in a recent issue of the british journal of anaesthesia , moloney and griffiths   reviewed basic issues surrounding the ongoing debate on ventilator induced / associated lung injury ( vili ) and the implications for patient care .
the potential importance of vili / biotrauma is not only that it can aggravate ongoing lung injury but also that it may have important systemic consequences , and may explain why most patients with acute respiratory distress syndrome ( ards ) who go on to die , succumb to multiple organ failure ( mof ) . vili / biotrauma offers a clinically relevant window of therapeutic opportunity in the management of ards / acute lung injury ( ali ) .
often the process of systemic inflammatory response syndrome has been initiated hours if not days before admission to the intensive care unit .
in contrast , we know exactly when vili / biotrauma begins  with intubation and initiation of mechanical ventilation
. a full understanding of the mechanisms that mediate lung injury may permit potential strategies directed at reducing the incidence of vili - induced mof to be instituted early in the course of illness .
this is no small issue for a syndrome with an incidence of 64.2 cases per 105 person - years and with a 4050% mortality rate .
results from the ardsnet trial   have underscored the potential importance of biotrauma in the management of ards : the results from that large multicenter trial showed a relative risk reduction of 22% in patients ventilated with the lower tidal volume .
this improvement in mortality in patients ventilated with low tidal volumes was not due to a decrease in barotrauma between groups .
it is postulated that injurious strategies of mechanical ventilation can cause pulmonary inflammation with release of various cytokines / mediators  biotrauma .
the initial insult ( pneumonia , acid aspiration , or contusion are a few examples ) ' primes ' the lung .
a ' second hit ' , or subsequent insult , such as mechanical ventilation , leads to an overwhelming pulmonary inflammatory response .
loss of pulmonary compartmentalization allows for important mediators to escape the confines of the lung and gain access to the systemic circulation .
recent experiments have shown that this is associated with apoptosis of cells in distal organs ( kidney , villi of colon ) and end - organ dysfunction ( kidney ) , which potentially underlies the development of mof . in a randomized controlled trial conducted in 44 patients , ranieri and coworkers demonstrated that a lung protective strategy attenuated the levels of proinflammatory cytokines in plasma and bronchoalveolar lavage fluid , and was associated with a lower incidence of mof .
however , the measurement of proinflammatory cytokines does not address the issue of maintenance of alveolar  epithelial barrier integrity .
in a recent study conducted by eisner and coworkers , circulating levels of surfactant protein ( sp)-a and sp - d were evaluated in plasma samples from participants in the ardsnet randomized trial .
baseline plasma sp - a levels were not found to be related to clinical outcome .
in contrast , higher baseline plasma sp - d levels were associated with a greater risk for death ( odds ratio 1.21 per 100 ng / ml increment ; 95% confidence interval 1.08 to 1.35 ) as well as higher overall morbidity .
in addition , use of a lower tidal volume strategy significantly attenuated the rise in plasma sp - d levels ( p = 0.0006 ) .
because injury to the alveolar  epithelial barrier is a hallmark of ali , levels of circulating sps may not only represent a potential biomarker for ali / ards but they may also , in the future , be used to gauge the effects of treatment .
ample evidence supports the use of a relatively low tidal volume , but what about the use of a open lung strategy ( e.g. recruitment maneuvers , positive end - expiratory pressure [ peep ] , proning ) ?
the alveoli study ( prospective , randomized , multi - center trial of higher end - expiratory lung volume / lower fio2 versus lower end - expiratory lung volume / higher fio2 ventilation in acute lung injury and acute respiratory distress syndrome ) , performed by the ardsnet investigators to study the use of higher peep levels , was discontinued prematurely because of lack of efficacy .
accumulating evidence from both animals and human experiments suggest that not all patients are recruitable ; moreover , if improved oxygenation does not seem to affect outcome , then should recruitment be pursued for the sole purpose of decreasing atelectrauma ?
data have been reported that suggest that recruitment maneuvers may be deleterious if sufficient peep is not used to maintain recruitment .
repeated de - recruitments accentuate lung injury during mechanical ventilation , and it has also been suggested that allowing the lung to remain in a state of de - recruitment may mitigate biotrauma .
one of the mechanisms for upregulation of cytokines during mechanical ventilation of acutely injured lungs is alteration in alveolar mechanics ( i.e. the dynamic change in alveolar size and shape during ventilation ) 
alveolar instability and recruitment / de - recruitment . using direct visualization of subpleural alveoli , schiller and
coworkers   demonstrated that normal alveoli are extremely stable with minimal movement during mechanical ventilation .
in contrast , surfactant deactivation ( also a classic finding in ards ) causes a continuum of altered alveolar mechanics seen as repetitive collapse of alveoli at end - expiration and re - inflation at end - inspiration . in a recent follow - up study ,
steinberg and coworkers   demonstrated that alveolar instability can mechanically injure the lung independent of inflammatory damage .
moreover , the application of peep in this animal model was sufficient to stabilize the alveoli .
that group also noted that alveolar instability was associated with modest increases in interleukin-6 levels after 4 hours of mechanical ventilation , even in the absence of neutrophil infiltration , and that this increase could be attenuated by the application of peep .
these data suggest that mechanical injury alone is sufficient to cause a rise in tissue and bronchoalveolar lavage levels of proinflammatory cytokines , and that stabilization of alveoli is a key issue in reducing atelectrauma .
this probably occurs via a direct attenuation of the mechanical injury to the capillary  alveolar membrane , thereby limiting the effects of mechanotransduction ( the response of cells to mechanical force ) on cellular molecular physiology .
preliminary evidence suggests that use of strategies that stabilize alveoli are lung protective , but definitive clinical outcome data are not yet available .
further research is required to determine whether alveolar stabilization is achievable , measurable , and desirable .
again , the answer is probably ' yes ' , both as a consequence of mechanical injury and as the mechanism underlying the development of mof in this patient population .
however , as pointed out by moloney and griffiths , a definitive answer to this latter question requires a study that monitors outcomes after specifically targeting certain mediator(s ) .
ali = acute lung injury ; ards = acute respiratory distress syndrome ; mof = multiple organ failure ; peep = positive end - expiratory pressure ; sp = surfactant protein ; vili = ventilator - induced / associated lung injury . 1
 in a recent issue of the british journal of anaesthesia , moloney and griffiths reviewed clinically pertinent issues surrounding the management of the acute respiratory distress syndrome ( ards ) patient , particularly as it pertains to the treatment of ventilator induced / associated lung injury ( vili ) . 
 in addition to highlighting the important observations that have contributed to further our understanding of the relationship between the mechanical ventilator and inflammatory lung injury , the authors also offer a concise reappraisal of the clinical strategies used to minimize vili in ards . 
 special emphasis is placed on the theory of biotrauma , which attempts to explain how multi - organ failure may develop in patients who ultimately succumb to this syndrome . 
None
Competing interests
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