American Journal of Respiratory and Critical Care Medicine

To the Editor:

Negative pressure swings generated by patients’ muscles (Pmus)—which add up to airway pressure generated by the ventilator—are increasingly recognized as a potential source of injury for the lungs, particularly in patients with acute respiratory distress syndrome (1). Precise monitoring of this component requires transduction of esophageal pressure or electrical activity of the diaphragm (2). Recently, however, two surrogated methods, relying on airway pressure waveforms only, have been proposed and validated to estimate the total driving pressure. The first is the static method. Our group reappraised (3) the end inspiratory technique (originally described by Foti and colleagues [4]), which takes advantage of patients’ relaxation, normally occurring at the end of inspiration, to estimate the “real plateau pressure,” which is often unpredictably higher than peak pressure (5). The derived driving pressure has the same meaning as during controlled ventilation and is independently associated with outcome. The other is the dynamic method. Bertoni and colleagues (6) proposed to calculate the Pmus from the inspiratory effort of a patient during a quick expiratory pause and sum this value (after application of a correction factor) to the dynamic driving pressure of the airways during tidal ventilation to calculate a dynamic transpulmonary pressure.

Because both methods aim to estimate the total pressure distending the respiratory system, these should lead to similar results, albeit with a difference because of the static versus dynamic conditions.

The purpose of this retrospective study is 1) to compare the results of the two methods and 2) to verify the hypothesis that the results obtained by the two methods differ mainly for the resistive pressure drop.

Methods

This is a retrospective analysis of waveform tracings obtained from three previously published studies conducted over the last 10 years (79) at a tertiary referral university hospital, which were approved by an ethics committee and for which informed consent had been obtained.

A detailed description of the studies can be found in the original publications. All studies enrolled patients with acute respiratory failure who were ventilated in Pressure Support (PS) or Neurally Adjusted Ventilatory Assist, and the main interventions were the changes in support level and/or positive end-expiratory pressure (PEEP) level according to the specific protocol. For this analysis, only the phases of PS were considered. During each step, inspiratory and expiratory holds were performed.

For the present study, we retrieved the pairs of expiratory and inspiratory occlusions performed in each patient at the same ventilatory setting level, if the Vt and peak flow of the breath preceding the expiratory occlusion and the breath of the inspiratory occlusion would not differ by more than 10%, to compare breaths with similar respiratory efforts.

Dynamic method

From expiratory holds, Pmus was measured, as described by Bertoni and colleagues (6), as the difference between the level of total PEEP and the low level of pressure during the expiratory hold (ΔPocc), multiplied by 0.75. This was added to the pressure support level (dynamic driving pressure) to calculate the total dynamic driving pressure (ΔPdyn), extrapolated from the original method by Bertoni in which Pmus was multiplied by two-thirds to calculate dynamic transpulmonary pressure.

Static method

For the inspiratory occlusions, driving pressure was calculated as plateau pressure minus PEEP (ΔPst), excluding holds with airway pressure tracing considered unreadable, as previously described (3).

As for a subset of patients, a phase in square flow controlled mechanical ventilation was present, and respiratory system resistances were calculated according to standard formulas. The resistive load of the assisted breaths was calculated as the product between the resistances at the peak of inspiratory flow during the inspiratory hold per each couple of occlusions.

Paired t test and linear correlations were used to compare or to test association among variables obtained by the two methods.

Bland-Altman analysis was performed to compare ΔPdyn with ΔPst adjusted for the resistive component.

Results

Overall traces from 39 patients with a total of 174 conditions were available, and a total of 103 pairs of inspiratory and expiratory occlusions from 29 patients were analyzed.

The average ΔPdyn was significantly higher than ΔPst (14.5 ± 4.7 vs. 10.3 ± 3.0 cm H2O; P < 0.001). The measurements obtained by the two methods were tightly correlated (R2, 0.77; Figure 1), albeit with a slope (0.55) significantly lower than the identity. When the resistive component was added to ΔPst, this led to a tighter correlation with ΔPdyn (R2, 0.81; Figure 1) and a slope close to identity (0.97). A Bland-Altman comparison between the last two methods shows an average difference of 1.3 cm H2O with a 95% confidence interval of −2.6 to 5.2.

Discussion

In this study, we compared two methods aimed at taking into account the Pmus contribution on distending the respiratory system (Figure 2). The two methods cannot be directly compared, as Bertoni and colleagues aim to estimate the transpulmonary pressure (as opposed to Bellani and colleagues, who estimate total pressure applied to respiratory system). We reasoned that total respiratory system pressure calculated according to their method would be the sum of Pocc multiplied by 0.75 (correction factor from static to dynamic conditions) plus PS. Not surprisingly, the dynamic method led to higher values of ΔP than the static one, as it includes the pressure spent to overcome the airway resistance.

It is unknown which value (static or dynamic) should be the target of a lung-protective assisted ventilation. During fully controlled ventilation, resistive pressure drop is not considered as injurious as elastic pressure variation because it does not contribute to alveolar wall strain. During assisted ventilation instead, higher resistive pressure drops lead to more negative alveolar pressures (10). At the same time, it is important to keep in mind that absolute thresholds of driving pressures cannot be directly translated from static to dynamic conditions.

In conclusion, with the limitations of a retrospective report, we show that the two methods lead to coherent and complementary information in regard to the total pressure applied to the respiratory system during assisted ventilation, reinforcing the clinical usefulness of both approaches.

1. Brochard L, Slutsky A, Pesenti A. Mechanical ventilation to minimize progression of lung injury in acute respiratory failure. Am J Respir Crit Care Med 2017;195:438442.
2. Mauri T, Yoshida T, Bellani G, Goligher EC, Carteaux G, Rittayamai N, et al.; PLeUral pressure working Group (PLUG—Acute Respiratory Failure section of the European Society of Intensive Care Medicine). Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives. Intensive Care Med 2016;42:13601373.
3. Bellani G, Grassi A, Sosio S, Foti G. Plateau and driving pressure in the presence of spontaneous breathing. Intensive Care Med 2019;45:9798.
4. Foti G, Cereda M, Banfi G, Pelosi P, Fumagalli R, Pesenti A. End-inspiratory airway occlusion: a method to assess the pressure developed by inspiratory muscles in patients with acute lung injury undergoing pressure support. Am J Respir Crit Care Med 1997;156:12101216.
5. Bellani G, Grassi A, Sosio S, Gatti S, Kavanagh BP, Pesenti A, et al. Driving pressure is associated with outcome during assisted ventilation in acute respiratory distress syndrome. Anesthesiology 2019;131:594604.
6. Bertoni M, Telias I, Urner M, Long M, Del Sorbo L, Fan E, et al. A novel non-invasive method to detect excessively high respiratory effort and dynamic transpulmonary driving pressure during mechanical ventilation. Crit Care 2019;23:346.
7. Patroniti N, Bellani G, Saccavino E, Zanella A, Grasselli G, Isgrò S, et al. Respiratory pattern during neurally adjusted ventilatory assist in acute respiratory failure patients. Intensive Care Med 2012;38:230239.
8. Bellani G, Mauri T, Coppadoro A, Grasselli G, Patroniti N, Spadaro S, et al. Estimation of patient’s inspiratory effort from the electrical activity of the diaphragm. Crit Care Med 2013;41:14831491.
9. Bellani G, Bronco A, Arrigoni Marocco S, Pozzi M, Sala V, Eronia N, et al. Measurement of diaphragmatic electrical activity by surface electromyography in intubated subjects and its relationship with inspiratory effort. Respir Care 2018;63:13411349.
10. Bellani G, Grasselli G, Teggia-Droghi M, Mauri T, Coppadoro A, Brochard L, et al. Do spontaneous and mechanical breathing have similar effects on average transpulmonary and alveolar pressure? A clinical crossover study. Crit Care 2016;20:142.
*Corresponding author (e-mail: ).

Originally Published in Press as DOI: 10.1164/rccm.202004-1281LE on July 17, 2020

Author disclosures are available with the text of this letter at www.atsjournals.org.

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