Peter N Cox*
MBChB, FFARCS, FRCPC, Professor, Anaesthesia & Paediatrics, University of Toronto, Clinical Director, Critical Care Unit, Department of Critical Care Medicine, The Hospital for Sick Children. *
Despite the increase in our understanding of the etiology of acute respiratory distress syndrome (ARDS) and a recognition that mechanical ventilation per se may further aggravate this lung injury, there is still no consensus as how to optimally ventilate the damaged lung. It appears that inadequate levels of PEEP and large tidal volumes are associated with this iatrogenic lung injury. Whether it is the end expiratory or end inspiratory volume that is important has been a matter of some debate. However, there is an increasing body of evidence to suggest that it is a repeated closing and snapping open of atelectatic alveoli that contribute to most of this ventilator induced lung injury. Therefore, the concept of opening the lung and maintaining it open should be a primary consideration in our ventilator strategy.

In a series of elegant, computerized tomographic studies, Gattinoni and colleagues in Milan have clearly demonstrated that the lung disease in patients with ARDS is heterogenous, with atelectatic consolidated lung units being representative of the dependent lung regions. Without appropriate recruitment maneuvers, mechanical ventilation would be directed to the relatively healthy, aerated non-dependent lung regions. This baby lung would be expected to accomplish gas exchange during ventilation. While the use of larger tidal volumes with the associated higher pressures may recruit some of the atelectatic dependent alveoli, as the airway pressure falls to zero during expiration, these alveoli would once again collapse. It is these sheer forces during the reopening and closing of alveoli that significantly contribute to lung injury.

The pressure volume curve of lungs in the early phases of ARDS is characterized by an inflection zone (point) on the ascending (inflation) limb of the curve. This zone is representative of the recruitment of the previously collapsed, atelectatic alveoli which once recruited tend to behave as a relatively normal lung. It would follow that if one were able to maintain the recruited lung volume, gas exchange would improve and the potential for lung injury should be decreased. Is the evidence to support this? A number of animal studies have been done, of which three will be highlighted. In a canine acid aspiration model. Corbridge and colleagues maintained end-inspiratory pressure and volume constant and then compared a large tidal volume, low PEEP ventilatory strategy (30 ml/kg, 3 cm H20) with a smaller tidal volume, high PEEP strategy (15 ml/kg, 12.5 cmH20). Shunt fraction remained significantly lower in the small Vt, high PEEP group throughout the 4 hour experiment when compared to the large Vt, low PEEP group. As well, pulmonary edema was noted to be greater in the large Vt, low PEEP group. Using surfactant depleted rabbit model of ARDS. Sandhar and colleagues demonstrated significantly improved oxygenation in animals where PEEP was set above the measured inflection point (14 cm H20) when compared with animals where PEEP was set at 1-2 cm H20). Mean airway pressures were equal and normocarbia was maintained in both groups. The histological findings in the two groups were markedly different with significantly less hyaline membrane formation in the high PEEP groups. A third important study was of Muscadere et al where isolated non-perfused rat lungs were excised immediately after surfactant depletion and randomized either to be ventilated at ZEEP, PEEP = 4 cm H2a0 (below PNF), PEEP > PNF, or not ventilated with a CPAP of 4 cm H20). Tidal volume was set at 5-6 ml/kg. PNF was measured around 15 cm H20. They demonstrated that those lungs ventilated at ZEEP, or PEEP below Pinf had a significant decrease in compliance compared to those ventilated with PEEP > PNF and control. There was no significant difference between control and PEEP > PNF. Importantly, the ZEEP and PEEP < PNF group had severe hyaline membrane formation when compared to the other groups. They again postulated that the opening and closing of small airways may cause sheer stress and lung injury during mechanical ventilation with PEEP acting as a splint to the airways and reducing the stress factor. In addition to maintaining alveoli in the open state and thus reducing stress, PEEP may also maintain surfactant function (Greenfield, Faridy, and Wyszogrodski) which itself would help to maintain alveoli in the open state. The above is but a small sample of an increasing body of work supporting the argument that maintaining the lung in the open state not only improves gas exchange but also minimizes ventilator induced lung injury. Should this be so, what other lung volume recruitment and maintenance maneuvers are available to us and are they as effective?

High Frequency Oscillation (HFO):
High frequency ventilators have the advantage of transporting CO2 out of the lungs with smaller pressure and volume fluctuations than are required during conventional mechanical ventilation. Although it was initially thought that adequate gas exchange could be obtained at relatively low mean airway pressures, it has since been convincingly demonstrated that recruiting lung volume is essential in not only optimizing oxygenation but also in minimizing lung injury. Using two models of lung disease (oleic acid and lung lavage). Kolton and colleagues demonstrated that, at matched mean airway pressures, PaO2 was significantly greater during high frequency oscillation than during conventional mechanical ventilation, provided that mean airway pressure was greater than the inflection point characteristic of these lesions. Of particular importance, he noticed that in the oleic acid injured lung, a sustained inflation was essential to open the lung and thus ventilate at a much larger lung volume. When using sustained inflations in the conventional ventilated group, the pressure was allowed to drop back to a PEEP which did not match the mean airway pressure of the high frequency oscillated group (HFO group). The recruited lung volume was therefore not maintained. In another study, McCulloch et al, using a surfactant depleted rabbit model, demonstrated that when lung volume was maintained in HFO, not only was oxygenation better than a low lung volume group but also less hyaline membrane was formed. Also, both HFO groups were better than a comparative CMV group. Current technology limits the use of oscillators to infants and children. However, new innovations may soon allow us to use this in larger individuals.

Sustained Inflations and PEEP:
Work in our own laboratories has demonstrated that using a sustained inflation, one boosts the ventilatory cycle onto the deflation limb of the PV curve. As such, the inflection point on the inflation limb is no longer a relevant factor to consider in recruitment and maintenance maneuvers. Providing PEEP is kept greater than the closing volume of the lung, we have demonstrated that lung volume is maintained with the associated improvements in oxygenation and carbon dioxide removal. Using the same isolated non-perfused saline lavaged rat lung model as Muscadere, we have shown that lung injury in our sustained inflation, PEEP > closing volume group is indeed no worse than his PEEP > PNF group. The sustained inflation maneuver is an extrapolation from the HFO group described above where an inflation pressure of 30 cm H20 is applied for a period of 30 seconds. This boosts the cycle onto the deflation limb of the curve and small tidal volumes can then be used ensuring that alveoli are firstly opened and then not overstretched during the ventilatory cycle. The above methods of volume recruitment and maintenance assume a single compartment where equal pressures are applied to the non-dependent and dependent parts of the lung. However, there may still be over distention of non-dependent lung units in order to achieve recruitment of dependent lung units. To overcome this potential problem, applying a range of PEEP values, lowest in the non-dependent and highest in the dependent lung, would be ideal.

Perfluorochemicals which have high solubilities for both oxygen and carbon dioxide as well as a density of approximately twice that of water have the potential to keep collapsed alveoli open. Their high spreading coefficient and low surface tension would allow them to recruit atelectatic lung and maintain this recruitment by filling the alveoli with the oxygen rich, non-compressible fluid. Unfortunately, total liquid ventilation requires specialized equipment and because of the high viscosity of perfluorochemicals (similar to water) would preclude its use in spontaneous ventilation. However, partial liquid ventilation allows for gas ventilation with standard mechanical ventilators superimposed on a lung partially filled with perfluorocarbon. The advantages of liquid breathing will thus be preserved without the disadvantages mentioned above. Liquid will thus act as a bottled PEEP providing a vertical gradient of pressure which will be maximal in the most dependent, most atelectatic part of the lung. Numerous animal studies have demonstrated a marked improvement in pulmonary mechanics and gas exchange with partial liquid ventilation when compared to conventional gas ventilation. As well, lung architecture is maintained and further ventilator induced injury prevented. Currently, partial liquid ventilation is undergoing clinical trials and PLV may soon become an accepted adjunct in our management of patients with ARDSO.

Prone positioning may offer similar advantage in a graded PEEP and will be discussed in another forum at this meeting.

How best to achieve adequate gas exchange without further inducing lung injury remains the goal of clinicians and therapists alike. There is no doubt that opening the lung and keeping it open is one important.
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