Esophageal pressure (P es ) measurement offers a good estimate of the respiratory variability of the pleural pressure. It is a minimally invasive method that can be used at bedside to quantify the respiratory effort and to determine the transpulmonary pressure. It can measure the intensity of spontaneous breathing and calculate the respiratory muscle effort known as the work of breathing (WOB). It has been used initially as a research tool to study the chest wall and lung mechanics in healthy subjects, but also in patients with acute lung injury. It has also been used in the clinical diagnostic recording of sleep. P es is usually measured by inserting a catheter with an air-filled latex balloon in the esophagus via the nose or the mouth. Recent studies have demonstrated that P es measurement can be useful in the management of patients with acute respiratory failure (ARF) who require invasive mechanical ventilation. Due to the fact that it can detect patient‐ventilator asynchronies and assess respiratory muscle effort, P es measurement can improve patient‐ventilator interaction and optimize the process of ventilator weaning. Furthermore, it allows positive end-expiratory pressure (PEEP) titration, which avoids the deleterious effects of intrinsic PEEP and improves oxygenation in mechanically ventilated patients. In patients with ARF requiring non‐invasive ventilation, P es measurement has been used as a research tool only, but benefits similar to those seen in invasive mechanical ventilation are to be expected and thus further studies are required to acknowledge this fact.
Based on the assumption that pressure in the adja-cent pleura is transmitted to the esophagus, esophageal pressure (Pes) monitoring, a minimally invasive respira-tory method that has been used for decades (for the first time in 1949), has proved to be an accurate estimate of pleural pressure and consequently of transpulmonary pressure(1). It has enhanced the knowledge regarding mechanical properties of the chest wall and the lung. Furthermore, it has led to a better understanding of the pathophysiological mechanisms of acute respiratory failure in mechanically ventilated patients.
Pes measurement can provide a measure of the inten-sity of spontaneous effort and thus measure the work of breathing. This is especially useful in patients with acute respiratory distress syndrome in which esophageal
pressure measurement has been shown to optimize and guide ventilator management, improving patient venti-lator interaction and ventilator weaning(2-4). It is also used during polysomnography to quantitively assess the respiratory effort, aiding in the diagnosis of sleep-relat-ed diseases(5).
Despite its proven usefulness, monitoring of Pes is still rarely used in clinical practice, being more frequent-ly seen as a research tool only. This may be related to technical difficulties such as insertion and proper posi-tioning of the esophageal catheter, obtaining accurate readings and interpretation of measurements.
In this article we discuss the physiological back-ground behind Pes measurement and we focus on the description of the technique and the current clinical implementations of this method.
The respiratory system is comprised of lungs and chest wall, each of these components generating a certain load. Intrathoracic pressures must overcome this load to inflate the lungs. In spontaneous breathing, the contraction of respiratory muscles generates pressure (Pmus – muscular pressure), which results in lung inflation. The mechanical ventilation can completely substitute or assist the activity of respiratory muscles. In ventilated patients, the pressure generated by the ventilator (Paw – airway pressure) and Pmus form the total pressure applied to the respiratory system (Ptotal = Paw + Pmus). Ptotal must overcome the elastic and resistive opposing forces of the respiratory system to inflate the lung. This relation is expressed in the following equa-tion (also called the equation of motion):
Ptotal = P0 + Ers x V + Rrs x F(1),
where P0 = Paw at the beginning of the respiratory cycle (zero or positive value if intrinsic PEEP or PEEPi is pre-sent), Ers = the respiratory system elastance, Rrs = the respiratory system resistance, V = the difference in volume between instantaneous volume and the relaxation volume of the respiratory system, and F is the airflow(6).
It has been shown that changes in Pes match the chang-es in pleural pressure (Ppl) applied to the lung surface(7). Transpulmonary pressure (PL) is the difference between Paw and Ppl, which is equivalent to PL = P aw – Pes (Figure 1)(7). Given the fact that absolute Pes values can be influenced by many factors (lung volume, weight of the mediastinum, abdominal pressure, posture, etc.), they may not always reflect the exact absolute values of Ppl, but in the clinical setting variaton of Pes (ΔPes) is considered to be equivalent to ΔPpl during stable conditions(8).
Elastance (also called elastic resistance) is a measure of the work needed to be generated by the respiratory muscles and/or ventilator to expand the lungs. It is equal to the change in pressure that is required to achieve one unit of volume change.
Elastance = ΔP/ΔV = 1/Compliance
Ers = Ecw +EL, where Ecw is the elastance of the chest wall and EL is the elastance of the lung. So, equation 1 can be expressed as:
Ptotal = P0 + (Ecw x V) + (EL x V) + Rrs x F
In conditions where there is no muscular activity (passive conditions), Pmus = 0 and consequently Ptotal = Paw, where Paw is generated and monitored by the venti-lator. V and F are also measured by the ventilator. During end-expiratory occlusion maneuvers, F=0 and in such a situation the equation will become:
Paw = P0 + (Ecw x V) + (EL x V)
As Ecw = ΔPcw/ΔV and E L = ΔPL/ΔV, Pes measurement (and consequently of PL) is useful to estimate what frac-tion of Paw is applied to overcome each of Ecw and EL.
In conditions where there is respiratory muscle activ-ity (i.e., spontaneous breathing effort) Pmus becomes an important component for the equation for motion (equa-tion 1) and the estimation of PL is only possible through Pes measurement.
The work of breathing (WOB) and the pressure-time product of the esophageal pressure (PTPes) allow for an estimation of the respiratory muscle effort which may provide useful information regarding ventilator effi-ciency in patients with invasive or non-invasive ventila-tion during spontaneous breathing. They can be calculated using Pes measurement.
WOB done in each respiratory cycle is considered as the area enclosed in the pressure volume loop and is graphically referred to as the Campbell diagram(9) (Figure 2). Mathematically it is expressed as:
WOB = ∫ Pressure x Volume
Elastic and resistive forces of the respiratory system must be overcome by the Pes swings during inspiration to allow air movement through the airways. These forces can be estimated by comparing the difference between Pes during active inspiration and Pes during passive condi-tions. Pes during passive conditions is measured on the pressure-volume curve when the respiratory muscles are completely relaxed and the airways are closed, and reflects the static recoil pressure of the relaxed chest wall (Pcw).
Pcw can only be obtained during passive inflation (i.e., muscle paralysis). This measurement can be used later as a reference value when the patient recovers spontaneous breathing. In circumstances where passive inflation is not possible, Pcw is calculated using the equation that describes the elastic forces of the chest wall(10):
Pcw = Vt/2Ccw,
where Ccw is the compliance of the chest wall, and it can be given a theoretical value (i.e., 4% of the predicted vital capacity per cmH2O)(11).
Consequently, Pmus can be expressed as:
Pmus = Pcw – Pes
and given the fact that Wmus (work performed by respiratory muscles) is expressed as:
Wmus = ∫ Pmus x ΔV
the following equation can be used to calculate WOB:
Wmus = ∫ (Pcw – Pes) x ΔV(6).
PTPes refers to the integral of pressure over time and can be expressed as:
PTP = ∫ P x Δt.
Therefore, PTPes = Pmus x Tmus (cm H2O x seconds) with Tmus being the time of muscle contraction(6).
WOB is expressed in joules (J). One J represents the energy required to move 1L of air through a 10 cm H2O pressure gradient. WOB can be either expressed as work per liter of ventilation (WOB per 1 breathing cycle divided by the tidal volume: 0.35J/L in healthy individual), or as work per unit of time (joules are multiplied per cycle by the respiratory rate to obtain the power of breathing: 2.4 J/minute in healthy individual)(12).
To measure Pes, a catheter or a small transducer must be inserted and correctly positioned in the esophagus(13). The most common technique is to use a catheter with an air-filled latex balloon at its sealed distal end and a pres-sure transducer at its proximal open end. The patient must be positioned in a semi-recumbent position. Small quan-tity of local anesthetic must be delivered to the nose and oropharynx to improve tolerance. The catheter is inserted through one of the nostrils. The catheter is then advanced into the stomach. The balloon must be inflated with a specific amount of air (ranging from 0.5 to 4 ml, depend-ing on the catheter design) and the pressure transducer connected to a dedicated acquisition system (which may be part of the ventilator) or a patient monitoring sys-tem(14). A positive pressure deflection during spontaneous inspiration indicates that the balloon is in the stomach. The catheter has to be slowly withdrawn until a negative pressure deflection during inspiration is recorded, mean-ing that the balloon is in the esophagus(15). The estimation of Ppl is most accurate when the balloon is in the lower third of esophagus. Another method of estimating the length required to reach the lower third of the esophagus is by using the Stanford formula for esophageal manom-etry: 0.228 x height (cm)(16).
After the recording has started, the validation of the measurement is required. The classic method of validating Pes measurement is the dynamic occlusion test which measures the ratio of change in airway opening pressure during three spontaneous respiration cycles against a closed airway, regardless of patient cooperation. If ΔPes/ ΔPaw ratio is close to 1 (acceptable range: 0.8-1.2), than the measurement is valid(17). It can also be performed by applying manual chest compression during airway occlu-sion (for example, in paralyzed or sedated patients)(18).
It is important to underline that the amplitude of Pes signal ca be influenced by a series of factors such as patient position, lung volume, esophageal peristaltic and balloon position(19). Moreover, cardiac activity can distort the Pes signal. Swallowing is not affected by the catheter and thus its position can be maintained for several days.
Clinical use of Pes – invasive ventilation
In patients with severe acute respiratory failure who require invasive mechanical ventilation, monitoring and understanding patient-ventilator interaction are a key component of a successful treatment in the intensive care unit (ICU). The adjustment of ventilator settings is usually based on Paw-flow waveforms, arterial blood gas analysis, and peripheral oxygen saturation. These parameters alone cannot properly determine the presence of patient-venti-lator asynchrony(20), nor can they quantify respiratory muscle activity (the amount of WOB). Thus, excessive respiratory muscle work is difficult to detect(21,22).
By using Pes real time measurement, the patient’s respira-tory muscle activity and patient-ventilator synchrony during assisted ventilation can be accurately monitored. This can be useful in several potential deleterious situations. It can detect: ineffective or missed (wasted) respiratory efforts during assisted ventilation(23), excessive PL and Vt values during synchronized pressure-targeted ventilation modes especially when lung protective ventilation is desired(24), excessive flow or excessively short inspiratory time(25), res-piratory muscle contraction triggered by the ventilator in sedated patients (respiratory entrainment)(26). Improving patient-ventilator interaction by adjusting ventilatory parameters such as inspiratory pressure, Vt, inspiration time, mandatory respiratory rate, etc. can lead to shortening of the duration of mechanical ventilation.
Another important issue in mechanical ventilation is the failure to detect or correctly estimate intrinsic PEEP (PEEPi), an event that is common in severe COPD or asthma exacerbation. It can lead to increased WOB, barotrauma, inappropriate ventilator triggering, hemodynamic instabil-ity and shock in mechanically ventilated patients(27). Before any volume of air can be displaced within the lung, an amount of pressure equal to PEEPi has to be generated. Pes measurement is the most accurate method of quantifying PEEPi. The value of PEEPi is the drop in Pes at end of the expiration, when the inspiratory muscles contract right before inspiratory flow starts(28).
Weaning, the process of removing the patient from mechanical ventilation and endotracheal intubation, must be considered as early as possible, as prolonged mechanical ventilation is associated with increased morbidity and mor-tality(29). During the weaning trial, estimation of WOB through Pes measurement can be extremely useful. Studies have shown that progressive increase in PTPes is associated with weaning failure, while lack of change in PTPes is seen in weaning success patients(30). Moreover, during spontane-ous breathing, change in PTPes during weaning is associ-ated with acute left heart failure(31). Thus, Pes measurement could be a simple tool in monitoring patients during wean-ing and may provide early signs for failure, giving time for therapeutical intervention and avoid reintubation.
Lastly, Pes measurement has proved to be a useful tool in improving ventilator parameters in patients with ARDS in the Esophageal Pressure-Directed Ventilation study (EPVent) (2). Pes strategy led to a higher PEEP at 72 hours (18 ± 5 cm H2O vs. 12 ± 5 cm H2O in the control arm). Despite failing to show any significant change in ventilator‑free days, length of stay or duration of ventilation, Pes strategy markedly improved arterial oxygenation and respiratory system com-pliance when compared to the control arm which used a standard protocol for adjusting ventilator parameters. Consequently, Pes-based adjustment of ventilatory parame-ters has been integrated in some ICU ventilators.
Clinical use of Pes – non-invasive ventilation
There are only a few studies regarding Pes measure-ment in patients with acute respiratory failure requiring non-invasive ventilation. All have used Pes measurement as a research tool to estimate WOB in order to compare different ventilation modes: CPAP with bi-level ventila-tion in acute pulmonary edema(32) or different types of non-invasive ventilation to spontaneous breathing in patients with severe COPD exacerbation(33-35)”.
As opposed to invasive mechanical ventilation, Pes measurement has not been studied as a tool that could improve patient ventilator interaction in non-invasive ventilation in patients with acute respiratory failure, although we believe it might prove to be of similar use-fulness. The ability to quantify PEEPi, to detect patient-ventilator asynchrony, to adjust inspiratory/expiratory pressure and backup respiratory rate by estimating WOB could reduce NIV failure rate and thus improve morbid-ity and mortality. Furthermore, given the fact that the correct amount of NIV has not been studied in published trials(36) and is based solely on blood gas measurement and the experience of the medical staff, Pes measure-ment could provide useful information in the process of weaning from NIV.
Pes monitoring is a simple method that allows a better understanding of respiratory mechanics. It can provide valuable information regarding the respiratory muscle effort in an acute setting. It can be safely performed at the bedside inside and even outside of ICU. Beside its value as a research tool, it has proven its usefulness in the clinical setting in mechanically ventilated patients, being able to quantify the level of muscle unloading during ventilation or during weaning trial. It is also useful in titrating PEEP and provides better ventilation strategy in ARDS patients. Despite this, Pes measurement in patients with ARF requir-ing ventilatory assistance (either invasive or non-invasive) is surprisingly low, with little data being published regard-ing the use of Pes in acute non-invasive ventilation.
While Pes measurement has been demonstrated to improve ventilator management in intubated patients with ARF, further research is required to ascertain the benefits in non-invasive ventilation.
- Cherniack RM, Farhi LE, Armstrong BW, Proctor DF. A comparison of esophageal and intrapleural pressure in man. J Appl Physiol. 1955; 8(2):203–11.
- Talmor D, Sarge T, Malhotra A, O’Donnell CR, Ritz R, Lisbon A, et al. Mechanical Ventilation Guided by Esophageal Pressure in Acute Lung Injury. N Engl J Med. 2008; 359(20):2095–104.
- Grasso S, Terragni P, Birocco A, Urbino R, Del Sorbo L, Filippini C, et al. ECMO criteria for influenza A (H1N1)-associated ARDS: role of transpulmonary pressure. Intensive Care Med. 2012; 38(3):395–403.
- Bellani G, Pesenti A. Assessing effort and work of breathing. Curr Opin Crit Care. 2014; 20(3):352–8.
- Chervin RD, Aldrich MS. Effects of Esophageal Pressure Monitoring on Sleep Architecture. Am J Respir Crit Care Med. 1997; 156(3):881–5.
- Akoumianaki E, Maggiore SM, Valenza F, Bellani G, Jubran A, Loring SH, et al. The Application of Esophageal Pressure Measurement in Patients with Respiratory Failure. Am J Respir Crit Care Med. 2014; 189(5):520–31.
- Agostoni E, Hyatt RE. Static Behavior of the Respiratory System. In: Comprehensive Physiology [Internet]. American Cancer Society; 2011 [cited 2018 Jul 29], p 113–30. Available from: https://onlinelibrary.wiley. com/doi/abs/10.1002/cphy.cp030309
- Loring SH, O’Donnell CR, Behazin N, Malhotra A, Sarge T, Ritz R, et al. Esophageal pressures in acute lung injury: do they represent artifact or useful information about transpulmonary pressure, chest wall mechanics, and lung stress? J Appl Physiol. 2010; 108(3):515–22.
- Cabello B, Mancebo J. Work of breathing. In: Applied Physiology in Intensive Care Medicine [Internet]. Springer, Berlin, Heidelberg; 2006 [cited 2018 Jul 31], p11–4. Available from: https://link.springer.com/ chapter/10.1007/3-540-37363-2_3
- Truwit JD. Lung mechanics. Compr Respir Care. 1995; 18–31.
- Fleury B, Murciano D, Talamo C, Aubier M, Pariente R, Milic-Emili J. Work of breathing in patients with chronic obstructive pulmonary disease in acute respiratory failure. Am Rev Respir Dis. 1985; 131(6):822–7.
- Mancebo J, Isabey D, Lorino H, Lofaso F, Lemaire F, Brochard L. Comparative effects of pressure support ventilation and intermittent positive pressure breathing (IPPB) in non-intubated healthy subjects. Eur Respir J. 1995; 8(11):1901–9.
- Dornhorst AC, Leathart GL. A method of assessing the mechanical properties of lungs and air-passages. Lancet Lond Engl. 1952; 2(6725):109–11.
- Hedenstierna G. Esophageal pressure: benefit and limitations. Minerva Anestesiol. 2012; 78(8):959–66.
- Benditt JO. Esophageal and gastric pressure measurements. Respir Care. 2005; 50(1):68–75; discussion 75-77.
- Virkkula P. Diagnosis of sleep-related breathing disorders: esophageal pressure monitoring, nasal resistance and postural cephalometry. Helsinki, 2003.
- Baydur A, Behrakis PK, Zin WA, Jaeger M, Milic-Emili J. A simple method for assessing the validity of the esophageal balloon technique. Am Rev Respir Dis. 1982; 126(5):788–91.
- Lanteri CJ, Kano S, Sly PD. Validation of esophageal pressure occlusion test after paralysis. Pediatr Pulmonol. 1994; 17(1):56–62.
- Baydur A, Cha EJ, Sassoon CS. Validation of esophageal balloon technique at different lung volumes and postures. J Appl Physiol (Bethesda Md 1985). 1987; 62(1):315–21.
- Leung P, Jubran A, Tobin MJ. Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Care Med. 1997; 155(6):1940–8.
- Marini JJ, Rodriguez RM, Lamb V. The inspiratory workload of patient- initiated mechanical ventilation. Am Rev Respir Dis. 1986; 134(5):902–9.
- Marini JJ, Smith TC, Lamb VJ. External work output and force generation during synchronized intermittent mechanical ventilation. Effect of machine assistance on breathing effort. Am Rev Respir Dis. 1988; 138(5):1169–79.
- de Wit M, Miller KB, Green DA, Ostman HE, Gennings C, Epstein SK. Ineffective triggering predicts increased duration of mechanical ventilation. Crit Care Med. 2009; 37(10):2740–5.
- Richard JCM, Lyazidi A, Akoumianaki E, Mortaza S, Cordioli RL, Lefebvre JC, et al. Potentially harmful effects of inspiratory synchronization during pressure preset ventilation. Intensive Care Med. 2013; 39(11):2003–10.
- Thille AW, Rodriguez P, Cabello B, Lellouche F, Brochard L. Patient-ventilator asynchrony during assisted mechanical ventilation. Intensive Care Med. 2006; 32(10):1515–22.
- Simon PM, Zurob AS, Wies WM, Leiter JC, Hubmayr RD. Entrainment of respiration in humans by periodic lung inflations. Effect of state and CO(2). Am J Respir Crit Care Med. 1999; 160(3):950–60.
- Blanch L, Bernabé F, Lucangelo U. Measurement of air trapping, intrinsic positive end-expiratory pressure, and dynamic hyperinflation in mechanically ventilated patients. Respir Care. 2005; 50(1):110–23; discussion 123-124.
- Brochard L. Intrinsic (or auto-) positive end-expiratory pressure during spontaneous or assisted ventilation. Intensive Care Med. 2002; 28(11):1552–4.
- Boles J-M, Bion J, Connors A, Herridge M, Marsh B, Melot C, et al. Weaning from mechanical ventilation. Eur Respir J. 2007; 29(5):1033–56.
- Jubran A, Tobin MJ. Pathophysiologic basis of acute respiratory distress in patients who fail a trial of weaning from mechanical ventilation. Am J Respir Crit Care Med. 1997; 155(3):906–15.
- Lemaire F, Teboul JL, Cinotti L, Giotto G, Abrouk F, Steg G, et al. Acute left ventricular dysfunction during unsuccessful weaning from mechanical ventilation. Anesthesiology. 1988; 69(2):171–9.
- Chadda K, Annane D, Hart N, Gajdos P, Raphaël JC, Lofaso F. Cardiac and respiratory effects of continuous positive airway pressure and noninvasive ventilation in acute cardiac pulmonary edema. Crit Care Med. 2002; 30(11):2457–61.
- Girault C, Richard JC, Chevron V, Tamion F, Pasquis P, Leroy J, et al. Comparative physiologic effects of noninvasive assist-control and pressure support ventilation in acute hypercapnic respiratory failure. Chest. 1997; 111(6):1639–48.
- Wysocki M, Richard J-C, Meshaka P. Noninvasive proportional assist ventilation compared with noninvasive pressure support ventilation in hypercapnic acute respiratory failure. Crit Care Med. 2002; 30(2):323–9.
- Pankow W, Becker H, Köhler U, Schneider H, Penzel T, Peter JH. Patient- ventilator interaction during noninvasive pressure supported spontaneous respiration in patients with hypercapnic COPD. Pneumol Stuttg Ger. 2001; 55(1):7–12.
- Davidson AC, Banham S, Elliott M, Kennedy D, Gelder C, Glossop A, et al. BTS/ICS guideline for the ventilatory management of acute hypercapnic respiratory failure in adults. Thorax. 2016; 71, Suppl 2:ii1-35.