Pressure-Volume Curves
Searching for the Grail or Laying Patients with Adult Respiratory Distress Syndrome on Procrustes' Bed?

Didier Dreyfuss

Service de Réanimation Médicale Hôpital Louis Mourier (Assistance Publique-Hôpitaux de Paris) Colombes, France

and Georges Saumon

Unité 82 Institut National de la Santé et de la Recherche Médicale Faculté de Médecine Xavier Bichat, Paris, France

	ARTICLE

TOP ARTICLE REFERENCES

The prognosis of the acute respiratory distress syndrome (ARDS) has considerably improved (1, 2). This is the result of more than two decades of basic and clinical research. The most productive avenue, in terms of improving outcome, has proved to be the analysis of the mechanical properties of lungs during ARDS. This was pioneered by Mead (3), who made a visionary statement not more than 3 yr after ARDS had been described. He concluded from studying a model of lung elasticity that "mechanical ventilators, by applying high transpulmonary pressure to the nonuniformly expanded lungs of some patients who would otherwise die of respiratory insufficiency, may cause the hemorrhage and hyaline membranes found in such patients' lungs at death." This generated a huge amount of experimental research that led to the concept of what is now known as "ventilator-induced lung injury" (VILI). Credit must also be given to Webb and Tierney, who performed the first comprehensive experimental study demonstrating without any ambiguity the reality of VILI (4). That VILI may have a clinical counterpart called ventilator-associated lung injury (VALI) (5) was debated for a long time.

Considerable progress stemmed from a better understanding of lung pathology and mechanics during ARDS. It was initially viewed as a homogeneous disease with a diffuse change in lung mechanical properties, but now ARDS is rightly considered to be a heterogeneous involvement of the lungs in which there are both relatively well-preserved areas and severely diseased areas. This was made possible by the availability of modern imaging techniques and by a considerable effort to interpret lung mechanics, in particular the pressure-volume (PV) curve (6, 7). The term baby lung was coined by Gattinoni and coworkers (6) to illustrate the fact that the alteration of lung compliance during ARDS reflects not a diffuse involvement, but a reduction in the amount of the ventilatable lung. In addition, more attention was paid to the shape of the PV curve. The presence of an upper inflection point at a rather low volume (sometimes within "normal" tidal volume) was interpreted as indicating lung overdistention (7). The importance of these concepts is considerable. If the amount of ventilatable lung is reduced, the logical implication is that the tidal volume must be reduced. The reality of VALI was deduced from well-conducted randomized clinical trials. These culminated in the demonstration of a 25% improvement in ARDS prognosis when the stress applied to diseased lungs was limited by reducing the tidal volume (8).

This could be a happy ending, but this would be to ignore that, like the PV curve, this story also has a beginning. Long before the shape of the upper part of the inspiratory PV curve interested researchers, the presence of its lower inflection point (LIP) puzzled them. This peculiarity was interpreted as indicating that a minimal pressure is necessary to recruit alveoli excluded from ventilation. Setting the positive end-expiratory pressure (PEEP) according to this point resulted in improved oxygenation (9). Indeed, many clinicians consider that the PEEP should be set at the level of (or slightly above) the LIP. But we still do not know the beginning of the story. Setting the PEEP according to the LIP might reduce VALI, but the validity of this concept has not been clinically assessed. The possibility that an insufficient PEEP (below the LIP) may promote further damage of injured lungs in vivo was raised by Sykes and coworkers (12). Damage might occur because of repeated opening and closing of distal airways, and the resulting increase in tissue shear stress. However, this hypothesis suffers from three major flaws. First, setting the PEEP above the LIP does not always lessen lung injury (13); second, there is no clear evidence that distal airways close and reopen during acute lung injury (14); third, setting the PEEP above the LIP may favor lung overdistention. This was suspected by Rimensberger and coworkers (15), who showed that ventilation occurs on the deflation rather than the inflation limb of the PV curve after a recruitment maneuver in rabbits with saline lavage-induced lung injury, and thus at a much higher lung volume than expected. Thus, placing the PEEP above the LIP seen on the inflation limb might result in an unnecessarily high PEEP. The notion that setting the PEEP at a well-defined level with respect to the LIP would sort out all difficulties is nicely challenged by the study by Lichtwark-Aschoff published in the December 2000 issue of the Journal (pp. 2125- 2133) (16). These authors measured compliance with the interrupter technique in piglets with saline-induced lung injury during tidal ventilation as the PEEP was varied from 3 to 24 cm H₂O. Sequential measurements were performed at each PEEP level, while the tidal volume was increased from 1.2 to 12 ml/kg body weight after performing an initial recruitment maneuver. They found that chord compliance (i.e., the slope of the line connecting end-expiratory and end-inspiratory coordinates on the PV curve) was not optimal when the PEEP was set at the LIP or above, and low in some animalssuggesting that the lungs of these animals became overinflated. No single PEEP level could be determined that optimized both lung mechanics and/or oxygenation in animals without an obvious LIP.

The clinical importance of the debate on the meaning of the LIP is illustrated by the work of Amato and coworkers (17). They reported a reduction in mortality during ARDS when a reduction in tidal volume was combined with setting a PEEP level above the LIP. Unfortunately, the lesson to be drawn from this study is not as evident as suggested by the above summary. Were these results due to a reduction in mortality by the high PEEP-low tidal volume (VT) settings or to an increase in mortality in the " normal" VT group, whose settings resulted in rather high plateau pressures? The answer may come from the results of the new study launched by the ARDSnet, in which ventilation with low tidal volume and either low or high PEEP are compared.

What can the clinician reasonably conclude, pending these results? To summarize, experimental studies such as those by Lichtwarck-Aschoff and colleagues (16) and by Rimensberger and coworkers (15) question the safety of high PEEP levels. Low mortality rates have been observed in patients with severe ARDS ventilated with a low (i.e., less than or equal to 10 cm H₂O) PEEP level (2, 8). It is clear that improved arterial oxygenation is not an acceptable predictor of improved survival (8). Thus adjusting the PEEP according to this criterion is no longer acceptable. As the LIP is not always visible on the PV curve, is it reasonable to set the PEEP at an arbitrary value, say 16 cm H₂O (17)? This sounds like Procrustes' (a mythical Greek brigand) habit of laying wretched travelers on his bed: if the legs were sticking out, they were cut; if the person was too short, he was stretched to death (18). In fact, we may acknowledge, in the words of Lichtwarck-Aschoff and coworkers (16), that "the question arises as to whether the change in lung volume as manifested in the pressure-volume loop reflects what occurs at the level of 300 million alveoli." The search for the best PEEP looks like the search for the Grail. But is there just one?

	References

TOP ARTICLE REFERENCES

1. Milberg JA, Davis DR, Steinberg KP, Hudson LD. Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993. JAMA 1995; 273: 306-309 .

2. Jardin F, Fellahi JL, Beauchet A, Vieillard-Baron A, Loubieres Y, Page B. Improved prognosis of acute respiratory distress syndrome 15 years on. Intensive Care Med 1999; 25: 936-941 .

3. Mead J, Takishima T, Leith D. Stress distribution in lungs: a model of pulmonary elasticity. J Appl Physiol 1970; 28: 596-608 .

4. Webb HH, Tierney DF. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures: protection by positive end-expiratory pressure. Am Rev Respir Dis 1974; 110: 556-565 .

5. International Consensus Conference in Intensive Care Medicine. Ventilator-associated lung injury in ARDS. Am J Respir Crit Care Med 1999; 160:2118-2124.

6. Gattinoni L, Pesanti A, Avalli L, Rossi F, Bombino M. Pressure-volume curves of total respiratory system in acute respiratory failure: computed tomographic scan study. Am Rev Respir Dis 1987; 136: 730-736 .

7. Roupie E, Dambrosio M, Servillo G, Mentec H, El Atrous S, Beydon L, Brun-Bruisson C, Lemaire F, Brochard L. Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome. Am J Respir Crit Care Med 1995;152:121-128.

8. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-1308.

9. Falke KJ, Pontoppidan H, Kumar A, Leith DE, Geffin B, Laver MB. Ventilation with end-expiratory pressure in acute lung disease. J Clin Invest 1972; 51: 2315-2323 .

10. Suter PM, Fairley HB, Isenberg MD. Optimum end-expiratory airway pressure in patients with acute pulmonary failure. N Engl J Med 1975; 292: 284-289 .

11. Matamis D, Lemaire F, Harf A, Brun-Buisson C, Ansquer JC, Atlan G. Total respiratory pressure-volume curves in the adult respiratory distress syndrome. Chest 1984; 86: 58-66 .

12. Argiras EP, Blakeley CR, Dunnill MS, Otremski S, Sykes MK. High PEEP decreases hyaline membrane formation in surfactant deficient lungs. Br J Anaesth 1987; 59: 1278-1285 .

13. Sohma A, Brampton WJ, Dunnill MS, Sykes MK. Effect of ventilation with positive end-expiratory pressure on the development of lung damage in experimental acid aspiration pneumonia in the rabbit. Intens Care Med 1992; 18: 112-117 .

14. Martynowicz MA, Minor TA, Walters BJ, Hubmayr RD. Regional expansion of oleic acid-injured lungs. Am J Respir Crit Care Med 1999; 160: 250-258 .

15. Rimensberger PC, Cox PN, Frndova H, Bryan AC. The open lung during small tidal volume ventilation: concepts of recruitment and "optimal" positive end-expiratory pressure. Crit Care Med 1999; 27: 1946-1952 .

16. Lichtwarck-Aschoff M, Mols G, Hedlund AJ, Kessler V, Markström AM, Guttmann J, Hedenstierna G, Sjöstrand UH. Compliance is nonlinear over VT irrespective of PEEP level in surfactant-depleted piglets. Am J Respir Crit Care Med 2000; 162: 2125-2133 .

17. Amato MBP, Barbas CSV, Medeiros DM, Magaldi RB, Schettino GDPP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CRR. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338: 347-354 .

18. Graves R. Greek myths. London: Cassell; 1958.