servative fluid strategy after resolution of shock,
may reduce the risk of progression to ARDS.
RESTRICTIVE TRANSFUSION PROTOCOLS
There is growing evidence that transfusion of
blood products plays an important role in the
pathogenesis of ARDS in at-risk patients. Transfu-
sion-related acute lung injury (TRALI) is the best
characterized of the “two hit” models for ARDS.95
The pulmonary vascular endothelium is first acti-
vated by one or more endogenous stimuli (ie, sep-
sis or trauma) facilitating adherence of activated
neutrophils.96,97 Transfusion of blood products con-
taining antibodies to leukocyte antigens or bioac-
tive lipids then serve as a second hit, resulting in
neutrophil-mediated injury of the vascular endo-
thelium leading to increased vascular permeability
and pulmonary edema.95,98
Current criteria for TRALI exclude patients with
known risk factors for ARDS, which limits recogni-
tion of the true risk of transfusion.99,100 Reported
rates of TRALI, based on recognition of overt cases
in patients without known risk factors for ARDS, are
fractions of a percent.101,102 However, in a series of
901 consecutively transfused ICU patients, Gajic et
al observed a TRALI incidence of 8%.92 Addition-
ally, 12% of patients with ARDS had worsening of
their oxygenation following transfusion. In a sepa-
rate analysis, expanding the definition to include
delayed TRALI (development of ARDS 6 to 72
hours after transfusion and regardless of existing
risk factors) increased the incidence to 25% and
was associated with a mortality of 40%.103 Also,
risk of TRALI is not limited to patients receiving
large quantities of red cells. Plasma-rich products
(ie, fresh frozen plasma and platelets), particularly
from multiparous female donors, actually carry a
greater risk of TRALI than packed red cells.92,104
Removing female donors from the plasma donor
pool beginning in 2006 has been associated with
reduced rates of TRALI.105 Widespread adoption of
restrictive transfusion protocols in high-risk patients
may provide further reductions in rates of ARDS.
LUNG PROTECTIVE VENTILATION
While currently established only for patients with
existing ARDS, additional benefit may be derived
from implementing lung protective ventilation strategies in at-risk patients. Gajic at el found a nearly 30%
increased risk of ARDS for every 1 mL/kg increase
in tidal volume above 6 mL/kg in mechanically
ventilated patients without ARDS (odds ratio 1.29,
95% CI 1. 12 to 1.51).88 A subsequent clinical trial
comparing tidal volumes of 6 mL/kg to 10 mL/kg
predicted body weight in mechanically ventilated
patients without ARDS was stopped early due to
higher rates of ARDS in the higher tidal volume
group.106 More recently, a trial comparing tidal
volumes of 6 to 8 mL/kg and PEEP of 6 to 8 cm
H2O to 10 to 12 mL/kg and no PEEP during intraoperative mechanical ventilation in intermediate- to
high-risk patients undergoing abdominal surgery
found reduced rates of pulmonary complications
(including ARDS) at 7 and 30 days after surgery.107
It is unclear whether sufficient downsides to lung
protective ventilation exist to prevent recommending it for all mechanically ventilated patients. Theoretical concerns exist regarding higher levels of
PEEP and permissive hypercapnia in patients with
critical levels of increased intracranial pressure or
pulmonary hypertension and compromised right
ventricular dysfunction. Higher mean airway pressures may also be a risk factor for persistent air
leaks and bronchopleural fistulas in patients with
pneumothoraces. Lung protective ventilation may
also require deeper levels of sedation, which could
prolong mechanical ventilation in low-risk patients.
However, maintaining a tidal volume between
