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440 PART 4: Pulmonary Disorders

examination of the thorax of patients with ARDS has demonstrated that TABLE 51-2 The Scope of Ventilator-Induced Lung Injury
the airspace disease is patchy, with marked heterogeneity and regional
6,7
differences in lung injury. Regions of lung with airspace disease are jux- Oxygen toxicity
taposed to adjacent areas with normal-appearing alveoli. In addition, an Tracheal and upper airway injury
exaggerated vertical gradient of lung inflation has been demonstrated Macroscopic
in ARDS, with compression of alveoli and a decrease in aerated lung as
one progresses from nondependent to more dependent lung regions. Pneumothorax
8
As emphasized by Mead and coworkers in the early 1970s, it is likely Pneumomediastinum
this degree of heterogeneity of the lung injury that makes the lung Pneumopericardium
particularly susceptible to the effects of ventilator-induced injury. The
9
heterogeneity of the injury is also responsible for the decrease in lung Pneumoperitoneum
compliance that characterizes ARDS. It is worth emphasizing that this Subcutaneous emphysema
loss of compliance is due to a functional reduction in alveolar units and Parenchymal emphysema
not due to the development of “stiff” lungs. Indeed the recognition that
ARDS is characterized by a loss of functional lung units with preserva- Cystic lung spaces
tion of other alveoli resulting in normal lung specific lung compliance Microscopic
is central to the current notion of lung-protection strategies. In many Regional
10
respects owing to the reduction in effective lung volume, the 70-kg adult Epithelial/endothelial activation (inflammatory mediators release) and injury
patient with ARDS must be treated, from the pulmonary point of view,
as a 30-kg pediatric patient. Consequently the use of traditional tidal Damage to the alveolar-capillary barrier and vascular permeability decreases
volumes of 10 to 15 mL/kg (700-900 mL in our 70-kg patient) would be alveolar fluid clearance
inappropriate and will result in overdistention of lung units with rela- Surfactant dysfunction
tively normal compliance. Bronchiolar injury
The need to modify the approach to mechanical ventilation in ARDS
is further emphasized by three decades of investigations that demon- Leukocytes sequestration and activation
strate that overdistention of lung units may itself lead to lung injury Fibrosis (late phase of ARDS)
identical to that seen in ARDS. ARDS is also a syndrome characterized Biotrauma
by inflammation of the lung with various cytokines and other mediators
thought to play a major role. In recent years, there has been a large body Systemic
of evidence indicating that mechanical ventilation may have an impact Multisystem organ dysfunction
on this aspect of the pathophysiology of ARDS, and indeed there is the
suggestion that the improvement in mortality with lung-protective strat-
egies may be partly due to a reduction in release of various mediators
by these strategies. correlation between air leaks and PEEP levels. Eisner and colleagues,
using data from the ARDS Network trial, reported that higher PEEP was
VENTILATOR-INDUCED LUNG INJURY associated with an increased risk of barotrauma (relative risk = 1.5; 95%
■ MACROSCOPIC INJURY center clinical trials failed to demonstrate an association between higher
confidence interval [CI] 0.98-2.3). More recently however, two multi-
15
• Macroscopic injury caused by mechanical ventilation is termed baro- PEEP levels and barotrauma. 16,17 Whether patient-ventilator interaction
may lead to barotrauma is suggested by a recent clinical trial testing the
trauma. The severity of lung injury and excessive inflation pressures efficacy of the neuromuscular blocking agent (NMBA), cisatracurium in
associated with high transpulmonary pressures appear to be risk factors. severe ARDS patients. The probability of death at 90 days and incidence
In clinical practice, plateau pressure (Pplat) is often used as a surrogate of of pneumothorax were less in the NMBA group. Ideally, these results
18
transpulmonary pressure (Ptp) to assess the propensity for development should to be confirmed in future trials. Of particular importance, seda-
of VILI. However, Pplat can be very misleading as a surrogate for Ptp in tion and paralysis are risk factors for the development of muscular weak-
view of range of different chest wall compliances in ventilated patients. ness and prolonged ventilator dependence in ARDS. 19-21
Recent evidence suggests that mechanical ventilation may have both There is also evidence that increased blood flow through the lungs
regional and systemic effects. VILI may be broadly classified into macro- can lead to greater VILI manifest by severe hemorrhage, increased
22
scopic and microscopic injury (Table 51-2). Macroscopic injury consists of filtration coefficient, and heavier lungs. Injury to conducting airways
what has been classically described as barotrauma. Pneumothorax, pneu- could also potentially lead to an increase in regional airways resistance,
momediastinum, pneumoperitoneum, and subcutaneous emphysema are with resultant gas trapping and progressive downstream regional lung
recognized complications of mechanical ventilation, and are character- distention. Regions of local superinfection and resultant inflammation
ized by the presence of extraalveolar air. Gattinoni and coworkers have may intensify bronchiolar injury. Goldstein and associates used a piglet
11
described the appearance of bullae and cystic parenchymal lesions located model and found cystic lung changes and areas of bronchiolectasis in
23
predominantly in the dependent (dorsal) lung regions. These lesions are animals that received intrabronchial inoculation with Escherichia coli.
6
often occult and are not readily detected on plain chest radiographs. The importance of bronchiolectasis in the pathogenesis of VILI is fur-
Macroscopic barotrauma correlates with a variety of factors. In a ret- ther highlighted by observations that dead space (a potential prognostic
24
rospective study in 139 intubated patients, barotrauma occurred in 34 marker in ARDS ) correlated with the presence and severity of bronchio-
25
patients. Peak airway pressure, level of PEEP, tidal volume, and minute lar injury and dilation. In summary, macroscopic lung injury represents
12
ventilation correlated with the development of barotrauma. However, in a continuum from airspace enlargement through interstitial emphysema
a subsequent prospective study of 168 patients over a 1-year period, only and eventually to radiographically apparent extraalveolar air.
The relationship of PEEP to the development of extraalveolar ■
the presence of ARDS was associated with the development of baro-
trauma. 12,13 MICROSCOPIC INJURY
air is inconsistent. 13,14 Patients with severe underlying lung disease often • Numerous animal and human studies demonstrate that in otherwise
require higher levels of PEEP to maintain oxygenation, and it is possible healthy lungs mechanical ventilation with large tidal volumes may
that it is the underlying lung disease in such patients that explains the initiate lung inflammation and may lead to development of acute lung

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