The esophagus ... not just for food anymore?

Background 
Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); the optimal level of PEEP has been difficult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention. 
 
Methods 
Objective 
To evaluate the effectiveness of using an esophageal balloon catheter to measure pleural pressure and guide PEEP titration to achieve normal physiologic parameters in individual patients. 
 
Design 
Single center, randomized-controlled pilot trial. Setting: Medical and surgical ICUs at Beth Israel Deaconess Medical Center. 
 
Subjects 
61 patients with acute lung injury or ARDS as defined by the American-European Consensus Conference definition. 
 
Intervention 
Patients with acute lung injury or ARDS were randomly assigned to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure (the esophageal-pressure-guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). 
 
Outcomes 
The primary end point was improvement in oxygenation at 72 hours after randomization. Secondary end points included indexes of lung mechanics and gas exchange, number of ventilator free days, length of ICU stay, and death at 28 days and 180 days. 
 
Results 
The study reached its stopping criterion and was terminated after 61 patients had been enrolled. The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mmHg higher in the esophageal-pressure-guided group than in the control group (95% confidence interval, 78.1 to 98.3; P = 0.002). This effect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P = 0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also significantly better at 24, 48, and 72 hours in the esophageal-pressure-guided group (P = 0.01 by repeated-measures analysis of variance). 
 
Conclusions 
As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)


Background
Survival of patients with acute lung injury or the acute respiratory distress syndrome (ARDS) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure (PEEP); the optimal level of PEEP has been diffi cult to determine. In this pilot study, we estimated transpulmonary pressure with the use of esophageal balloon catheters. We reasoned that the use of pleural-pressure measurements, despite the technical limitations to the accuracy of such measurements, would enable us to fi nd a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention.

Methods
Objective: To evaluate the eff ectiveness of using an esopha geal balloon catheter to measure pleural pressure and guide PEEP titration to achieve normal physiologic parameters in individual patients. Design: Single center, randomized-controlled pilot trial. Setting: Medical and surgical ICUs at Beth Israel Deaconess Medical Center. Subjects: 61 patients with acute lung injury or ARDS as defi ned by the American-European Consensus Conference defi nition. Intervention: Patients with acute lung injury or ARDS were randomly assigned to undergo mechanical ventilation with PEEP adjusted according to measure ments of esophageal pressure (the esophageal-pressure-guided group) or according to the Acute Respiratory Distress Syndrome Network standard-of-care recommendations (the control group). Outcomes: Th e primary end point was improvement in oxygenation at 72 hours after randomization. Secondary end points included indexes of lung mechanics and gas exchange, number of ventilator free days, length of ICU stay, and death at 28 days and 180 days.

Results
Th e study reached its stopping criterion and was terminated after 61 patients had been enrolled. Th e ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mmHg higher in the esophageal-pressure-guided group than in the control group (95% confi dence interval, 78.1 to 98.3; P = 0.002). Th is eff ect was persistent over the entire follow-up time (at 24, 48, and 72 hours; P = 0.001 by repeated-measures analysis of variance). Respiratory-system compliance was also signifi cantly better at 24, 48, and 72 hours in the esophageal-pressure-guided group (P = 0.01 by repeatedmeasures analysis of variance).

Conclusions
As compared with the current standard of care, a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure signifi cantly improves oxygena tion and compliance. Multicenter clinical trials are needed to determine whether this approach should be widely adopted. (ClinicalTrials.gov number, NCT00127491.)

Commentary
In 2000, the landmark ARDS Network Trial was published [2]. It concluded that low tidal volume ventilation led to a signifi cant decrease in mortality [2]. In this trial, positive end expiratory pressure (PEEP) was adjusted according to a scale based on fraction of inspired oxygen (FiO 2 ) requirements. Th is did not allow for the appreciation of individual patient physiology with regard to chest wall or lung mechanics. Th e actual levels of PEEP used were relatively low (5 to 13 cmH 2 O). Following the publication of the ARDS Network Trial, three additional large randomized controlled trials were concluded comparing the eff ects of higher PEEP and recruitment strategies on clinical outcomes and mortality. Th e ALVEOLI study [3], LOVS study [4], and the EXPRESS study [5] utilized the universally accepted low tidal volume strategy, but implemented higher levels of PEEP (10 to 20 cmH 2 O) to increase alveolar recruitment and improve oxygenation. Th ese studies concluded that better arterial oxygenation and lung compliance were achieved with higher levels of PEEP. However, better arterial oxygenation and lung mechanics did not translate into any signifi cant mortality benefi t.
Th e disappointing results of the previous three studies may have been due in part to the fact that patients with ARDS have a non-homogenous lung injury pattern and a 'one size fi ts all' PEEP titration strategy may be not be adequate for all patients. For a given level of PEEP, transpulmonary pressures may vary widely from patient to patient. If the clinician could measure transpulmonary pressure at the bedside he/she may be able to fi nd the 'best' individual PEEP to maintain oxygenation while minimizing atelectrauma and volutrauma.
In the critiqued pilot trial, Talmor, et al. evaluated a ventilator strategy using esophageal pressures to estimate actual transpulmonary pressures in individual patients, thus allowing for determination of 'best' individual PEEP. Critically-ill patients (80% ARDS/20% Acute Lung Injury) were randomized to either ARDS Network protocol ventilation or a ventilation strategy utilizing esophageal pressures to estimate individual patients' transpulmonary pressures and guide application of PEEP to maintain normal physiologic parameters. All patients had an esophageal balloon catheter placed allowing for the measurement of esophageal pressures during mechanical ventilation. Each patient underwent mechanical ventilation according to the treatment assignment. In the study arm, PEEP was titrated to maintain normal physiologic trans pulmonary pressure (0 to 10 cmH 2 O at end expiration).
Th e study concluded that arterial oxygenation and respiratory system compliance improved in the esophageal-pressure guided group as compared with the control group. Consistent with all prior studies to date, there was no statistically signifi cant diff erence in mortality between the treatment groups at 180 days. Additionally, there was no signifi cant diff erence between groups with regard to ventilator-free days or length of ICU stay.
Th is study has several limitations. It was a single-center study utilizing physiologic expert staff . Th e sample size was small. Th e fi ndings cannot be generalized until confi rmed in a larger trial powered to detect changes in clinical end points. Th is study does have signifi cant appeal. Few clinicians question the physiologic eff ect of PEEP as it relates to arterial oxygenation, but optimal PEEP titration for individual patients remains elusive. Adjusting PEEP to maintain normal physiologic transpulmonary pressure is a reasonable premise. However, measurement of true pleural pressure is not readily attainable at the bedside. In this sense, utilizing esophageal pressure to estimate pleural pressure seems reasonable. However, many assumptions must be made in order to accept that the pressure at one locus of the esophagus reliably refl ects actual pleural pressure over the entire physiologic system. One must assume that the transmural pressure in the esophagus is 0 cmH 2 O and that actual pleural pressure is uniform throughout the entire thorax (unlikely in the setting of a nonhomogenous lung injury pattern). In addition, a correction of 5 cmH 2 O was subtracted from the measured esophageal pressure in an attempt to account for the weight of mediastinal structures overlying the balloon in the esophagus. Th is correction is subject to much debate, as the exact correction factor for this artifact may be highly variable among supine, critically-ill patients. Prior research yielding the stated correction factor of 5 cmH 2 O was conducted in healthy subjects, maintained in an upright posture [6,7].
Th is study, using an invasive balloon catheter to guide PEEP titration, ultimately led to the same conclusion as all prior studies to date: increased levels of PEEP improve arterial oxygenation and lung compliance. However, better oxygenation does not convey a signifi cant mortality benefi t. When comparing the conclusions of the ALVEOLI, LOVS, and EXPRESS studies to the Talmor and colleagues study, it is realized that all use similarly higher levels of PEEP (10 to 20 cmH 2 O). Th is is in contrast to the PEEP used in the ARDS Network Trial (5 to 12 cmH 2 O). Th e question that remains unanswered is whether the improvement in oxygenation found in the Talmor, et al. study is a true refl ection of a unique response to PEEP titration based on esophageal pressures or just a generic response to the utilization of higher PEEP overall.

Recommendation
In conclusion, as compared with standard ARDS Network ventilation, a ventilation strategy using esophageal pressures to titrate PEEP improves arterial oxygenation and lung compliance. However, since improved oxygenation is not a surrogate end point for mortality, this study is not suffi cient to recommend a change in current clinical practice. It seems reasonable to conduct further, larger, randomized trials to assess the clinical viability of utilizing this invasive technique.