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468 PART 4: Pulmonary Disorders

mechanisms by which IRV improves gas exchange in some patients the use of high-frequency jet ventilation and HFOV, even as a salvage
with ARDS remain obscure, but are believed to involve both alveolar intervention.
recruitment at lower airway pressures and more optimal distribution of Extracorporeal Membrane Oxygenation and Extracorporeal CO Removal The use of extra-
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ventilation. 349,350 Although it is tempting to attribute the beneficial effect corporeal gas exchange, such as extracorporeal membrane oxygenation
of IRV to intrinsic PEEP, anecdotal reports have excluded intrinsic PEEP (ECMO) or extracorporeal CO removal (ECCO R), to adequately oxygenate
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or gas trapping as the mechanism by which gas exchange improves in and ventilate the patient while allowing the lung to remain at rest was viewed
at least some patients. An important caution when using this mode as an attractive strategy for the management of patients with ALI/ARDS.
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is that both auto-PEEP and the higher mean alveolar pressure typical However, this promise has not been supported by clinical outcome studies.
of IRV tend to reduce cardiac output. In one study that examined PCV The earliest large-scale attempt to use ECMO in patients with severe
with or without IRV, cardiac output fell with IRV so that systemic oxy- ARDS in the 1970s demonstrated no survival benefit to its use, although
gen delivery actually worsened. Some investigators have noted a very it did generate a large database and a great deal of insight into patients
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gradual (over several hours) but progressive tendency for oxygenation to with this problem. Unfortunately, enrollment criteria in this study were
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improve following a change to IRV. This phenomenon has led some such that the mortality among all patients entered into it was certain to be
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to suggest that a subset of lung units may be recruitable only through the high (eg, ~90% in both groups). Hence it was unlikely that any difference
combined effects of prolonged inspiration and time. Further studies are would be demonstrated between groups. Some believe that more careful
needed to shed light on this interesting aspect of IRV. patient selection, earlier randomization of patients, and better technology
Inverse ratio PCV has been employed as part of the open-lung might have demonstrated a benefit to ECMO. A second wave of stud-
strategy for ventilating patients with ARDS, with specific attention to ies using ECMO or ECCO R was reported throughout the 1980s. 361,362
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keeping the tidal volume at or less than 6 mL/kg and limiting the driv- A number of techniques have been described, including venovenous
ing (inspiratory) pressure. The role of volume-control IRV remains ECMO, to assist in the elimination of carbon dioxide. Based on these
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poorly defined, and it is best regarded as a salvage therapy for patients advancements, a second ECMO trial in adults was conducted; however,
with hypoxia refractory to more conventional approaches. Whichever the second trial also failed to demonstrate any survival benefit. Despite
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approach is used, the intensivist should monitor auto-PEEP regularly, these results, some specialized centers have continued to offer ECMO
since the shortened expiratory times of IRV predispose to this effect. to adults with severe ARDS, based on their opinion that it is a relatively
Clinicians have also used other modalities of ventilation in ALI (eg, safe life-saving salvage intervention. In 2009, two studies reinvigorated
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airway-pressure release ventilation), none of which have been compared the debate regarding the use of ECMO for refractory cases of respiratory
to current low-tidal-volume strategies in RCTs (see Chap. 50). failure. 365,366 In an observational report from Australia and New Zealand,
High-Frequency Oscillatory Ventilation If excessive lung excursion during tidal investigators detailed their use of ECMO for 68 refractory influenza A
volume breathing is associated with injury to the lung, then it seems rea- H1N1 cases and reported favorable outcomes, as 71% of patients survived
365
sonable that ventilation with very small tidal volumes at high frequen- to ICU discharge at the time of publication. In the same year, the long-
cies would be associated with the least possible VILI and potentially with awaited trial results were published for the CESAR trial (conventional
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improved outcome. Although the FDA has approved a ventilator for ventilatory support versus ECMO for severe adult respiratory failure).
adults that provides high-frequency oscillatory ventilation (HFOV), its The design randomized patients to conventional ventilatory support
role in clinical practice remains unclear. A study of HFOV published at the referring hospital or transfer to a specialized ECMO center for
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in 2002 demonstrated a trend toward decreased mortality compared to consideration of ECMO. Of 90 patients randomized for consideration
conventional mechanical ventilation. However, the conventional venti- of ECMO, 68 (75%) received ECMO; overall, 63% (57/90) of patients
lation was not based on a low-tidal-volume strategy such as ARDSNet randomized for consideration of ECMO survived without disability,
(see Table 52-9). Further, because the mean airway pressure (±SD) was compared to 47% (41/87) of patients randomized to the conventional
higher in the group of patients treated with HFOV than the convention- arm. It remains unclear if the significant mortality benefit was due to
ally treated group (eg, 29 ± 6 cm H O vs 23 ± 6 cm H O during the first ECMO, ECMO provided at a highly experienced center, or care that
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24 hours), caution was raised about the possibility of VILI due to the included the option to initiate ECMO by experienced providers or failure
high distending pressures. to provide lung-protective ventilation systematically in the conventional
Two large, multicenter, randomized controlled trials have recently arm. Based on available evidence, we recommend that consideration for
been conducted and found that HFOV is not beneficial in ARDS and ECMO be limited to cases of refractory ARDS and to centers with signifi-
may, in fact, be harmful. 355,356 The Oscillation in ARDS Study Group cant experience. We recommend that less experienced centers coordinate
[OSCAR] Trial, sponsored by the National Institute for Health Research with local, more experienced centers to ensure safe and timely transport
Health Technology Assessment Programme and conducted in England, for patients identified as potential beneficiaries of ECMO.
Wales, and Scotland, found that the use of HFOV was associated with
increased NMBA use without a mortality benefit as all-cause mortality Experimental (Non-FDA-Approved) Interventions
was 42% in the HFOV group and 41% in the conventional ventilation Partial Liquid Ventilation Partial liquid ventilation using perfluorocarbons
group. The Canadian Institute of Health Research, in collaboration instilled into the trachea of adults and children with the respiratory dis-
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with the Canadian Critical Care Trials Group, sponsored a multina- tress syndrome (RDS) has been described. 367,368 Preliminary results from
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tional trial (the Oscillation for ARDS Treated Early [OSCILLATE] Trial) adult usage and the more extensive experience in pediatric patients
comparing HFOV to a modified ARDSNet protocol (low tidal volumes suggest that this mode of therapy may be both safe and efficacious in
but with higher PEEP and Pplat as target) in early ARDS. The trial was improving gas exchange. Partial liquid ventilation may allow oxygen-
terminated early as the early use of HFOV was associated with increased ation in patients who might otherwise be quite difficult to oxygenate
NMBA use and increased in-hospital mortality as mortality was 47% in with conventional modes of ventilation, in part because the perfluoro-
the HFOV group and 35% in the control group. 356 carbon is able to recruit dependent alveoli (by virtue of the hydraulic
High-frequency jet ventilation is different from HFOV. High- column) that PEEP is not. A practical problem is that perflubron is
frequency jet ventilation typically employs tidal volumes of 1 to 5 mL/kg radiodense, making the lungs appear white, so it is impossible to use
(or higher) and respiratory rates of 60 to 300 breaths per minute. Multiple chest radiographs to detect infection or to follow the progress of healing.
trials of high-frequency ventilation have failed to demonstrate any Currently, perfluorocarbons are available only as experimental agents.
benefit compared with conventional mechanical ventilation. 357-359 Nor Exogenous Surfactant It has long been known from both animal models and
has high-frequency jet ventilation been associated with either improved human studies that surfactant levels are decreased or that the ratios of
oxygenation, reduced barotrauma, or decreased days of mechanical ven- the surfactants are abnormal in humans and animals with ARDS. 370,371
tilation. On the basis of these negative results, we recommend avoiding Intensivists caring for adults have been encouraged by the dramatic

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