Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis
Warren J Davidson
2
Del Dorscheid
1
2
Roger Spragg
0
Michael Schulzer
2
Edwin Mak
2
Najib T Ayas
1
2
3
Corresponding author: Warren J Davidson
0
University of California at San Diego, California
,
USA
1
Intensive Care Unit Providence Healthcare
,
Vancouver, British Columbia
,
Canada
2
Department of Medicine University of British Columbia
,
Vancouver, British Columbia
,
Canada
3
Centre for Clinical Epidemiology and Evaluation, Vancouver Coastal Health Research Institute
,
Vancouver, British Columbia
,
Canada
Introduction The purpose of this study was to perform a systematic review and meta-analysis of exogenous surfactant administration to assess whether this therapy may be useful in adult patients with acute respiratory distress syndrome. Methods We performed a computerized literature search from 1966 to December 2005 to identify randomized clinical trials. The primary outcome measure was mortality 28-30 days after randomization. Secondary outcome measures included a change in oxygenation (PaO2:FiO2 ratio), the number of ventilation-free days, and the mean duration of ventilation. Metaanalysis was performed using the inverse variance method.
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Introduction
Acute respiratory distress syndrome (ARDS) is a common
cause of respiratory failure in the intensive care unit. Patients
with ARDS exhibit an intense inflammatory reaction centered
in the lung parenchyma, resulting in alveolar flooding and
collapse, in reduced lung compliance, in increased work of
breathing, and in severe impairments in gas exchange [1-4].
Patients with ARDS have an inhospital mortality rate ranging
from 34% to 60% [5]. Treatment of patients with ARDS is
largely supportive, and includes mechanical ventilation with
low tidal volumes [6], positive end expiratory pressure to open
collapsed alveoli [7], supplemental oxygen, and supportive
care of other organ system failures. Given the high mortality
rate of patients with ARDS, other therapies are clearly needed.
Administration of exogenous pulmonary surfactant is an
adjunctive therapy that may help adult patients with ARDS.
Pulmonary surfactant is produced by type II alveolar cells and
is composed of two major fractions: phospholipids (90%) and
surfactant-specific proteins (10%). Surfactant decreases
alveolar surface tension, thereby preventing alveolar collapse and
allowing efficient gas exchange at low transpulmonary
pressures. Furthermore, surfactant has important roles in host
immune defense, through both specific and nonspecific
mechanisms [8].
Patients with ARDS show injury to the alveolar epithelial
barrier with consequent surfactant dysfunction. Indeed, surfactant
recovered from bronchoalveolar lavage fluid from ARDS
patients has alterations of the phospholipid and fatty acid
profile, has decreased levels of surfactant-specific proteins, and
has impaired surface-tension-lowering properties. Causes of
this impairment include the inhibition of surfactant function by
protein-rich edema fluid, by surfactant lipid peroxidation, and
by surfactant protein degradation [1,9]. Given these
abnormalities, administration of exogenous pulmonary surfactant has
been considered a possible treatment option in adult patients
with ARDS [8].
The purpose of this study was to perform a systematic review
and meta-analysis of exogenous surfactant administration to
assess whether this therapy, as currently administered, may be
useful in adult patients with ARDS.
Materials and methods
Study identification
We performed a computerized search to identify articles that
compared treatment with exogenous pulmonary surfactant
against the usual therapy for patients diagnosed with ARDS.
For our analysis, we only included studies that were
randomized controlled clinical trials, that compared the use of
exogenous pulmonary surfactant to an appropriate control
group (defined as patients receiving standard therapy with or
without a placebo), that evaluated mortality and/or pulmonary
physiological parameters, and that used objective
documentation of ARDS using accepted criteria at the time of the
individual study publication. Abstracts, case reports, editorials,
nonhuman studies, and nonEnglish studies were excluded.
We performed a computerized literature search of MEDLINE
(1966December 2005), EMBASE (1980December 2005),
Cochrane Database of Systematic Reviews (1996December
2005), Cochrane controlled trials register (1996December
2005), and the Database of Abstracts and Reviews of Effects
(1994December 2005) to identify clinical studies and
systematic reviews. We conducted the search for human studies
using the following combination of exploded medical subject
headings and text words: ('adult respiratory distress
syndrome' or 'acute respiratory distress syndrome' or 'ARDS') and
('pulmonary surfactant' or 'lung surfactant') and ('adult'). The
reference lists of all articles selected were then hand-searched
for additional citations missed in the search.
Study selection
Two authors (WJD, NTA) independently reviewed the
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