Page 641 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

460 PART 4: Pulmonary Disorders

lung injury, but that high inflation pressure in the absence of large-tidal-
Basic research Clinical research
(Animals and in vitro) (CT scans correlated with volume excursion was not. Surprisingly, PEEP had the effect of limiting
High-tidal-volume ventilation respiratory mechanics) the injury that occurred in animals ventilated with large tidal volumes
causes acute lung injury Lung is non homogeneous and high pressures. The application of PEEP not only preserved gas
PEEP exerts a protective effect Compartment of aerated alveoli exchange, but also prevented the morphologic progression of the lesion
on ventilator-induced lung (the “baby lung”) is subject to caused by this pattern of ventilation. These observations have been veri-
injury overdistension
fied in larger animals 259-262 (see Chap. 51 for more details).
A summary of these and subsequent animal experiments indicated
that (1) high-tidal-volume ventilation results in a lung injury morpho-
ARDSNet large randomized logically similar to ARDS in humans, (2) PEEP is protective to some
clinical trial in ALI/ARDS degree against this injury, (3) high-tidal-volume ventilation can also
Lower-tidal-volume ventilatory 263,264
strategy result in multiorgan system failure in otherwise healthy animals,
vs and (4) high-tidal-volume ventilation results in the release of inflamma-
Higher-tidal-volume ventilatory tory cells and proinflammatory cytokines. 265,266
strategy
Clinical Research Utilizing Lung Imaging The second parallel line of research, noted
above, studied patients with ARDS by use of CT scans (see Fig. 52-7).
ARDSNet randomized clinical The initial observations indicated that despite a homogeneous “white-
trial results out” pattern of diffuse pulmonary edema infiltrates on chest radiographs
Lower-tidal-volume ventilatory of patients with ALI and ARDS, the CT scans of the same patients often
strategy had a 22% relative decrease proved the infiltrates to have remarkable heterogeneity. 245,267 Based on
in mortality vs higher-tidal-volume strata of Hounsfield units to define different densities, the lung in ARDS
ventilatory strategy could be partitioned into various compartments: nonaerated, poorly
(p = 0.007)
aerated, and normally aerated. Moreover, these compartments could
244
be tracked before and after PEEP was added or subtracted and before
and after tidal volumes of different sizes were delivered to the lung.
Recommendation The end result was a reconceptualization of the mechanical changes
Use ARDSNet lung-protective in the ARDS lung. The traditional interpretation was that the stiffness
244
ventilatory strategy as the of lungs and chest wall (ie, the respiratory system) in ARDS (eg, low
standard approach for ALI and static compliances of 20 to 40 mL/cm H O with normal range of
ARDS in clinical practice and 2
in future clinical trials 50-100 mL/cm H O) represented many alveoli with similarly low spe-
2
cific compliances (ie, essentially a single compartment in terms of its
mechanical properties). Instead, studies using CT scans and their patho-
FIGURE 52-7. Schematic illustration of the confluence of basic and clinical research that physiologic correlations indicated that a more accurate picture is that
resulted in a large randomized clinical trial by investigators in the NHLBI ARDS Clinical Trials the lung in ARDS is multicompartmental and that there is a small part
Network (ARDSNet). This trial showed that a lower-tidal-volume ventilatory strategy was superior of the ARDS lung that has relatively normal compliance. Gattinoni and
3
to a traditional-tidal-volume ventilatory strategy. As such, it confirmed that the hypothesis of ven- coworkers coined the term “baby lung” when referring to this compart-
tilator-induced lung injury was important in the augmentation of the lung injury in ARDS. It also ment and its vulnerability to overdistension. In this revised conception
244
established that a lung-protective ventilatory strategy should be generally used to treat patients of the acutely injured lung, some alveoli are normally compliant and
with ARDS. Finally, until there is new evidence to suggest otherwise, the ARDSNet lung-protective vulnerable to overdistension while others are flooded or collapsed. The
protocol is recommended as the standard approach in clinical practice and future clinical trials. loss of functional alveoli necessitates that the tidal volume be distributed
to far fewer aerated alveoli than in a healthy lung. Indeed, the apparent
stiffness of the lungs of ARDS patients is regarded as the result of a small
ARDS. In 1974, Webb and Tierney reported that mechanical ventilation fraction of the lung containing relatively normal alveoli that becomes
using large tidal volumes and high inflation pressures could cause a fatal stiff as those alveoli reach their limits of distension, rather than due to
lung injury (similar morphologically to ARDS) in rats with otherwise generalized parenchymal “stiffness.”
normal lungs. In 1985, Dreyfuss and colleagues reproduced these Based on the consistent results from the animal and in vitro studies
257
256
experiments and carefully studied the changes that occurred within referred to above and the insights provided by the results of the CT scans,
the lung. They observed that the injury that occurred was morphologi- it was hypothesized that traditional tidal volumes (eg, 10-15 mL/kg)
cally and pathophysiologically similar to ARDS and hypothesized that caused overdistension of alveoli in the lungs of patients with ALI and
mechanical ventilation with large tidal volumes or high inflation pres- ARDS. This in turn not only resulted in exacerbation and perpetuation of
sures might exacerbate or perpetuate the lung injury in patients suffer- their lung injury, but also, through the possible release of proinflamma-
ing from ARDS. Two major questions were raised by this early work: Did tory cytokines and other mechanisms, possibly contributed to the devel-
high inflation pressures or large-tidal-volume excursions cause the lung opment and worsening of multiorgan system dysfunction and failure.
injury? Did PEEP worsen or attenuate this injury?
Dreyfuss and associates then designed a set of experiments to Intersection of Basic and Clinical Research The intersection of these two lines of
258
answer these questions. They studied animals with normal lungs research, one basic and one clinical, resulted in two hypotheses of how
subjected only to varied protocols of mechanical ventilation. Some patients with ALI and ARDS should be ventilated (see Fig. 52-7). First,
were ventilated with high pressures and large tidal volumes. Others the end-inspiratory lung volume should be limited to avoid alveolar
had chest banding to limit chest wall and tidal volume–induced lung overdistension (so-called “volutrauma”) and second, sufficient PEEP
excursion during ventilation at high airway pressures. Another group should be applied so as to prevent cycles of end-expiratory derecruit-
was subjected to negative-pressure ventilation to assess the effect of ment followed by inspiratory recruitment (Chap. 51 discusses the basis
large-tidal-volume excursions in the absence of high airway pressures. for both of these ventilatory recommendations in detail).
PEEP (10 cm H O) was applied to the lungs of some animals undergoing The next step was to test these hypotheses in prospective RCTs (see
2
high-pressure/large-tidal-volume ventilation. Finally, control animals Fig. 52-7). Four large multicenter RCTs were conducted (Table 52-6). Three
were ventilated using parameters typical of conventional ventilation. RCTs tested lower- versus higher-tidal-volume strategies. 3,8,9 The fourth RCT
These investigators found that large tidal volumes were associated with tested a multifactorial lung-protective strategy (including lower tidal volume,

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