Article

Blood product use in trauma resuscitation: Plasma deficit versus plasma ratio as predictors of mortality in trauma (CME)

Department of Surgery, University of Maryland, Baltimore, Baltimore, Maryland, United States
Transfusion (Impact Factor: 3.23). 02/2011; 51(9):1925-32. DOI: 10.1111/j.1537-2995.2010.03050.x
Source: PubMed
ABSTRACT
Resuscitation of rapidly bleeding trauma patients with units of red blood cells (RBCs) and plasma given in a 1:1 ratio has been associated with improved outcome. However, demonstration of a benefit is confounded by survivor bias, and past work from our group has been unable to demonstrate a benefit.
We identified 438 adult direct primary trauma admissions at risk for massive transfusion who received 5 or more RBC units in the first 24 hours and had a probability of survival of 0.010 to 0.975. We correlated survival with RBC and plasma use by hour, both as a ratio (units of plasma/units of RBC) and as a plasma deficit (units of RBC - units of plasma) in the group as a whole and among those using 5 to 9 and more than 9 units of RBCs.
Resuscitation was essentially complete in 58.3% by the end of the third hour and 77.9% by the end of the sixth hour. Mortality by hour was significantly associated with worse plasma deficit status in the first 2 hours of resuscitation (p < 0.001 and p < 0.01) but not with plasma ratio. In a subgroup with a Trauma Revised Injury Severity Score of 0.200 to 0.800, early plasma repletion was associated with less blood product use independently of injury severity (p < 0.001).
1) The efficacy of plasma repletion plays out in the first few hours of resuscitation, 2) plasma deficit may be a more sensitive marker of efficacy in some populations, and 3) early plasma repletion appears to prevent some patients from going on to require massive transfusion.

Full-text

Available from: John R Hess
TRANSFUSION PRACTICE
Blood product use in trauma resuscitation: plasma deficit
versus plasma ratio as predictors of mortality in trauma
_3050 1925..1932
Andreas R. de Biasi, Lynn G. Stansbury, Richard P. Dutton, Deborah M. Stein, Thomas M. Scalea,
and John R. Hess
BACKGROUND: Resuscitation of rapidly bleeding
trauma patients with units of red blood cells (RBCs) and
plasma given in a 1:1 ratio has been associated with
improved outcome. However, demonstration of a benefit
is confounded by survivor bias, and past work from our
group has been unable to demonstrate a benefit.
STUDY DESIGN AND METHODS: We identified 438
adult direct primary trauma admissions at risk for
massive transfusion who received 5 or more RBC units
in the first 24 hours and had a probability of survival of
0.010 to 0.975. We correlated survival with RBC and
plasma use by hour, both as a ratio (units of plasma/
units of RBC) and as a plasma deficit (units of
RBC - units of plasma) in the group as a whole and
among those using 5 to 9 and more than 9 units of
RBCs.
RESULTS: Resuscitation was essentially complete in
58.3% by the end of the third hour and 77.9% by the
end of the sixth hour. Mortality by hour was significantly
associated with worse plasma deficit status in the first 2
hours of resuscitation (p < 0.001 and p < 0.01) but not
with plasma ratio. In a subgroup with a Trauma Revised
Injury Severity Score of 0.200 to 0.800, early plasma
repletion was associated with less blood product use
independently of injury severity (p < 0.001).
CONCLUSIONS: 1) The efficacy of plasma repletion
plays out in the first few hours of resuscitation, 2)
plasma deficit may be a more sensitive marker of effi-
cacy in some populations, and 3) early plasma repletion
appears to prevent some patients from going on to
require massive transfusion.
R
esuscitation of rapidly bleeding trauma patients
with units of red blood cells (RBCs) and plasma
given in a 1:1 ratio has been associated with
improved outcome.
1-10
However, this finding is
confounded by the speed at which massively hemorrhag-
ing patients die and the rate at which type-specific plasma
is thawed and delivered to the bedside.
11,12
These two
events interact to create survivor bias, which accounts
for some of the apparent association. In addition, blood
product use in trauma patients is strongly associated with
injury severity. Controlling for this association is difficult,
particularly in retrospective studies dependent on registry
data and the use of one or another of the injury scoring
systems, and can lead to inappropriate attribution of
either adverse or improved outcomes to the effects of
transfusion.
Previous work from our institution has not demon-
strated a survival advantage from the use of 1:1 ratio resus-
citation
13
despite a large patient experience with massive
transfusion
14
and our having been early proponents of this
approach.
15-17
One reason for this finding may be that
when very large transfusions are given, the plasma : RBC
ratio is not a good metric; a patient receiving 30 units of
ABBREVIATIONS: ISS = injury severity score; LOS = length of
stay; RTS = Revised Trauma Score; TRISS = Trauma Revised
Injury Severity Score; TRU = trauma receiving unit.
From the Departments of Anesthesia, Surgery, and Pathology,
University of Maryland School of Medicine, Baltimore,
Maryland.
Address reprint requests to: John R. Hess, MD, MPH, FACP,
FAAAS, University of Mar yland School of Medicine, c/o Blood
Bank, N2W50a, University of Maryland Medical Center, 22
South Greene Street, Baltimore, MD 21201; e-mail: jhess@
umm.edu.
RPD, TMS, and JHR received support from NHLBI Grant
5U01HL072359-07.
Received for publication August 22, 2010; revision received
December 3, 2010, and accepted December 6, 2010.
doi: 10.1111/j.1537-2995.2010.03050.x
TRANSFUSION 2011;51:1925-1932.
Volume 51, September 2011 TRANSFUSION 1925
Page 1
RBCs and 20 units of plasma would have an acceptable
ratio of 2:3, but in reality have a substantial deficit of
plasma. Calculation of overall ratio also fails to capture the
time course of transfusion. The patient who receives 10
units of RBCs followed an hour or so later by 10 units of
plasma may not do as well as one who receives the same
total number of blood products with RBC and plasma
units alternating.
In an attempt to control for survivor bias; to provide
insight into the scale, time course, and outcome of
severely injured, rapidly bleeding civilian patients; and to
characterize in detail our institutional experience with
plasma resuscitation, we reviewed RBC and plasma usage
and sur vival in a 5-year cohort. We had three hypotheses
in this work. First, in rapidly bleeding trauma patients, the
efficacy of plasma repletion in improving survival will be
obvious in the first few hours of resuscitation, when most
deaths from uncontrolled hemorrhage occur. Second, the
deficit of plasma to RBC units may provide a more sensi-
tive marker than does the ratio of plasma to RBC. Third,
early plasma repletion will prevent some patients from
requiring massive transfusion.
MATERIALS AND METHODS
The University of Maryland R. Adams Cowley Shock-
Trauma Center is the primary adult trauma referral center
for a catchment population of roughly 6 million. It admits
5500 patients a year directly from the scene of injury and
has maintained a trauma registry since the mid-1980s.
Details of the scope, staffing, and procedures of this regis-
try have been published elsewhere.
12
Using a database query process, we identified all
primary trauma admissions 18 years or older admitted
directly from the scene of injury from July 1, 2003, through
June 30, 2008, who survived at least 15 minutes after
admission and who received at least 1 unit of uncross-
matched group O RBCs in the trauma receiving unit
(TRU). The use of uncrossmatched group O RBCs is a
marker of the need for urgent transfusion.
18
We do not
have a trauma transfusion protocol but do keep 10 units of
uncrossmatched group O D+ and 2 units of group O D-
RBCs available in the TRU at all times. Since January 27,
2007, 4 units of thawed AB plasma have also been imme-
diately available. Readmissions for prior trauma, non-
trauma admissions, and admissions through the TRU for
other services were excluded.
This preliminary cohort was described by age, sex,
mechanism and type of injury, injury severity score (ISS),
19
probability of survival (using Trauma Revised Injury
Severity Score [TRISS] methodology),
20
hospital length of
stay (LOS), and in-hospital death; these data were then
transferred to a computer database program (Excel,
Microsoft Corp., Redmond, WA). Hourly blood product
issue for each patient over the first 24 hours was deter-
mined from the blood bank data management system
(Cerner Millennium, Cerner Corp., Kansas City, MO) and
timing and cause of death for nonsurvivors was gleaned
from the database (Excel, Microsoft Corp., Redmond, WA)
maintained by the Quality Management office.
We then examined three subgroups of interest: those
patients receiving more than 9 units of RBCs in the first 24
hours of admission (“massive transfusion”) and those who
received 5 to 9 or 1 to 4 units in the same time period. In an
attempt to control for the association between blood
product use and injury severity but also to address the
relative insensitivity of ISS in the assessment of penetrat-
ing injury and bleeding
20
and the age diversity of our
population, we examined plasma and RBC use as well as
mortality in a subgroup of patients who had received at
least 5 units of RBCs in the first 24 hours and whose prob-
ability of sur vival or TRISS was between 0.010 and 0.975.
By eliminating from analysis patients who were either very
likely to die (TRISS < 0.010) or almost certain to survive
(TRISS > 0.975), we hoped to achieve a better focus on the
impact of transfusion therapy.
Statistical analysis
Plasma resuscitation was calculated as plasma ratio (units
of plasma/units of RBCs) and plasma deficit (RBC
units - plasma units) at hourly intervals over the first 24
hours after admission. Overall mean plasma use among
those receiving more than 9 units of RBCs in the first 24
hours was 4 units, so we defined “low deficit” as 2 or fewer
units and “high deficit as more than 6 units. Plasma ratio
was calculated as a decimal and defined as greater than
0.66 (“better” than 2:3), 0.66 to 0.34 (2:3 to “better than
1:3), and less than 0.34 (1:3 or less), in keeping with previ-
ously published work from other centers.
7,8
A t test (Excel, Microsoft Corp.) and analysis of vari-
ance (ANOVA)
21
were used to assess differences in means
(age, ISS, TRISS, blood product use). Chi square analyses
were used to assess differences in categorical variables
(plasma deficit, mortality).
22
Probability values for results
being due to chance (p) of 0.05 or less were considered
significant. Corrections for repeat measures were not used
in this exploratory study. p values of more than one
decimal place less than 0.01 are shown as less than 0.001.
RESULTS
Demographic and other summary information
A total of 844 primary trauma admission patients met
the basic inclusion criterion of having received 1 unit of
uncrossmatched group O RBC in the first hour of care.
This group was 79% male and had a mean age of 39 years,
a mean ISS of 32, and probability of survival of 0.639. They
were in the trauma center for a mean of 12 days. Injuries
were 53% vehicle related, 21% gunshot wounds, 16% stab-
DE BIASI ET AL.
1926 TRANSFUSION Volume 51, September 2011
Page 2
bings, 6% falls, 4% other. A total of 301 of these patients
died, 49% from uncontrolled hemorr hage, 33% from brain
injury, and 9% from multiple organ failure.
Table 1 summarizes RBC and plasma transfusion in
the first 24 hours among those on whom complete infor-
mation was available. Of those 835 individuals, 320 (38.3%)
used 1 to 4 units in the first 24 hours, 208 (24.9%) used 5 to
9 units, and 307 (36.8%) used 10 units or more in that same
period. Mean RBC and plasma usage was 10 and 7 units,
respectively, and mean product usage in the three sub-
groups increased proportionately. In each RBC use group,
some patients received no plasma at all (Table 2); in the
1-to-4-units group this proportion was almost 70% (217/
320). Age and injury severity (reflected in mortality, LOS,
time to death, and both trauma scores) var ied significantly
but not always progressively through the three groups. ISS
and LOS did vary progressively. The difference in age
between the three groups was attributable to the relative
youth of the 1 to 4 and more than 9 units groups and most
of the difference in time to death was attributable to the
relatively short time t o death in the 1-to-4-units group.
(The calculations regarding attribution are not shown.)
The significant differences in mortality between the three
groups are largely related to worse probability of survival/
TRISS in the massive transfusion (>9 units) group.
Blood product use
The above data suggested that the group of patients who
received 1 to 4 units of RBC in the first 24 hours, despite
having been identified by the transfusion of at least 1 unit
of uncrossmatched RBCs in the TRU, represented too het-
erogeneous a population and had too low a total RBC and
plasma use to support realistic analysis of the efficacy of
plasma resuscitation. Therefore, this group was not ana-
lyzed fur ther.
The next stage of analysis focused on those who
received 5 or more units of RBCs in the first 24 hours and
whose predicted probability of survival/TRISS was 0.010
to 0.975.
Timing of plasma repletion
Figure 1 and Tables 2 and 3 summarize RBC and plasma
use in this cohort. Of the 393 patients who received any
plasma, 130 received 5 to 9 units of RBCs in the first 24
hours with 32 deaths (24.6%), and 263 received more than
9 RBC units with 125 deaths (47.5%, p < 0.001). More than
half (58.3%) of these patients received more than two-
thirds of their total plasma replacement before the end
of the third hour of resuscitation. Almost 80% (77.9%)
received more than two-thirds of their total plasma
TABLE 1. Patterns of RBC usage in primary trauma admission patients who received at least 1 unit of
uncrossmatched RBCs in the first 24 hours of resuscitation and among whom complete data were available*
Patient characteristics
RBC use (units) in first 24 hours
1to4 5to9 >9 units RBC All patients p value†
Number of patients (%) 320 (38.3) 208 (24.9) 307 (36.8) 835
Units used in first 24 hr
RBCs 2 (1) 7 (1) 21 (15) 10 (12)
Plasma 1 (2) 4 (3) 15 (13) 7 (10)
Age 37.6 (19.1) 41 (20) 37.3 (18.8) 39.5 (19.2) 0.01
ISS 25 (17) 32 (15) 37 (15) 32 (16) <0.001
Probability of survival‡ 0.695 (0.370) 0.704 (0.330) 0.577 (0.370) 0.637 (0.366) <0.001
LOS (days) 7.9 (11.4) 12.5 (13.7) 16.9 (23.1) 12.4 (17.5) <0.001
Deaths (%) 99 (30.9) 54 (25.9) 148 (48.2) 301 (36.1) <0.001
Mean time to death (hr) 37.3 (169.8) 76.2 (154.9) 97.1 (287.5) 74.2 (235.3) 0.002
* Values are presented as mean (SD) unless otherwise specified.
Probability of no true difference between plasma status groups by ANOVA F statistic for continuous and chi square for categorical
variables.
Probability of survival calculated as the TRISS.
TABLE 2. RBC and plasma transfusion in the first 24 hours among 438 primary trauma patients who received at
least 5 units of RBCs in the first 24 hours and whose probability of survival score (TRISS) was 0.010 to 0.975
Units of RBCs used in first 24 hr Number
Any plasma No plasma
Lived Died (%)* All Lived Died (%)† All
5-9 169 98 32 (24.6) 130 19 20 (51.3) 39
>9 269 138 125 (47.5) 263 1 5 (83.3) 6
Totals 438 236 257 393 20 25 45
* Probability of no difference in mortality between RBC usage groups 0.001.
Probability of no difference in mortality between RBC usage groups = 0.1.
PLASMA USE IN TRAUMA RESUSCITATION
Volume 51, September 2011 TRANSFUSION 1927
Page 3
replacement before the end of the sixth hour. In the
group as a whole, and in the two subgroups, proportional
mortality was less among those who received more
plasma after 3 or 6 hours, but the differences were not
significant. Probability of survival/TRISS also appeared
more favorable among those who got additional plasma
after 3 hours and in the massive transfusion group—this
difference was significant (p = 0.02). Median times to
death were shorter in all the groups who achieved high
ratios of plasma early.
Fig. 1. Mean hourly usage of units of RBC and plasma among patients with probability of survival scores (TRISS) between 0.010
and 0.975 and categorized as (A) all patients receiving at least 5 units of RBCs in the first 24 hours, (B) patients receiving 5 to 9
units of RBCs in the first 24 hours, and (C) patients receiving more than 9 units of RBCs in the first 24 hours. (
) RBCs; ( ) plasma.
TABLE 3. Timing of plasma transfusion, probability of survival, mortality, and time to death
Patient outcomes
Plasma repletion by third hour Plasma repletion by sixth hour
>2/3 all units <2/3 all units p value* >2/3 all units <2/3 all units p value*
All patients, n = 393 (%) 229 (58.3) 164 (41.7) 306 (77.9) 87 (22.1)
Probability of survival (SD) 0.577 (0.359) 0.625 (0.317) 0.2 0.578 (0.343) 0.666 (0.354) 0.03
Deaths (%) 97 (42.4) 60 (36.6) 0.3 129 (42.2) 28 (32.2) 0.09
Median time to death (hr) 5.7 53.8 7.5 58.1
5-9 units of RBCs, n = 130 (%) 81 (62.3) 49 (37.7) 105 (80.8) 25 (19.2)
Probability of survival (SD)† 0.659 (0.338) 0.609 (0.280) 0.4 0.633 (0.333) 0.673 (0.241) 0.6
Deaths (%) 19 (23.5) 13 (26.5) 0.7 28 (26.7) 4 (16) 0.3
Median time to death (hr) 15.1 44.1 25 73
>9 units of RBCs, n = 263 (%) 148 (56.3) 115 (43.7) 201 (76.4) 62 (23.6)
Probability of survival (SD) 0.533 (0.364) 0.632 (0.332) 0.02 0.549 (0.365) 0.663 (0.297) 0.03
Deaths (%) 78 (52.7) 47 (40.9) 0.06 101 (50.3) 24 (38.7) 0.1
Median time to death (hr) 5.2 55.3 6.4 58.1
* Probability of no true difference between those with minimal versus those with substantial plasma change at time interval by t test for con-
tinuous and chi square for categorical variables.
Probability of survival: TRISS.
DE BIASI ET AL.
1928 TRANSFUSION Volume 51, September 2011
Page 4
Plasma deficit versus plasma ratio as predictors
of mortality
The three panels of Fig. 2 show mortality (number of
deaths in the stated inter val divided by number of those
surviving to that interval) in three plasma deficit status
categories at intervals over the first 24 hours. Figure 2A
includes all 438 patients; Fig. 2B, the 169 patients who
received 5 to 9 units of RBC in the first 24 hours; and
Fig. 2C, the 269 massive transfusion patients, those who
got more than 9 units in that period. Overall and in the
massive transfusion group (Figs. 2A and 2C), high, moder-
ate, and low deficit status are associated, respectively, with
high, midrange, and lower mortality in the first hour of
resuscitation (p < 0.001). By the end of the second hour of
resuscitation, this association is fading in the overall
group (Fig. 2A, p = 0.01) and has disappeared in the
massive transfusion group (Fig. 2C, p = 0.3).
The 5 to 9 RBC units group (Fig. 2B) presents quite a
distinct picture. As noted above, overall mortality is sig-
nificantly less in this group, and this difference is clearly
visible by the end of the first hour. Mortality in the high-
deficit-status category varies markedly in the first 3 hours
but after 3 hours, no more deaths are recorded in this
deficit category. Mortality in the moderate-deficit cat-
egory is elevated in the first hour, approaching signifi-
cance (0.06), and decreases thereafter, reprising the
gradient appearance of the plasma deficit categories
across time in the overall and more than 9 units RBC
groups. Mortality in the low-deficit category in this 5 to
9 RBC units group remains essentially unchanged at
approximately 20% throughout the 24-hour period but by
12 and 24 hours is significantly greater than in either the
midrange or high-deficit categories (p = 0.03 and p = 0.02,
respectively).
The two sections of Table 4 examine plasma deficit
and plasma ratio as predictors of mortality. At 24 hours in
the overall group, plasma ratio did not distinguish mortal-
ity (p = 0.5). In contrast, plasma deficit category in these
patients at 24 hours was clearly associated with mortality
(p 0.001). However, it was also clearly associated with
probability of survival/TRISS (p = 0.001); that is, those
with a high deficit had significantly higher mortality but
also significantly worse probability of survival/TRISS. At
24 hours into resuscitation in the 5 to 9 RBC units group,
neither deficit status nor ratio predicted mortality. In the
massive transfusion group at 24 hours, as in the overall
group, worse plasma deficit status was associated with
mortality (p = 0.007) and with TRISS (p = 0.01), but plasma
ratio was not associated with either mortality or TRISS
(p = 0.4 for both). Likewise, at 3 hours into resuscitation,
ratio was not associated with mortality in the combined,
the 5 to 9 RBC units, or the more than 9 RBC units groups
(p = 0.2, p = 0.5, and p = 0.4, respectively), whereas
worsening plasma deficit was clearly associated with mor-
tality in these same groupings (p < 0.001, p = 0.03, and
p = 0.003, respectively).
Early plasma repletion status as a predictor of
RBC use at 24 hours
Low-deficit status at 3 hours did not independently
predict use of less than 10 units of RBCs at 24 hours (data
not shown). However, when we repeated this analysis
among a further subgroup with a probability of survival/
TRISS between 0.200 and 0.800 (SD, <0.200; mortality,
35.1%-63.6%) an effect emerged. In these patients, low-
deficit status at 3 hours did predict the use of less than 10
units of RBCs at 24 hours (Table 5) as well as lower mor-
tality (p = 0.02), independent of probability of survival
(p = 0.3 for likelihood of true difference between TRISS
among the three deficit status categories).
DISCUSSION
Our trauma patient cohort was selected for receiving at
least 1 unit of uncrossmatched group O RBCs in the first
hour of care and broken down into groups and categories
based on specific subsequent patterns of RBC and plasma
Fig. 2. (A) Proportional mortality among patients who had
probability of survival scores (TRISS) between 0.010 and 0.975
and who survived to specific time points, grouped by deficit
status at that time point as low deficit (
), 0 to 2 units of
plasma; moderate deficit (
), 3 to 6 units of plasma; high
deficit ( ), 6 or more units of plasma and categorized as (A) all
patients receiving at least 5 units of RBCs in the first 24 hours,
(B) patients receiving 5 to 9 units of RBCs in the first 24 hours,
and (C) patients receiving more than 9 units of RBCs in the
first 24 hours.
PLASMA USE IN TRAUMA RESUSCITATION
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Page 5
use. The cohort was drawn from a civilian population of
trauma patients who often require massive transfusion:
young, predominantly male, and with predominantly
blunt injuries but with a slightly higher proportion of pen-
etrating injuries than would be anticipated.
12
However, the
cohort also contains a sizeable group of older female
patients admitted after motor vehicle–associated injury
(including pedestrians struck by motor vehicles) or after
falls. These new trauma demographics” are the probable
explanation for the significantly older mean age of the
subgroup who received 5 to 9 units of RBCs in the first 24
hours. They also require consideration when choosing
scoring systems to compare injury severity.
Overall mortality among those undergoing massive
transfusion at our center has improved somewhat since
2000
14
but remains very high. Likewise, our patterns of
plasma use have changed somewhat with the availability
of thawed AB plasma in our TRU, but overall, our center
has been in the vanguard of advocating 1:1 plasma to RBC
repletion in rapidly bleeding trauma patients for more
than a decade, which we assume is part of the explanation
for our past inability to demonstrate strong differences in
mortality between massively transfused patients from
more recent and historical control groups.
11,13
Because we developed our study groups from retro-
spective trauma registry data derived routinely as an insti-
tutional process rather than from the dedicated activity of
an independent prospective cohort or case-control study,
we chose to limit analyses to those descriptive statistics
and univariate analytic procedures that we felt best repre-
sented the degree of inference legitimately possible from
these data. We specifically chose not to apply Cox
TABLE 4. Plasma deficit (units of RBCs transfused minus units of plasma transfused) and ratio of plasma
repletion (expressed as units of plasma divided by units of RBCs) as predictors of mortality in rapidly bleeding
trauma patients
Patient characteristics
Deficit status Ratio status
Low 0-2 3-6 High > 6 p value* Good > 0.66 0.66-0.34 Poor < 0.34 p value
A. At 24 hr into resuscitation
All patients (%)† 184 (40.0) 148 (33.8) 106 (24.2) 249 (56.9) 111 (25.3) 78 (17.8)
TRISS, mean (SD)‡ 0.658 (0.32) 0.571 (0.75) 0.501 (0.36) 0.001 0.625 (0.34) 0.537 (0.35) 0.559 (0.36) 0.06
Deaths, number (%) 59 (32.1) 62 (41.9) 61 (57.5) <0.001 97 (39) 50 (45.1) 35 (44.9%) 0.5
5 to 9 units (%) 83 (49.1) 71 (42.0) 15 (8.9) 80 (43.3) 36 (21.3) 53 (31.4)
TRISS, mean (SD) 0.659 (0.31) 0.581 (0.34) 0.586 (0.40) 0.3 0.658 (0.31) 0.580 (0.32) 0.589 (0.37) 0.1
Deaths, number (%) 21 (25.3) 25 (32.2) 6 (40.0) 0.3 21 (26.3) 9 (25) 22 (41.5) 0.1
>9 units (%) 101 (37.6) 77 (28.6) 91 (33.8) 169 (62.8) 75 (27.9) 25 (9.3)
TRISS, mean (SD) 0.658 (0.34) 0.561 (0.36) 0.492 (0.35) 0.01 0.609 (0.35) 0.519 (0.35) 0.496 (0.34) 0.4
Deaths, number (%) 38 (37.6) 37 (48.1) 55 (60.4) 0.007 76 (45) 41 (54.7) 13 (52) 0.4
B. At 3 hr into resuscitation
All patients (%) 176 (40.2) 170 (38.8) 92 (21) 202 117 119
TRISS, mean (SD)‡ 0.667 (0.32) 0.561 (0.35) 0.500 (0.36) <0.001 0.622 (0.35) 0.526 (0.35) 0.602 (0.34) 0.05
Deaths, number (%) 54 (30.7) 72 (42.4) 56 (60.9) 0.001 80 (39.6) 57 (48.7) 45 (37.8) 0.2
5 to 9 units (%) 87 (51.5) 68 (40.2) 14 (8.3) 63 32 74
TRISS, mean (SD) 0.678 (0.31) 0.562 (0.34) 0.537 (0.40) 0.06 0.674 (0.33) 0.555 0.602 0.2
Deaths, number (%) 19 (21.8) 27 (39.7) 6 (42.9) 0.03 16 (25.4) 11 (34.4) 25 (33.8) 0.5
>9 units (%) 89 (33.1) 102 (37.9) 78 (29) 139 85 45
TRISS, mean (SD) 0.656 (0.33) 0.560 (0.35) 0.493 (0.36) 0.01 0.598 (0.35) 0.514 (0.35) 0.603 (0.34) 0.2
Deaths, number (%) 35 (39.3) 45 (44.1) 50 (64.1) 0.003 64 (46.0) 46 (54.1) 20 (44.4) 0.4
* Probability of no true difference between plasma status groups by ANOVA F statistic for continuous and chi square for categorical variables.
All = 5 or more units of RBCs at 24 hours into resuscitation.
TRISS: probability of survival.
TABLE 5. Plasma deficit (units of RBCs transfused minus units of plasma transfused) at 3 hours as a predictor
of RBC use by 24 hours into resuscitation in a subgroup of 154 rapidly bleeding patients with probability of
survival (TRISS) between 0.200 and 0.800
Patient characteristics Low deficit Moderate deficit High deficit p value*
Patients, number (%) 57 64 33
Use at 24 hr, mean (SD)
RBCs 9.9 (4.4) 12.6 (8.5) 23.8 (19.3) <0.001
Plasma 9.4 (5.5) 8.3 (8.1) 12.6 (16.9) <0.001
Probability of survival† 0.537 (0.180) 0.511 (0.181) 0.474 (0.180) 0.3
Deaths (%) 20 (35.1) 25 (39) 21 (63.6) 0.02
* Probability of no true difference between plasma status groups by ANOVA F statistic for continuous and chi square for categorical
variables.
Probability of survival: TRISS.
DE BIASI ET AL.
1930 TRANSFUSION Volume 51, September 2011
Page 6
regression analysis to our data because the usefulness of
the resulting inferences is highly dependent on the inde-
pendence of the variables. Given both the general nature
of registries as data repositories and the intense correla-
tion of blood use with injury severity, we felt that a more
cautious approach to analysis was justified.
Our decision to use probability of survival or TRISS,
rather than the more conventional ISS, as our principal
means of attempting to control for injury severity emerges
from this same dependence on registry data. Our registry
routinely provides Revised Trauma Score (RTS), ISS, and
TRISS. The RTS is a physiologic score derived from the
Glasgow Coma Scale, systolic blood pressure, and respira-
tory rate at admission to the trauma center but does not
include any anatomic assessment or factors for age or
mechanism of injury. The ISS is a sum-of-squares weight-
ing of injury severity in the three worst injured of six body
regions but allows only one score per body region and
incorporates only anatomic injury assessment. The TRISS
method for assessing probability of survival combines the
RTS and ISS with additional factors for age and blunt
versus penetrating injury and thus incorporates the limi-
tations and problems associated with both RTS and ISS.
23
With that acknowledged, among the scoring systems
available to us, we felt that probability of survival/TRISS
best reflected the diversity of anatomic and physiologic
injury in our population and would be the best tool to
tease out the confounding effects of injury severity on
our data.
Overall, our study illustrates very clearly the problems
associated with trying to draw conclusions based on ret-
rospective data and inclusion criteria and outcomes at 24
hours in massively bleeding patients. The problem of sur-
vivor bias in such studies was elegantly displayed by
Snyder and colleagues
24
from the University of Alabama.
In that study, the authors tracked massively transfused
patients through low- to high-plasma-repletion groups
over the course of the first 24 hours of treatment and dem-
onstrated that what looks like decreased mortality among
those with better plasma-to-RBC replacement ratios is
just a matter of surviving long enough to move from a
low-repletion group (the majority of patients in the early
hours after admission) into higher-repletion groups.
The Alabama study is also interesting in that it pro-
vides the key both to our inability to demonstrate
decreased mortality on the basis of ratio of plasma reple-
tion and on our success in demonstrating decreased mor-
tality on the basis of deficit. In the Alabama study, the
median time to first plasma replacement was 93 minutes.
Our data, which also follow a group of massively bleeding
patients through the early hours of resuscitation, show a
different aspect of the survivor bias issue in a situation
where median time to first plasma replacement was less
than half that observed by Snyder and colleagues. In a
situation where massively bleeding patients begin aggres-
sive RBC and plasma resuscitation within moments of
admission, as they do at our center, the movement of
patients from a low-ratio (or high-deficit) group into a
mid- or high-ratio/low-deficit group happens quickly. The
people who remain in the low-ratio/high-deficit group at
the end of the second and third hours are to a large extent
not those who got left behind but rather are those who
could survive without aggressive plasma replacement.
The striking disappearance, in Fig. 2B, after the third hour
of resuscitation, of mortality associated with high-deficit
status is a clear illustration of this.
On the other hand, at our center, massively bleeding
patients are not only recognized immediately and cor-
rectly (as judged by the close association with the subse-
quently derived TRISS), but their plasma use status is
immediately differentiated by the transfusion of 10 to 12
units of uncrossmatched group O RBCs and 4 units of
thawed AB plasma, thereby automatically thrusting them
into a moderate- to high-deficit status. The results shown
in Table 5 suggest that at least in some severely but not
overwhelmingly injured patients, early 1:1 repletion of
plasma may have decreased mortality and prevented the
need for massive transfusion. Acknowledging their ques-
tionable epidemiologic legitimacy as a retrofitted analysis,
the results in Table 5 nevertheless support the advocacy of
some major trauma centers, including Vanderbilt and the
University of Copenhagen, for protocol-based preemptive
trauma transfusion packages at roughly 1:1 repletion
levels that, in the experience of those groups, have not
only improved mortality but also appear to decrease RBC
and plasma use.
8,9
SUMMARY AND CONCLUSIONS
The recent explosion of clinical studies and expert com-
mentary on plasma repletion in trauma patients with
massive transfusion has tended to fall out into two general
patterns. Most clinical studies show benefit from early
repletion approaching 1:1 and are confounded by survival
bias, and most expert opinion seeks to define, one way or
another, an optimal replacement ratio. Here we present a
large 5-year retrospective review of blood products issued
and mortality from a large center and draw somewhat
different inferences. First, the effects of plasma repletion
play out in the first 2 to 3 hours of care for massively
bleeding individuals and plasma deficit rather than
unit ratios may be a more indicative measure. Second,
the achievable differences in outcome are real but
far less dramatic than suggested in most earlier reports on
plasma repletion. Finally, although we would like to see
randomized controlled trials, what is probably more
important is a refocus of research into the clinical predic-
tors that will allow clinicians on the front line to know who
is going to need early plasma repletion and who will do
well without it.
PLASMA USE IN TRAUMA RESUSCITATION
Volume 51, September 2011 TRANSFUSION 1931
Page 7
CONFLICT OF INTEREST
The authors report no financial conflict of interest with the
content of this manuscript.
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DE BIASI ET AL.
1932 TRANSFUSION Volume 51, September 2011
Page 8
  • Source
    • "An alternative strategy is " 1:1, " which calls for early FFP transfusion in patients predicted to require MT, such that the FFP:packed red blood cell (PRBC) ratio approaches approximately 1:1 to 2 from the start [5]. Many observational studies comparing low (b 1:2) vs high (≥ 1:2) FFP:PRBC ratio [6] or deficit [7] have shown that the use of equivalent units of FFP and PRBC was associated with improved survival. How to transfuse with platelets is almost as controversial. "
    [Show abstract] [Hide abstract] ABSTRACT: Traditional transfusion guidelines suggest that fresh frozen plasma (FFP) should be given based on laboratory or clinical evidence of coagulopathy or acute loss of 1 blood volume. This approach tends to result in a significant lag time between the first units of erythrocytes and FFP in trauma requiring massive transfusion. In severe trauma, observational studies have found an association between increased survival and aggressive use of FFP and platelets such that FFP:platelet:erythrocyte ratio approaches 1:1:1 to 2 from the first units of erythrocytes given. There are considerable concerns over either approach, and no randomized controlled trials have been published comparing the 2 approaches. Nowadays, trauma clinicans are incorporating the strenghts of both approaches and are no longer treating them as a dichotomy. Specifically, "1:1:1" proponents have devised 1:1:1 activation criteria to minimize unnecessary FFP and platelet transfusion and are prepared to deactivate the protocol as soon as patient is stabilized. Similarly, 1:1:1 skeptics are more mindful of the need to be proactive about trauma coagulopathy and the inherent delays in FFP administration in trauma patients. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Oct 2015 · The American journal of emergency medicine
  • Source
    • "Similarly, Teixeira et al. [18] conducted a 6-year retrospective study to analyze the effect of plasma transfusion (≥10 PRBC) among massively transfused patients and observed a survival benefit for higher FFP: PRBC ratio during initial 24 h. De Baisi et al. [25] reported that mortality was significantly correlated with worse plasma deficit during the initial 2 h of resuscitation but no association with plasma ratio was reported. A similar association was observed among the massive transfusion group at 24 h. "
    [Show abstract] [Hide abstract] ABSTRACT: Objective: We aimed to evaluate whether early administration of high plasma to red blood cells ratios influences outcomes in injured patients who received massive transfusion protocol (MTP). Methods: A retrospective analysis was conducted at the only level 1 national trauma center in Qatar for all adult patients(≥18 years old) who received MTP (≥10 units) of packed red blood cell (PRBC) during the initial 24 h post traumatic injury. Data were analyzed with respect to FFB:PRBC ratio [(high ≥ 1:1.5) (HMTP) vs. (low < 1:1.5) (LMTP)] given at the first 4 h post-injury and also between (>4 and 24 h). Mortality, multiorgan failure (MOF) and infectious complications were studied as well. Results: During the study period, a total of 4864 trauma patients were admitted to the hospital, 1.6 % (n = 77) of them met the inclusion criteria. Both groups were comparable with respect to initial pH, international normalized ratio, injury severity score, revised trauma score and development of infectious complications. However, HMTP was associated with lower crude mortality (41.9 vs. 78.3 %, p = 0.001) and lower rate of MOF (48.4 vs. 87.0 %, p = 0.001). The number of deaths was 3 times higher in LMTP in comparison to HMTP within the first 30 days (36 vs. 13 cases). The majority of deaths occurred within the first 24 h (80.5 % in LMTP and 69 % in HMTP) and particularly within the first 6 h (55 vs. 46 %). Conclusions: Aggressive attainment of high FFP/PRBC ratios as early as 4 h post-injury can substantially improve outcomes in trauma patients.
    Full-text · Article · Aug 2015 · World Journal of Emergency Surgery
  • Source
    • "Our Level 1 trauma center admits more than 5000 trauma patients annually directly from the scene of injury, of whom 5–8 % will require transfusion, and 2–3 % massive transfusion (MT), defined in this analysis as [4 units of packed red blood cells in \4 h. Most transfusions occur within the first few hours of admission and often occur as un-crossmatched universal donor group O blood on an emergency basis111213. This study is a planned subgroup study analysis as part of the ongoing resuscitation vital signs data-gathering project titled Oximetry and Non-Invasive Predictors Of Intervention Need after Trauma (ONPOINT) at the University of Maryland School of Medicine, R Adams Cowley Shock Trauma Center. "
    [Show abstract] [Hide abstract] ABSTRACT: Early detection of hemorrhagic shock is required to facilitate prompt coordination of blood component therapy delivery to the bedside and to expedite performance of lifesaving interventions. Standard physical findings and vital signs are difficult to measure during the acute resuscitation stage, and these measures are often inaccurate until patients deteriorate to a state of decompensated shock. The aim of this study is to examine a severely injured trauma patient population to determine whether a noninvasive SpHb monitor can predict the need for urgent blood transfusion (universal donor or additional urgent blood transfusion) during the first 12 h of trauma patient resuscitation. We hypothesize that trends in continuous SpHb, combined with easily derived patient-specific factors, can identify the immediate need for transfusion in trauma patients. Subjects were enrolled if directly admitted to the trauma center, >17 years of age, and with a shock index (heart rate/systolic blood pressure) >0.62. Upon admission, a Masimo Radical-7 co-oximeter sensor (Masimo Corporation, Irvine, CA) was applied, providing measurement of continuous non-invasive hemoglobin (SpHb) levels. Blood was drawn and hemoglobin concentration analyzed and conventional pulse oximetry photopletysmograph signals were continuously recorded. Demographic information and both prehospital and admission vital signs were collected. The primary outcome was transfusion of at least one unit of packed red blood cells within 24 h of admission. Eight regression models (C1-C8) were evaluated for the prediction of blood use by comparing area under receiver operating curve (AUROC) at different time intervals after admission. 711 subjects had continuous vital signs waveforms available, to include heart rate (HR), SpHb and SpO2 trends. When SpHb was monitored for 15 min, SpHb did not increase AUROC for prediction of transfusion. The highest ROC was recorded for model C8 (age, sex, prehospital shock index, admission HR, SpHb and SpO2) for the prediction of blood products within the first 3 h of admission. When data from 15 min of continuous monitoring were analyzed, significant improvement in AUROC occurred as more variables were added to the model; however, the addition of SpHb to any of the models did not improve AUROC significantly for prediction of blood use within the first 3 h of admission in comparison to analysis of conventional oximetry features. The results demonstrate that SpHb monitoring, accompanied by continuous vital signs data and adjusted for age and sex, has good accuracy for the prediction of need for transfusion; however, as an independent variable, SpHb did not enhance predictive models in comparison to use of features extracted from conventional pulse oximetry. Nor was shock index better than conventional oximetry at discriminating hemorrhaging and prediction of casualties receiving blood. In this population of trauma patients, noninvasive SpHb monitoring, including both trends and absolute values, did not enhance the ability to predict the need for blood transfusion.
    Full-text · Article · Mar 2015 · Journal of Clinical Monitoring and Computing
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