies despite the administration of sedoanalgesia, PPlat >32 
cmH2O or that needed prone positioning to improve oxygenation.  
Mechanical variables and PaO2/FiO2 were registered daily for 14 days or until initiating 
assisted ventilation. These data were obtained in passive mechanical conditions. 
Ventilator-induced lung injury vortex was defined as a progressive increase in driving 
pressure (ΔP) as Vt remained constant or even decreased.   
Refractory hypoxemia was defined as PaO2/FiO2 <100 despite the optimization of 
mechanical ventilation and prone positioning.  
 
Respiratory mechanics: Peak airway pressure, plateau pressure, and total PEEP were 
measured. The value of driving pressure (ΔP: PPlat - PEEP total), static compliance of 
the respiratory system (CRS = Vt/ΔP) and specific mechanical power (SMP: 
mechanical power/CRS) were calculated. Mechanical power was computed as: Peak 
airway pressure x Vt - (ΔP x Vt/2) x respiratory rate x 0.098 (13). 
 
Complications: The following variables and complications were also observed during 
the period of analysis: incidence of pneumonia associated with mechanical ventilation 
(14), need for noradrenaline over 0.1 γ/kg/min for more than 24 h, positive blood 
cultures, 
accumulated 
fluid 
balance, 
dialysis 
treatment, 
clinical 
and/or 

echocardiographic evidence of heart failure, lactate ≥2 mmol/L in at least two 
consecutive samples, presence of persistent fever (≥38º at least once a day for three 
consecutive days), and the highest value of ferritin, D-dimer, C-reactive protein, 
troponin I and LDH obtained during the first 14 days of invasive mechanical 
ventilation.  
 
Statistical analysis:  Dichotomic data are reported as frequencies and percentages 
while continuous data are presented as mean (standard deviation) or median 
(interquartile range) as appropriate, depending on the normality of distribution. 
Kolmogorov–Smirnov test was used to test normality of distribution for continuous 
variables. Comparisons between the two groups (VILI vortex vs. No VILI vortex) and 
intragroup (day: 7 vs. day: 14) were analyzed by either an independent t-test or the 
Mann–Whitney test. Differences in categorical variables were assessed using the χ2 or 
Fisher's exact test.  
The mortality predictive model following refractory hypoxemia as well as mortality for 
any reason was analyzed on day 90 by means of ROC curves. Survival difference 
between both groups was analyzed through longrank test. Cox's proportional hazards 
regression test was used to study the relationship between VILI vortex intensity and 
accumulative risk of death from refractory hypoxia. The difference of driving pressure 
(ΔΔP) between days 7 and 14 was regarded as VILI vortex intensity expression. That 
was the period in which we more frequently observed VILI vortex development. 
Data analysis was conducted with MedCalc 11.4.3.0 statistical software (Mariakerke, 
Belgium) and a p-value of <0.05 was considered statistically significant.