An Observational Study to Determine Feasibility and Validity of Esophageal and Transpulmonary Pressure Measurements During One Lung Ventilation
Conditions: Surgery, One-lung Ventilation
Sponsor: Beth Israel Deaconess Medical Center

NCT04725318 October 20, 2020 
 
Title 
An observational study to determine the feasibility and validity of esophageal and 
transpulmonary pressure measurements during one-lung ventilation 
Specific aim 
- 
To investigate feasibility and validity of measurements of esophageal and 
transpulmonary pressure in patients undergoing one-lung ventilation 
Background and rationale 
Postoperative pulmonary complications (PPC) increase hospitalization, mortality and health 
care costs.1 Improved patient outcome with avoidance of high tidal volumes and application of 
positive end-expiratory pressure (PEEP)2,3 indicate that intraoperative lung injury through 
mechanical stress or atelectasis greatly contributes to the development of PPC. 
PPC occur in up to 30% of patients undergoing non-cardiac intrathoracic surgery with one-lung 
ventilation (OLV).4 During OLV, the ventilated single lung is vulnerable to mechanical stress due 
to a decrease in total lung volume, and limitation of inspiratory pressure can reduce PPC.5 
Ventilation guided by transpulmonary pressure (PL), which is defined as the difference between 
intra-alveolar and intrapleural pressure, facilitates assessment and further limitation of 
mechanical stress, as well as adjustment of adequate PEEP to avoid atelectasis.6,7 In the 
clinical setting, intra-alveolar pressure can be determined from airway pressure at end-
inspiratory or end-expiratory hold, while intrapleural pressure is estimated from esophageal 
pressure (Pes).  
Previous investigations have described postural changes in PL and Pes when switching from the 
standing to supine and lateral position in spontaneously breathing patients.8,9 These 
investigations proposed corrections for Pes measurements due to the weight of the mediastinum 
in relationship to the esophageal catheter.9 It remains unclear how lateral positioning with OLV, 
e.g. during intrathoracic surgery, affect measurements of Pes. Furthermore, it is unclear to what 
extend Pes reflects intrapleural pressure within the dependent part of the single ventilated lung, 
which is vulnerable to atelectasis and might therefore benefit from PL-guided PEEP titration.  
In this study, we aim to describe the changes in Pes and PL associated with OLV and lateral 
positioning. Additionally, we aim to estimate adjustments accounting for 1. differences in Pes in 
lateral position between two-lung and one-lung ventilation and 2. the difference between Pes and 
intrapleural pressure of the dependent lung areas of the single ventilated lung 

NCT04725318 October 20, 2020 
 
 
Measurements 
Measurement of esophageal pressure  
Pes will be measured using an orogastric tube equipped with an additional balloon catheter 
(AVEA Ventilator Nasogastric Pressure Monitoring Tube Set; CareFusion, USA). In brief, the 
catheter is placed after induction of anesthesia with the balloon at 40 cm from the mouth in the 
patients esophagus. Positioning is confirmed and adjusted by observation of cardiac artefacts in 
the esophageal pressure curve and by artefacts caused by compression of the patient’s thorax. 
Airway and Pes waveforms will be recorded and stored on a dedicated laptop computer. 
Measurements of airway opening / closing pressure 
- 
Electrical Impedance Tomography  
Lung aeration will be assessed using Electrical Impedance Tomography (EIT) (ENLIGHT 1800, 
Timpel, Sao Paolo, Brazil). In brief, a 16-electrode silicone belt is equipped around the patient’s 
thorax at the level of the 5th intercostal space. Closing pressure of dependent lung areas will be 
estimated during a static, decremental PEEP trial with continuous EIT recording10: patients will 
be ventilated in volume-controlled mode as to institutional standard (typically 6ml/kg PBW). After 
positioning of the patient in the lateral position and initiation of OLV within clinical routine, a 
recruitment maneuver using CPAP of 40 cm H2O for 30 seconds will be conducted. Volume-
controlled ventilation will then be resumed, and PEEP will be decreased from 20 to 0 cm H2O 
by steps of 3 cm H2O every 2-3 min. Corresponding Pes waves and airway pressures will be 
continuously recorded during the trial. End-expiratory closing pressure of dependent lung areas 
will be defined as the PEEP at which lung collapse occurs, which will be determined by 
visualization of EIT images during the trial, and ultimately by a decrease in localized aeration 
and localized compliance (“pixel compliance”) through post-hoc analyses of the stored EIT 
recordings.11,12  
Assuming that PL at lung collapse of the dependent lung areas approaches zero and end-
expiratory PL can be calculated as PL=PEEP-PPL, PPL at lung collapse of the dependent lung 
should be equal to the PEEP at lung collapse.  
The decision to conduct the PEEP trial will be at the discretion of the attending anesthesiologist. 
An inspiratory plateau airway pressure higher than 60 cm H2O, a reduction of SpO2 below 85%, 

NCT04725318 October 20, 2020 
 
a mean arterial pressure lower than 60 mmHg, or a sudden change in cardiac rhythm will be 
used as criteria for interrupting the decremental PEEP titration maneuver.  
- 
Pressure-volume curves 
Airway opening pressure will be estimated from the lower inflection point, derived from routinely 
measured pressure-volume curves.13–15  
Determination of corrections for Pes-derived PL during OLV and lateral positioning 
1. Adjustment for esophageal pressure differences between two and one-lung ventilation in the 
lateral position 
Due to the position of the esophagus in relation to surrounding structures of the mediastinum, 
esophageal pressure measurements depend on patient positioning. When changing from the 
standing to the supine position, postural artifacts need to be accounted for. For example, the 
weight of the heart increases esophageal pressure by about 5 cmH2O.9 Since it is unknown to 
which extend OLV exerts changes in esophageal pressure, we will calculate differences in 
esophageal pressure in the lateral position between two- and one-lung ventilation.  
 
2. Adjustment for differences between esophageal and intrapleural pressure of the dependent 
lung areas during one-lung ventilation in the lateral position. 
In the lateral position with OLV, esophageal pressure is expected to reflect intrapleural pressure 
of the upper (i.e. non-dependent) areas of the ventilated lung, comparable to ventral areas in 
the supine position. However, the lower (i.e. dependent) areas of the ventilated lung are 
expected to be subject to atelectasis formation (comparable to the dorsal areas in the supine 
position) and might benefit the most from PL-guided PEEP titration. Thus, we will assess the 
esophageal pressure at which lung collapse of the dependent lung areas occurs (see above). 
The correction factor c for the esophageal pressure-derived intrapleural pressure will be 
calculated as the difference in airway pressure at lung collapse (i.e. closing pressure, defined 
either as the PEEP derived from EIT-guided PEEP trial, or the pressure at the lower inflection 
point from pressure-volume curves) and the corresponding esophageal pressure Pes: c = Pclosing 
- Pes, which equals the Pes- derived PL at lung collapse. 
 
Study protocol 

NCT04725318 October 20, 2020 
 
Figure 1 provides an overview of study procedures (see below). Patients will be equipped with 
the EIT belt before induction of anesthesia, and a one-minute EIT recording during spontaneous 
breathing will be conducted. Anesthesia will be induced as to institutional standards and upon 
the discretion of the attending anesthesiologist. Typically, propofol (2 mg/kg), fentanyl (0.5-1.5 
yg/kg) and rocuronium (0.6 mg/kg) are used and the double-lumen endotracheal tube will be 
placed with endoscopic verification of the correct positioning. Then, an orogastric tube will be 
passed, as is routinely done for these procedures. For this study, the orogastric tube will contain 
an additional esophageal balloon.  
After placement of the catheter, esophageal pressure, transpulmonary pressure and closing 
pressure from pressure-volume curves will be assessed (“baseline”). Subsequently, the patient 
is positioned in the lateral position and a second measurement series is conducted (“lateral”). 
OLV will then be initiated and a third measurement (“OLV”) is made. During this measurement, 
EIT-guided assessment of closing pressure during a decremental PEEP trial will be conducted, 
as described above. Constant and adequate muscle paralysis throughout the measurements 
will be confirmed through quantitative neuromuscular monitoring. After completion of the third 
measurement, the EIT belt is opened and removed from the surgical field to avoid interference. 
Finally, when surgery is finished, before reversal of neuromuscular blockade and extubation, 
two-lung-ventilation will be re-established, a recruitment maneuver will be conducted and the 
patient will be repositioned in the supine position. Finally, a final measurement is conducted. 

NCT04725318 October 20, 2020 
 
 
Figure 1 Study diagram.  2LV: Two-lung ventilation; OLV: One-lung ventilation; EIT: Electrical Impedance Tomography; Pes: Esophageal 
pressure; PL: Transpulmonary pressure; PV curve: pressure-volume curve 
 

NCT04725318 October 20, 2020 
 
Study subjects  
We will include adult patients undergoing non-cardiac, intrathoracic surgery with general 
anesthesia and one-lung ventilation. Exclusion criteria will be the 
- 
Inability to give written informed consent 
- 
Pregnancy 
- 
Structural lung disease, COPD, active Asthma 
- 
Active respiratory infections 
- 
Prior lung resection 
- 
Prior esophageal or gastric surgery 
- 
Esophageal varices 
- 
Patients under effective anticoagulation 
- 
Pacemaker or internal cardioverter/defibrillator (ICD) 
 
Statistical analysis and sample size estimation 
The primary hypothesis will be that esophageal pressure changes from the supine to the lateral 
position, and from the lateral position to one-lung ventilation. The co-primary hypothesis will be 
that in lateral position with OLV, there is a difference (“correction factor”) between PL derived 
from esophageal pressure and the closing pressure of the dependent lung areas. Our 
secondary hypothesis will be that the “correction factor” differs depending on whether the right 
or left lung is down and subject to OLV due to anatomical differences (e.g. positioning of the 
heart). Comparison of esophageal pressure between baseline, lateral and OLV will be made 
using repeated measures ANOVA (Sidak post-hoc test). Comparison to the “Post” 
measurement will only be made within an exploratory analysis to avoid alpha inflation due to 
multiple comparisons. All calculations will be made with alpha set to 0.05. 
In a previous investigations in patients undergoing general anesthesia with mechanical 
ventilation, we found esophageal pressure to be 16.2 ±3.8 cmH2O after intubation in the supine 
position. We consider a 20% change in esophageal pressure when changing from the supine to 
the lateral position to be relevant. Therefore, we would need 8 patients to achieve a 90% power 
for detecting this difference (paired t-test, alpha 0.05). To adjust for multiple comparison (supine 
to lateral to OLV), we plan to include 25 patients (3*8 + 1 patient to account for failed 
measurements) into this study. 

NCT04725318 October 20, 2020 
 
 
 
 

NCT04725318 October 20, 2020 
 
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