Ventilator - Induced Lung Injury

By Neil R. MacIntyre, MD, FCCP

**Table 1–**The PEEP/FIO₂ Table Used by the NIH ARDS Network*
Step	FIO₂ levels	Corresponding PEEP level
1	0.3	5
2	0.4	5
3	0.4	8
4	0.5	8
5	0.5	10
6	0.6	10
7	0.7	10
8	0.7	12
9	0.7	14
10	0.8	14
11	0.9	14
12	0.9	16
13	0.9	18
14	1.0	18
15	1.0	22–24
*Data from the NIH ARDS Network.²⁷ The oxygenation goals are a PaO₂ of 55 to 80 mm Hg or an SpO₂ of 88 to 95. Adjust settings by steps to meet these goals.

Future Directions

New approaches to PPV. A number of important questions still remain regarding the use of lung-protective strategies during conventional mechanical ventilation. First, it is still unclear what are the important aspects of the tidal breath pressure/volume pattern (eg, frequency, flow magnitude, inspiratory time, tidal stretch) that affects injury? Second, what are the optimal tradeoffs in gas exchange, pH, and FIO₂ when considering aggressive reductions in minute ventilation? Third, where is the optimal PEEP setting with regard to PV plots? Indeed, does it matter? Fourth, what is the role of positioning (especially proning^76-78) in redistributing lung water, lung perfusion, and lung ventilation so as to optimize a lung-protective strategy? Finally, do these lung-protective principles also apply to nonparenchymal lung disease (eg, obstructive diseases)? Logic would suggest that overdistention injury can also occur in any lung disease if excessive pressures and volumes are directed at healthier regions of the lung.

Potential nonconventional respiratory support strategies and adjuncts that might enhance lung protection include two approaches: high-frequency ventilation (HFV) and techniques to alter surface active properties. HFV, by providing low maximal pressures and high recruitment pressures, might be the ultimate lung-protective strategy for a PPV system.⁷⁹ Indeed, in infants at risk for overdistention injury, HFV has been shown to offer benefit. Adult data, however, are scant, although a recent unpublished randomized trial of HFV suggests a trend in survival improvement.

Surface active properties can be altered by either partial liquid ventilation or by surfactant administration. Partial liquid ventilation uses an oxygen-soluble fluorocarbon to provide alveolar recruitment (liquid PEEP) and thereby improve lung mechanics.⁸⁰ The need for high distending pressures should be reduced accordingly. Unfortunately, although lung mechanics and ventilation-perfusion matching appear improved with partial liquid ventilation, these substances are cumbersome to use and outcome data is lacking. The rationale behind the use of surfactant replacement is similar to that for partial liquid ventilation: By improving lung mechanics, high distending pressures can be avoided. Surfactant replacement in the premature neonate clearly improves outcome. Surfactant replacement in the adult has been less successful, but with newer preparations that include surfactant proteins and better delivery strategies, it may find utility in the future.⁸¹

Pharmacologic approaches to VILI. As noted above, VILI has many features in common with ARDS and sepsis. Strategies to limit inflammation in these two processes might therefore be expected to apply to VILI.⁵ It should be pointed out, however, that there are some differences in the inflammatory signal transduction pathways in sepsis vs VILI, and thus anti-inflammatory strategies in one may not necessarily apply to the other.⁵ In animal studies, agents that modulate membrane ion/fluid channels,^82,83 antibodies to TNF-a,⁸⁴ glucocorticoids,⁸⁵ selective enzyme blockers,⁸⁶ and interleukin 1 receptor antagonist⁸⁷ have all been shown to ameliorate VILI. In their comprehensive review of VILI, Dos Santos and Slutsky⁵ suggested areas for future research that included studies on epithelial/endothelial barrier function, microbiologic translocation, surfactant function, alveolar repair mechanisms, dysregulation of cellular mediators, regulation of the inflammatory response, and apoptotic control in inflammation.

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