A 35-year-old male with a BMI of 52 develops ARDS. He is mechanically ventilated on FiO2 of 100% and PEEP of 20. Plateau pressure (Ppalt) is 32 and PaO2 is 50. The treating team is hesitant to increase PEEP further as Pplat is already >30. How will you set PEEP for this patient?
In a recent article, we took the first step towards identifying indices of lung stress. We established that peak inspiratory pressure is not relevant at all in this regard (as it also includes the resistive component) and Pplat brings you closer to the truth. We also commonly look at the PEEP while determining the lung stress during expiration (too much PEEP may overinflate lungs). In this post, we will explore how the value of pleural pressure (Ppl) affects the ability of PEEP and Pplat to represent lung stress.
The concept of transmural pressure
The idea of transmural pressure is incredibly important in both pulmonary and cardiovascular physiology. Consider an air-filled balloon that is placed in a pressure chamber (Figure 1).
- Pressure inside the balloon = intramural pressure, Pim
- Pressure outside the balloon = extramural pressure, Pem
- Pressure ‘across’ the balloon = transmural pressure, Ptm (i.e., pressure gradient between inside and outside the chamber)
Mathematically, Ptm = Pim – Pem; or Pim = Ptm + Pem
It is the transmural pressure (Ptm) that determines the degree of stretch in the wall of the balloon. In other words, Ptm determines the wall stress.
Let’s apply this principle to a single alveolus (Figure 2). Transalveolar pressure (Ptm) = alveolar pressure (Palv) – pleural pressure (Ppl). Straight away, it becomes clear that it is not the alveolar pressure that decides stress, but instead the transalveolar pressure.
Now, let’s extend this idea to the whole lung in a clinical scenario. Say you are checking Pplat in a mechanically ventilated patient. To do this, you have to do an end-inspiratory hold (zero airflow) so that any resistive pressure is eliminated. Similarly, we perform an expiratory hold to determine total PEEP. Hence, while checking Pplat and PEEP, the airway pressure (Paw) read on the ventilator is a reflection of alveolar pressure (Palv). But remember that it’s the transalveolar pressure (Ptm) that determines stress, not Palv. You can now deduce that if you want to determine lung stress, the key piece of information missing here is the value of Ppl.
Definitions of transmural pressures.
There’s a lot of confusion in terminology and it’s important we all speak the same language.
Transmural pressure: A generic term reflecting the difference between intramural and extramural pressures in an elastic chamber. It is used in both cardiovascular and pulmonary physiology.
Transalveolar pressure: Transmural pressure of a single alveolus. This reflects alveolar wall stress but is not clinically relevant since the lung is composed of several alveoli/lung units. We need a special name for ‘pressure across the lung parenchyma’.
Transpulmonary pressure: This is, in fact, the difference in pressure at the airway opening (Pao or Paw) and the pleural pressure (Ppl). Note that this includes the pressure difference across the airways, which is the resistive pressure. In conditions of zero airflow (e.g., while checking Pplat and total PEEP), resistive pressure is zero, and transpulmonary pressure indeed reflects the pressure across the lung parenchyma: the true surrogate of lung stress. For better clarity, these should be specifically referred to as end-inspiratory transpulmonary pressure (Pplat – Ppl) & end-expiratory transpulmonary pressure (totalPEEP – Ppl).
(P.S.: If you read classic texts on respiratory mechanics, the pressure across the lung parenchyma is referred to as ‘elastic recoil pressure of the lung’ or Pel(L). Stephen Loring et al have written an entire article addressing this point!)
It should become clear from the discussion so far that one cannot purely rely on PEEP and Pplat as indices of lung stress. The knowledge of Ppl becomes extremely relevant here. E.g., if two patients have the same Pplat but very different Ppl, their end-inspiratory transpulmonary pressure (lung stress) would vary significantly. In a healthy supine subject, end-expiratory Ppl is quite close to zero. So, what are some of the patient populations where Ppl varies significantly from the average? The two important ones are (a) Morbidly obese patients, and (b) Patients with abdominal compartment syndrome.
In morbidly obese patients, excessive weight of the chest wall increases the pleural pressure. This effect is especially magnified in a recumbent position. In fact, Ppl can be significantly reduced in obese patients if they are placed in a sitting or reverse trendelenberg position. In abdominal compartment syndrome, the high intraabdominal pressure pushes against the diaphragm. Remember that from the perspective of respiratory mechanics, diaphragm is a part of the ‘chest wall’. A hypothetical comparison is presented in Figure 3. (These numbers are very realistic and not an exaggeration!)
Let’s now address the case in the pre-brief. Since this morbidly obese patient is expected to have high Ppl, PEEP and Pplat will not be reflective of actual lung stress during expiration and inspiration respectively. The major clinical challenge for setting PEEP here is the lack of knowledge of Ppl. Esophageal pressure can be used as a surrogate of Ppl and this approach has been studied in two trials, EP-Vent1 and EP-Vent2. EP-Vent2 failed to show any clinical benefit of universal esophageal-pressure guided PEEP selection. However, it is quite likely that if esophageal pressure monitoring is used in populations at high risk of increased Ppl (e.g. morbidly obese), a clinical benefit may be found.
If esophageal pressure monitoring is not feasible, attention to driving pressure can be extremely helpful in these patients. As lung tissue is overinflated, it becomes stiffer (compliance is reduced). In this state, a given tidal volume will require a higher driving pressure. Revisiting the example in Figure 3, lung compliance of patient A would be much lower than patient B (due to overinflation with PEEP). Hence, a given tidal volume will result in a much higher driving pressure in patient A. From personal experience, we have seen morbidly obese patients can require a PEEP of up to ~30 cmH20; yet, we are able to ventilate with a driving pressure of 10 – 12.
A final point worth noting is that the fixed Pplat target of <30 does not take Ppl into account. We have already seen how a certain PEEP or Pplat may indicate very different lung stress based on the Ppl value. This becomes relevant if high PEEP is used in obese patients. E.g. consider a patient where PEEP = 30, Pplat = 40 (driving pressure = 10), and end-inspiratory Ppl = 28. In this case, end-inspiratory transpulmonary pressure would be 40 – 28 = 12, which is a very safe value. End-inspiratory transpulmonary pressure of < 20 is generally considered safe.
- End-inspiratory and end-expiratory transpulmonary pressures are the best surrogates of inspiratory and expiratory lung stress respectively.
- Mathematically, end-inspiratory transpulmonary pressure = Pplat – Ppl & end-expiratory transpulmonary pressure = totalPEEP – Ppl
- Patient populations at special risk of developing high Ppl are those with (a) Class-III obesity and (b) abdominal compartment syndrome. Optimal PEEP for these patients is higher than average.
- The major challenge in determining true lung stress is the lack of knowledge of Ppl. Esophageal pressure can be used as a surrogate. If not feasible, driving pressure can be extremely helpful to guide PEEP selection.
- Loring SH, Topulos GP, Hubmayr RD. Transpulmonary Pressure: The Importance of Precise Definitions and Limiting Assumptions. Am J Respir Crit Care Med. 2016 Dec 15;194(12):1452-1457.
- Talmor D, Sarge T, Malhotra Aet al. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008 Nov 13;359(20):2095-104.
- 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 Mar 5;321(9):846-857.
- Grieco DL, Chen L, Brochard L. Transpulmonary pressure: importance and limits. Ann Transl Med. 2017 Jul;5(14):285. doi: 10.21037/atm.2017.07.22. PMID: 28828360; PMCID: PMC5537111.
Had a case not too long ago that esophageal manometry worked out wonderfully. Transferred to us from OSH for ECLS consult, COVID-19+, came in on 100%/PEEP+20, SpO2 barely 85%, BMI 60s. Patient wasn’t profoundly hypercapnic, but definitely hypoxemic.
Dropped a balloon in as soon as patient was sorted out, and Ptpex was -10 (!). Of course, I cranked that PEEP all the way to 30cmH2O; lo and behold, Ptpex was hovering between 0 to +1. FiO2 was weaned down to 40% later that night, and by day 2/3, patient was extubated to 4L nasal oxygen. Should’ve seen the resident’s reaction when I was asking an order for PEEP+30.