WTA 2014 PLENARY PAPER

Adult respiratory distress syndrome risk factors for injured patients

undergoing damage-control laparotomy:
AAST multicenter post hoc analysis
Martin D. Zielinski, MD, Donald Jenkins, MD, Bryan A. Cotton, MD, Kenji Inaba, MD,
Gary Vercruysse, MD, Raul Coimbra, MD, Carlos V.R. Brown, MD, Darrell E.R. Alley, MD,
Joseph DuBose, MD, Thomas M. Scalea, MD,
and the AAST Open Abdomen Study Group, Rochester, Minnesota

BACKGROUND: Severely injured patients undergoing damage-control laparotomy (DCL) have multiple risk factors for adult respiratory distress
syndrome (ARDS), making it challenging to differentiate the contributions of individual causative factors. We aimed to
determine the relative contributions of ARDS risk factors.
METHODS: Analysis of the prospectively collected American Association for the Surgery of Trauma Multi-institutional Open Abdomen
Database was performed. Inclusion criteria were any patient, 18 years or older, undergoing DCL at 1 of 14 participating Level I
trauma centers. Univariable and multivariable Cox regression analyses were performed to determine the association of var-
iables with the development of ARDS during hospitalization.
RESULTS: A total of 563 patients (78% men; mean [SD] age, 40 [18] years) were identified, of whom 77 developed ARDS (14%). Overall
mortality was 23%, with a 39% mortality rate for ARDS patients. Univariable analysis demonstrated that Injury Severity Score
(ISS, 1.03; 95% confidence interval [CI], 1.02Y1.05), intraoperative (IO) estimated blood loss (hazard ratio [HR], 1.09; 95%
CI, 1.04Y1.13), IO plasma transfusion (HR, 1.17; 95% CI, 1.10Y1.25), 24-hour colloid volume (HR, 1.07; 95% CI, 1.04Y1.10),
and 24-hour crystalloid volume (HR, 1.01; 95% CI, 1.00Y1.01) were associated with the development of ARDS. Cox
multivariable analysis demonstrated that ISS, IO plasma transfusions, and total fluid balance through 23 hours all increased the
risk of ARDS development.
CONCLUSION: Severity of injury, plasma transfusions, and greater fluid administration by 24 hours were independently associated with ARDS
development. Judicious use of plasma and other fluids may reduce rates of ARDS in this critically injured population. (J Trauma
Acute Care Surg. 2014;77: 886Y891. Copyright * 2014 by Lippincott Williams & Wilkins)
LEVEL OF EVIDENCE: Prognostic study, level III; therapeutic study, level IV.
KEY WORDS: Damage control; open abdomen; adult respiratory distress syndrome; trauma; laparotomy.

D amage-control resuscitation (DCR) has been promoted as

the standard of care to reduce mortality in the most se-
verely injured, hemorrhaging patients. Several points are crit-
ical to DCR: (1) high ratio transfusions of plasma and platelets
to packed red blood cell (PRBC) units via massive transfusion
(MT) protocols, (2) limited crystalloid administration, (3) ab-
breviated procedures, and (4) permissive hypotension.1 In-
corporation of these practices has been associated with a 62%
mortality benefit for patients requiring MT (Q10 PRBC units in
24 hours).2 Damage-control laparotomy (DCL) was the initial
procedure introducing the concept of DCR and remains the
Submitted: January 7, 2014, Revised: May 20, 2014, Accepted: May 21, 2014,
Published online: September 22, 2014.
From the Mayo Clinic (M.D.Z., D.J.), Rochester, Minnesota; University of Texas at
Houston (B.A.C.), Houston; University of Texas, Austin (C.V.R.B.), Austin; and
East Texas Medical Center (D.E.R.A.), Tyler, Texas; University of Southern
California (K.I.), Los Angeles; University of California, San Diego (R.C.), La
Jolla, California; University of Arizona (G.V.), Tucson, Arizona; University of
Maryland (J.D., T.M.S.), College Park, Maryland.
This study was presented in part at the 44th Annual Meeting of the Western Trauma
Association, March 2Y7, 2014, in Steamboat Springs, Colorado.
Address for reprints: Martin D. Zielinski, MD, Division of Trauma, Critical Care and
General Surgery, Mary Brigh 2Y810, St. Mary’s Hospital, Mayo Clinic, 1216
Second St. SW, Rochester, MN 55902; email: zielinski.martin@mayo.edu.
DOI: 10.1097/TA.0000000000000421
886
most commonly applied procedure within the DCR manage-
ment scheme.3Y6 These abbreviated laparotomies allow trauma
surgeons to gain source control of life-threatening injuries
while allowing for the delay in definitive treatment until
physiologic stabilization and subsequent reexploration. This
approach, hand in hand with the other DCR elements, remains
the standard of care for critically ill, unstable patients with
abdominal injuries.7
Despite demonstrated mortality benefits with DCR
techniques, controversy remains. Integral in the counter ar-
gument to DCR is the potential three times greater risk of adult
respiratory distress syndrome (ARDS).8,9 This syndrome,
characterized by a profound dysfunction of gas exchange at the
alveoli secondary to inflammation, can occur in up to 8.4% of
patients undergoing MT, with an associated 17% mortality in
severely injured patients.2,9 The etiology of ARDS in this
critically ill patient population remains elusive and is likely
multifactorial.10 The combination of phenotypic, environ-
mental, and clinical ‘‘hits’’ have been implicated in ARDS
development. These hits are both inherent to the patient (ge-
netic predisposition, injury severity, preexisting lung disease,
advanced age, ischemia/reperfusion) and potentially modifi-
able by the clinician (i.e., fraction of inhaled oxygen [FIO2],
J Trauma Acute Care Surg
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J Trauma Acute Care Surg
Volume 77, Number 6 Zielinski et al.

positive end-expiratory pressure, blood product age/volume,
limited crystalloid administration).9Y13 Severely injured trauma
patients universally have some, and potentially all, of these risk
factors. For this reason, it can be challenging to differentiate the
contributions each of these individual causal factors provides to
the development of ARDS. Depending on the factors identified,
alterations in the treatment of severe hemorrhage such as
whole-blood transfusion or elimination of crystalloid may be
entertained.14 In this study, we aimed to determine the risk
factors for the development of ARDS in severely injured
trauma patients undergoing DCL and to elucidate the specific
contributions of blood product and crystalloid volumes to the
overall risk of ARDS. Specifically, we hypothesized that (1)
increasing crystalloid resuscitation volumes will increase the
risk of ARDS and (2) plasma will provide a beneficial effect in
helping to prevent the development of ARDS.
PATIENTS AND METHODS
This was a post hoc analysis of the prospective obser-
vational multi-institutional study sponsored by the American
Association for the Surgery of Trauma (AAST). The AAST
Multi-Institutional Trials Committee approved the study pro-
tocol, and each participating center had previously obtained
institutional review board approval for the use of the
deidentified data. This database, previously described, included
a total of 563 patients represented by the combined efforts of 14
trauma centers throughout the country between 2010 and
2011.7 Inclusion criteria were any patient, 18 years or older,
undergoing DCL as a result of injury. During the data col-
lection, acute lung injury (ALI) and ARDS were defined as the
ratio of the partial pressure of arterial oxygen (PaO2) divided by
the fraction of inhaled oxygen (FIO2; i.e., the P/F ratio) of less
than 300 mm Hg and 200 mm Hg, respectively, in the absence
of signs of heart failure. New expert opinion has broadened the
definition into mild, moderate, and severe ARDS (based on the
P/F ratio) and eliminated the term ALI.15,16 PaO2 and FIO2
variables, however, were not collected during the prospective
data collection. As a result, both ALI and ARDS terms were
considered equivalent without differentiation into mild, mod-
erate, and severe categories. Nonblood colloid included any
colloid resuscitation (i.e., albumin, hydroxyethyl starch) fluid
except plasma, PRBC, platelets, or cryoprecipitate. Total col-
loid fluid refers to the combination of nonblood colloids plus
blood product.17Y19
Descriptive statistics are reported as n (%) or as mean (SD)
as appropriate. Patients were assessed for the development of
ARDS following up a patient to either the postoperative day
(POD) of ARDS diagnosis (event) or the POD of hospital dis-
charge (censor). The Cox proportional hazards model was used to
assess risk factors for association with ARDS. Variables known at
baseline, patient characteristics, organ injury and operative
intervention pattern, and intraoperative (IO) resuscitation char-
acteristics were examined in all 563 patients. Resuscitation
characteristics through 24 hours were examined in the 510 pa-
tients still followed up at the end of POD 1, excluding patients
who died through POD 1 or those who had ARDS diagnosed by
POD 1. Similarly, resuscitation characteristics through 48 hours
were examined in the 480 patients still followed up at the end of
POD 2. All models included a variable for the medical center in
the study; therefore, a ‘‘univariate’’ model is a model containing a
class variable for medical centers and one additional variable of
interest. The medical center was included to account for possible
differences in practice between medical centers. A multivariable
model was examined for the 510 patients still followed up at the
end of POD 1. Patient characteristics and resuscitation charac-
teristics known through POD 1 with a univariate significance of
0.2 or less were examined. A backward selection method was
used retaining variables with significance less than 0.05. The
> level was set at 0.05 for statistical significance.
RESULTS
In total, 563 patients were in the AAST Open Abdomen
Database, of whom 77 (14%) developed ARDS. There was no
significant association of either age or sex with the risk of
developing ARDS (Table 1). Univariable analysis demon-
strated that a greater Injury Severity Score (ISS), Abbreviated
Injury Scale (AIS) score, and lower pH value were associated
with an increased risk of ARDS development. In addition,
ARDS was associated with a prolonged intensive care unit stay
when all deaths were excluded (28.5 [17.7] days vs. 16.0 [14.0]
days, p G 0.001). The same held true for hospital length of stay
when excluding all deaths (41.5 [23.8] vs. 24 [24.8], p G 0.001).

TABLE 1. Patient Characteristics

Cox Model Including
Univariate Cox Model Medical Center
No ARDS (n = 486) ARDS (n = 77) HR (95% CI) p HR (95% CI) p
Age, y 39.7 (17.4) 43.0 (18.9) 1.12A (0.99Y1.27) 0.062 1.09 (0.95Y1.24) 0.221
Male sex 375 (77.2%) 62 (80.5%) 1.09 (0.62Y1.92) 0.765 1.07 (0.60Y1.90) 0.812
ISS 27.9 (13.2) 35.1 (14.5) 1.03B (1.02Y1.05) G0.001 1.03 (1.01Y1.05) G0.001
Head AIS score 1.1 (1.7) 1.8 (1.8) 1.26B (1.11Y1.43) G0.001 1.16 (0.996Y1.34) 0.056
Abdomen AIS score 3.5 (1.1) 3.8 (0.9) 1.42B (1.12Y1.80) 0.004 1.28 (0.995Y1.65) 0.055
Chest AIS score 2.2 (1.6) 2.8 (1.4) 1.26B (1.08Y1.47) 0.004 1.19 (1.01Y1.40) 0.041
Hemoglobin, g/dL 11.5 (3.1) 11.6 (3.2) 1.00B (0.92Y1.08) 0.942 0.98 (0.90Y1.06) 0.629
Lowest pH 7.1 (0.8) 7.1 (0.1) 1.00B (0.74Y1.35) 0.988 0.97 (0.65Y1.45) 0.885
Hypothermia (G35-C) 161 (33.1%) 28 (36.4%) 1.33 (0.84Y2.12) 0.225 1.34 (0.83Y2.18) 0.230
Continuous variables are provided as HR with 95% CI for Cox regression and as means (SD) for the descriptive statistics.

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 J Trauma Acute Care Surg
Zielinski et al. Volume 77, Number 6

The rate of death was nearly double if a patient developed
ARDS (20.6% vs. 39.0%, p = 0.001).
Resuscitation volumes of crystalloid, colloid, and blood
products were substantially different between the patients who
developed ARDS from presentation throughout the first
48 hours on univariable analysis (Table 2). Specifically, crys-
talloid was associated with a significant risk for ARDS with
greater volumes infused at both 24 hours and 48 hours after
injury. IO estimated blood loss and plasma resuscitation volumes
were greater in patients who developed ARDS. In addition, the
colloid volume transfused throughout the first 48 hours of re-
suscitation continued to be greater in the patients who developed
ARDS. As a result, the total volumes of fluid infused were also
greater in the ARDS population.
There was a broad range of injury patterns and other
procedures performed for patients undergoing DCL (Table 3).
The most common abdominal organ requiring intervention was
the liver, followed by major vascular interventions and the
spleen. A minority of patients underwent thoracotomy con-
current with the DCL procedure (n = 62). There were no dif-
ferences between organs injured and thoracotomy procedures
for patients who did and did not develop ARDS.
Cox multivariable regression analysis showed a signifi-
cant increased risk of ARDS with increased IO plasma use
(hazard ratio [HR], 1.16; 95% confidence interval [CI],
1.07Y1.25). Each liter of IO plasma was associated with a 3%
increased risk of developing ARDS (Table 4). For an additional
10 L of total fluids, there was a 10 % increase in the rate of
ARDS (HR, 1.10 per 10 L; 95% CI, 1.05Y1.15). In addition,
each ISS unit increase was associated with a 3% increased risk
of ARDS. Alternatively, a 25-point gain in ISS nearly doubled
the ARDS risk (HR, 1.95; 95% CI, 1.24Y3.07). There were no
variables under study which conferred a benefit to prevent
ARDS development. The primary fascial closure rate was 66%.
DISCUSSION
DCR techniques, despite their beneficial associations
with mortality, have significant limitations. Similarly, DCL, as
an integral portion of DCR, has substantial drawbacks including
enterocutaneous fistulae, sepsis, and ARDS.2,8,20 These com-
plications, however, can only develop if the patient survives the
initial hemorrhagic event. Therefore, the real risk of death
outweighs the theoretical risk of complications from DCL and
should be performed if indicated. Naturally, the intensive care
unit portion of the patient’s course is fraught with further
complications, stemming not only from the initial physiologic
insult but also from subsequent ‘‘second hits,’’ which have their
own associated complications.10 It is the summation of these
primary and secondary hits that place critically ill trauma pa-
tients at risk for ARDS.21,22
ARDS has its own related mortality independent of the
traumatic insult. In the current study, ARDS was associated
with a doubling in the risk of death. As such, the development
of ARDS should not be viewed as an inevitable disease process
but as a preventable complication with the use of risk miti-
gation strategies throughout the resuscitation phase. As dem-
onstrated, increasing reliance on plasma and fluids for
resuscitation promoted an increased risk of ARDS. The infu-
sion of 10 L of fluid (both crystalloid and blood products)
during the first 24 hours after injury increased the risk of ARDS
development by an additional 10%.
This study is not unique in finding that fluid administration
is associated with poor outcomes in significantly injured patients.

TABLE 2. Resuscitation Characteristics

Cox Model Including
Univariate Cox Model Medical Center
No ARDS (n = 485) ARDS (n = 77) HR (95% CI) p HR (95% CI) p
IO
Estimated blood loss, L 2.38 (3.22) 3.83 (5.39) 1.09 (1.04Y1.13) 0.398 1.10 (1.05Y1.16) G0.001
Nonblood colloid, L 0.57 (1.26) 0.32 (0.55) 0.70 (0.44Y1.11) 0.128 0.77 (0.50Y1.20) 0.250
Total fluid balance, L 6.68 (13.75) 8.10 (7.96) 1.00 (0.99Y1.02) 0.395 1.00 (0.99Y1.02) 0.524
PRBC volume, L 2.84 (7.27) 3.90 (3.86) 1.01 (0.99Y1.03) 0.191 1.01 (0.99Y1.03) 0.245
Plasma volume, L 1.63 (2.06) 2.91 (3.39) 1.17 (1.10Y1.25) 0.001 1.21 (1.12Y1.31) G0.001
Platelet volume, L 0.44 (0.98) 0.62 (1.00) 1.14 (0.96Y1.35) 0.001 1.13 (0.92Y1.38) 0.254
Plasma/PRBC, U 0.7 (0.5) 0.7 (0.5) 0.88A (0.54Y1.42) 0.585 0.76 (0.43Y1.32) 0.325
C/PRBC, U 4.5 (6.5) 3.5 (5.9) 1.40A (1.13Y1.72) 0.002 0.96 (0.91Y1.00) 0.072
24 h
Total colloid, L 1.36 (3.02) 3.80 (7.33) 1.09 (1.05Y1.13) G0.001 1.10 (1.05Y1.15) G0.001
Total crystalloid, L 6.33 (8.70) 15.36 (54.59) 1.01 (1.00Y1.01) G0.001 1.005 (1.00Y1.01) 0.057
Total fluids, L 7.69 (9.51) 19.16 (57.65) 1.01 (1.00Y1.01) G0.001 1.005 (1.001Y1.01) 0.022
48 h
Total colloid, L 1.01 (2.91) 2.05 (5.42) 1.06 (1.00Y1.12) 0.034 1.10 (1.02Y1.19) 0.014
Total crystalloid, L 6.85 (7.94) 8.60 (6.94) 1.03 (1.00Y1.05) 0.058 1.02 (0.99Y1.05) 0.206
Total fluids, L 7.86 (9.04) 10.64 (10.59) 1.03 (1.01Y1.05) 0.016 1.03 (1.002Y1.05) 0.036
Continuous variables are provided as HR with 95% CI for Cox regression as well as means (SD) for descriptive statistics.
A
= Hazard Ratio based on smoothing spline result where values greater than 3 reset as equivalent to 3.

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J Trauma Acute Care Surg
Volume 77, Number 6 Zielinski et al.

TABLE 3. Organ Injury and Operative Intervention Patterns

Cox Model Including
Univariate Cox Model Medical Center
No ARDS (n = 485) ARDS (n = 77) HR (95% CI) p HR (95% CI) p
Abdominal organ injuries, n (%)
Liver 178 (36.0) 36 (46.8) 1.46 (0.93Y2.29) 0.097 1.37 (0.75Y2.52) 0.304
Major vascular 140 (28.3) 19 (24.7) 0.88 (0.52Y1.48) 0.624 0.72 (0.34Y1.52) 0.381
Spleen 115 (23.7) 20 (26.0) 1.10 (0.66Y1.84) 0.705 1.49 (0.79Y2.80) 0.218
Small bowel 109 (22.0) 11 (14.3) 0.62 (0.33Y1.17) 0.142 0.74 (0.33Y1.70) 0.482
Colon 77 (15.8) 13 (16.9) 1.01 (0.55Y1.83) 0.984 0.87 (0.38Y1.96) 0.732
Diaphragm 57 (11.5) 14 (18.2) 1.46 (0.82Y2.61) 0.198 1.41 (0.62Y3.20) 0.417
Stomach 57 (11.5) 8 (10.4) 0.86 (0.41Y1.79) 0.684 1.57 (0.65Y3.78) 0.318
Kidney 33 (6.7) 3 (3.9) 0.56 (0.18Y1.79) 0.331 0.67 (0.16Y2.80) 0.585
Thoracotomy incision, n (%)
Posterolateral 5 (1.0) 2 (2.6) 3.29 (0.81Y13.42) 0.097 4.78 (0.63Y36.34) 0.131
Anterolateral 30 (6.2) 8 (10.4) 2.07 (1.00Y4.31) 0.051 1.64 (0.49Y5.44) 0.421
Resuscitative 15 (3.0) 2 (2.6) 1.25 (0.31Y5.11) 0.753 1.92 (0.25Y14.55) 0.527
Continuous variables are provided as HR 95% CI for Cox regression as well as means (SD) for descriptive statistics.

A greater crystalloid-to-PRBC (C/PRBC) ratio has been asso-
ciated with multisystem organ failure, ARDS, and abdominal
compartment syndrome, although, interestingly, not death.11
This effect was dose responsive as a C/PRBC greater than 1.5:1
conferred a two times higher likelihood of developing ARDS.
Correspondingly, the PRospective Observational Multicenter
Major Trauma Transfusion (PROMMTT) study confirms that
chest injury severity, advanced age, and greater use of crystalloid
were independent risk factors for ARDS development.16 Our
study, however, also demonstrated that blood product adminis-
tration, specifically plasma, was associated with the ARDS risk
on multivariable analysis.
While transfusion-related ALI may no longer be a recog-
nized entity, the risk of transfusion-associated ARDS cannot be
eliminated because of nomenclature alone. Previous reports in
similar patient populations have demonstrated an increased risk
of ARDS with blood product transfusions.23,24 These studies,
however, considered ARDS as an single end point rather than one
that evolves throughout hospitalization as a time-dependent
complication. More precisely, the current study allows for the
true analysis of ARDS risk factors over time. In addition, the
multi-institutional, prospective nature of the current study should
confer a wider applicability of these results.
The next evolution in hemorrhage resuscitation, re-
presenting the ultimate culmination of DCR techniques, is the
transfusion of whole blood. That crystalloid, rather than blood
products, increases the risk of ARDS makes intuitive sense.
Hemorrhaging patients are losing volume, but this volume is not
crystalloid. Rather, the fluid being lost is whole blood. Recent
data suggest that warm fresh whole blood (WFWB) and modified
whole blood have significant improvement in mortality but the
risk of ARDS after whole-blood transfusion is less clear. In a
retrospective analysis of military data, survival at 24 hours was
improved in the WFWB cohort when compared with component
therapy (96% vs. 88%, p = 0.018).25 The rate of ARDS, however,
was nonsignificantly greater (7% vs. 3%, p = 0.08). It should be
noted that neither component nor WFWB products were
leukoreduced, which potentially increased the risk for ARDS. In
a randomized clinical trial, Cotton et al.14 demonstrated similar
rates of both 24-hour mortality (16% vs. 12%, p = 0.58) and
ARDS (0.0% vs. 1.9%. p = 0.32) with the use of leukoreduced,
modified whole blood. Whether whole blood products will have a
demonstrable improvement in the rates of ARDS remains to be
elucidated.
Despite our hypothesis, plasma was identified as an in-
dependent ARDS risk factor. This correlates with the ac-
knowledgement that blood products can cause ARDS. In all
likelihood, there are multiple hits that are associated with
ARDS development, particularly in severely injured trauma
patients.10,12,26 The number of individual risk factors that have
been associated with ARDS is substantial. A single blood
product unit may only cause 1:5,000 to 1:74,000 cases of
ARDS.27Y29 As a result, the influence that blood products
contribute can easily be overwhelmed by additional risk factors

TABLE 4. Multivariable Features Associated With the Development of ARDS

Multiple Variable Cox Model Cox Model Including Medical Center
HR (95% CI) p HR (95% CI) p
ISS, per 1 point 1.03 (1.01Y1.05) 0.004 1.02 (1.002Y1.04) 0.031
IO plasma volume, mean (SD), L 1.16 (1.07Y1.25) G0.001 1.17 (1.06Y1.28) 0.001
Total fluids at 24 hours, mean (SD), L 1.010 (1.005Y1.014) G0.001 1.005 (1.001Y1.010) 0.028

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Zielinski et al.
including crystalloid resuscitation, lung injury, endothelial
damage, and coagulopathy. The patients included in the current
study should be considered as some of the most severely in-
jured patients and therefore will have some, if not all, of these
identified risk factors for ARDS. Given that DCL was required
to be included in this study, we were able to effectively control
for severity of injury in the multivariable analysis.
Despite the multi-institutional design of this study, there
were significant limitations encountered. Chief among these
limitations is the post hoc nature of our analysis because the
original study was designed to identify risk factors for the lack
of primary fascial closure after DCL for trauma.7 As a result,
the data points collected were not aimed directly for an end
point of ARDS. Significantly, the P/F ratio, a major determi-
nant for the diagnosis of ARDS, was not collected and there-
fore not analyzed. While the definitions of transfusion-related
ALI and ARDS were standardized, the ability to convert into
the new system of ARDS severity was limited. As a result,
ARDS was a binary variable for the purposes of this report. An
additional limitation was the uncertainty of the exact blood
product transfusion rates at 24 hours. Nonblood colloid and
blood products were combined into a single data point. This
ambiguity has limited impact, however, as the overall volume
of IO nonblood colloid was far less than IO blood product
transfusion rates. Another limitation to consider is the presence
of confounding variables we were unable to account for in our
model. Certainly, given the myriad risk factors for ARDS de-
velopment, this is likely and may be represented by the greater
plasma requirements acting as a surrogate rather than the cause
of the ARDS. Similarly, the greater plasma use may result in
transfusion-associated circulatory overload, which is misdiag-
nosed as ARDS given the difficulty in differentiating the two
entities. Finally, the lack of ventilator management standardi-
zation and data collection compromises our analysis. The ARDS
definition is primarily based on the P/F ratio, which can be af-
fected by greater positive end-expiratory pressure and alternative
ventilator strategies such as airway pressure release ventilation.
This study demonstrates that higher volume plasma re-
suscitations were associated with a greater risk of ARDS in
significantly injured patients. Given the limitations of the
current study, we believe that plasma remains the standard of
care for resuscitation of the severely injured patient but con-
sideration to the limitation of plasma when the patient stabilizes
should be entertained to potentially avoid ARDS.
AUTHORSHIP
M.D.Z. contributed in the project idea development, study design, data
collection, data analysis, manuscript preparation, manuscript review, and
data interpretation. D.J. contributed in the project idea development,
study design, data collection, data analysis, manuscript review, and data
interpretation. B.A.C. contributed in the project idea development, data
collection, study design, manuscript review, and data interpretation. K.I.
contributed in the project idea development, data collection, study design,
manuscript review, and data interpretation. G.V. contributed in the data
collection, manuscript review, study design, and data interpretation. R.C.
contributed in the data collection, manuscript review, and critical revision,
C.V.R.B. contributed in the data collection, manuscript review, and critical
revision, D.E.R.A. contributed in the data collection, manuscript review,
and critical revision, J.D. was an originator of the AAST database and
contributed in the project idea development, data collection, manuscript
review, critical revision, and project liaison. T.M.S. was an originator of the
890
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J Trauma Acute Care Surg
Volume 77, Number 6
AAST database and contributed in the project idea development, manu-
script review, and critical revision.
ACKNOWLEDGMENT
The AAST Open Abdomen Study group thanks the following individuals,
without whom this study could not have been completed: Mohammad
Alzghari, MBBS; Mahmoud A. Amr, MBBS; Meghan Spencer; Rebecca
Grace Lopez MS4; Jinfeng Han, BSN; Judith S. Katzen, MS, RN; Terry
Curry, RN; Sadia Ali, MPH; and Mary Waage.
AAST Open Abdomen Study Group Authors
In addition, we would like to acknowledge all participating members
and institutions included as authors in the AAST Open Abdomen Study
Group; Binod Shrestha, MD, and John Holcomb, MD, from the Uni-
versity of Texas Houston Medical Center; Kenji Inaba, MD, Obi Okoye,
MD, and Agathoklis Konstantinidis, MD, from the Los Angeles County +
University of Southern California Hospital; Tom Scalea, MD, Jay
Menaker, MD, and Joe DuBose, MD, from the R Adams Cowley Shock
Trauma Center, University of Maryland Medical Center; James F.
Whelan, MD, Rao Ivatury, MD, and Stephanie R. Goldberg, MD, from
the Virginia Commonwealth University; Martin D. Zielinski, MD, Donald
Jenkins, MD, Karla V. Ballman, PhD, and William S. Harmsen, from the
Mayo Clinic Trauma Centers; Stephen Rowe, MD, Darrell Alley, MD,
John Berne, MD, and LaDonna Allen, RN, from the East Texas Medical
Center; Paola G. Pieri, MD, and Starre Haney, RN, MS, from the
Maricopa Integrated Health System; Jeffrey A. Claridge, MD, and
Katherine Kelly, MD, from the MetroHealth Medical Center; Tiffany Bee,
MD, and Timothy Fabian, MD, from the University of Tennessee Health
Science Center; Raul Coimbra, MD, PhD, and Jay Doucet, MD, from the
University of California San Diego School of Medicine; Ben Coopwood,
MD, David Keith, MD, and Carlos Brown, MD, from the University of
Texas Southwestern-Austin, University Medical Center Brackenridge;
James M. Haan, MD, and Jeanette Ward, BA, from the Via Christi Hos-
pital, St. Francis Campus; Stuart M. Leon, MD, Evert Eriksson, MD, and
Debbie Couillard, RN, BSN, from The Medical University of Southern
Carolina; and Marc A. de Moya, MD, and Gwendolyn M. van der
Wilden, MSc, from the Massachusetts General Hospital.
DISCLOSURE
The authors declare no conflicts of interest.
REFERENCES
1. Duchesne JC, McSwain NE Jr, Cotton BA, Hunt JP, Dellavolpe J, Lafaro
K, Marr AB, Gonzalez EA, Phelan HA, Bilski T, et al. Damage control
resuscitation: the new face of damage control. J Trauma. 2010;69(4):
976Y990.
2. Murad MH, Stubbs JR, Gandhi MJ, Wang AT, Paul A, Erwin PJ, Montori
VM, Roback JD. The effect of plasma transfusion on morbidity and
mortality: a systematic review and meta-analysis. Transfusion. 2010;50:
1370Y1383.
3. Rotondo MF, Schwab CW, McGonigal MD, et al. ‘Damage control’: an
approach for improved survival in exsanguinating penetrating abdominal
injury. J Trauma. 1993;35:375Y382; discussion 382Y373.
4. Lucas CE, Ledgerwood AM. Prospective evaluation of hemostatic tech-
niques for liver injuries. J Trauma. 1976;16(6):442Y451.
5. Stone HH, Strom PR, Mullins RJ. Management of the major coagulopathy
with onset during laparotomy. Ann Surg. 1983;197:532Y535.
6. Hatch QM, Osterhout LM, Ashraf A, Podbielski J, Kozar RA, Wade CE,
Holcomb JB, Cotton BA. Current use of damage-control laparotomy,
closure rates, and predictors of early fascial closure at the first take-back. J
Trauma. 2011;70(6):1429Y1436.
7. Dubose JJ, Scalea TM, Holcomb JB, Shrestha B, Okoye O, Inaba K, Bee
TK, Fabian TC, Whelan J, Ivatury RR; AAST Open Abdomen Study
Group. Open abdominal management after damage-control laparotomy for
trauma: a prospective observational American Association for the Surgery
of Trauma multicenter study. J Trauma Acute Care Surg. 2013;74(1):
113Y120; discussion 1120Y1122.
* 2014 Lippincott Williams & Wilkins
J Trauma Acute Care Surg
Volume 77, Number 6
8. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory
distress in adults. Lancet. 1967;2:319Y323.
9. Park P, Cannon JW, Ye W, Blackbourne LH, Holcomb JB, Beninati W,
Napolitano LM. Transfusion strategies and development of acute respi-
ratory distress syndrome in combat casualty care. J Trauma Acute Care
Surg. 2013;75(2 Suppl 2):S238YS246.
10. Matthay MA, Zimmerman GA, Esmon C, et al. Future research directions
in acute lung injury: summary of a National Heart, Lung, and Blood In-
stitute working group. Am J Respir Crit Care Med. 2003;167:1027Y1035.
11. Neal MD, Hoffman MK, Cuschieri J, Minei JP, Maier RV, Harbrecht BG,
Billiar TR, Peitzman AB, Moore EE, Cohen MJ, et al. Crystalloid to
packed red blood cell transfusion ratio in the massively transfused patient:
when a little goes a long way. J Trauma Acute Care Surg. 2012;72:
892Y898.
12. Gajic O, Rana R, Mendez JL, Rickman OB, Lymp JF, Hubmayr RD, Moore
SB. Acute lung injury after blood transfusion in mechanically ventilated
patients. Transfusion. 2004;44:1468Y1474.
13. Garcia JG, Moreno Vinasco L. Genomic insights into acute inflammatory
lung injury. Am J Physiol Lung Cell Mol Physiol. 2006;291:L1113YL1117.
14. Cotton BA, Podbielski J, Camp E, Welch T, del Junco D, Bai Y, Hobbs R,
Scroggins J, Hartwell B, Kozar RA, et al.; Early Whole Blood
Investigators. A randomized controlled pilot trial of modified whole
blood versus component therapy in severely injured patients requiring
large volume transfusions. Ann Surg. 2013;258(4):527Y532; discussion
532Y533.
15. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan
E, Camporota L, Slutsky AS, ARDS Definition Task Force. Acute re-
spiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):
2526Y2533.
16. Robinson BRH, Cotton BA, Pritts TA, Branson R, Holcomb JB, Muskat P,
Fox EE, Wade CE, del Junco DJ, Bulger EM, et al.; PROMMTT study
group. Application of the Berlin definition in PROMMTT patients: the
impact of resuscitation on the incidence of hypoxemia. J Trauma Acute
Care Surg. 2013;75(1):S61YS67.
17. Campion EM, Pritts TA, Dorlac WC, Nguyen AQ, Fraley SM, Hanseman
D, Robinson BRH. Implementation of a military-derived damage-control
resuscitation strategy in a civilian trauma center decreases acute hypoxia
in massively transfused patients. J Trauma Acute Care Surg. 75(2):
S221YS227.
* 2014 Lippincott Williams & Wilkins
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Zielinski et al.
18. Kleinman S, Caulfield T, Chan P, Davenport R, McFarland J, McPhedran S,
Meade M, Morrison D, Pinsent T, Robillard P, et al. Toward an under-
standing of transfusion-related acute lung injury: statement of a consensus
panel. Transfusion. 2004;44(12):1774Y1789.
19. Toy P, Lowell C. TRALIVdefinition, mechanisms, incidence and clinical
relevance. Best Pract Res Clin Anaesthesiol. 2007;21(2):183Y193.
20. Hatch QM, Osterhout LM, Podbielski J, Kozar RA, Wade CE, Holcomb
JB, Cotton BA. Impact of closure at the first take back: complication
burden and potential overutilization of damage control laparotomy.
J Trauma. 2011;71(6):1503Y1511.
21. Borgman MA, Spinella PC, Perkins JG, et al. The ratio of blood products
transfused affects mortality in patients receiving MTs at a combat support
hospital. J Trauma. 2007;63:805Y813.
22. Rosengart MR, Maier RV, Billiar TR, Peitzman AB, Sperry JL, Ochoa JB,
Gunn SR, Alarcon LH, Minei JP, Cuschieri J, et al. An FFP:PRBC
transfusion ratio 9/=1:1.5 is associated with a lower risk of mortality after
MT. J Trauma. 2008;65:986Y993.
23. Edens JW, Chung KK, Pamplin JC, Allan PF, Jones JA, King BT, Cancio
LC, Renz EM, Wolf SE, Wade CE, et al. Predictors of early acute lung
injury at a combat support hospital: a prospective observational study.
J Trauma. 2010;69(Suppl 1):S81YS86.
24. Plurad D, Martin M, Green D, Salim A, Inaba K, Belzberg H, Demetriades
D, Rhee P. The decreasing incidence of late posttraumatic acute respiratory
distress syndrome: the potential role of lung protective ventilation and
conservative transfusion practice. J Trauma. 2007;63(1):1Y7; discussion 8.
25. Spinella PC, Perkins JG, Grathwohl KW, Beekley AC, Holcomb JB. Warm
fresh whole blood is independently associated with improved survival for
patients with combat-related traumatic injuries. J Trauma. 2009;66(Suppl 4):
S69YS76.
26. Popovsky MA, Abel MD, Moore SB. Transfusion-related acute lung injury
associated with passive transfer of antileukocyte antibodies. Am Rev Respir
Dis. 1983;128:185Y189.
27. Wallis JP, Lubenko A, Wells AW, Chapman CE. Single hospital experience
of TRALI. Transfusion. 2003;43:1053Y1059.
28. Popovsky MA, Moore SB. Diagnostic and pathogenetic considerations in
transfusion-related acute lung injury. Transfusion. 1985;25:573Y577.
29. Zielinski MD, Park MS, Jenkins D. Appropriate evidence-based practice
guidelines for plasma transfusion would include a high ratio of plasma to
red blood cells based on the available data. Transfusion. 2010;50(12):2762.
891