By Vibhu Sharma, MD, MS

Associate Professor of Medicine, University of Colorado, Denver

SYNOPSIS: High airway pressure is required to recruit lung atelectasis in patients with acute respiratory distress syndrome and body mass index ≥ 35 kg/m2.

SOURCE: De Santis Santiago R, Droghi MT, Fumagalli J, et al. High pleural pressure prevents alveolar overdistension and hemodynamic collapse in ARDS with class III obesity. Am J Respir Crit Care Med 2020;203:575-584.

This was an interventional crossover trial in obese adults with acute respiratory distress syndrome (ARDS). The authors also studied a swine model of ARDS to assess the impact of recruitment maneuvers and high plateau pressures. For the clinical part of the study, the obese adults with ARDS enrolled in the trial underwent esophageal manometry to estimate pleural pressures; all were paralyzed and sedated. Esophageal pressures (Pes) were used as a surrogate for plateau pressures (Pplat). Electrical impedance tomography (EIT) was used to determine whether lungs were collapsed or overdistended.

Electrical conductance in lung tissue varies with the amount of blood and air in the lung at any given time. These changes can be measured and plotted over time and converted into two-dimensional images that generate the distribution of conductance (or impedance) in lung tissue. Transthoracic echocardiography was used to assess the tricuspid annular plane systolic excursion (TAPSE) and the tricuspid systolic excursion velocity (S’) to assess right ventricle (RV) function in the standard apical four-chamber view at baseline and in response to the recruitment maneuver. RV failure is associated with a TAPSE < 17 cm and an S’ < 10 cm/s.

A cohort of 19 obese ARDS patients were recruited. The EIT data from this group were compared to five non-obese patients from the Alveolar Recruitment Trial (ART).1 The obese patients received initial ventilation with ARDS Network (LungARDSnet) criteria for 30 minutes using the positive end-expiratory pressure/fraction of inhaled oxygen (PEEP/FiO2) table and then were crossed over to a standardized sequence of procedures including recruitment maneuvers to determine optimal PEEP (LungRECRUITED). The Pressure-Volume (PV) tool was used to determine optimal PEEP by first applying a lung recruitment maneuver. Pressure-controlled ventilation (PCV) with a delta pressure of 10 cm H2O was used for recruitment at a set respiratory rate of 20 breaths/minute. PEEP was increased until a Pplat of 50 cm H2O was reached, which was maintained for one minute. Thereafter, volume-controlled ventilation (VCV) was reinstituted, and PEEP was reduced by 2 cm H2O every 30 seconds. The optimal PEEP was set at the PEEP value with the best static compliance of the respiratory system (Crs) plus 2 cm H2O. A second recruitment maneuver was performed, and VCV with optimal PEEP instituted.

The experimental part of the study compared similar maneuvers in sedated and paralyzed swine with simulated abdominal obesity and ARDS and swine with normal lungs. Abdominal obesity was simulated in swine by application of external abdominal weights, which induced an increase in Pplat. The swine underwent left and right heart catheterization as well to assess hemodynamic response to recruitment maneuvers. Mean arterial pressure (MAP), mean pulmonary artery pressure (mPAP), systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated. Cardiac transmural pressures were computed in systole and diastole by subtracting Pes during inspiratory and expiratory pauses from the relevant chamber pressure.

The primary aim was to determine the cardiovascular response to a recruitment maneuver in the setting of obesity. An additional aim was a descriptive comparison of recruitment maneuvers on lung mechanics in obese vs. non-obese patients.

The results for the clinical study demonstrated improved Crs and more homogenous ventilation in response to recruitment maneuvers among the obese patients studied. Driving pressure decreased, and the partial pressure of arterial oxygen/fraction of inspired oxygen (P/F) ratio improved by 129 mmHg in the LungRECRUITED approach. Right heart function parameters (TAPSE and S’) remained unchanged with higher airway pressures. MAP was unchanged, and no patient required either a fluid bolus or changes in vasopressor doses during or after the recruitment maneuver. Lung collapse was higher and overdistension was lower for the obese patients with ARDS compared to the non-obese ART cohort at similar PEEP levels. 

PV curves plotted by lung region (dependent and non-dependent) showed absence of overdistension for a pressure up to 25 cm H2O in the non-dependent region for obese patients. However, overdistension was seen in the non-dependent region among non-obese patients with ARDS in the historical comparator ART cohort. For dependent regions, the PV tool showed poorly compliant lung in obese ARDS patients with “exponential positive growth,” implying successful lung recruitment with recruitment maneuvers in this group. In contrast, overdistension was seen in the historical non-obese ART cohort with ARDS.

The results for the experimental part of the study were nearly identical to results in the obese patients studied in that, among swine with modeled obesity (high Pes) and ARDS, the LungRECRUITED strategy was associated with a reduction in shunt fraction, increase in the P/F ratio by 125 mmHg, improved Crs, and improved driving pressure. While PVR was high at the onset, it decreased after the LungRECRUITED strategy. MAP and SVR were unchanged. Transmural cardiac pressures and left ventricular function also were unchanged. The LungRECRUITED strategy resulted in increased homogeneity of ventilation.

COMMENTARY

The original ARDSNet trial (and others) typically has excluded patients with morbid obesity (defined as > 1 kg/cm body weight). The study reported here is a valuable clinical and experimental endeavor to inform management of ARDS in the obese patient. A single-center study that assessed use of the esophageal balloon to adjust PEEP showed that compliance and oxygenation improved relative to the standard of care.2 A subsequent multicenter randomized trial of patients with moderate to severe ARDS (EPVent2)found that PEEP titration guided by Pes did not result in a significant difference in death or days free from mechanical ventilation compared with a standard high PEEP-FiO2 strategy.3 There were no differences between groups with respect to barotrauma or pneumothoraces requiring drainage. However, this trial was underpowered for the stated secondary endpoints (e.g., 28-day mortality). Although obese patients were not explicitly excluded, the mean actual body weight in the EPVent2 study was 80 kg; body mass index (BMI) was not reported. The mean BMI in the study reviewed here was 57 kg/m2.

In the study reviewed here, mean Pplat in the LungRECRUITED strategy was higher (30.4 cm H2O) compared with the LungARDSnet strategy (25.6 cm H2O); however, the transpulmonary pressure was -4.3 cm H2O in the LungARDSnet strategy compared with +1.4 cm H2O in the LungRECRUITED strategy, suggesting optimal PEEP-sustained lung recruitment with the LungRECRUITED strategy.

What should the clinician at the bedside take away from this study? A lung recruitment strategy may be useful in morbidly obese patients with ARDS with no adverse effects in the setting of a properly performed recruitment maneuver. A reduction in driving pressure, an improvement in P/F ratio, and more homogenous ventilation/perfusion (VQ) matching can be expected. Clinicians ought to be careful to include only those patients with a BMI ≥ 35, with expected benefits possibly higher for more obese patients. It is imperative to ensure that a properly trained respiratory therapist with experience in the placement of an esophageal balloon is present continuously at the bedside while recruitment maneuvers are being performed.

The ARDSNet trial demonstrated the mortality benefit of a lower Pplat. The Pplat in the LungRECRUITED group was higher than in the LungARDSnet group but was likely necessary to maintain VQ matching as evidenced by the positive transpulmonary pressure in the former. The driving pressure was lower, however, and this bodes well from a mortality perspective given the association of a lower driving pressure with lower mortality.4 Oxygenation was better, as evidenced by the improved P/F in the LungRECRUITED group; however, the P/F ratio does not predict mortality in the setting of ARDS.

A few caveats apply. Previous studies have suggested that recruitment maneuvers may delay other interventions shown to affect mortality (e.g., proning). Further, paralysis and deep sedation required for these maneuvers are not the standard of care in ARDS management and may be harmful. There are associated risks to placement of the esophageal balloon and the need for trained respiratory therapists to perform and interpret the study.

In summary, this study shows that a Lung-RECRUITED strategy is safe and results in improved driving pressure as well as sustained improvements in VQ matching in morbidly obese adults with ARDS. All maneuvers can be safely performed with careful monitoring by trained staff. Translation of a LungRECRUITED strategy into a mortality benefit remains to be demonstrated with a randomized trial exclusively recruiting morbidly obese patients randomized to a LungARDSnet vs. a LungRECRUITED strategy. 

REFERENCES

  1. Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators, Cavalcanti AB, Suzumura É, Laranjeira LN, et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: A randomized clinical trial. JAMA 2017;318:1335-1345.
  2. Talmor D, Sarge T, Malhotra A, et al. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med 2008;359:2095-2104.
  3. Beitler JR, Sarge T, Banner-Goodspeed VM, et al. Effect of titrating positive end-expiratory pressure (PEEP) with an esophageal pressure-guided strategy vs an empirical high PEEP-Fio2 strategy on death and days free from mechanical ventilation among patients with acute respiratory distress syndrome: A randomized clinical trial. JAMA 2019;321:846-857.
  4. Amato MB, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. N Engl J Med 2015;372:747-755.