ACUTE RESPIRATORY FAILURE
ICUs were first developed to manage patients with acute
respiratory failure as a result of poliomyelitis. Since then,
management of patients with acute respiratory failure
has been revolutionized by the development of modern
mechanical ventilators. Ashbaugh and associates first
reported ARDS in 1967.76 They described 12 patients with
acute respiratory distress, cyanosis refractory to oxygen
therapy, decreased lung compliance, and diffuse bilateral
infiltrates on chest radiography. Because this initial
definition lacked specific criteria that could be used to
identify patients for research, the American-European
Consensus Conference Committee recommended new
definitions in 1994.77
Although critical for providing a framework for the
ARDS network (ARDSnet) and other studies, it was recognized
that the American-European consensus definitions
had significant limitations as a result of the variability in
the PaO2/FiO2 ratio with ventilator settings, poor reliability
of chest radiographic criteria, and difficulties distinguishing
hydrostatic edema. Therefore, a new consensus
conference was convened to update the definitions, and
the Berlin Definition of ARDS was formed.78 Table 101-2
compares the two lists of criteria used to define acute lung
injury (ALI) and ARDS.
Treatment of ALI or ARDS is primarily supportive and
consists of mechanical ventilation, which allows time for
treatment of the underlying cause of the lung injury and
for natural healing.79 Until recently, most studies of ALI
or ARDS reported a mortality rate of 40% to 60%, with
death attributed to sepsis or multiorgan failure rather
than the primary respiratory causes.80,81
Several clinical trials have addressed one of the hallmarks
of ALI or ARDS—decreased lung compliance. The
National Institutes of Health (NIH) ARDSnet reported the
definitive study on protective mechanical ventilation in
2000.38 In this prospective study of patients with ALI, the
mortality rate was reduced from 40% in patients receiving
tidal volume ventilation of 12 mL/kg to 31% in those
receiving 6 mL/kg. The low–tidal volume group also had
more ventilator-free and organ failure–free days than did
the higher–tidal volume group. Several reasons have been
postulated for the discrepancy between this study and
the previous inconclusive studies. First, the NIH study
may have been better able to show a difference because it
used lower tidal volumes than used in the other studies.
Second, the NIH study allowed treatment of respiratory
acidosis with high respiratory rates or with sodium bicarbonate.
Treatment of respiratory acidosis may have prevented
deleterious effects. Third, the NIH study enrolled
861 patients, which was by far the largest study and
increased the statistical power to find a positive effect of
low–tidal volume ventilation.82
In a second study using the same patient database, Eisner
and associates83 did not find any evidence that the
to the clinical cause of ARDS. Although the mortality rate
was highest (43%) in patients with sepsis, intermediate
(36%) in patients with pneumonia and aspiration pneumonitis,
and lowest (11%) in patients with trauma, no
evidence of differential efficacy of low–tidal volume ventilation
was found in different groups with ALI or ARDS.
The investigators concluded that the recommendations
for low–tidal volume ventilation should be applied to
all patients with ALI or ARDS, regardless of the inciting
cause.
Important advances in the ventilatory management
of patients with ALI or ARDS have led to improvements
in the care of patients in the ICU. With the impressive
9% absolute reduction in mortality demonstrated by the
ARDSnet trial, low–tidal volume mechanical ventilation
should be considered the standard of care for patients
with ALI or ARDS unless a more efficacious strategy is
demonstrated. Figure 101-2 shows the protocol used at
the University of California, San Francisco, for mechanical
ventilation of patients with ALI or ARDS. An unanswered
question remains regarding whether patients
without ARDS should be managed with a lung-protective
strategy. A recent meta-analysis showed that in patients
without lung injury, low tidal volume was associated with
less progression to lung injury and lower mortality.84
Nontraditional Ventilatory Interventions
In addition to low tidal volume, other therapies have
been used for the care of patients with ALI. Most have
tried to improve the ventilation-perfusion (V˙ /Q˙ ) mismatching
and hypoxemia that result from ALI. The following
sections discuss data associated with high PEEP,
recruitment maneuvers, prone positioning, inhaled nitric
oxide (iNO), neuromuscular blocking agents, and early
tracheostomy.
High Positive End-Expiratory Pressure. The use of
PEEP has been proposed as a mechanism to minimize
cyclical alveolar collapse and shear injury (atelectrauma).
Brower and coworkers (Assessment of Low–Tidal Volume

and increased End-Expiratory Volume to Obviate Lung