S3P4Q14EA1_ClinicsArticle

					                                          Clin Chest Med 27 (2006) 549–557




           Clinical Epidemiology of Acute Lung Injury
           and Acute Respiratory Distress Syndrome:
               Incidence, Diagnosis, and Outcomes
           Jaime F. Avecillas, MDa,b, Amado X. Freire, MD, MPHa,
                        Alejandro C. Arroliga, MDc,*
                         a
                           Division of Pulmonary, Critical Care, and Sleep Medicine, University
             of Tennessee Health Science Center at Memphis, 956 Court Avenue, Memphis, TN 38163, USA
            b
              Memphis VA Medical Center, 1030 Jefferson Avenue, Room G401H, Memphis, TN 38104, USA
          c
           Division of Pulmonary and Critical Care Medicine, Scott & White/Texas A&M University System,
                                     2401 South 31st Street, Temple, TX 76508, USA



    Acute respiratory distress syndrome (ARDS)                 by the development of newer therapeutic ap-
and acute lung injury (ALI) are devastating                    proaches that have resulted in decreased mortality
clinical syndromes that are characterized by the               and increased number of days without ventilator
sudden onset of severe hypoxemia and diffuse                    use in patients who have ARDS [5,6]. Many ques-
bilateral pulmonary infiltrates in the absence of               tions remain regarding the incidence, diagnosis,
left atrial hypertension [1]. The severity of the              and outcomes of these entities, however.
hypoxemia differentiates these two entities, with                  This article reviews the currently used defini-
a ratio of partial pressure of oxygen in arterial              tions of ARDS and ALI and the different studies
blood (PaO2) to inspired fraction of oxygen                    that have advanced the understanding of the
(FIO2) of less than 200 mm Hg for ARDS and of                  epidemiology and outcomes of these entities. It
less than 300 mm Hg for ALI. Both ALI and                      also discusses several diagnostic issues that are
ARDS can occur from a wide diversity of causes                 important for both clinicians and researchers.
or associated conditions, such as sepsis, pneumo-
nia, aspiration, trauma, pancreatitis, massive
blood transfusions, and smoke or toxic gas inhala-
                                                               Incidence
tion [2,3].
    Although ARDS initially was reported in 1967                   Although significant progress has been made in
by Ashbaugh and colleagues [4], it was not until               the understanding of the natural history and
1992 that the American-European Consensus                      pathogenesis of ARDS, its incidence has remained
Conference (AECC) on ARDS developed a stan-                    uncertain. One of the first estimates of the in-
dardized definition for ARDS and ALI [1]. Dur-                  cidence of ARDS in the United States is from
ing the last 4 decades significant advances have                a National Heart, Lung and Blood Institute
been made in the understanding of the etiology,                workshop organized in 1976 to provide a better
pathophysiology, and epidemiology of ALI and                   understanding of the mechanisms of ALI [7]. The
ARDS. These advances have been accompanied                     expert panel of this conference estimated that
                                                               there are 150,000 cases of ARDS per year in the
                                                               United States, an incidence of about 75 cases
                                                               per 100,000 persons. Since this initial estimate
   * Corresponding author.                                     [7], different estimates of the incidence of ARDS
   E-mail address: aarroliga@swmail.sw.org                     and ALI have been reported, varying from 1.5
(A.C. Arroliga).                                               to 78 cases per 100,000 persons depending on
0272-5231/06/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.ccm.2006.06.001                                                               chestmed.theclinics.com
550                                                AVECILLAS   et al

the population studied and the definition of                    about 3.5 million persons. Another population-
ARDS and ALI used (Table 1) [8–17].                            based study of patients who had ARDS performed
    From 1983 to 1995 most studies showed a rel-               in the United States by Thomsen and colleagues
atively low incidence for ARDS, ranging from 1.5               [10] estimated the incidence of ARDS as between
to 8.3 cases per 100,000 persons [8–11,18]. Between            4.8 to 8.3 cases per 100,000 person-years. This
1983 and 1985 Villar and colleagues [8] took ad-               study, however, included only 6 of the 40 general
vantage of the unique characteristics of the Canary            acute-care hospitals in the state of Utah. All these
Islands (an island with a relatively large popula-             studies were designed before the AECC definition
tion) to determine the incidence of ARDS. The                  of ARDS and ALI became available in 1994.
overall incidence of ARDS in that study was                    Therefore, no standard criterion for the diagnosis
reported to be as low as 1.5 to 3.5 cases per                  of ARDS was used.
100,000 persons, depending on the diagnostic crite-               Recent data have shown higher incidences for
ria used. In 1988 Webster and colleagues [9] re-               ALI and ARDS [14,16,17]. In a prospective co-
ported a similar incidence for ARDS (4.5 cases                 hort study with extrapolation to the United States
per 100,000 persons). This study was conducted                 population, Goss and colleagues [14] estimated
in a British health district with a population of              the incidence of ALI in the United States at 64.2


Table 1
Comparison of selected incidence studies for acute lung injury and acute respiratory distress syndrome
                           Geographic area, length,
Authors                    and year of study               Definition of ARDS/ALI           Incidence
Villar et al [8]           Canary Islands; 36 months;      PaO2 % 55 mm Hg with            1.5–3.5 cases per 105
                             1983–1985                       FIO2 O 0.5, bilateral           person-years for ARDS
                                                             infiltrates, no evidence of
                                                             left atrial hypertension
Webster et al [9]          UK; 12 months; 1985             Not specified                    4.5 cases per 105
                                                                                             person-years for ARDS
Thomsen et al [10]         Utah; 12 months;                PaO2/FIO2 %200 mm Hg,           4.8–8.3 cases per 105
                             1989–1990                       bilateral infiltrates, no        person-years for ARDS
                                                             evidence of left atrial
                                                             hypertension
Lewandowski et al [11]     Berlin; 8 weeks 1991            LIS R 2.5                       3 cases per 105
                                                                                             person-years for ARDS
Luhr et al [12]            Sweden, Denmark, Iceland;       AECC                            17.9 cases per 105
                             8 weeks; 1997                                                   person-years for ALI
                                                                                           13.5 cases per 105
                                                                                             person-years for ARDS
Arroliga et al [13]        Cleveland, OH; 35 months;       AECC                            15.3 cases per 105
                             1996–1999                                                       person-years for ARDS
Goss et al [14]            US; 1996–1999/ARDS              AECC                            22.4–64.2 cases per 105
                             network data                                                    person-years for ALI
Hughes et al [15]          Scotland; 8 months; 1999        AECC                            16 cases per 105
                                                                                             person-years for ARDS
Bersten et al [16]         Australia; 8 weeks; 1999        AECC                            34 cases per 105
                                                                                             person-years for ALI
                                                                                           28 cases per 105
                                                                                             person-years for ARDS
Rubenfeld et al [17]       King County, WA;                AECC                            78.9 cases per 105
                             12 months; 1999–2000                                            person-years for ALI
                                                                                           58.7 cases per 105
                                                                                             person-years for ARDS
   Abbreviations: AECC, American European Consensus Conference definition of acute lung injury and acute respira-
tory distress syndrome; ALI, acute lung injury; ARDS, acute respiratory distress syndrome; FIO2, inspired fraction of
oxygen; LIS, lung injury score; OH, Ohio; PaO2, partial pressure of oxygen in arterial blood; US, United States; UK,
United Kingdom; WA, Washington.
                                    CLINICAL EPIDEMIOLOGY OF ALI AND ARDS                                551

cases per 100,000 person-years. To obtain this es-         3. Different lengths of the study period
timate, they used prospective clinical trial screen-       4. Different study designs and assumptions
ing data (ARDS network) and conservative                      (sometimes unverified) to estimate incidence
assumptions about where patients who have ALI              5. Heterogeneity of diseases underlying ALI and
receive care (they assumed that ALI cases oc-                 ARDS
curred only at hospitals with 20 or more ICU               6. Differences in the structure of the health care
beds). Moreover, a recent large prospective,                  systems within the countries where studies
population-based cohort study by Rubenfeld                    have been performed (ie, different use of
and colleagues [17] showed that the crude inci-               ICU resources)
dence of ALI in King County, Washington was                7. Seasonal variation
78.9 per 100,000 person-years, and the incidence           8. Difficulties finding all cases in a given geo-
of ARDS was 58.7 cases per 100,000 person-years.              graphical area
This study included all 18 hospitals in King
                                                            It is important to determine the real incidence
County, and patients were identified according
                                                         of ALI and ARDS for the efficient distribution
to the definition of the AECC on ALI and
                                                         and allocation of clinical resources. Although it is
ARDS. This last study, however, was conducted
                                                         difficult to reconcile the different incidences re-
in a geographic area with a population that differs
                                                         ported by the different authors, the authors
significantly from the rest of the United States, be-
                                                         believe that the recent estimate by Rubenfeld
ing wealthier, younger, with more Asians, and
                                                         and colleagues [17] may be more accurate than
with fewer African-Americans.
                                                         previous estimates, because this study included
    Other factors (eg, age and the underlying risk
                                                         a large number of patients from multiple ICUs
factors associated with the syndrome) may affect
                                                         who were followed for a long period of time
the reported incidence of ALI and ARDS. The
                                                         (1 year). This study and other recent studies
incidence of ALI and ARDS seems to increase
                                                         [14,16] clearly show that ALI and ARDS are rel-
with age [2,17]. Rubenfeld and colleagues [17]
                                                         atively common conditions that have the potential
showed that the incidence of this entity increases
                                                         to become a public health burden.
with age, from 16 per 100,000 person-years for
those 15 through 19 years of age to 306 per
100,000 person-years for those 75 through 84
years of age. Few studies actually have mea-             Diagnosis
sured the incidence of ARDS prospectively in
                                                            The diagnosis of ALI and ARDS (Table 2) is
selected groups of patients thought to be at in-
                                                         based on clinical and radiologic information, ab-
creased risk for the syndrome [2,18]. Fowler
                                                         normalities of oxygenation, and occasionally on
and colleagues [18] found that the incidence of
                                                         lung biopsies. The accuracy of these criteria may
ARDS varies by predisposed groups, being low-
                                                         be limited by several factors, some of which are
est in most categories associated with nonpulmo-
                                                         discussed in this section.
nary injury and the highest after witnessed
                                                            The pathologic diagnosis of diffuse alveolar
pulmonary aspiration. On the other hand, in
                                                         damage (DAD) is considered the standard for the
a similar study Hudson and colleagues [2]
                                                         diagnosis of ALI and ARDS [19]. After reviewing
showed that the highest incidence of ARDS oc-
                                                         420 cases of DAD, however, Katzenstein and col-
curred in patients who had sepsis syndrome and
                                                         leagues [20] concluded that DAD is not a diagnosis
multiple transfusions, whereas the lowest inci-
                                                         but a nonspecific reaction of the lung to a multitude
dence was seen in trauma patients and patients
                                                         of injurious agents. The pathologic diagnosis of
who had drug overdose.
                                                         DAD is rarely available in clinical practice because
    The medical literature has reported a wide
                                                         of the low rates of open-lung biopsy seen in this
range of values for the incidence of ALI and
                                                         group of patients. Nonetheless, Patel and col-
ARDS, as already shown. Variations among
                                                         leagues [21], in a study involving 57 patients who
studies might be ascribed to the following factors:
                                                         had ARDS and who underwent open-lung biopsy,
 1. The use of different definitions of ALI and            showed that in selected patients who have clinical
    ARDS                                                 ARDS, open-lung biopsy can be performed safely,
 2. Cultural, demographic, and socioeconomic             often reveals an unsuspected diagnosis, and fre-
    differences in the different populations               quently leads to alterations in therapy. This study
    studied                                              revealed that a pathologic diagnosis other than
552                                                 AVECILLAS   et al

Table 2
American European Consensus Conference definition of acute lung injury and acute respiratory distress syndrome
Acute lung injury                                                       Acute respiratory distress syndrome
Acute onset                                                             Acute onset
PaO2/FIO2 of less than 300 mm Hg                                        PaO2/FIO2 of less than 200 mm Hg
Bilateral alveolar infiltrates on chest radiograph                       Bilateral alveolar infiltrates on chest radiograph
PAWP less than 18 mm Hg or no clinical evidence                         PAWP less than 18 mm Hg or no clinical evidence
  of left atrial hypertension                                             of left atrial hypertension
    Abbreviations: PaO2/FIO2, ratio of partial pressure of oxygen in arterial blood to inspired fraction of oxygen; PAWP,
pulmonary artery wedge pressure.
    (Data from Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS.
Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149
(3 Pt 1):819.)

DAD or fibroproliferation was found in up to 60%                 specificity of the AECC definition of ARDS may
of patients, biopsy results led to a change in man-             be different in clinical practice.
agement in most patients, and major complica-                       The AECC definition of ALI and ARDS
tions occurred in only 7% of cases [21].                        requires the presence of bilateral alveolar infil-
    In clinical practice the AECC definition of ALI              trates on chest radiograph. The identification of
and ARDS is used to diagnose these two entities,                individuals who have ARDS based on character-
even though the definitions were devised mainly to               istic radiographic findings can be challenging,
assist with clinical and epidemiologic research. The            however, and different studies have shown that
AECC definition of ALI and ARDS (see Table 2)                    the interpretation of chest radiographs in these
requires the acute onset of bilateral alveolar infil-            patients is not as reliable as one would expect
trates on chest radiograph, a PaO2/FIO2 ratio of                [23,24]. Rubenfeld and colleagues [23] asked 21
less than 200 mm Hg for ARDS and of less than                   experts to review 28 randomly selected chest ra-
300 mm Hg for ALI, and a pulmonary artery wedge                 diographs from critically ill hypoxemic patients
pressure (PAWP) less than 18 mm Hg or no clinical               and decide if the chest radiograph fulfilled the
evidence of left atrial hypertension [1]. Although              AECC definition for ALI and ARDS. The inter-
different authors have pointed out some of the lim-              observer agreement in applying the AECC defini-
itations of this definition [12,19,22], it is used widely        tion was moderate (k ¼ 0.55), and there was full
in research and in clinical practice.                           agreement on fewer than half of the chest radio-
    The definition suggested by the AECC has                     graphs (43%). Meade and colleagues [24] also
limitations. In a recent series of autopsy patients             found that intensivists are able to achieve only
Esteban and colleagues [19] compared the clinical               moderate levels of agreement in the radiologic di-
criteria for ARDS with autopsy findings and                      agnosis of ARDS. The level of agreement, how-
showed that the accuracy of the AECC definition                  ever, could increase substantially after consensus
of ARDS was only moderate, with a sensitivity of                training (some physicians participated in pilot
75% (95% confidence interval, 66%–82%) and                       training as part of a randomized trial of a pressure-
a specificity of 84% (95% confidence interval,                    and volume-limited ventilation strategy in patients
79%–88%). In this study the definition of                        at high risk for ARDS). Finally, in clinical prac-
ARDS was more accurate for patients who had                     tice it is common to encounter patients who
extrapulmonary risk factors (sepsis syndrome,                   have ALI or ARDS but who initially present
multiple trauma, several blood transfusions,                    with an atypical chest radiograph or with bilateral
shock, or pancreatitis) than for patients who had               infiltrates caused by chronic conditions such as id-
pulmonary risk factors (pneumonia, aspiration,                  iopathic pulmonary fibrosis, asbestosis, sarcoido-
near-drowning, inhalational injury, or lung contu-              sis, or lymphangitic carcinoma. In these cases it
sion). Nonetheless, this study included only pa-                is important for the clinician to do a general as-
tients who died and underwent autopsy;                          sessment of oxygenation and overall clinical con-
therefore, these results may not apply to less se-              dition to be able to make the right diagnostic
vere cases of ARDS. Another limitation of this                  and therapeutics decisions in a timely fashion.
study is that the diagnosis of ARDS was made us-                    Another limitation of the AECC definition is
ing retrospective analysis of clinical and radio-               that, besides using clinical information including
graphic findings. Therefore, the sensitivity and                 physical examination and radiologic evaluation, it
                                    CLINICAL EPIDEMIOLOGY OF ALI AND ARDS                                 553

may consider the measurement of PAWP to                  definition is developed (see the article by Rice
evaluate the presence of left atrial hypertension.       and Bernard in this issue).
The accuracy of this evaluation can vary
depending on the method used. Al-Kharrat and
colleagues [25] conducted a study to determine           Outcomes
inter- and intraobserver variability in measure-         Mortality
ment of pulmonary artery occlusion pressure
(Ppao). These authors compared values recorded               Different studies report a wide range of
by critical care nurses and physician specialists        mortality rates for patients who have ALI and
(cardiologists and critical care physicians) and         ARDS, varying between 23% and 71% (Table 3)
found significant differences in the measurement           [5,6,12,15–18,28–36]. Differences between reported
of Ppao tracings, not only between physicians            fatality rates may be explained by different factors:
and critical care nurses but also among physi-
                                                           1. The use of different proportions of patients
cians. The findings of this study are extremely im-
                                                              who have ARDS caused by pulmonary or ex-
portant, because critical care nurses perform the
                                                              trapulmonary causes, because significant dif-
measurements of Ppao in most hospitals, and sev-
                                                              ferences in mortality have been reported in
eral aspects of patient care depend these measure-
                                                              these two patient populations [2,18,32,33].
ments. A more recent study by Rizvi and
                                                              (For instance, a variable proportion of
colleagues [26] showed that the addition of an air-
                                                              ARDS cases caused by trauma or by Pneumo-
way pressure signal (Paw) to pressure tracings of
                                                              cystis jiroveci in patients who have AIDS
Ppao would improve interobserver agreement by
                                                              might affect the mortality rate, because these
facilitating identification of end-expiration. In
                                                              subsets of patients have been associated with
this study, agreement increased from 71% without
                                                              a lower and a higher mortality rate, respec-
Paw to 83% with Paw. The use of a PAWP of less
                                                              tively [15,28].)
than 18 mm Hg as the cut-off point for the diag-
                                                           2. Different severity of underlying illness in the
nosis of ALI and ARDS also has been challenged
                                                              populations studied and the use of different
because mild-to-moderate levels of elevated left
                                                              scoring systems for disease severity.
atrial pressure and ALI may coexist [22]. In
                                                           3. The use of different definitions of the main
a post hoc analysis of a randomized, controlled
                                                              outcome measure (ie, hospital, ICU, or
trial of pressure- and volume-limited ventilation
                                                              28-day mortality).
involving 120 patients who had ARDS but who
                                                           4. The type of ventilatory strategy used [5,6].
had no risk factors for congestive heart failure;
Ferguson and colleagues [22] found that                      Failure to control for these factors has resulted
a PAWP higher than 18 mm Hg is seen commonly             in results that vary widely from study to study,
in these patients, even though these patients had        making it more difficult to translate the reported
relatively high cardiac indices. Possible explana-       mortality rates to individual ICU populations.
tions for an increased PAWP in ARDS patients                 Early reports of the mortality of ARDS
include aggressive intravenous fluid resuscitation,       showed a high mortality rate (64%–70%) [8,18].
increased pleural pressures, or the use of positive      Over the last 20 years, however, the fatality rate
end-expiratory pressure during mechanical venti-         for patients who have ARDS has shown a trend
lation [27].                                             toward improvement, being between 29% and
    Finally, the AECC definition of ALI and               42% in more recent studies [17,37–40]. A retro-
ARDS does not specify the exact timing for the           spective study by Stapleton and colleagues [39]
evaluation of the chest radiograph and the PaO2/         showed that overall fatality has decreased at their
FIO2 ratio, and that timing could have a significant      institution during the last 2 decades (from 68% in
impact at the time of patient selection for the dif-     1981–1982 to 29% in 1996). In this study the in-
ferent studies. All the different factors discussed       creased survival was accounted for entirely by pa-
here can potentially alter the sensitivity and the       tients who presented with trauma, but survival for
specificity of the AECC definition of ALI and              patients whose risk factor was sepsis did not
ARDS, making comparisons among the different              change. Milberg and colleagues [37] also observed
studies more difficult to achieve. Therefore, all          a significant decline in fatality rates (ranging from
these limitations of the AECC definition of ALI           53%–68% between 1983 and 1987 to a low 36%
and ARDS must be considered at the time                  in 1993). In this study, however, the decline in
of study design, at least until a more suitable          mortality occurred largely in patients who had
554                                                AVECILLAS   et al

Table 3
Different reported mortality rates for acute lung injury and acute respiratory distress syndrome
                              Geographic area of
Authors                       study (year published)      Definition of ARDS/ALI           Mortality rate (%)
Baumman et al [28]            US (1986)                   PaO2/FIO2 % 200 mm Hg,          64 for ARDS
                                                            bilateral infiltrates, no
                                                            evidence of left atrial
                                                            hypertension
Hickling et al [29]           New Zealand (1994)          PaO2/FIO2 % 150 mm Hg,          26.6 for ARDS
                                                            bilateral infiltrates, no
                                                            evidence of left atrial
                                                            hypertension
Doyle et al [30]              US (1995)                   AECC                            58 for ALI
Lewandowski et al [11]        Germany (1995)              LIS R 2.5                       58.8 for ARDS
Zilberberg et al [31]         US (1998)                   AECC                            58 for ALI
                                                                                          58 for ARDS
Amato et al [6]               Brazil (1998)               LIS R 2.5, no evidence of       38–71 for ARDS
                                                            left atrial hypertension        depending on the
                                                                                            ventilation modality used
Roupie et al [32]             France (1999)               AECC                            60 for ARDS
Luhr et al [12]               Sweden, Denmark,            AECC                            42 for ALI
                                Iceland (1999)                                            41 for ARDS
ARDS Network [5]              US (2000)                   PaO2/FIO2 % 300 mm Hg,          31–39.8 for ARDS
                                                            bilateral infiltrates, no        depending on the
                                                            evidence of left atrial         ventilation modality
                                                            hypertension                    used
Suntharalingam et al [33]     UK (2001)                   AECC                            27.9–47.4 for ARDS
                                                                                            depending on the risk
                                                                                            factor
Bersten et al [16]            Australia (2002)            AECC                            32 for ALI
                                                                                          34 for ARDS
Estenssoro et al [34]         Argentine (2002)            AECC                            58 for ARDS
Arroliga et al [13]           US (2002)                   AECC                            48.5 for ARDS
Hughes et al [15]             Scotland (2003)             AECC                            60.9 for ARDS
Rubenfeld et al [17]          US (2005)                   AECC                            38.5 for ALI
                                                                                          41.1 for ARDS
   Abbreviations: AECC, American European Consensus Conference definition of acute lung injury and acute respira-
tory distress syndrome; ALI, acute lung injury; ARDS, acute respiratory distress syndrome; FIO2, inspired fraction of
oxygen; LIS, lung injury score; PaO2, partial pressure of oxygen in arterial blood; US, United States; UK, United
Kingdom.


sepsis syndrome as their risk factor for ARDS and              mortality of patients who had ARDS remained
in those younger than 60 years of age. Rubenfeld               constant (about 50%) throughout the period
and colleagues [17] recently showed that the in-               they studied (1967–1994), and other studies in
hospital mortality was 38.5% for patients who                  the ARDS literature still report mortality rates
had ALI and 41.4% for those who had ARDS.                      as high as 60% [15,34], keeping open the debate
This improvement in mortality may be explained                 about ARDS mortality. Therefore, intensivists
by a general improvement in supportive care for                who take care of ARDS patients in their daily
the critically ill and probably by the use of new              practice should be familiar with the most recently
strategies for mechanical ventilation in these pa-             reported data regarding fatality rates for this dis-
tients. Most of these studies are from academic                ease, because this information makes possible bet-
tertiary care centers, and the patient population              ter counseling of patients and their families.
and management of ARDS in these centers may                        ALI and ARDS do not occur in isolation, and
differ from that in community hospitals.                        mortality will vary according to the risk factor
    On the other hand, Krafft and colleagues [41]               implicated. Rubenfeld and colleagues [17] found
in a meta-analysis of older series found that the              that mortality varied from 24.1% among patients
                                     CLINICAL EPIDEMIOLOGY OF ALI AND ARDS                                   555

who had severe trauma, to 40.6% among patients            during the admission to the ICU, the presence of
who had severe sepsis with a suspected pulmonary          illness acquired during the ICU stay, and the
source, to 43.6% among patients in whom aspira-           rate of resolution of the lung injury and multior-
tion was witnessed. Sepsis syndrome with multiple         gan dysfunction during the ICU stay (as reflected
organ failure (see the article by Vincent in this is-     by the slope of the Lung Injury Score and the
sue), rather than isolated respiratory insufficiency,       Multiple Organ Dysfunction Score, respectively).
is the most common predisposing risk factor for           It seems that a significant proportion of ARDS
ALI and ARDS [1,17, 30,34] and is the most com-           survivors also have neurocognitive impairments,
mon cause of death in these patients [13,15,39].          including impaired memory, attention, concentra-
Martin and colleagues [42] analyzed the occur-            tion, mental processing speed, and global intellec-
rence of sepsis from 1979 trough 2000 using a na-         tual decline [46,47]. The neurocognitive and
tionally representative sample of all nonfederal          emotional morbidity and decreased quality of
acute care hospitals in the United States and             life persist at least 2 years in these patients, with
found an 8.7% annualized increase in the                  moderate to severe depression and anxiety in ap-
incidence of sepsis. Future research in ARDS              proximately 23% of patients [46]. In addition,
and ALI also should target the morbidity of sep-          Schelling and colleagues [49] evaluated a group
sis and the systemic inflammatory response                 of long-term ARDS survivors for posttraumatic
syndrome.                                                 stress disorder and found that 27.5% had this
                                                          condition [49]. Their data showed that all these
                                                          patients who had posttraumatic stress disorder
Morbidity
                                                          were deeply sedated (Ramsay sedation score 5 to
    Early studies that focused on aspects of re-          6) during the critical phase of their illness, suggest-
covery from ALI and ARDS paid more attention              ing that the majority of the traumatic events oc-
to respiratory symptoms and lung function                 curred during weaning, when the sedation is
[43,44]. In fact, most survivors present moderate-        usually decreased. A significant proportion of
to-severe impairment with low forced vital                ARDS survivors undergo rehabilitation, but
capacity (FVC), forced expiratory volume in 1 sec-        most of these patients are not evaluated for cogni-
ond (FEV1), FEV1/FVC ratio, total lung capacity           tive impairment [46]. Every rehabilitation center
(TLC), and carbon monoxide diffusing capacity              taking care of ARDS survivors should be able
(DLCO) [43,44]. McHugh and colleagues [43] in             to provide screening and therapy for neurocogni-
a prospective analysis of a cohort of 82 ARDS             tive deficits in a timely fashion.
survivors determined the rate of improvement in               Different studies have shown that a significant
pulmonary function abnormalities and self-                number of ARDS survivors will not resume
perceived health during the 12 months after the           normal activities or return to work within 1
episode of ARDS. At extubation the majority of            year of the acute event [43,47]. Some of these
patients had abnormally low FVC, TLC, and                 patients may need prolonged rehabilitation and
DLCO. Pulmonary function tests improved sub-              disability, representing a substantial health care
stantially between extubation and month 3, with           burden. If, in fact, the mortality rate after
additional slight improvement at 6 months.                ARDS is declining, more survivors will be at
    More recent studies have shown that patients          risk for ARDS-related morbidity, which seems
who survive ARDS also are at risk for other types         to be significant. Most of the available informa-
of physical, neuropsychologic, and emotional              tion regarding outcomes in patients who have
impairment and diminished quality of life [45–            survived ARDS comes from studies that have
48]. Herridge and colleagues [45] followed 109            not included a comparison group of ICU survi-
survivors of ARDS 3, 6, and 12 months after               vors who did not have ARDS. Therefore, it is
discharge from the ICU. This study showed that            necessary to use caution when interpreting these
these patients have persistent functional limita-         data, because all these sequelae may be related
tions, largely as a result of muscle wasting and          to morbidities from critical illness in general
weakness and, to a lesser extent, caused by entrap-       and not be unique to ARDS. More studies
ment neuropathy, heterotopic ossification, and de-         about ARDS demography and associated out-
creased lung function [45]. In this cohort of             comes are needed to provide more accurate in-
patients the most important determinants of the           formation to public health entities so they can
inability to exercise during the first year of             allocate resources to help in reintegrate these pa-
follow-up were use of systemic corticosteroids            tients to society.
556                                                    AVECILLAS   et al

Summary                                                                    failure in Berlin, Germany. Am J Respir Crit Care
                                                                           Med 1995;151(4):1121–5.
   A good understanding of the epidemiology of                     [12]    Luhr OR, Antonsen K, Karlsson M, et al. Incidence
ARDS is important for the allocation of health                             and mortality after acute respiratory failure and
care resources and research funds and also for the                         acute respiratory distress syndrome in Sweden,
evaluation of new therapeutic interventions and                            Denmark, and Iceland. The ARF Study Group.
health care delivery. Unfortunately, the only way                          Am J Respir Crit Care Med 1999;159(6):1849–61.
such data can be obtained is through large pro-                    [13]    Arroliga AC, Ghamra ZW, Perez Trepichio A, et al.
                                                                           Incidence of ARDS in an adult population of north-
spective population-based studies that could be
                                                                           east Ohio. Chest 2002;121(6):1972–6.
impractical and difficult to perform. Nonetheless,
                                                                   [14]    Goss CH, Brower RG, Hudson LD, et al. Incidence
the authors believe that there is enough informa-                          of acute lung injury in the United States. Crit Care
tion in the medical literature to show that ARDS                           Med 2003;31(6):1607–11.
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morbidity and mortality, and although different                             ratory distress syndrome: an audit of incidence and
studies suggest that the outcomes of ARDS may                              outcome in Scottish intensive care units. Anaesthesia
be improving, this entity still has the potential to                       2003;58(9):838–45.
have a significant burden on public health.                         [16]    Bersten AD, Edibam C, Hunt T, et al. Incidence and
                                                                           mortality of acute lung injury and the acute respira-
                                                                           tory distress syndrome in three Australian States.
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