The Incidence of Transfusion-Related Acute Lung Injury at a Large, Urban Tertiary Medical Center: A Decade's Experience.

BACKGROUND: While transfusion-related acute lung injury (TRALI) remains the primary cause of transfusion-related fatalities (37%), recent reports estimate the incidence of TRALI at 0.008% per unit of plasma transfused and 0.004% per all products transfused. Because blood banks have moved toward male-predominant plasma, TRALI appears, anecdotally, to have been reduced to an extremely rare event. The purpose of this study was to estimate the current incidence of TRALI at a large, urban center known for its early and aggressive use of plasma in the setting of trauma, hemorrhagic shock, and massive transfusion. METHODS: The Blood Bank Registry of our hospital was queried for all transfused patients admitted from September 2002 through March 2013. The blood bank collected and investigated all cases of clinical acute lung injury meeting the consensus definition for TRALI, as well as potential cases for which the donor product was recalled for having a high reactivity level of human leukocyte antigen antibodies (ie, the antibodies that could cause TRALI). Clinical reactions were reviewed in conjunction with independent serological testing and classified by transfusion medicine physicians as being "probable TRALI" or of "unrelated etiology." The total number of units transfused at our facility during this time period was also obtained, allowing the incidence of TRALI to be estimated. Cases were analyzed based on demographics, outcome, blood types, observed symptoms and their duration, and type of product transfused. RESULTS: Seven cases were identified at our center for the indicated time period, with only 3 of these occurring in trauma. A total of 714,757 units of blood products were transfused between September 2002 and March 2013. The incidence of TRALI was estimated to be 1 case per 100,000 units of product for the entire study period. A broad range of patients was affected. Consistent with previous descriptions, an acute duration of symptoms (average, 1.4 days) was observed and usually resolved with supportive care. Reactions were observed predominantly in plasma products, both type specific and nontype specific. CONCLUSIONS: This study demonstrates that while TRALI still occurs, clinically meaningful cases are rare. Moreover, TRALI rates remain low despite the increasingly aggressive use of plasma and platelets in the trauma setting.

Hypercoagulability after energy drink consumption.

BACKGROUND: Energy drink consumption in the United States has more than doubled over the last decade and has been implicated in cardiac arrhythmias, myocardial infarction, and even sudden cardiac death. We hypothesized that energy drink consumption may increase the risk of adverse cardiovascular events by increasing platelet aggregation, thereby resulting in a relatively hypercoagulable state and increased risk of thrombosis. METHODS: Thirty-two healthy volunteers aged 18-40 y were given 16 oz of bottled water or a standardized, sugar-free energy drink on two separate occasions, 1-wk apart. Beverages were consumed after an overnight fast over a 30-min period. Coagulation parameters and platelet function were measured before and 60 min after consumption using thrombelastography and impedance aggregometry. RESULTS: No statistically significant differences in coagulation were detected using kaolin or rapid thrombelastography. In addition, no differences in platelet aggregation were detected using ristocetin, collagen, thrombin receptor-activating peptide, or adenosine diphosphate-induced multiple impedance aggregometry. However, compared to water controls, energy drink consumption resulted in a significant increase in platelet aggregation via arachidonic acid-induced activation (area under the aggregation curve, 72.4 U versus 66.3 U; P = 0.018). CONCLUSIONS: Energy drinks are associated with increased platelet activity via arachidonic acid-induced platelet aggregation within 1 h of consumption. Although larger clinical studies are needed to further address the safety and health concerns of these drinks, the increased platelet response may provide a mechanism by which energy drinks increase the risk of adverse cardiovascular events.

An analysis of analgesia and opioid prescribing for veterans after thoracic surgery.

The opioid crisis is a public health issue and has been linked to physician overprescribing. Pain management after thoracic surgery is not standardized at many centers, and we hypothesized that excessive narcotics were being dispensed on discharge. As a quality improvement initiative, we sought to understand current prescribing practices to better align the amount of opioids dispensed on discharge to actual patient needs. This was a single-center, retrospective review of patients undergoing thoracic surgery from 7/2015 to 7/2018. Demographics, operative data, perioperative pain medication use, and discharge pain medication prescriptions were analyzed. Opioids were converted to Morphine Milligram Equivalents (MME). Among 124 patients, 103 (83%) received intraoperative nerve blocks and 106 (85.5%) used PCAs. Prescribed MME/day at discharge were significantly higher than MME/day received during hospitalization (Median 30 [IQR 30-45] vs. 15 [IQR 5-24], p < 0.001) and were not associated with receiving a nerve block or PCA. By procedure, prescribed MME/day were significantly higher than inpatient MME/day for wedge resections (p < 0.001), segmentectomies (p = 0.02), lobectomies (p = 0.003), and thymectomies (p = 0.02). Patients are being discharged with significantly more opioids than they are using as inpatients. Education among prescribers and a standardized approach with patient-specific dosing may reduce excessive opioid dispensing.

Splenectomy is associated with hypercoagulable thrombelastography values and increased risk of thromboembolism.

BACKGROUND: Previous investigators have demonstrated that postinjury thrombocytosis is associated with an increase in thromboembolic (TE) risk. Increased rates of thrombocytosis have been found specifically in patients after splenectomy for trauma. We hypothesized that patients undergoing splenectomy (1) would demonstrate a more hypercoagulable profile during their hospital stay and (2) that this hypercoagulable state would be associated with increased TE events. METHODS: This was a 14-month, prospective, observational trial evaluating serial rapid thrombelastography (rTEG) at 3 American College of Surgeons-verified, level 1 trauma centers. Inclusion criteria were highest-level trauma activation and arrival within 6 hours of injury. Exclusion criteria were <18 years of age, incarcerated, and burns>20% total body surface area. Serial rTEG (activated clotting time, k-time, α-angle, MA, lysis) and traditional coagulation testing (prothrombin time, partial thromboplastin time, fibrinogen and platelet count) were obtained at admission and then at 3, 6, 12, 24, 48, 72, 96, and 120 hours. Thromboembolic complications were defined as the development of deep-vein thrombosis, pulmonary embolism, acute myocardial infarction, or ischemic stroke during hospitalization. Patients were stratified into splenectomy versus nonsplenectomy cohorts. Univariate analysis was then conducted followed by longitudinal analysis using generalized estimating equations to evaluate the effects of time, splenectomy, and group-time interactions on changes in rTEG and traditional coagulation testing. We used an adjusted generalized estimating equation model to control for age, sex, ISS, admission blood pressure, base deficit, and hemoglobin. RESULTS: A total of 1,242 patients were enrolled; 795 had serial rTEG data. Of these, 605 had serial values >24 hours and made up the study population. Splenectomy patients were younger, more hypotensive, and in shock on arrival. Although there was no difference in 24-hour or 30-day mortality, splenectomy patients were more likely to develop TE events. Using the GEE model, we found that α-angle and MA in splenectomy patients were lesser (more hypocoagulable) within the first 6 hours; however, they became substantially greater (more hypercoagulable) at 48, 72, 96, and 120 hours; all P < .05. In addition, platelet counts were greater in the splenectomy group beginning at 72 hours and continuing through 120 hours; P < .05. CONCLUSION: This multicenter, prospective study demonstrates that patients undergoing splenectomy have a more hypercoagulable state than other trauma patients. This hypercoagulable state (identified by greater α-angle and mA values) begins at approximately 48 hours after injury and continues through at least day 5. Moreover, this hypercoagulable state is associated with increased risk of TE complications.

Early surgical intervention for blunt bowel injury: the Bowel Injury Prediction Score (BIPS).

BACKGROUND: Computed tomography (CT) scan of the abdomen has been used for 30 years to evaluate the stable blunt trauma patient. However, the early diagnosis of blunt hollow viscus injury (BHVI) remains a challenge. Delayed diagnosis and intervention of BHVI lead to significant morbidity and mortality. This study aimed to identify a combination of radiographic and clinical variables present at admission that could lead to earlier surgical intervention for BHVI. METHODS: Significant predictors were identified through a retrospective review of all blunt trauma patients admitted to a Level 1 trauma center from 2005 to 2010 with an admission CT of the abdomen/pelvis and diagnosed with any mesenteric injury. The Bowel Injury Prediction Score (BIPS) was calculated based on the following three elements with a point given for each outcome: white blood cell count of 17.0 or greater, abdominal tenderness, and CT scan grade for mesenteric injury of 4 or higher. RESULTS: A total of 18,927 blunt trauma patients were admitted during the study period. Of these, 380 had a mesenteric injury, 110 met inclusion criteria, 60 had a surgical intervention, and 43 had BHVI. Of the 110 study patients, 43 (39%) had an immediate operation, 17 (16%) had a delayed operation (>4 hours), and 50 (46%) had no surgical intervention. The median BIPS for the immediate and delayed group was 2, while for the no-surgery group, the score was 0. Patients with a BIPS of 2 or greater were 19 times more likely to have a BHVI than patients with a BIPS of less than 2 (odds ratio, 19.2; 95% confidence interval, 6.78-54.36; p < 0.001). CONCLUSION: Three predictors (admission CT scan grade of mesenteric injury, white blood cell count, and abdominal tenderness) were used to create a new bowel injury score, with a score of 2 or greater being strongly associated with BHVI. Prospective validation of these retrospective findings is warranted to fully assess the accuracy of the BIPS. LEVEL OF EVIDENCE: Prognostic study, level III.

Clinical gestalt and the prediction of massive transfusion after trauma.

INTRODUCTION: Early recognition and treatment of trauma patients requiring massive transfusion (MT) has been shown to reduce mortality. While many risk factors predicting MT have been demonstrated, there is no universally accepted method or algorithm to identify these patients. We hypothesised that even among experienced trauma surgeons, the clinical gestalt of identifying patients who will require MT is unreliable. METHODS: Transfusion and mortality outcomes after trauma were observed at 10 U.S. Level-1 trauma centres in patients who survived ≥ 30 min after admission and received ≥ 1 unit of RBC within 6h of arrival. Subjects who received ≥ 10 units within 24h of admission were classified as MT patients. Trauma surgeons were asked the clinical gestalt question "Is the patient likely to be massively transfused?" 10 min after the patients arrival. The performance of clinical gestalt to predict MT was assessed using chi-square tests and ROC analysis to compare gestalt to previously described scoring systems. RESULTS: Of the 1245 patients enrolled, 966 met inclusion criteria and 221 (23%) patients received MT. 415 (43%) were predicted to have a MT and 551(57%) were predicted to not have MT. Patients predicted to have MT were younger, more often sustained penetrating trauma, had higher ISS scores, higher heart rates, and lower systolic blood pressures (all p<0.05). Gestalt sensitivity was 65.6% and specificity was 63.8%. PPV and NPV were 34.9% and 86.2% respectively. CONCLUSION: Data from this large multicenter trial demonstrates that predicting the need for MT continues to be a challenge. Because of the increased mortality associated with delayed therapy, a more reliable algorithm is needed to identify and treat these severely injured patients earlier.

Measuring thrombin generation as a tool for predicting hemostatic potential and transfusion requirements following trauma.

BACKGROUND: Thrombin is the central coagulation protease that activates clotting proteins, triggers platelet aggregation, and converts fibrinogen to fibrin. Relationships between thrombin generation (TG) and clinical outcomes have not been defined following trauma. We hypothesize that TG is predictive of transfusion requirements and patient outcomes. METHODS: Plasma was collected from 406 highest-level activation trauma patients upon admission and 29 healthy donors. Standard coagulation tests were performed, and TG was measured by calibrated automated thrombogram. Mann-Whitney U-tests were used to compare healthy versus trauma patients, and subgroup analyses were used to compare hypocoagulable versus nonhypocoagulable patients. Hypocoagulability was determined by area under the receiver operating characteristic curve analysis and was defined as peak TG of less than 250 nM. Multiple logistic regressions were used to assess the ability of TG to predict massive transfusion and mortality. RESULTS: The median (interquartile range) age was 39 years (28-52 years), with an Injury Severity Score (ISS) of 17 (9-26). The trauma patients had greater TG (peak, 316.2 nM [270.1-355.5 nM]) compared with the healthy controls (124.6 nM [91.1-156.2 nM]), p < 0.001. The overall rate of hypocoagulability was 17%. The patients with peak TG of less than 250 nM were more severely injured (ISS, 25 [13-30] vs. 16 [9-25], p = 0.003); required more transfusions of red blood cells (p = 0.02), plasma (p = 0.003), and platelets (p = 0.006); had fewer hospital-free days (p = 0.001); and had increased mortality (10% vs. 3% at 24 hours, p = 0.006, and 29% vs. 11% at 30 days, p = 0.0004). Peak TG of less than 250 nM was predictive of massive transfusion (odds ratio, 4.18; p = 0.01) and 30-day mortality (odds ratio, 2.78; p = 0.02). Finally, peak TG was inversely correlated with standard coagulation tests. CONCLUSION: While the physiologic response to injury is to upregulate plasma procoagulant activity, the patients with reduced TG required more transfusions and had poorer outcomes. Measuring TG may provide an exquisitely sensitive tool for detecting disturbances in the enzymatic phases of coagulation in critically injured patients. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.

Early diagnosis of clinically significant hyperfibrinolysis using thrombelastography velocity curves.

BACKGROUND: Clot lysis values (LY30) determined by rapid thrombelastography (rTEG) predict postinjury transfusion needs and mortality risk. However, the first derivative velocity curve values generated by rTEG measuring lysis­maximum rate of lysis (MRL) and total lysis (TL)­have not been evaluated. Although recent data support use of antifibrinolytics in trauma, the population that would benefit remains poorly defined. The purpose of this study was to determine if velocity curves more accurately predict large volume transfusions and early mortality than conventional rTEG values. STUDY DESIGN: Conventional and velocity curve admission rTEG values of adult trauma patients were retrospectively evaluated for their ability to predict early transfusion of RBC and plasma, substantial bleeding, massive transfusion, and mortality. Patient outcomes were compared according to hyperfibrinolysis diagnosed by velocity curve values and the conventional LY30 cutoff. RESULTS: There were 1,625 patients included. Clot lysis values predicted early transfusion of RBC (p = 0.003), but not plasma (p = 0.298), within 3 hours of arrival. With respect to velocity curves, MRL and TL predicted both early RBC and plasma transfusion (p < 0.05). All 3 parameters predicted massive transfusion, but only MRL and TL predicted substantial bleeding (odds ratio [OR] 3.1 and 2.9, respectively). In addition, MRL was a stronger predictor of 24-hour and 30-day mortality (p < 0.001) and was also available earlier after arrival than LY30 (p < 0.001). CONCLUSIONS: Velocity curve measures of fibrinolysis are stronger predictors of early transfusion of blood components, bleeding, and mortality after trauma compared with conventional rTEG values. In addition, the MRL is more rapidly available after arrival, which may facilitate earlier diagnosis and treatment of clinically significant hyperfibrinolysis.

Time to first take-back operation predicts successful primary fascial closure in patients undergoing damage control laparotomy.

BACKGROUND: Failure to achieve primary fascial closure (PFC) after damage control laparotomy is costly and carries great morbidity. We hypothesized that time from the initial laparotomy to the first take-back operation would be predictive of successful PFC. METHODS: Trauma patients managed with open abdominal techniques after damage control laparotomy were prospectively followed at 14 Level 1 trauma centers during a 2-year period. Time to the first take-back was evaluated as a predictor of PFC using hierarchical multivariate logistic regression analysis. RESULTS: A total of 499 patients underwent damage control laparotomy and were included in this analysis. PFC was achieved in 327 (65.5%) patients. Median time to the first take-back operation was 36 hours (interquartile range 24-48). After we adjusted for patient demographics, resuscitation volumes, and operative characteristics, increasing time to the first take-back was associated with a decreased likelihood of PFC. Specifically, each hour delay in return to the operating room (24 hours after initial laparotomy) was associated with a 1.1% decrease in the odds of PFC (odds ratio 0.989; 95% confidence interval 0.978-0.999; P = .045). In addition, there was a trend towards increased intra-abdominal complications in patients returning after 48 hours (odds ratio 1.80; 95% confidence interval 1.00-3.25; P = .05). CONCLUSION: Data from this prospective, multicenter study demonstrate that delays in returning to the operating room after damage control laparotomy are associated with reductions in PFC. These findings suggest that emphasis should be placed on returning to the operating room within 24 hours after the initial laparotomy if possible (and no later than 48 hours).

Hypercoagulability after injury in premenopausal females: a prospective, multicenter study.

BACKGROUND: Recent studies suggest there are gender-specific differences in injury response that may be related to coagulation. The objective of this study was to test the hypothesis that rapid thrombelastography (rTEG) coagulation profiles differ by gender. METHODS: Adult trauma patients were prospectively followed at 3 level 1 trauma centers over a 14-month period. rTEG was obtained upon arrival and serially at several time points during the hospital stay. Female patients were stratified into premenopausal (≤50 years) and postmenopausal (>50 years) age groups with age-matched male cohorts. Values were analyzed using a repeated-measures multilevel linear model to evaluate the effect of gender on coagulation. RESULTS: A total of 795 patients had serial rTEG data (24% female and 76% male). Compared with age-matched males, premenopausal females were more hypercoagulable by rTEG on admission (P < .001) and for the first 12 hours after arrival. Gender was an effect modifier for alpha angle (P = .02) and maximum amplitude (P = .04). Controlling for Injury Severity Score and mechanism of injury, age-matched males had a >4-fold increased risk of hypercoagulable complications than premenopausal females (odds ratio, 4.7; P = .038). CONCLUSION: This prospective, multicenter study demonstrates that premenopausal females are relatively hypercoagulable compared with age-matched males early after injury. However, this did not translate into higher thromboembolic complications.