Thomas M. Scalea

Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients With Severe Trauma: The PROPPR Randomized Clinical Trial

IMPORTANCE Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. OBJECTIVE To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. DESIGN, SETTING, AND PARTICIPANTS Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. INTERVENTIONS Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). MAIN OUTCOMES AND MEASURES Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. RESULTS No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. CONCLUSIONS AND RELEVANCE Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01545232.

Lactate clearance and survival following injury.

Previous reports cite optimization of O2 delivery (DO2) to 660 mL/min/m2, O2 consumption (VO2) to 170 mL/min/m2, and cardiac index (CI) of 4.5 L/min as predicting survival. We prospectively evaluated 76 consecutive patients with multiple trauma admitted directly to the ICU from the operating room or emergency department. Patients had serum lactate levels and oxygen transport measured on ICU admission and at 8, 16, 24, 36, and 48 hours. Patients were analyzed with respect to survival (S) versus nonsurvival (NS), lactate clearance to normal (< or = 2 mmol/L) by 24 and 48 hours, hemodynamic optimization as defined above, as well as Injury Severity Score (ISS), ICU stay (LOS), and admission blood pressure. All patients achieved non-flow-dependent VO2. There was no difference in CI, DO2, VO2, or ISS when S was compared with NS. All 27 patients whose lactate level normalized in 24 hours survived. If lactate levels cleared to normal between 24 and 48 hours, the survival rate was 75%. Only 3 of the 22 patients who did not clear their lactate level to normal by 48 hours survived. Ten of the 25 nonsurvivors (40%) achieved the above arbitrary optimization criteria. Fifteen of the survivors never achieved any of these criteria. Optimization alone does not predict survival. However, the time needed to normalize serum lactate levels is an important prognostic factor for survival in severely injured patients.

Blood transfusion, independent of shock severity, is associated with worse outcome in trauma.

BACKGROUND We have previously shown that blood transfusion in the first 24 hours is an independent predictor of mortality, intensive care unit (ICU) admission, and increased ICU length of stay in the acute trauma setting when controlling for Injury Severity Score, Glasgow Coma Scale score, and age. Indices of shock such as base deficit, serum lactate level, and admission hemodynamic status (systolic blood pressure, heart rate) and admission hematocrit were considered potential confounding variables in that study. The objectives of this study were to evaluate admission anemia and blood transfusion within the first 24 hours as independent predictors of mortality, ICU admission, ICU length of stay (LOS), and hospital LOS, with serum lactate level, base deficit, and shock index (heart rate/systolic blood pressure) as covariates. METHODS Prospective data were collected on 15,534 patients admitted to a Level I trauma center over a 3-year period (1998-2000) and stratified by age, gender, race, Glasgow Coma Scale score, and Injury Severity Score. Admission anemia and blood transfusion were assessed as independent predictors of mortality, ICU admission, ICU LOS, and hospital LOS by logistic regression analysis, with base deficit, serum lactate, and shock index as covariates. RESULTS Blood transfusion was a strong independent predictor of mortality (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.82-4.40; p < 0.001), ICU admission (OR, 3.27; 95% CI, 2.69-3.99; p < 0.001), ICU LOS (p < 0.001), and hospital LOS (Coef, 4.37; 95% CI, 2.79-5.94; p < 0.001) when stratified by indices of shock (base deficit, serum lactate, shock index, and anemia). Patients who underwent blood transfusion were almost three times more likely to die and greater than three times more likely to be admitted to the ICU. Admission anemia (hematocrit < 36%) was an independent predictor of ICU admission (p = 0.008), ICU LOS (p = 0.012), and hospital LOS (p < 0.001). CONCLUSION Blood transfusion is confirmed as an independent predictor of mortality, ICU admission, ICU LOS, and hospital LOS in trauma after controlling for severity of shock by admission base deficit, lactate, shock index, and anemia. The use of other hemoglobin-based oxygen-carrying resuscitation fluids (such as human or bovine hemoglobin substitutes) in the acute postinjury period warrants further investigation.

Focused Assessment with Sonography for Trauma (FAST): results from an international consensus conference.

OBJECTIVE To assemble an international panel of experts to develop consensus recommendations on selected important issues on the use of ultrasonography (US) in trauma care. SETTING R Adams Cowley Shock Trauma Center, University of Maryland Medical System, Baltimore, Md. The conference was held on December 4, 1997. PARTICIPANTS A committee of two co-directors and eight faculty members, in the disciplines of surgery and emergency medicine, representing four nations. Each faculty member had made significant contributions to the current understanding of US in trauma. RESULTS Six broad topics felt to be controversial or to have wide variation in practice were discussed using the ad hoc process: (1) US nomenclature and technique; (2) US for organ-specific injury; (3) US scoring systems; (4) the meaning of positive and negative US studies; (5) US credentialing issues; and (6) future applications of US. Consensus recommendations were made when unanimous agreement was reached. Majority viewpoints and minority opinions are presented for unresolved issues. CONCLUSION The consensus conference process fostered an international sharing of ideas. Continued communication is needed to advance the science and technology of US in trauma care.

Hypotensive resuscitation during active hemorrhage: impact on in-hospital mortality.

BACKGROUND Traditional fluid resuscitation strategy in the actively hemorrhaging trauma patient emphasizes maintenance of a normal systolic blood pressure (SBP). One human trial has demonstrated improved survival when fluid resuscitation is restricted, whereas numerous laboratory studies have reported improved survival when resuscitation is directed to a lower than normal pressure. We hypothesized that fluid resuscitation titrated to a lower than normal SBP during the period of active hemorrhage would improve survival in trauma patients presenting to the hospital in hemorrhagic shock. METHODS Patients presenting in hemorrhagic shock were randomized to one of two fluid resuscitation protocols: target SBP > 100 mm Hg (conventional) or target SBP of 70 mm Hg (low). Fluid therapy was titrated to this endpoint until definitive hemostasis was achieved. In-hospital mortality, injury severity, and probability of survival were determined for each patient. RESULTS One hundred ten patients were enrolled over 20 months, 55 in each group. The study cohort had a mean age of 31 years, and consisted of 79% male patients and 51% penetrating trauma victims. There was a significant difference in SBP observed during the study period (114 mm Hg vs. 100 mm Hg, p < 0.001). Injury Severity Score (19.65 +/- 11.8 vs. 23.64 +/- 13.8, p = 0.11) and the duration of active hemorrhage (2.97 +/- 1.75 hours vs. 2.57 +/- 1.46 hours, p = 0.20) were not different between groups. Overall survival was 92.7%, with four deaths in each group. CONCLUSION Titration of initial fluid therapy to a lower than normal SBP during active hemorrhage did not affect mortality in this study. Reasons for the decreased overall mortality and the lack of differentiation between groups likely include improvements in diagnostic and therapeutic technology, the heterogeneous nature of human traumatic injuries, and the imprecision of SBP as a marker for tissue oxygen delivery.

External fixation as a bridge to intramedullary nailing for patients with multiple injuries and with femur fractures: damage control orthopedics.

BACKGROUND The advantages of early fracture fixation in patients with multiple injuries have been challenged recently, particularly in patients with head injury. External fixation (EF) has been used to stabilize pelvic fractures after multiple injury. It potentially offers similar benefits to intramedullary nail (IMN) in long-bone fractures and may obviate some of the risks. We report on the use of EF as a temporary fracture fixation in a group of patients with multiple injuries and with femoral shaft fractures. METHODS Retrospective review of charts and registry data of patients admitted to our Level 1 trauma center July of 1995 to June of 1998. Forty-three patients initially treated with EF of the femur were compared to 284 patients treated with primary IMN of the femur. RESULTS Patients treated with EF had more severe injuries with significantly higher Injury Severity Scores (26.8 vs. 16.8) and required significantly more fluid (11.9 vs. 6.2 liters) and blood (1.5 vs. 1.0 liters) in the initial 24 hours. Glasgow Coma Scale score was lower (p < 0.01) in those treated with EF (11 vs. 14.2). Twelve patients (28%) had head injuries severe enough to require intracranial pressure monitoring. All 12 required therapy for intracranial pressure control with mannitol (100%), barbiturates (75%), and/or hyperventilation (75%). Most patients had more than one contraindication to IMN, including head injury in 46% of cases, hemodynamic instability in 65%, thoracoabdominal injuries in 51%, and/or other serious injuries in 46%, most often multiple orthopedic injuries. Median operating room time for EF was 35 minutes with estimated blood loss of 90 mL. IMN was performed in 35 of 43 patients at a mean of 4.8 days after EF. Median operating room time for IMN was 135 minutes with an estimated blood loss of 400 mL. One patient died before IMN. One other patient with a mangled extremity was treated with amputation after EF. There was one complication of EF, i.e., bleeding around a pin site, which was self-limited. Four patients in the EF group died, three from head injuries and one from acute organ failure. No death was secondary to the fracture treatment selected. One patient who had EF followed by IMN had bone infection and another had acute hardware failure. CONCLUSION EF is a viable alternative to attain temporary rigid stabilization in patients with multiple injuries. It is rapid, causes negligible blood loss, and can be followed by IMN when the patient is stabilized. There were minimal orthopedic complications.

Status of nonoperative management of blunt hepatic injuries in 1995: a multicenter experience with 404 patients

INTRODUCTION Nonoperative management is presently considered the treatment modality of choice in over 50% of adult patients sustaining blunt hepatic trauma who meet inclusion criteria. A multicenter study was retrospectively undertaken to assess whether the combined experiences at level I trauma centers could validate the currently reported high success rate, low morbidity, and virtually nonexistent mortality associated with this approach. Thirteen level I trauma centers accrued 404 adult patients sustaining blunt hepatic injuries managed nonoperatively over the last 5 years. Seventy-two percent of the injuries resulted from motor vehicle crashes. The mean injury severity score for the entire group was 20.2 (range, 4-75), and the American Association for the Surgery of Trauma-computerized axial tomography scan grading was as follows: grade I, 19% (n = 76); grade II, 31% (n = 124); grade III, 36% (n = 146); grade IV, 10% (n = 42); and grade V, 4% (n = 16). There were 27 deaths (7%) in the series, with 59% directly related to head trauma. Only two deaths (0.4%) could be attributed to hepatic injury. Twenty-one (5%) complications were documented, with the most common being hemorrhage, occurring in 14 (3.5%). Only 3 (0.7%) of these 14 patients required surgical intervention, 6 were treated by transfusions alone (0.5 to 5 U), 4 underwent angio-embolization, and 1 was further observed. Other complications included 2 bilomas and 3 perihepatic abscesses (all drained percutaneously). Two small bowel injuries were initially missed (0.5%), and diagnosed 2 and 3 days after admission. Overall, 6 patients required operative intervention: 3 for hemorrhage, 2 for missed enteric injuries, and 1 for persistent sepsis after unsuccessful percutaneous drainage. Average length of stay was 13 days. Nonoperative management of blunt hepatic injuries is clearly the treatment modality of choice in hemodynamically stable patients, irrespective of grade of injury or degree of hemoperitoneum. Current data would suggest that 50 to 80% (47% in this series) of all adult patients with blunt hepatic injuries are candidates for this form of therapy. Exactly 98.5% of patients analyzed in this study successfully avoided operative intervention. Bleeding complications are infrequently encountered (3.5%) and can often be managed nonoperatively. Although grades IV and V injuries composed 14% of the series, they represented 66.6% of the patients requiring operative intervention and thus merit constant re-evaluation and close observation in critical care units. The optimal time for follow-up computerized axial tomography scanning seems to be within 7 to 10 days after injury.

Outcome in post-traumatic acute renal failure when continuous renal replacement therapy is applied early vs. late

Objective: To determine whether the timing of initiation of continuous renal replacement therapy (CRRT) affects outcome in patients with post-traumatic acute renal failure (ARF). Design: The medical records of patients treated with CRRT for post-traumatic ARF were retrospectively reviewed. Chi-square testing was used to test frequencies between groups, and Students t -test was used to compare means. Setting: A Level I trauma center. Patients: 100 Adult trauma patients treated with CRRT for ARF from 1989 to 1997. Patients were characterized as “early” or “late” starters, based upon whether the blood urea nitrogen (BUN) was less than or greater than 60 mg/dl, prior to CRRT initiation. Results: The mean BUN of the early and late starters was 42.6 and 94.5 mg/dl, respectively (p < 0.0001). CRRT was initiated earlier in the hospital course of early starters compared to late starters (hospital day 10.5 vs 19.4, p < 0.0001). Creatinine clearance prior to CRRT did not differ statistically between the two groups. No significant difference was found between early and late starters with respect to Injury Severity Score, admission Glasgow Coma Scale, presence of shock at admission, age, gender distribution, or trauma type. Admission laboratory values including BUN, serum creatinine, lactate, and bilirubin as well as fluid and blood requirements in the first 24 h were statistically the same for the two groups, suggesting a similar risk of developing renal failure. Survival rate was significantly increased among early starters compared to late starters (39.0 vs 20.0 %, respectively, p = 0.041). Conclusions: This retrospective review indicates that an earlier initiation of CRRT, based on pre-CRRT BUN, may improve the rate of survival of trauma patients who develop ARF.

Blood transfusion rates in the care of acute trauma

BACKGROUND:  Ten to 15 percent of all RBCs are used in the care of injury. Understanding patterns of RBC use is important. Routine resource allocation, planning for mass casualty situations, designing research, and optimizing triage all can be usefully informed.

Geriatric blunt multiple trauma: improved survival with early invasive monitoring.

Geriatric trauma survival rates are reported to approach 85%, but no series to our knowledge has included a predominance of multiply injured patients. In 1985, we treated 60 patients more than 65 years of age who sustained blunt multiple trauma, excluding burns and minor falls. A pedestrian-motor vehicle mechanism, initial BP less than 150 mm Hg, acidosis, multiple fractures, and head injuries all predicted mortality. To investigate this, in 1986, we began invasive monitoring in all patients with any of these risk factors and modified this in 1987 to emergent monitoring, postponing all but the most critical diagnostic studies. All patients included were hemodynamically stable after initial evaluation. Attempts were made to optimize all patients with volume, inotropes, and afterload reduction as needed. There was no difference between 1986 and 1987 in patient age, injury severity, or per cent of patients requiring operation. In 1986, mean time from ED admission to monitoring was 5.5 hours. Eight of 15 patients had an initial cardiac output (CO) less than 3.5 L/M and/or mixed venous saturation (MVO2) less than 50%. All developed progressive pump failure despite therapy and died within 24 hours. The other seven had an initial CO between 3.4-5.5 L/M, but five had an MVO2 less than 50%. All augmented their CO with therapy over 6-12 hours to a mean CO of 6.8 L/M and resolved their MVO2, but six died from MOF. Survival was 7%. In 1987-88, we reduced time to monitoring to 2.2 hours by limiting diagnostic tests. Thirteen of 30 patients treated had an initial CO less than 3.5 L/M.(ABSTRACT TRUNCATED AT 250 WORDS)