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Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients
Critical Care volume 27, Article number: 118 (2023)
The profile of changes in airway driving pressure (dPaw) induced by positive-end expiratory pressure (PEEP) might aid for individualized protective ventilation. Our aim was to describe the dPaw versus PEEP curves behavior in ARDS from COVID-19 patients.
Patients admitted in three hospitals were ventilated with fraction of inspired oxygen (FiO2) and PEEP initially adjusted by oxygenation-based table. Thereafter, PEEP was reduced from 20 until 6 cmH2O while dPaw was stepwise recorded and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was assessed. Each dPaw vs PEEP curve was classified as J-shaped, inverted-J-shaped, or U-shaped according to the difference between the minimum dPaw and the dPaw at the lowest and highest PEEP. In one hospital, hyperdistention and collapse at each PEEP were assessed by electrical impedance tomography (EIT).
184 patients (41 including EIT) were studied. 126 patients (68%) exhibited a J-shaped dPaw vs PEEP profile (PEEPmin_dPaw of 7.5 ± 1.9 cmH2O). 40 patients (22%) presented a U (PEEPmin_dPaw of 12.2 ± 2.6 cmH2O) and 18 (10%) an inverted-J profile (PEEPmin_dPaw of 14,6 ± 2.3 cmH2O). Patients with inverted-J profiles had significant higher body mass index (BMI) and lower baseline partial pressure of arterial oxygen/FiO2 ratio. PEEPmin_dPaw was associated with lower fractions of both alveolar collapse and hyperinflation.
A PEEP adjustment procedure based on PEEP-induced changes in dPaw is feasible and may aid in individualized PEEP for protective ventilation. The PEEP required to minimize driving pressure was influenced by BMI and was low in the majority of patients.
Hypoxemic respiratory failure is the leading cause of intensive care unit (ICU) admission in COVID-19, the majority of subjects meeting Acute Respiratory Distress Syndrome criteria (C-ARDS) . Initially, it was observed that many patients presented a disparity between well-preserved lung mechanics and severe hypoxemia  and 2 different phenotypes in C-ARDS were proposed, which should be managed with different ventilatory strategies . However, this was not confirmed in posterior published data, remaining recommendations to treat C-ARDS accordingly ARDS ventilation evidence-based . Several hypotheses were proposed to the wide range of respiratory system compliance (Crs) observed in many C-ARDS series, including hypoxemia due to impaired perfusion in patients with higher compliance or lungs with high recruitability and lower compliance .
Optimal positive end-expiratory pressure (PEEP) has been pursued  and the question of how to recognize patients that get benefit from higher PEEP levels has led to new technologies like Electrical Impedance Tomography (EIT), a bedside tool to monitor ventilation distribution, allowing PEEP titration to reduce both collapse and hyperdistention .
Airway driving pressure (dPaw) is a simple parameter to monitor on the ventilator and, when diminished with increased PEEP was associated with reduced mortality risk in ARDS . In C-ARDS, a lower dPaw was associated with better survival [7, 8].
In the present study, we aim to describe the profile of PEEP-induced changes in dPaw during a PEEP adjustment procedure as aid for individualized protective ventilation, including a group where it was done together with an EIT monitor.
In this prospective observational physiologic study, adults patients admitted to the ICU of three hospitals with C-ARDS confirmed by positive nasopharyngeal polymerase chain reaction for SARS-CoV-2 and receiving invasive mechanical ventilation (MV) ≤ 48 h were analyzed. Patients with barotrauma assessed by computed tomography (CT), chronic pulmonary disease, and increased intracranial pressure were excluded.
Mechanical ventilation settings
After analgesia and sedation adjustment, all subjects were initially ventilated in volume-controlled ventilation, tidal volume of 6 mL/kg with constant inspiratory flow, plateau pressure ≤ 30 cmH2O, FiO2 and PEEP adjusted to keep SaO2 > 90% based on the ARDSNetwork table  and respiratory rate to maintain normal partial pressure of carbon dioxide (PaCO2). Fluids and vasopressors were provided to maintain mean arterial pressure above 60 mmHg and, neuromuscular blocking used to avoid ventilatory asynchronies.
PEEP adjustment procedure
After initial ventilatory settings, PEEP was reduced, 2 cmH2O every thirty seconds , from 20 until 6 cmH2O while dPaw was assessed in each step, and the lowest PEEP that minimized dPaw (PEEPmin_dPaw) was identified. The posterior PEEP adjustment was at the discretion of the clinical team responsible for patient care.
In one of the hospitals, patients were investigated by EIT (Enlight 1800, Timpel, São Paulo, Brazil) during the PEEP adjustment procedure. Regional variations in impedance (∆Z) during ventilation, map the Vt distribution in the lung and creates a PEEP titration tool which was used to assess PEEP-induced pulmonary hyperdistention and collapse and its effects on dPaw during the PEEP adjustment procedure. The EIT optimal PEEP (PEEPEIT) was defined as the PEEP that represents the best compromise between hyperdistention and collapse estimated [5, 11].
Evaluation of dPaw vs PEEP curve profile
After the PEEP adjustment procedure, each dPaw vs PEEP curve was recorded and retrospectively classified into one of three categories according to the difference between the minimum dPaw  and the dPaw at the lowest (ΔdPlow) and highest (ΔdPhigh) PEEP . If ΔdPlow < 0.2 × ΔdPhigh, the curve was classified as J-shaped; if ΔdPhigh < 0.2 × ΔdPlow, the curve was classified as inverted-J-shaped; otherwise, the curve was U-shaped.
Results are reported without imputation as mean (standard deviation), or count (percentage), after testing for normality using the Shapiro–Wilk test. One-way ANOVA was used for the comparison between the three groups. A Bonferroni-Holm post hoc test was applied to correct multiple testing. Hyperdistention and collapse curves at different PEEP levels were assessed by computing areas under the curves (AUCs)  by adding the areas under each pair of consecutive observations:
where Y was the estimated hyperdistention or collapse. The AUCs were compared only between U-shaped and J-shaped PEEP vs dPaw groups, because just one patient with Inverted-J shape had EIT measurement.
Statistical analysis was performed in R (The R Foundation, Vienna, Austria), and a p < 0.05 was considered significant.
Between Jul 27th, 2020, and Feb 24th, 2021, a total of 184 patients were included, and a PEEP adjustment procedure was performed before 48 h on invasive MV. Table 1 shows clinical characteristics in each curve profile dPaw vs PEEP. Patients with inverted J-Shaped dPaw versus PEEP profile presented significantly higher body mass index (BMI) (Table 1) and lower partial pressure of arterial oxygen and fraction of inspired oxygen ratio (PaO2/FiO2) and Crs at baseline (Table 2).
Respiratory mechanics and PEEP titration
Based on the analysis of the dPaw vs PEEP profile, most of the COVID-19 patients (n = 126) exhibited a J-shaped dPaw vs PEEP profile with dPaw starting to increase for PEEPs ≥ 7.5 ± 1.9 cmH2O, only a few COVID-19 patients had mostly inverted-J profiles (n = 18), usually requiring higher levels of PEEP (PEEPmin_dPaw ranging from 14 to 20 cmH2O) (Table 2, Fig. 1). Only 21.7% of COVID-19 patients presented the U-shaped profile with the PEEPmin_dPaw ranging from 10 to 14 cmH2O.
The J-shaped dPaw vs PEEP profile was associated with increased hyperdistention, and collapse reduction as PEEP increased and, in this group, PEEPmin_dPaw was lower than PEEP based on the ARDSNetwork table (Table 2). At the range of the PEEPmin_dPaw both hyperdistention and collapse were minimized independent of the dPaw vs PEEP profile (Table 2, Fig. 1).
Our study interpreted the dPaw vs PEEP curve profile among C-ARDS patients. The main findings were: (1) 90% of C-ARDS-19 patients presented a J- or U-shaped dPaw vs PEEP curve profile usually requiring PEEPs < 12 cmH2O to minimize dPaw; (2) PEEPs > 15 cmH2O would be necessary in only 10% of C-ARDS, and those patients presented an inverted-J dPaw vs PEEP curve profile and higher BMI; and (3) PEEPmin_dPaw was associated with a reduction of both alveoli collapse and hyperdistention. All these patients averaged PaO2/FiO2 below 150 which there is evidence of benefit from using higher levels of PEEP in ARDS .
ARDS and C-ARDS are heterogeneous conditions with uncertainty about to set PEEP [2, 3] commonly based by oxygenation targets . However in C-ARDS this strategy frequently resulted in worse lung mechanics , and cardiac output impairment .
Our EIT data and an experimental CT study  show that, at constant VT, dPaw and compliance respond to both hyperdistention and collapse. 126/184 of our patients presented a J-shaped curves, with the largest hyperdistention AUC, where increasing PEEP to improve oxygenation may not work. In U-shaped curves the balanced risk of collapse and hyperdistention was obtained with about 12 cmH2O PEEP. In these two groups, higher PEEPs would carry a greater risk of iatrogenesis. Finally, patients with an inverted-J-shaped required higher PEEPs to minimize dPaw and presented higher BMI and lower initial PaO2/FiO2 ratio. In the only patient with this profile on EIT, PEEP decreased collapsed areas without increasing hyperdistention up to 20 cmH2O. The interpretation of the PEEP with respiratory system mechanics or with the amount of recruitment and overdistension on EIT seems to give the same information.
At least one-third of patients were obese in C-ARDS different cohorts [3, 7, 8], even though the effect of obesity on respiratory mechanics is well known, a relationship between BMI and compliance has not been described as an explanation, at least in part, for the COVID-19 different phenotypes. Obesity reduce Crs with the major contribution coming from the lung and not the chest wall  in spite of no significant association between compliance and BMI has been detected in a large cohort study of C-ARDS . Mezidi et al. comparing a group of obese vs non-obese in C-ARDS patients monitoring esophageal pressure in a decremental PEEP trial demonstrated a significant difference in PEEP level for the same transpulmonary driving pressure (∆PL) and dPaw . ∆PL also did not enhance significant information concerning the prediction of outcome in ARDS patients compared to dPaw itself .
The observational nature of this study is its major limitation, and although data were acquired prospectively, they were interrogated retrospectively. The heavy workload upon COVID-19 pandemic made impossible to perform a clinical trial comparing clinical outcomes considering the observed profiles. The small proportion of patients investigated with EIT did not allow an appropriate comparison between the two methods, but data suggest a similar result to obtain the best PEEP for protective ventilation with a much simpler bedside procedure.
The dPaw vs PEEP curve is a feasible method and provides individualized information. A range of compliance and PEEPmin_dPaw was observed in all 3 groups and its interpretation suggested that just in a minority of C-ARDS patients, higher PEEP improves compliance, and even in these cases, it appears that obesity, together with disease severity, determines this behavior. The overall influence of personalizing PEEP on clinical outcomes remains to be determined.
Availability of data and materials
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Acute Respiratory Distress Syndrome
Area under the curve
Body mass index
ARDS from COVID-19
Corona Virus Disease-19
Respiratory system compliance
- ∆P L :
Transpulmonary driving pressure
Airway driving pressure
Electrical impedance tomography
- FiO2 :
Fraction of inspired oxygen
Ideal body weight
Intensive care unit
Positive end-expiratory pressure
- PEEPEIT :
EIT optimal PEEP
- PEEPmin_dPaw :
The lowest PEEP that minimized dPaw
- PaO2/FiO2 :
Partial pressure of arterial oxygen and fraction of inspired oxygen ratio
- V t :
Sequential organ failure assessment score
- ∆Z :
Regional variation in impedance
Driving pressure at lowest PEEP
Driving pressure at highest PEEP
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The authors thank the management of Instituto Nacional de Infectologia Evandro Chagas/Fundacão Oswaldo Cruz and Hospital Universitário Pedro Ernesto/Universidade do Estado do Rio de Janeiro for their support of the study. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES). In addition, we thank the physiotherapy team, mainly Érica Paixão da Costa, for her contribution to this study.
This research was supported by Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz (INI/Fiocruz), Rio de Janeiro, Brasil. Brazilian Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, Grants Nos. 302702/2017-2 and 302839/2017-8) and the Rio de Janeiro State Research Supporting Foundation (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Grants Nos. E26/211.867/2016, E-26/202.785/2017, E-26/203.001/2018). Institutional Incentive Program for Scientific, Technological and Artistic-Cultural Production—PROCIÊNCIA 2019-2020, from the Federal Institute of Education, Science and Technology, Rio de Janeiro (IFRJ).
Ethics approval and consent to participate
Protocols were approved by institutional review boards of the National Institute of Infections Diseases (CAAE 31050420.8.2001.5262), Pedro Ernesto University Hospital (CAAE 31050420.8.1001.5259), Brazilian clinical trials (RBR-2z3f7k).
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da Cruz, M.R., Camilo, L.M., da Costa Xavier, T.B. et al. Positive end-expiratory pressure induced changes in airway driving pressure in mechanically ventilated COVID-19 Acute Respiratory Distress Syndrome patients. Crit Care 27, 118 (2023). https://doi.org/10.1186/s13054-023-04345-5
- Positive end-expiratory pressure
- Acute Respiratory Distress Syndrome
- Electrical impedance tomography
- Mechanical ventilation