Apr 282019

Jon-Emile S. Kenny MD [@heart_lung]

I am suffocated and lost when I have not the bright feeling of progression”

-Margaret Fuller

A recent letter and review in Critical Care have called for adoption of the ‘Open Lung Approach’ to patients with severe ARDS.  More specifically, in refractory ARDS whilst prone, it is argued that esophageal manometry be used to guide an end-inspiratory trans-pulmonary pressure [Ptp - airway pressure less the estimated pleural pressure] of 25 cm H2O.

The authors cite a small, retrospective analysis from their own institution; eight patients reviewed had severe ARDS and had an indication for veno-venous extracorporeal membrane oxygenation [vvECMO] according to the EOLIA trial.  The patients had an average PaO2/FiO2 [P/F] ratio of 62 ± 7 mmHg even with neuromuscular blocking agents and pronation.

Rather than immediately trying vvECMO, the patients received a ‘recruitment maneuver,’ PEEP augmentation and then end-inspiratory Ptp guided by esophageal manometry – aiming for a Ptp of ≤ 25 cm H2O.

Fortunately, all 8 patients avoided vvECMO as their aggregate P/ F ratio rose to 201 ± 87 mmHg with an average PEEP of 20.6 ± 4.0 cm H2O.


Recruit at your own risk?

Proponents of the ‘open lung approach’ argue that a high ‘opening pressure’ must be applied at the airway to open collapsed alveoli.  Not all phenotypes of ARDS are amendable to ‘recruitment,' but for those that are, three ‘types’ of pressure sum – and must be overcome – at the mouth of the terminal bronchioles and alveoli.  These three pressures are required to surmount the: 1. molecular attraction of water – or surface tension – in collapsed airways, 2. the interstitial pressure of the surrounding lung tissue and lastly, 3. the chest wall.  Typically, these summed pressures are between 45 and 60 cm H2O, for most patients and is why recruitment maneuvers are routinely of this magnitude.  However, opening pressures of this scale may open as little as 3% of collapsed airways and the peak effect may occur in as little as 10 seconds meaning that very high recruitment over many minutes may be of small incremental benefit.

The recently-published EPVENT2 provides an excellent foil for the controversial ART trial.  Both trials enrolled moderate-to-severe ARDS patients with similar P/F ratios and predicted mortality based on their baseline APACHE II, SAPS 3 and SOAP scores [predicated mortality may have been slightly higher in EPVENT2 based purely on these scores].  Importantly, after the first day of randomization, the 4 arms between the two trials all had similarly ‘higher’ level of PEEP applied [12 versus 16 cm H2O in ART and 17 versus 16 cm H2O in EPVENT2].  Despite these similar baseline risks and similar early, higher PEEP levels, EPVENT2 had a dramatically better 28-day mortality rate [28-day mortality was 49.3% and 55.3% in ART and 32.4% and 30.6% in EPVENT2].  Indeed, the mortality rates from EPVENT2 were comparable to those from a subgroup analysis of moderate-to-severe ARDS in a previous meta-analysis comprising the ALVEOLI, LOVS and EXPRESS trials.  What might explain these disparate results?

West Zone II & Cor pulmonale

As described previously, the ‘open lung’ arm of the ART trial began with, in my opinion, an exceptionally aggressive recruitment maneuver.  The initial protocol called for a driving pressure of 15 cm H2O on top of incrementally higher levels of PEEP [25 cm H2O for 1 minute, 35 cm H2O for 1 minute and 45 cm H2O for 2 minutes].  While some of this pressure certainly recruited collapsed alveoli, as above, this may have been a relatively small fraction of lung tissue and the duration of the maneuvers may have been excessively long.

If, for example, a patient with pulmonary ARDS – and little recruitment reserve – sustained the initial ART trial recruitment maneuver [RM], the following trans-pulmonary pressures would have been ‘felt’ by the pulmonary circulation [assuming 70% of the respiratory system elastance is pulmonary and an I:E ratio of 1:3].  At the first level of the RM, the trans-pulmonary pressure would oscillate between 45 seconds of 13 mmHg and 15 seconds of 21 mmHg; at the third level of the RM, the trans-pulmonary pressure would rise and fall between 23 mmHg for 90 seconds and 31 mmHg for 30 seconds!

Note that these pressures are also felt by the pulmonary capillaries and veins and that West Zone II occurs when the trans-pulmonary pressure is greater than the pulmonary venous pressure.  If patients were being managed with a fluid-conservative strategy – as warranted by the FACTT Trial – then it is fair to presume a left atrial filling pressure of 6-8 mmHg.  At this pulmonary venous pressure – and assuming a distance from the dorsal-most lung to the left atrium of 12 cm – it is entirely possible that the whole lung is placed at risk for West Zone II for the entire 4 minute recruitment maneuver!  Acute right ventricular failure is a common and dreaded complication of severe ARDS.

Open Lung Target?

If one were to open the lung with a lighter recruitment maneuver, what is the target of both PEEP and Ptp?  It is known that pulmonary strain above 1.5 results in lethal VILI in animal data; this strain corresponds to a Ptp of 18-20 cm H2O in humans.  For this, it has been argued that the absolute upper limit of Ptp be limited to 25 cm H2O, but not all agree.  Indeed, because of pulmonary ‘stress raisers’ some think that the Ptp should be no more than 12 cm H2O.  Nevertheless, choosing the right method to titrate PEEP and distending pressure was previously evaluated by Gattinoni’s group.  Stress index, esophageal manometry, recruitment-compliance based selection and the high PEEP table from the LOVS trial were compared and all resulted in roughly the same PEEP selection in moderate and severe ARDS.  More importantly, the massively consequential EPVENT2 trial has demonstrated that both esophageal manometry and the high-PEEP table from the OSCILLATE trial [the same as the high PEEP table from LOVS trial] do not increase expected mortality in moderate-to-severe ARDS.

Undoubtedly, there is a fraction of severe ARDS patients who can be placed in prone and who can violate an end-inspiratory plateau pressure of 30 cm H2O based on Ptp and therefore avoid vvECMO.  But these patients require highly individualized ventilator titration based on close monitoring of respiratory mechanics and hemodynamics.  Esophageal manometry can provide more certainty, but the EPVENT2 trial also reiterates that in moderate-to-severe ARDS, a gentle recruitment followed by PEEP titration using a higher PEEP-FiO2 table may be just as adequate to keep the lung open.



Dr. Kenny is the cofounder and Chief Medical Officer of Flosonics Medical; he also the creator and author of a free hemodynamic curriculum at heart-lung.org


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Open the Lung with Esophageal Manometry to Avoid VV-ECMO?