Page 623 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 51: Ventilator-Induced Lung Injury 443

respiratory system compliance. 35,47,48 In addition to lung overdistention, localization of inflammatory cytokines mRNA expression. Moreover,
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ventilation at low lung volumes may also lead to lung injury. in an isolated lung injury model it has been demonstrated that lungs
In patients with ARDS, providing PEEP may have one of four effects ventilated with 6 mL/kg and low levels of PEEP had more ultrastructural
on the state of lung inflation. First, lung units that are already aerated evidence of cell damage possibly through mitogen-activated protein
may become overdistended, which could contribute to VILI (overdisten- kinase (MAPK)–mediated pathway compared to those ventilated with
sion). Second, partially aerated lung units or those that collapse at the higher PEEP levels. In addition to serving as a purely mechanical stent,
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end of a tidal breath may be kept patent during the entire respiratory PEEP may keep alveoli patent by preserving surfactant function, and in
cycle (prevents derecruitment). Third, previously closed alveoli may be so doing may reduce surface tension and in turn reduce the tendency of
recruited, leading to an increase in functional lung and resulting in an alveoli to close. 58,59
increase in total lung compliance (alveolar recruitment). Fourth, in the PEEP may also potentially improve gas exchange and lung mechan-
absence of adequate levels of PEEP, VILI is associated with distal airway ics by redistributing lung water from the alveolar to the extraalveolar
injury in both atelectatic and nonatelectatic lung regions (prevents distal interstitial space. Finally, PEEP has also significant hemodynamic
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airways injury). The latter two points deserve further emphasis. effects and typically results in a reduction in ventricular preload and a
To understand the physiological effects of PEEP on the lung and respi- reduction in cardiac output. Dreyfuss and Saumon postulated that the
ratory system, it is useful to consider the respiratory system pressure- benefits of PEEP in ARDS stem from its effect on pulmonary perfusion,
volume (P-V) curve, which plots changes in volume versus changes in and demonstrated that the reduction of lung edema produced by PEEP
pressure. At the beginning of the lung inflation, a lower inflection point was negated when dopamine was administered to keep arterial blood
(LIP) has been described in patients with ARDS, reflecting the point pressure constant. 31
where there is a rapid increase in volume in response to the incremental In summary, in patients with ARDS, PEEP may improve lung com-
change in pressure. However, using this point to set PEEP has problems, pliance and oxygenation by recruiting alveoli and maintaining patency
49
as a unique value of PEEP corresponding the pressure at which all alveoli throughout the respiratory cycle (Fig. 51-3). Furthermore, a ventilation
will be opened does not exist. Rather there is a progressive increase in strategy that fails to optimize end-expiratory volume with PEEP may
alveolar patency until the upper inflection point (UIP) is reached. At contribute to VILI through the development of shear stress during
this point overinflation of alveoli predominates. Examination of the repetitive opening and closing of lung units. It is also clear that atelec-
pressure-volume curve, however, does not inform the observer about tasis and inhomogeneity of alveolar patency can have adverse effects on
regional differences in lung inflation where regional overinflation of lung and cardiac function. Consequently, the notion of best PEEP needs
alveoli in some regions may occur even if the UIP is not reached.
This variability in PEEP-mediated lung recruitment was demonstrated
by Gattinoni et al. Patients with ALI/ARDS underwent CT scans after
random application of different levels of PEEP (5, 15 cm H O random) Alveoli
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2
(Fig. 51-2). The percentage of potentially recruitable lung varied widely
among these patients corresponding to an absolute weight of 217 ±
232 g of recruitable lung tissue. In addition to the observed variabil- D
50
ity in recruitable lung volume, PEEP may recruit new lung units and/
or merely overdistend those already open. Therefore, a sophisticated
and tailored ventilation strategy to limit the deleterious consequences 500
of excessive PEEP is required. Grasso et al demonstrated that ARDS C Upper deflection
patients with CT-scan evidence of focal loss of aeration developed alveo- point
lar overdistension and release of inflammatory mediators when they
table from the ARDSNet study.
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were ventilated using the PEEP/Fi O 2
The extent to which this influenced the failure of the trials of higher Volume (mL)
PEEP and lung recruitment in ARDS remains speculative. Low PEEP
52
levels associated with low-tidal-volume ventilation have been recog- 250
nized to be deleterious as well. In ARDS patients, a high percentage of B
potentially recruitable lung seems to be an independent risk factor for
mortality. Therefore in this subgroup of patients the beneficial impact
of reducing atelectasis by increasing PEEP prevails over the effects of Lower inflection
increasing alveolar strain and overinflation. 53 A point
The relative importance of maintaining airway patency and using
relatively high levels of PEEP is emphasized by several studies suggest- 0 15 30
ing lung underdistension may be as injurious as lung overdistension Pressure (cm H 2 O)
and may contribute to the development of VILI. In animal studies, FIGURE 51-3. The sigmoidal shape of the pressure-volume curve of the respiratory
ventilation with zero PEEP or at levels of PEEP that did not produce system in a patient with ARDS. The outlines across the top of the graph indicate the relative
adequate lung recruitment has been shown to cause respiratory and state of inflation of alveoli. At airway pressures above the upper inflection point C (30 cm H O),
2
membranous bronchiolar injury, a reduction in lung compliance, and the curve flattens as the limits of lung compliance are reached, and there is progressive over-
hyaline membrane formation. 54,55 In theory, ventilation at low lung distention of alveoli. Airway pressures below the lower inflection point B are also associated
volumes causes repetitive opening and closure of alveoli. This in turn with lower compliance and result in alveolar collapse. A typical ventilation strategy using 15 cm
may lead to the development of shear stress along the bronchial and H O of PEEP and a PIP of 40 cm H O (points B to D) would lead to repetitive inflation above the
2
2
alveolar walls. Repetitive stress is known to disrupt surfactant and may upper inflection point, and potentially to disruption of alveoli and the alveolar-capillary barrier
disrupt epithelial structures contributing to stress failure of the alveolar- (see text). A strategy that attempts to reduce lung distention by reducing PIP (points A to C)
capillary barrier. Several recent in vivo and ex vivo animal studies have would still lead to repetitive opening and closure of alveoli (also associated with lung injury).
attempted to clarify the deleterious effects of atelectatic regions, which An optimal ventilation strategy should consider both the lower and upper inflection points of
could be associated with insufficient levels of PEEP. 56,57 The presence the pressure-volume curve (points B to C). Note also that for the same driving pressure (the seg-
of atelectatic regions is associated with damage to distal airways of ments from A to B, B to C, or C to D), a change in pressure from points B to C is associated with
atelectatic and predominantly nonatelectatic alveoli as demonstrated by the largest change in lung volume. Thus an optimal ventilation strategy should aim for volume
higher histological damage, myeloperoxidase protein expression, and excursions along the steepest portion of the pressure-volume curve (maximal compliance).

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