Abstract
Objectives
To expedite delivery and transfusion of plasma through implementation of an emergency department (TP-ED) protocol.
Design
Retrospective cohort study
Setting
ACS-verified level 1 trauma center
Patients
Protocol was initiated February 2010, placing four units of AB plasma in the ED. All trauma patients admitted eight months before (TP-BB) and after implementing the TP-ED protocol. Patients were included if they received at least one unit of RBC and one unit of plasma in the first six hours after ED admission.
Main Outcome Measures
Primary outcome was time to first unit of plasma. Secondary outcomes included 24-hour blood use and 24-hour and 30-day mortality.
Results
294 patients met study criteria (130 TP-BB, 164 TP-ED). While demographics were similar, TP-ED patients had greater anatomic injury (median ISS 18 vs. 25, p=0.018) and more physiological disturbances (median w-RTS 6.81 vs. 3.83, p=0.008). TP-ED had shorter time to first plasma transfusion (83 min vs. 42 min, p<0.001). TP-ED was associated with a reduction in 24-hour transfusion of RBC (p=0.036), plasma (p=0.044), and platelets (p<0.001). Logistic regression identified TP-ED as an independent predictor of decreased 30-day mortality (OR 0.43, 95% C.I. 0.194–0.956, p=0.038).
Conclusions
We demonstrated that implementation of a ED-TP protocol expedites transfusion of plasma to severely injured patients. This approach is associated with a reduction in overall blood product use and a 60% decreased odds in 30-day mortality.
Keywords: plasma, thawed, transfusion and trauma
BACKGROUND
Hemorrhage is the leading cause of death within the first hour of arrival to a trauma center, and one of the leading overall causes of death in trauma patients (30–40%).1,2 Of these hemorrhagic deaths, patients with a trauma induced coagulopathy account for more than 50% and its presence correlated with a three-fold increase in mortality.3–5 Upon arrival to trauma centers, at least 25% of severely injured patients are already coagulopathic and thrombocytopenic.4,6 When this group of patients receives effective higher ratios of plasma and platelets, a dramatic reduction in mortality has been observed.7 These findings have lead to the evolution and promotion of Damage Control Resuscitation (DCR).8 DCR aims to rapidly address hemorrhage and coagulopathy through permissive hypotension, minimizing early crystalloid use, and immediate delivery of high ratios of plasma to red blood cells (RBC).3
Early transfusion of RBC is already a core element of trauma resuscitation, with most trauma centers storing uncross-matched RBC in their emergency departments (ED). However, few centers store plasma in their ED, making it difficult to achieve high plasma: RBC ratios early in the resuscitation of the severely injured patient. By only delivering RBC and crystalloids in the ED, low plasma: RBC ratios are observed, which are associated with worsening of coagulopathy and increased mortality.3,9
To expedite the delivery of higher plasma: RBC ratios, many trauma centers have implemented massive transfusion (MT) protocols.10–13 Trauma centers that have implemented such protocols have reported improved survival following implementation. These outcomes appear to be closely correlated with the early achievement of higher ratios of plasma: RBC.11 While these protocols vary extensively from one trauma center to another, those centers reporting the most dramatic changes in survival are those who have implemented concurrent thawed plasma (TP) programs.11,14,15 In addition to an associated reduction in mortality, centers that developed TP programs concurrent with their MT protocols have demonstrated reductions in time to first plasma transfusion and reduction in the overall number of blood and components transfused.11,14,15 Prior to having TP readily available for release, Blood Banks had to thaw their frozen plasma inventories (FFP or FP24) before it could be packaged and delivered to the trauma team. Such strategies easily add up to a thirty-minute delay on the first unit of plasma transfused.9
We have had TP stored in our Blood Bank for over twenty years, and have advocated for the early use of plasma as a primary resuscitation product for patients in hemorrhagic shock.8,12,16 However, a recent Performance Improvement audit noted that while physicians were requesting and ordering plasma early (through activation of our MT protocol), actual transfusion of the first unit of plasma in MT protocol patients was often delayed by 60 minutes or more. To expedite delivery and transfusion of plasma, we recently implemented an Emergency Department (ED) thawed plasma program by placing four units of thawed AB plasma in the ED emergency release blood refrigerator. We hypothesized that having TP in the ED would (1) reduce time to first plasma transfusion, (2) reduce 24-hour blood product use, and (3) reduce mortality rates.
METHODS
Study setting
The University of Texas Health Science Center-Houston and the Memorial Hermann Hospital Institutional Review Boards approved this study. Memorial Hermann Hospital is an American College of Surgeons verified level I trauma center that is the primary teaching hospital for the University of Texas Health Science Center. Memorial Hermann is one of only two level-1 trauma centers in Houston, Texas, the fourth largest city in the United States. The hospital is an 800-bed facility within Texas Medical City and is home to the John S. Dunn Helistop, the busiest heliport in the United States for its size. The trauma center admits well over 5,000 trauma patients annually with the most severely injured cared for in the 25-bed Shock-Trauma ICU (STICU).
When clinically indicated, the Massive Transfusion Protocol (MTP) is activated. To do so, the Trauma Attending contacts the MHH Blood Bank, states their name, the patient’s Stat Name, patient’s gender and approximate age and that they would like to activate the MTP. A type and screen is sent immediately to the Blood Bank. The ED tech delivers the type and screen and retrieves the first cooler of blood (six group O RBC and 6 AB thawed plasma) and one package of aphaeresis platelets. The products are delivered to the patient’s bedside (ED, OR or IR). As soon as typing is complete, type specific products are released for subsequent coolers. The second and subsequent coolers contain 6 type specific RBC and 6 type specific plasma units along with one aphaeresis platelet. Once hemostasis declared by surgeon and anesthesiologist, the MTP is discontinued and products are delivered based on clinical and laboratory evaluation.
Beginning 02/01/10, our institution began placing thawed plasma in the ED (ED-TP). Two (2) jumbo group AB thawed plasma units were added to the ED refrigerator (at 1–6° C) to accompany the four (4) group O-negative RBC already kept there. Such availability allows for the immediate transfusion of products in a 1:1 ratio of plasma: RBC. The products are evaluated by Blood Bank staff each shift, assessing whether the products have reached their shelf life (or will in the next 24 hours). Those TP units that are 96 hours post-thaw at the time of inspection are repatriated to the Blood Bank to avoid expiration (120 hour post-thaw). As units are transfused, the Blood Bank is notified by telephone and these products are replaced immediately. Prior to February 2010, all thawed plasma products were kept in the Blood Bank (approximately 20–30 units of various blood groups). Our Blood Bank is on the same floor as our ED and is less than a three (3) minute round trip. All TP is derived from fresh frozen plasma. All blood products are provided by Gulf Coast Regional Blood Center. In the ED refrigerator, we store only jumbo (group AB) TP units and these are from male only donors. With respect to those units kept in the BB, all group A and O plasma units are male-only donors. However, group B and AB are from both male and female donors, due to the limited number of products acquired from these less common blood types.
Selection of Participants
Using the institution’s Trauma Registry of the American College of Surgeons (TRACS) database, we evaluated all adult trauma patients admitted between June 2009 and August 2010 who: (1) arrived directly from the scene, (2) were the institution’s highest level trauma activation, and (3) received at least one unit of RBC and one unit of plasma in the first six hours following admission. Patients who were <18 years of age, had burn wounds greater than 20% total body surface area, or who died within 30 minutes of arrival were excluded. Patients were then divided into two groups: those admitted eight (8) months before (TP-BB) and eight (8) months after implementing TP location change (TP-ED).
Definitions and Outcomes
We evaluated standard demographic data including age, gender, race, and mechanism of injury. As well, injury scores such as initial Glasgow Coma Scale (GCS) score, weighted Revised Trauma Score (RTS), and Injury Severity Scale (ISS) score were collected. Weighted RTS is a physiology-based scoring system that incorporates initial GCS, systolic blood pressure, and respiratory rate.17 These values are then coded and weighted and range from 4 (normal) to 0 (poor) for each variables (yielding a high of 7.841 and a low of 0). AIS is an anatomic injury scoring system that quantifies injuries in various body regions from a score of 1 (minor injury) to 6 (non-survivable). A patient’s ISS is calculated by summing the squares of the three highest AIS scores in three different body regions (values range from 1–75). Massive transfusion was defined as ten or more units of PRBC in the first 24 hours after injury.
ED vital signs were defined as the initial set of vital signs captured and documented in the trauma bay. All patients had a single comprehensive ED laboratory panel obtained in the ED. The results of these labs were used for populating the ED laboratory value data fields through an electronic medical records data query. While all ED labs and vital signs are standardized and performed at a uniform time (time zero), repeat laboratory values and intra-operative and post-operative laboratory values are not. These are performed as the patient’s status dictates and often missing, especially with early deaths. As such, we did not capture these variables in our database. ED crystalloid administration was defined as the sum of all normal saline, lactated Ringer’s solution, and other crystalloid solutions received while in the ED. ED blood products (red blood cells, plasma, and platelets) were defined as those products received while in the ED. 24-hour blood product calculations were defined as the total number of products received 24 hours from time of arrival to the hospital. This included blood in the trauma bay, operating room, and post-operatively up to the 24-hour post-admission time point.
Primary outcome of interest was time to first unit of plasma transfusion. This was defined as the time from arrival at our trauma center to the time the first unit of plasma was initiated. Time to first unit of RBC was defined in a similar fashion. Secondary outcomes included 24-hour blood product utilization (RBC, plasma, platelets, and cryoprecipitate), 24-hour mortality, 30-day mortality, and hemorrhage-related mortality.
Statistical Analysis
Continuous data are presented as medians with 25th and 75th inter-quartile range (IQR) with comparisons between groups performed using the Wilcoxon rank sum (Mann-Whitney U test). Categorical data are reported as proportions and, where appropriate, tested for significance using χ2 or Fisher exact tests. The primary data analysis evaluated time to first unit of plasma transfused, blood product utilization, and mortality. A secondary analysis included the effect on those receiving MT. All statistical tests were two tailed with p < 0.05 set as significant. STATA Statistical software (version 10.0; College Station, TX) was used for analysis.
Purposeful regression modeling was then used to construct a multivariate logistic regression model evaluating 30-day mortality. This was done using the technique of purposeful selection of covariates described by Hosmer and Lemeshow. 18 Clinically sound and independent variables were then chosen, including age, gender, injury severity (ISS), w-RTS, ED lab values, 24-hr fluid administration and transfusions. Following this the variables were entered into step-wise regression that selected four variables of significance (ISS, w-RTS, base deficit, and mechanism of injury). These were then applied to a multivariate logistic regression analysis evaluating these four variables and thawed plasma (TP).
A multivariate linear regression model was then performed evaluating blood and blood component transfusions as a continuous variable. A multivariable logistic regression model was constructed to evaluate receipt of specific volumes of products. The variables included in the multivariate analyses were anatomic injury (ISS), physiologic injury (w-RTS), and tissue/metabolic injury (base deficit). In an effort to minimize the risk of falsely identifying significant results with multiple comparisons, all variables were pre-specified and judged a priori to be clinically sound.
RESULTS
Demographic and baseline data
6997 trauma patients were admitted to our facility during the 16-month study period. Of these, 1833 were major trauma activations (highest level activation criteria). 1539 were excluded leaving 294 patients that met entry criteria. There were 164 patients in the TP-ED group and 130 in the TP-BB group. The demographics and injury scoring for these patients is shown in Table 1. While basic demographics were similar between those admitted during the two time periods, patients in the TP-ED group were more physiologically (w-RTS) and anatomically injured (ISS) on arrival. Median head, chest and abdominal AIS scores were higher in the TP-ED group compared to the TP-BB group. However, there was no difference between the TP-ED and TP-BB groups with respect to face AIS (median 0 with IQR 0, 2 vs. 0 with IQR 0, 0; p=0.070), extremity AIS (0 with IQR 0, 3 vs. 0 with IQR 0, 3; p=0.740), or external AIS (median 0 with IQR 0, 0 vs. 0 with IQR 0, 0; p=0.084). Admission labs, obtained as part of the routine trauma panel value, are shown in Table 2. Admission laboratory values were also similar with the exception of rapid thromboelastography (rTEG) values. These differences in demographics and coagulopathy are not surprising given our inclusion criteria that biased against the TP-ED group. Many severely ill patients that did not receive a unit of plasma before they died were excluded from the TP-BB group.
Table 1.
Demographics and injury data
| TP-ED (n=164) | TP-BB (n=130) | p-value | |
|---|---|---|---|
| Median age, years (IQR) | 33 (23, 50) | 37 (24, 52) | 0.267 |
| Male gender, % | 71% | 80% | 0.070 |
| White race, % | 59% | 54% | 0.390 |
| Blunt mechanism of injury, % | 75% | 62% | 0.013 |
| Median admit GCS (IQR) | 6 (3, 14) | 13 (3, 15) | 0.042 |
| Median admit SBP, mmHg (IQR) | 105 (84, 126) | 98 (85, 120) | 0.310 |
| Median admit pulse, bpm (IQR) | 107 (91, 128) | 102 (88, 124) | 0.285 |
| Median w-RTS (IQR) | 3.83 (2.93, 7.11) | 6.81 (2.93, 7.84) | 0.008 |
| Median AIS-head (IQR) | 0 (0, 3) | 0 (0, 2) | 0.005 |
| Median AIS-chest (IQR) | 3 (0, 3) | 0 (0, 3) | <0.001 |
| Median AIS-abdomen (IQR) | 2 (0, 4) | 0 (0, 3) | <0.001 |
| Median ISS (IQR) | 25 (16, 32) | 18 (12, 30) | 0.018 |
TP-ED: thawed plasma in emergency department; TP-BB: thawed plasma in Blood Bank; IQR: 25th–75th inter-quartile range; GCS: Glasgow coma scale; SBP: systolic blood pressure; w-RTS: weighted Revised Trauma Score; AIS: abbreviated injury scale; ISS: Injury severity score; mmHg: millimeters mercury; bpm: beats per minute
Table 2.
Admission diagnostic testing and laboratory results
| TP-ED (n=164) | TP-BB (n=130) | p-value | |
|---|---|---|---|
| Positive FAST exam, % | 37% | 35% | 0.773 |
| Median admit base deficit, mMol/L (IQR) | 5 (3, 7) | 5 (2, 8) | 0.526 |
| Median pH value (IQR) | 7.32 (7.25, 7.35) | 7.30 (7.26, 7.35) | 0.638 |
| Median PT value, sec (IQR) | 15.4 (14.3, 17.2) | 15.0 (14.3, 16.3) | 0.070 |
| Median platelet count x 109/L (IQR) | 235 (277, 182) | 244 (197, 299) | 0.244 |
| Median hemoglobin, g/dL (IQR) | 12.2 (10.7, 13.9) | 12.3 (10.9, 13.8) | 0.467 |
| Median rTEG-ACT, sec (IQR) | 121 (113, 128) | 113 (105, 121) | <0.001 |
| Median rTEG-split point, min (IQR) | 0.7 (0.6, 0.8) | 0.6 (0.4, 0.7) | <0.001 |
TP-ED: thawed plasma in emergency department; TP-BB: thawed plasma in Blood Bank; FAST: focused assessment for the sonography for trauma; IQR: 25th–75th inter-quartile range; PT: prothrombin time; rTEG: rapid thromboelastography; ACT: activated clotting time; sec: seconds; nMol/L: millimoles per liter; L: liter; g/dL: grams per deciliter; min: minutes
Transfusion and outcome data
While median times to the first unit of RBC were similar between the two groups, time to first unit of plasma was significantly less in the TP-ED group (Table 3). While trends towards less product transfusions were observed for RBC and plasma, the TP-ED group had less transfusion of cryoprecipitate in the first 24-hours of admission. Consistent with this, TP-ED had a significantly lower massive transfusion rate. As well, the median crystalloids in the ED were 2.0 L (IQR 1.5, 2.6) in the TP-ED group compared to 3.0 L (IQR 1.9, 3.1); p=0.112. As this appears to be a clinically meaningful reduction in fluids, this may represent a type II error.
Table 3.
Primary and secondary outcome data
| TP-ED (n=164) |
TP-BB (n=130) | p-value | |
|---|---|---|---|
| Median time to first unit of RBC, min (IQR) | 18 (11, 73) | 20 (10, 72) | 0.854 |
| Median time to first unit of plasma, min (IQR) | 43 (21, 106) | 89 (48, 192) | <0.001 |
| Median 24-hour RBC transfusions, U (IQR) | 5 (2, 10) | 6 (3, 11) | 0.128 |
| Median 24-hour plasma transfusion, U (IQR) | 6 (3, 11) | 7.5 (4, 14) | 0.080 |
| Median 24-hour platelet, U (IQR) | 12 (6, 18) | 12 (6, 18) | 0.772 |
| Median 24-hour cryoprecipitate, U (IQR) | 0 (0, 0) | 0 (0, 0) | 0.028 |
| Massive transfusion rate, % | 27% | 39% | 0.045 |
| 24-hour mortality, % | 9.7% | 6.9% | 0.387 |
| 30-day mortality, % | 20.7% | 22.3% | 0.743 |
| Hemorrhage-related mortality, % | 14.7% | 27.5% | 0.210 |
TP-ED: thawed plasma in emergency department; TP-BB: thawed plasma in Blood Bank; RBC: red blood cells; IQR: 25th–75th inter-quartile range; min: minutes; U: units
Univariate analyses demonstrated similar 24-hour and 30-day mortality between the groups. There were no differences in length of stay (TP-ED: median 17 days with IQR of 9, 26 versus TP-BB: 15 days with IQR of 7, 27) or ICU length of stay (6 days with IQR of 3, 13 versus 8 days with IQR of 3, 16) between the groups. With respect to cause of death, there were no statistically significant differences between the groups. Hemorrhage-related mortality was seen in 14.7% of TP-ED and 27.5% of TP-BB patients. 14.7% of deaths were attributed to respiratory failure/ARDS in the TP-ED group, compared with 13.7% in the TP-BB group. Cardiovascular events accounted for 10.2% and 10.3% of deaths in the TP-ED and TP-BB groups, respectively. While the majority of deaths in both groups were attributed to traumatic brain injury (48.8% in the TP-ED and 41.7% in the TP-BB), deaths from multi-organ failure (2.9% vs. 3.4%), sepsis (2.9% vs. 3.4%) and withdrawal of care were also observed (5.8% vs. 0%).
During the study period, a simultaneous quality improvement process was in place. In tracking the use and wastage of thawed plasma during this time frame, only three units of jumbo AB thawed plasma were deemed “wasted” during this time frame. All of these units were during the TP-ED period and were attributed to not cycling the product out in a timely fashion. While the protocol was to rotate the units out of the ED refrigerator at the beginning of day four (4), these three units were not rotated out until late on day four (4) or into day five (5).
Massive transfusion group analyses
Between the two groups, 44 patients in the TP-ED group (27%) and 50 in the TP-BB group (39%) received a massive transfusion. The groups were similar with respect to age, gender, race and mechanism of injury. However, the TP-ED arrived with more physiological disturbances (median w-RTS of 2.93 vs. 4.29, p=0.046) and more anatomically injured (median ISS of 32 vs. 25, p=0.032). As well, the TP-ED group had lower hemoglobin (10.8 g/dL vs. 12.3, p=0.042) and more prolonged rTEG ACT (121 vs. 113 seconds, p=0.033). All other laboratory values were similar between groups with the exception of admission PT that showed a trend towards being more prolonged (17.3 vs. 15.9 seconds, p=0.093). These data further support that our study design led to the TP-ED group having more severely injured patients. This is the result of the TP-BB group suffering from availability bias (delay in receiving at least one unit of plasma), as all TP was stored in the Blood Bank. With respect to outcomes, the effect of moving the TP from the Blood Bank to the ED was associated with a significant reduction in time to first plasma transfusion in the MT patients (median time of 14 minutes vs. 59 minutes, p<0.001). There were no differences in mortality or transfusion volumes by univariate analyses.
Multivariate analyses
Multivariate linear regression was then carried out to evaluate the impact of TP in the ED on blood product utilization. When controlling for anatomic, physiologic and tissue measures of injury and shock, TP-ED was associated with significant reductions in 24-hour RBC (coef. −2.938, 95% C.I. −5.683 to −0.193, p=0.036), plasma (coef. −2.722, 95% C.I. −5.365 to −0.079, p=0.044), platelet (coef. −7.270, 95% C.I. −10.849 to −3.691, p<0.001) and cryoprecipitate transfusions (coef. −26.710, 95% C.I. −45.798 to −7.622, p=0.007). A multivariate logistic regression model was then constructed. After controlling for anatomic severity of injury (ISS), physiological instability (w-RTS), shock (arrival base deficit) and mechanism of injury, thawed plasma in the ED was an independent predictor of decreased 30-day mortality (Table 4).
Table 4.
Multiple logistic regression model predicting 30-day mortality
| Odds ratio | 95% C.I. | p-value | |
|---|---|---|---|
| Thawed plasma in ED | 0.43 | 0.194, 0.956 | 0.038 |
| Injury severity (ISS) | 1.12 | 1.070, 1.174 | <0.001 |
| Physiologic status (w-RTS) | 0.84 | 0.694, 1.012 | 0.067 |
| Arrival base deficit | 0.99 | 0.921, 1.070 | 0.845 |
| Blunt mechanism of injury | 2.32 | 0.608, 8.825 | 0.218 |
95% C.I.: 95% confidence interval; ED: emergency department; ISS: injury severity score; w-RTS: weighted Revised Trauma Score
COMMENT
While thawed plasma has been in use by some Blood Banks for several decades, it first appeared in the 17th edition of the AABB Standards for Blood Banks and Transfusion Services in 1996.19 TP is derived from either FFP (frozen with eight hours) or FP24 (frozen within 24 hours). Once thawed and labeled TP, both FFP and FP24 may be used for an additional 96-hours past their traditional 24-hour post-thaw shelf life. Centers using TP consider all three products (FFP, FP24 and TP) to be equivalent products with the exception of use in neonates (where FFP or FP24 must be used) and when higher levels of Factors V and VIII are needed (where FFP should be used).20 Moreover, the use of TP has been shown to provide acceptable levels of coagulation factors reduce plasma wastage and be a cost-effective strategy for plasma utilization.20–22 The current study evaluated the impact of moving TP to the ED, making the product immediately available for treating severely injured. After implementation of an ED TP protocol, we noted a reduction in time to first unit of plasma transfusion, decreased 24-hour blood product utilization, lower massive transfusion rates, and a 60% reduction in 30-day mortality.
In an effort to expedite delivery of plasma for patients with substantial bleeding and those requiring massive transfusion, US medical centers have increasingly turned to thawed plasma programs.23 By keeping TP in their blood banks, time to release of plasma has been dramatically reduced, allowing it to be provided (along with RBCs) with the first batch MT of blood products. Investigators at Stanford University began storing four units of TP in their blood bank for their MTP in 2005.15 They found that by making plasma available in the BB, time to first plasma transfusion was reduced from 254 to 169 minutes. Though the investigators had a MT protocol, this delay was still excessively long and, not surprisingly, the ratios of products did not impact outcome. Similarly, investigators at the University of Alabama-Birmingham have argued that the improved survival associated with higher ratios is due to survival bias.24 At their institution, this is likely true as they experience significant delays in plasma delivery as a result of availability bias. In other words, you can't give what you don't have. Despite receiving their first unit of RBC at 18 minutes, it was 93 minutes before the first unit of plasma was transfused. Again, it is difficult to achieve high ratios early and transfuse plasma rapidly in the absence of a TP protocol.
Despite having a mature MT protocol at our institution, and a focus on earlier transfusion of plasma, an internal audit recently revealed that time to first unit of plasma was delayed by 60–75 minutes.16 To address this, we implemented a TP protocol in which four units of group AB plasma were available in the ED/trauma bay refrigerator. After implementation, median time to first plasma transfusion was reduced from 89 to 43 minutes. Even more dramatic, time to first plasma transfusion among those receiving a MT was reduced from 59 to 14 minutes. The earliest plasma was infused 3 minutes after arrival. Of note, time to first unit of RBC transfusion was similar across the groups and remained unchained during the study period.
In 2006, Cotton and colleagues began a TP program in their Blood Bank to make plasma readily available for delivery in their MT protocol.10,12 This process involved keeping at least ten units of AB thawed plasma (and some A plasma) available at all times. In addition to dramatic decreases in blood product utilization, the authors noted a decrease in mortality from 66% to 51%. Similarly, the Stanford group demonstrated a significant reduction in mortality (from 45% to 19%) after implementation of their TP program. By taking this concept from the Blood Bank to the ED, the current study demonstrated dramatic reductions in massive transfusion rates and 24-hour blood product utilization. More importantly, this TP-ED protocol was associated with a 60% odds reduction in 30-day mortality.
Limitations to this study include the relatively small sample size for each cohort and the retrospective design. While the TP-ED group was collected in a prospective cohort fashion, the comparison cohort (TP-BB) was obtained using data collected via a trauma registry database and computerized patient chart. In addition, a notable limitation is that based on the study design, the population is not homogenous and the cohorts are not identically matched, resulting in a bias against the TP-ED group. Specifically, our inclusion criteria required that the patient receive at least one unit of plasma. Therefore, patients admitted prior to thawed plasma being stored in the ED would be expected to be less severely injured and less physiologically disturbed. Put another way, because of delays in plasma delivery, many severely ill patients in the TP-BB group did not receive a unit of plasma before they died and were therefore were excluded. These same patients were, however, included in the TP-ED group as plasma was immediately available. The differences noted in univariate analyses were addressed with the use of multivariable regression strategies. Therefore, if an availability bias (often called survival bias) were present, this would only strengthen our hypothesis and findings that suggest better outcome with the use of an ED-based TP protocol.
The current study examined the impact of implementing a thawed plasma protocol in the Emergency Department. We demonstrated that such a protocol expedites transfusion of plasma to severely injured patients. The TP-ED protocol was also associated with a reduction in overall blood product use and decreased MT rates. Moreover, this protocol was associated with a 60% odds reduction in 30-day mortality when controlling for admission injury severity and physiology. This may be the result of being able to provide a more hemostatic resuscitation immediately after arrival. Given the immediate availability of plasma and RBC and our recent findings, these blood products have replaced (at our institution) initial resuscitation using crystalloid-based strategies. However, a prospective, randomized trial is warranted to validate these findings.
Acknowledgments
This work was supported in part by a grant from the State of Texas Emerging Technology Fund (BAC), the Department of Defense via W81XWH-08-C-0712 (BAC, JBH) and the P50 GM38529 from the National Institute of Health (BAC, JBH).
Footnotes
No other support was used and the remaining authors have no conflicts or other financial disclosures (ZAR, YB, NM, DJD, JJM, CEW).
Presented in oral form at the Advanced Technology Applications for Combat Casualty Care (ATACCC) Annual Conference, August 16, 2011. Fort Lauderdale, FL.
Contributor Information
Zayde A. Radwan, Email: zayde.a.radwan@uth.tmc.edu.
Yu Bai, Email: yu.bai@uth.tmc.edu.
Nena Matijevic, Email: nena.matijevic@uth.tmc.edu.
Deborah J. del Junco, Email: deborah.j.deljunco@uth.tmc.edu.
James J. McCarthy, Email: james.j.mccarthy@uth.tmc.edu.
Charles E. Wade, Email: charles.e.wade@uth.tmc.edu.
John B. Holcomb, Email: john.holcomb@uth.tmc.edu.
REFERENCES
- 1.Acosta JA, Yang JC, Winchell RJ, et al. Lethal injuries and time to death in a level I trauma center. J. Am. Coll. Surg. 1998;186(5):528–533. doi: 10.1016/s1072-7515(98)00082-9. [DOI] [PubMed] [Google Scholar]
- 2.Kauvar DS, Lefering R, Wade CE. Impact of hemorrhage on trauma outcome: an overview of epidemiology, clinical presentations, and therapeutic considerations. J.Trauma. 2006;60(6 Suppl):S3–S11. doi: 10.1097/01.ta.0000199961.02677.19. [DOI] [PubMed] [Google Scholar]
- 3.Duchesne JC, McSwain NE, Jr, Cotton BA, et al. Damage control resuscitation: the new face of damage control. J Trauma. Oct;69(4):976–990. doi: 10.1097/TA.0b013e3181f2abc9. [DOI] [PubMed] [Google Scholar]
- 4.MacLeod JB, Lynn M, McKenney MG, Cohn SM, Murtha M. Early coagulopathy predicts mortality in trauma. J Trauma. 2003 Jul;55(1):39–44. doi: 10.1097/01.TA.0000075338.21177.EF. [DOI] [PubMed] [Google Scholar]
- 5.Maegele M, Lefering R, Yucel N, et al. Early coagulopathy in multiple injury: an analysis from the German Trauma Registry on 8724 patients. Injury. 2007;38(3):298–304. doi: 10.1016/j.injury.2006.10.003. [DOI] [PubMed] [Google Scholar]
- 6.Niles SE, McLaughlin DF, Perkins JG, et al. Increased mortality associated with the early coagulopathy of trauma in combat casualties. J Trauma. 2008 Jun;64(6):1459–1463. doi: 10.1097/TA.0b013e318174e8bc. discussion 1463-1455. [DOI] [PubMed] [Google Scholar]
- 7.Holcomb JB, Wade CE, Michalek JE, et al. Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients. Ann Surg. 2008 Sep;248(3):447–458. doi: 10.1097/SLA.0b013e318185a9ad. [DOI] [PubMed] [Google Scholar]
- 8.Holcomb JB, Jenkins D, Rhee P, et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J.Trauma. 2007;62(2):307–310. doi: 10.1097/TA.0b013e3180324124. [DOI] [PubMed] [Google Scholar]
- 9.Malone DL, Hess JR, Fingerhut A. Massive transfusion practices around the globe and a suggestion for a common massive transfusion protocol. J.Trauma. 2006;60(6 Suppl):S91–S96. doi: 10.1097/01.ta.0000199549.80731.e6. [DOI] [PubMed] [Google Scholar]
- 10.Cotton BA, Au BK, Nunez TC, Gunter OL, Robertson AM, Young PP. Predefined massive transfusion protocols are associated with a reduction in organ failure and postinjury complications. J Trauma. 2009 Jan;66(1):41–48. doi: 10.1097/TA.0b013e31819313bb. discussion 48–49. [DOI] [PubMed] [Google Scholar]
- 11.Cotton BA, Dossett LA, Au BK, Nunez TC, Robertson AM, Young PP. Room for (performance) improvement: provider-related factors associated with poor outcomes in massive transfusion. J Trauma. 2009 Nov;67(5):1004–1012. doi: 10.1097/TA.0b013e3181bcb2a8. [DOI] [PubMed] [Google Scholar]
- 12.Cotton BA, Gunter OL, Isbell J, et al. Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization. J Trauma. 2008 May;64(5):1177–1182. doi: 10.1097/TA.0b013e31816c5c80. discussion 1182-1173. [DOI] [PubMed] [Google Scholar]
- 13.O'Keeffe T, Refaai M, Tchorz K, Forestner JE, Sarode R. A massive transfusion protocol to decrease blood component use and costs. Arch Surg. 2008 Jul;143(7):686–690. doi: 10.1001/archsurg.143.7.686. discussion 690-681. [DOI] [PubMed] [Google Scholar]
- 14.Duchesne JC, Kimonis K, Marr AB, et al. Damage control resuscitation in combination with damage control laparotomy: a survival advantage. J Trauma. Jul;69(1):46–52. doi: 10.1097/TA.0b013e3181df91fa. [DOI] [PubMed] [Google Scholar]
- 15.Riskin DJ, Tsai TC, Riskin L, et al. Massive transfusion protocols: the role of aggressive resuscitation versus product ratio in mortality reduction. J Am Coll Surg. 2009 Aug;209(2):198–205. doi: 10.1016/j.jamcollsurg.2009.04.016. [DOI] [PubMed] [Google Scholar]
- 16.Gonzalez EA, Moore FA, Holcomb JB, et al. Fresh frozen plasma should be given earlier to patients requiring massive transfusion. J. Trauma. 2007;62(1):112–119. doi: 10.1097/01.ta.0000250497.08101.8b. [DOI] [PubMed] [Google Scholar]
- 17.Voskresensky IV, Rivera-Tyler T, Dossett LA, Riordan WP, Jr, Cotton BA. Use of Scene Vital Signs Improves TRISS Predicted Survival in Intubated Trauma Patients. J Surg Res. 2008 May 6; doi: 10.1016/j.jss.2008.04.010. [DOI] [PubMed] [Google Scholar]
- 18.Hosmer DW, Lemeshow S. Applied Logistic Regression. New York: Wiley; 2000. [Google Scholar]
- 19.AABB. Standards for blood banks and transfusion services. Bethesda (MD): 1996. [Google Scholar]
- 20.Wehrli G, Taylor NE, Haines AL, Brady TW, Mintz PD. Instituting a thawed plasma procedure: it just makes sense and saves cents. Transfusion. 2009 Dec;49(12):2625–2630. doi: 10.1111/j.1537-2995.2009.02342.x. [DOI] [PubMed] [Google Scholar]
- 21.O’Neill EM, Rowley J, Hansson-Wicher M, McCarter S, Ragno G, Valeri CR. Effect of 24-hour whole-blood storage on plasma clotting factors. Transfusion. 1999 May;39(5):488–491. doi: 10.1046/j.1537-2995.1999.39050488.x. [DOI] [PubMed] [Google Scholar]
- 22.Yazer MH, Cortese-Hassett A, Triulzi DJ. Coagulation factor levels in plasma frozen within 24 hours of phlebotomy over 5 days of storage at 1 to 6 degrees C. Transfusion. 2008 Dec;48(12):2525–2530. doi: 10.1111/j.1537-2995.2008.01913.x. [DOI] [PubMed] [Google Scholar]
- 23.Young PP, Cotton BA, Goodnough LT. Massive Transfusion Protocols for Patients With Substantial Hemorrhage. Transfus Med Rev. Jun;8 doi: 10.1016/j.tmrv.2011.04.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Snyder CW, Weinberg JA, McGwin G, Jr, et al. The relationship of blood product ratio to mortality: survival benefit or survival bias? J Trauma. 2009 Feb;66(2):358–362. doi: 10.1097/TA.0b013e318196c3ac. discussion 362-354. [DOI] [PubMed] [Google Scholar]