DOI: 10.1097/01.CCM.0000288089.54158.32
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PMID: 18075380
Issn Print: 0090-3493
Publication Date: 2007/11/01
Inadequate mechanical ventilation as the first or the second hit in a two-hit model: Is there any difference in the injurious impact?*
Excerpt
Mechanical ventilation is a supportive modality in many clinical settings. Patients may have established acute lung injury (ALI) before assistance with mechanical ventilation or may acquire ALI subsequent to the initiation of mechanical ventilation. It has long been known that inadequate mechanical ventilation is detrimental (1). The possible injury mechanisms underlying ventilator-induced ALI include disruption of the integrity of the epithelium and endothelium in the lungs by mechanical forces (barotrauma/volutrauma) and increases in production of pulmonary inflammatory mediators due to aberrant cell stretch or decompartmentalization (biotrauma) (2, 3). Owing to differences in their pathogenic mechanisms, the development of barotrauma is more rapid than that of biotrauma. An important concept with respect to the injurious impact of mechanical ventilation has emerged in recent years. This concept is that mechanical ventilation may synergistically interact with pathologic lungs, a process termed the two-hit mechanism. Two clinical studies have reported that the release of inflammatory cytokines (4) and the mortality (5) of patients with defined acute respiratory distress syndrome are decreased when a protective ventilation strategy is used. These findings suggest that the detrimental effects of mechanical ventilation may serve as the second hit in a two-hit mechanism. Support for this notion has come from a number of animal studies showing that mechanical ventilation may amplify the production of inflammatory cytokines in already injured lungs (6, 7) and may exacerbate preexisting lung injury (8) induced by experimental interventions such as ischemia-reperfusion, hydrochloric acid treatment, and induction of sepsis. On the other hand, an analysis from a retrospective cohort study (9) revealed that the use of a large tidal volume is one of the main risk factors associated with the secondary acquisition of ALI. This important investigation (9) suggested that the detrimental effects of mechanical ventilation may serve as the first hit in a two-hit mechanism. Thus, a new research area has been opened up—exploring whether mechanical ventilation serves as the first hit that promotes the subsequent development of ALI and how this may occur.
In this issue of Critical Care Medicine, Dr. Bouadma and coworkers (10) designed a simple but ingenious study for investigating the injurious impacts of inadequate mechanical ventilation (tidal volume = 30 mL/kg) as the first or the second hit in a two-hit rat model. The investigators employed hemorrhagic shock and resuscitation (HSR) as the other hit. They measured the levels of three types of inflammatory cytokines in the lungs and plasma as the end points. The investigators found that when applied alone, HSR increased all lung and plasma cytokines, whereas high tidal volume ventilation failed to do this. A tidal volume of 30 mL/kg is indeed rather high in the rat model, and it can be assumed that inadequate mechanical ventilation caused some barotrauma in the animals but did not result in any increase in cytokine levels within the time limits of the study. The investigators further demonstrated that high tidal volume ventilation significantly increased cytokine release when it was combined with HSR, whatever the sequence of injuries. Their finding regarding inadequate mechanical ventilation serving as the second hit confirms previous findings (6, 7) and moves this area of investigation forward. On the other hand, the investigators’ observation regarding inadequate mechanical ventilation serving as the first hit is novel. It appears that inadequate mechanical ventilation can prime the lungs and increase their susceptibility to the insult by a secondary hit.
Dr. Bouadma and coworkers’ (10) observation provides the first experimental evidence to support previous speculation that patients initially ventilated with a high tidal volume are more prone to developing ALI (9).
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