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CHAPTER 52: Acute Lung Injury and the Acute Respiratory Distress Syndrome 463

conventional ventilation (see Table 52-6), it was unclear which interven-
Priority of higher Priority of lower PEEP
PEEP ventilatory approach ventilatory approach tion or combination of interventions was responsible for the observed
To keep alveoli open To decrease the risk of improvement. Was the lower mortality due to the low-tidal-volume
during respiratory cycle ventilator-induced lung ventilatory strategy, the higher-than-traditional levels of PEEP, or the
and prevent lung injury injury (VILI) due to recruitment maneuvers, or a combination of two or all three?
due to repeated overdistension of alveoli To try to answer these questions, which had also been raised in an
opening and closing during inspiration earlier report by Amato and colleagues, the NHLBI ARDSNet investi-
276
(”atelectrauma”) gators decided to study one intervention at a time in separate RCTs. As
noted above, the first ARDSNet RCT compared a lower-tidal-volume
ventilatory strategy to a strategy using traditional tidal volumes. This
3
RCT found a significant decrease in mortality in the group treated
Use higher PEEP ± Use low tidal volumes with the lower-tidal-volume ventilatory strategy (see Table 52-6). After
add recruitment with traditional levels completion of this RCT, the ARDSNet investigators conducted a second
maneuvers of PEEP
RCT (ALVEOLI) to try to answer the question: When used in addition
to the lower-tidal-volume strategy of ventilation, do higher PEEP levels
improve survival?
The results of the ALVEOLI study are presented in Table 52-8. In
4
Higher plateau Lower plateau summary, ALVEOLI found that mortality rates were similar in those
pressures pressures
treated with higher and traditional levels of PEEP despite significant
. The higher-PEEP group had a higher mean
increases in Pa O 2 : Fi O 2
FIGURE 52-9. Schematic diagram illustrating the conflicting priorities of higher- and plateau pressure despite a lower mean tidal volume (see Table 52-8).
lower-PEEP ventilator approaches and their hypothetical associated effects. Studies that use a Although hypothetical, it is possible that the benefits of the higher
higher PEEP approach may combine the higher PEEP with recruitment maneuvers, which are PEEP in reducing the ALI due to shear stress created by recruitment-
sustained inflations (eg, 35-40 cm H O of CPAP for 30 seconds or more ). For a given low tidal derecruitment were negated by its adverse effects, such as worsening
4,7
2
volume, using a higher PEEP will result in a higher plateau (end-inspiratory) pressure than lung injury by overdistension (see Fig. 52-9). Two subsequent RCTs
using a lower PEEP. Hypothetically, this higher plateau pressure, which represents the static have confirmed that higher levels of PEEP consistently improve oxy-
end-inspiratory distending pressure in open alveoli, may increase the risk of ventilator-induced genation without deriving a mortality benefit in patients with ALI and
lung injury due to overdistension (see text and Chap. 51 for details). ARDS. 277,278 A recent meta-analysis of the three trials found no overall
benefit; however, in-hospital mortality was significantly lower in the
higher PEEP arm in the subgroup of patients with ARDS at baseline
Clinical Studies of Higher PEEP Ventilator Strategies Proponents of a high-PEEP (34.1% vs 39.1%), suggesting that the risk to benefit profile may favor
strategy (also called “open-lung” strategy) were encouraged by a rela- the use of higher levels of PEEP in more severe cases. 279
tively small but statistically significant RCT performed by Amato and
colleagues and published in 1998 (see Table 52-6). As noted above, in Recommended Core Ventilator Management: As the core ventilator
7
this RCT the group of subjects with ARDS in the “open-lung” arm were management strategy for ALI and ARDS, it is recommended that
treated by a combination of three interventions: (1) a low-tidal-volume clinicians use the low-tidal-volume ventilatory strategy (“ARDSNet
ventilatory strategy, (2) higher-than-traditional levels of PEEP as dictated lung- protective strategy”) that the ARDSNet investigators showed to
by the patient’s LIP as described below, and (3) recruitment maneuvers. be superior to a traditional-tidal-volume strategy (Table 52-9). Because
The control group of subjects was treated by a conventional ventilatory this strategy that used traditional levels of PEEP was shown to yield sim-
strategy for the participating ICUs, which did not include any of the ilar outcomes compared to using higher PEEP levels (see Table 52-8),
4
three interventions of the open-lung group and was not protocolized. it is recommended to use the same combinations of PEEP and Fi O 2
In this study, the higher level of PEEP was determined by using a super that were an integral part of the ventilator protocol for the lower-tidal-
syringe to derive a static pressure-volume curve on paralyzed subjects volume strategy in patients with ALI and ARDS. In addition, consid-
at the start of the study. From inspection of the static pressure-volume eration of higher PEEP levels should be given for patients with severe
curve, the LIP (see Fig. 52-8) was identified and the PEEP was set at ARDS, for example, P/F <150 mm Hg on at least 10 cm H O of PEEP
2
2 cm H O above the LIP. If a sharp LIP could not be determined on the (see Table 52-9). Clinicians should be cautious in utilizing the lung-
2
pressure-volume curve, then the PEEP was set empirically at 16 cm H O. 7 protective ventilation protocol strictly for patients with ALI and ARDS
2
Although this study found that the group receiving the open-lung who have conditions for which respiratory acidosis due to permissive
approach had significantly lower mortality than the group receiving hypercapnia are contraindicated (Tables 52-10 and 52-11).
TABLE 52-8 ARDSNet Clinical Trial of Lower Versus Higher Levels of PEEP in Patients With Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS)
a
Number of Subjects Plateau Pressure Tidal Volume (mL/kg Adjusted Mortality e
c
c
d
b
Group Enrolled PEEP (cm H O) Ratio c (cm H O) Predicted Body Weight) Mortality (95% CI ) f (95% CI ) f
2 Pa O 2 : Fi O 2 2
Lower PEEP 273 8.3 ± 3.2 169 ± 69 24 ± 6 6.1 ± 1.1 24.9% (19.8%-30.0%) 27.5% (23.0%-31.9%)
Higher PEEP 276 13.2 ± 3.5 206 ± 76 26 ± 7 5.8 ± 1.0 27.5% (22.3%-32.8%) 25.1% (20.7%-29.5%)
p value <0.001 <0.01 <0.05 <0.05 0.48 0.47
a NHLBI Acute Respiratory Distress Syndrome Clinical Trials Network.
b Means (±SD) over the first 4 days after randomization.
c Means (±SD) on study day 3.
d Mortality before discharge to home without assisted ventilation or as of 60 days, whichever occurred first.
e Mortality adjusted for imbalances in baseline variables by multivariable modeling. 4
f 95% Confidence interval.
Data from The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network: higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med.
July 22, 2004;351(4):327-336.

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