Background

Obesity, which is usually associated with better outcome for acute respiratory distress syndrome (ARDS) patients, is considered as a risk factor of acquiring a severe form of SARS COV-2-associated ARDS for SARS-CoV-2 [1]. Impact of obesity on respiratory mechanics of SARS-CoV-2-associated ARDS has not been investigated.

We hypothesized that respiratory mechanics including esophageal pressure (Pes) measurements might be different in obese and non-obese patients.

Therefore, the first objective of this study was to investigate transpulmonary pressures (PL) in intubated SARS-CoV-2 patients according to their body mass index (BMI) during a decremental PEEP trial. Secondary objective was to assess lung and chest wall elastances (ELLand ELCW, respectively).

Methods

Patients

We conducted a prospective observational study in two intensive care units both in tertiary university hospitals (Hôpital de la Croix-Rousse, Hospices Civils de Lyon and Hôpital Nord, Assistance Publique-Hôpitaux de Marseille).

Patients were included in the study from 15 March to 15 April 2020 if they fulfilled inclusion criteria: adult admitted into the ICU for SARS-CoV-2, intubated and mechanically ventilated with moderate-to-severe ARDS criteria, sedated and paralyzed for clinical purpose and monitored by Pes catheter. As part of routine clinical management, we performed a decremental PEEP trial from 20 to 6 cm H2O by 2 cm H2O-steps in each patient during volume-controlled ventilation while other parameters were kept constant.

Esophageal pressure monitoring, transpulmonary pressures and elastances calculations

Pes catheter (Nutrivent TM, Sidam, Mirandola, Italy, or C7680U (Marquat, Boissy-St-Leger, France) was in place. The correct placement of esophageal catheter was confirmed by presence of cardiac artifacts on the esophageal curve and by an occlusion test (expiratory hold on the ventilator) in passive conditions with gentle chest compression. The occlusion test was considered as positive when the correlation between ∆Pes and ∆ airway pressure (Paw) was 0.8–1.2. To avoid overestimation or underestimation of esophageal pressures, we inflated the esophageal balloon with the minimal filling volume among the recommended range for each catheter which was within the flat portion of the volume–pressure curve of the balloon [2, 3].

At each PEEP step, 2-s end-inspiratory occlusion pause allowed measurement of respiratory system (RS) and esophageal plateau pressure (Pplat and Pes, insp, respectively), whereas 5-s end-expiratory occlusion pause allowed, respectively, measurement of RS and esophageal total PEEP (PEEPtot and Pes,exp respectively). RS driving pressure (∆PRS) was calculated as Pplat minus PEEPtot. RS, chest wall and lung elastances (ELRS, ELCW, and ELL, respectively) and elastance ratio were computed according standard formula.

PL absolute values were calculated as airway pressures minus esophageal pressures during inspiration (PL,insp = Pplat–Pes,insp) and expiration (PL, exp = PEEPtot–Pes,exp), transpulmonary driving pressure (∆PL) = PL,insp–PL,exp. Elastance ratio derived PL (PL,ER) was calculated as Pplat x (ELL/ELRS).

Statistics

Obesity was defined by a BMI ≥ 30. Results are reported as medians [interquartile range] or count (percentage) and compared between groups by Mann–Whitney U. Friedman test was used for repeated variables. p value < 0.05 was considered as significant.

Results

Fifteen patients were included in the study, 8 in the obese group (median BMI 34 [33–41]) and 7 in the non-obese group (mean BMI 26 [25–29]). Patient’s characteristics were comparable between groups except for age (66 [53–73] years for non-obese group vs. 44 [39–49] years for obese group, p = 0.04). Table 1 compares respiratory mechanics for each BMI group according to the PEEP levels. Figure 1a represents Pplat and ∆PRS for each BMI group according to the PEEP levels. Figure 1b represents transpulmonary pressures and ∆PL.

Table 1  Respiratory mechanics according to BMI group and PEEP level
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Fig. 1
figure 1

a Boxplots of respiratory system plateau pressures (Pplat) according to set PEEP and group. Black dots represent individual values. Red dashed line denotes 28 cm H2O. *p < 0.05 between obese and non-obese group for a given PEEP by Mann–Whitney U test. Boxplots of respiratory system driving pressures (∆PRS) according to set PEEP and group. Black dots represent individual values. Red dashed line denotes 14 cm H2O. *p < 0.05 between obese and non-obese group for a given PEEP by Mann–Whitney U test. b Boxplots of end-inspiratory elastance-ratio derived (PL, ER), end-inspiratory absolute method (PL, insp) and end-expiratory (PL, exp) transpulmonary pressures according to set PEEP and group. Black dots represent individual values. Red dashed lines denote 20 cm H2O for PL, ERand PL, insp plots, and 0 cm H2O for PL, exp plot. *p < 0.05 between obese and non-obese group for a given PEEP by Mann–Whitney U test

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PEEP ≥ 16 cm H2O for obese patients and PEEP ≥ 10 cm H2O for non-obese patients were necessary to obtain positive PL, exp (Fig. 1b). At 16 cm H2O of PEEP, 71% of non-obese patients had PL, insp ≥ 20 cm H2O and 0% of obese patients, whereas with PL, ER was ≥ 20 cm H2O in, respectively, 86% of non-obese patients and 75% of obese patients. Change of PEEP did not alter significantly ∆PLor elastances in obese patients (Table 1). However, in non-obese patients ELRS and ELL increased significantly with PEEP increase. ELCW was not affected by PEEP variations in both groups.

Differences between obese and non-obese groups were significant at 18–20 cm H2O of PEEP with higher Pplat, ∆PRS, PL,insp, ∆PL in non-obese patients.

Discussion

During decremental PEEP trial, we found differences in transpulmonary pressures and respiratory mechanics in COVID-19 ARDS patients according to the presence of obesity. First, PL,insp, ∆PLwere higher in non-obese patients at high PEEP (≥ 18 cm H2O), as Pplat and ∆PRS. Second, ELCW and ELL were not statistically different between groups. However, increase of PEEP was significantly associated with an increase of ELL in non-obese patients. Third, high PEEP levels (i.e., 16 cm H2O) were associated with potential injurious PL,ER(≥ 20 cm H2O).

Preliminary studies with CT-scan have reported diffuse and bilateral pulmonary lesions during COVID-19 ARDS, which is usually associated with recruitability by PEEP in ARDS [4].

Recent studies using the same method to assess recruitability (recruitment-to-inflation ratio) reported conflicting data in those patients [5,6,7] with range from 17 to 56% of highly recruitable patients and possible less recruitable patients at a more advanced time point of the disease [5].

However, the lower driving pressures (∆PRS and (∆PL) observed for obese patients cannot discriminate lung recruitment from less lung overdistension without appropriate evaluation (CT-scan or electrical impedance tomography for instance).

We did not check for airway flow limitation in all patients that could have led to overestimate lung and respiratory system elastances, in particular in obese patients.

Finally, we were not able to compare respiratory mechanics of this cohort with non COVID-19 ARDS patients.

In conclusion, assessment of respiratory mechanics of COVID-19 ARDS patients with transpulmonary pressure monitoring might be useful when targets of protective lung ventilation could not be reached. The characteristics of obesity on respiratory mechanics airway opening pressure, recruitability of COVID-19 ARDS patients need further investigations.