Deborah M. Stein

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.

Blunt cerebrovascular injuries: does treatment always matter?

BACKGROUND Blunt cerebrovascular injuries (BCVI) have become an increasingly recognized entity. Stroke as a result of these injuries can have devastating consequences. Optimal screening criteria, diagnostic imaging, and therapy for BCVIs have not been elucidated. Our institution began to apply liberal screening criteria using a whole-body scanning protocol with multidetector computed tomographic (WB-MDCT) scans to diagnose these injuries. The purpose of this study is to describe a single institutions large experience in patients with BCVI in an effort to provide insight into the diagnosis and management of these injuries. METHODS All patients with a BCVI admitted to the R Adams Cowley Shock Trauma Center during a 30-month period were included in this study. Choice of diagnostic evaluation and treatment regimens were at the discretion of the treating attending physician. Review of medical records and all relevant radiographic studies were retrospectively performed for the purposes of this study. RESULTS During the study period, there were 12,667 patients admitted to the R Adams Cowley Shock Trauma Center. There were 147 patients identified with 200 carotid or vertebral artery injuries. The incidence of BVCI was 1.2%. Mortality was 13%. Anatomic injury risk factors for BCVI (major facial fractures, skull base fractures, cervical spine fractures or spinal cord injury, or traumatic brain injury) were found in only 78%. Major thoracic injury was found in 63% of patients with carotid artery injuries and cervical spine fractures or spinal cord injury was found in 74% of patients with vertebral artery injuries. The initial screening test employed was a WB-MDCT in 96% of patients of which 84% detected a BCVI. Treatments included endovascular therapy (22%), antiplatelet medications (36%), anticoagulation (10%), and combination therapy with antiplatelet agents and anticoagulation (18%). Thirty percent received no therapy, primarily due to contraindications from concomitant injuries. There were 18 (12%) patients who had a stroke. Of these patients, 8 (44%) had evidence of infarction at admission, 6 were diagnosed within 72 hours, and 4 were diagnosed after 1 week. Stroke-related mortality was 50%, whereas clinical follow-up after hospital discharge demonstrated only one patient with disability as a result of infarction. Of 10 patients who did not have stroke at admission, 3 were fully treated, 5 had specific contraindications to therapy, and 2 had no or false-negative imaging before infarction. Stroke rates for untreated patients were 25.8% and patients treated with any therapy had a stroke rate of 3.9% (p = 0.0003). Radiographic follow-up >1 month after injury demonstrated improvement in over 50% of patients. CONCLUSIONS BCVIs are not infrequent after blunt trauma. These injuries occur even in the absence of classically described risk factors. Liberal screening with WB-MDCT incorporates detection of these injuries into the initial diagnostic evaluation. Stroke occurs in a substantial number of patients and carries a very high mortality. However, nearly one third of patients with BCVI are not candidates for therapy. Treatment does reduce the risk of infarction in patients with BCVI, but strokes, when they occur, are not preventable.

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

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.

Controversy in Trauma Resuscitation: Do Ratios of Plasma to Red Blood Cells Matter?

Since a report in October 2007 of dramatic improvements in trauma mortality in a military population when massive transfusion of red blood cells (RBC) was accompanied by plasma replacement at 1:1 proportions, interest in the plasma-to-RBC ratio during resuscitation in both the trauma and transfusion communities has been intense. Over the 7-month period from August 2008 through February 2009, a further 9 major studies examining experience with plasma replacement in massively transfused civilian trauma patients have been published. This flood of observational studies is likely to continue. In this review, the authors examine the findings of these initial studies, highlighting the epidemiologic and analytic methodologies used, and the likely influence of these methodologies on the reported outcomes.

Brief episodes of intracranial hypertension and cerebral hypoperfusion are associated with poor functional outcome after severe traumatic brain injury.

BACKGROUND Management strategies after severe traumatic brain injury (TBI) target prevention and treatment of intracranial hypertension (ICH) and cerebral hypoperfusion (CH). We have previously established that continuous automated recordings of vital signs (VS) are more highly correlated with outcome than manual end-hour recordings. One potential benefit of automated vital sign data capture is the ability to detect brief episodes of ICH and CH. The purpose of this study was to establish whether a relationship exists between brief episodes of ICH and CH and outcome after severe TBI. MATERIALS Patients at the R Adams Cowley Shock Trauma Center were prospectively enrolled over a 2-year period. Inclusion criteria were as follows: age >14 years, admission within the first 6 hours after injury, Glasgow Coma Scale score <9 on admission, and placement of a clinically indicated ICP monitor. From high-resolution automated VS data recording system, we calculated the 5-minute means of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Brain Trauma Index (BTI = CPP/ICP). Patients were stratified by mortality and 6-month Extended Glasgow Outcome Score (GOSE). RESULTS Sixty subjects were enrolled with a mean admission Glasgow Coma Scale score of 6.4 ± 3.1, a mean Head Abbreviated Injury Severity Scale score of 4.2 ± 0.7, and a mean Marshall CT score of 2.5 ± 0.9. Significant differences in the mean number of brief episodes of CPP <50 and BTI <2 in patients with a GOSE 1-4 versus GOSE 5-8 (9.4 vs. 4.7, p = 0.02 and 9.3 vs. 4.9, p = 0.03) were found. There were significantly more mean brief episodes per day of ICP >30 (0.52 vs. 0.29, p = 0.02), CPP <50 (0.65 vs. 0.28, p < 0.001), CPP <60 (1.09 vs. 0.7, p = 0.03), BTI <2 (0.66 vs. 0.31, p = 0.002), and BTI <3 (1.1 vs. 0.64, p = 0.01) in those patients with GOSE 1-4. Number of brief episodes of CPP <50, CPP <60, BTI <2, and BTI <3 all demonstrated high predictive power for unfavorable functional outcome (area under the curve = 0.65-0.75, p < 0.05). CONCLUSIONS This study demonstrates that the number of brief 5-minute episodes of ICH and CH is predictive of poor outcome after severe TBI. This finding has important implications for management paradigms which are currently targeted to treatment rather than prevention of ICH and CH. This study demonstrates that these brief episodes may play a significant role in outcome after severe TBI.

Traditional systolic blood pressure targets underestimate hypotension-induced secondary brain injury.

BACKGROUND: Vital signs, particularly blood pressure, are often manipulated to maximize perfusion and optimize recovery from severe traumatic brain injury (sTBI). We investigated the utility of automated continuously recorded vital signs to predict outcomes after sTBI. METHODS: Sixty patients with head Abbreviated Injury Scale score ≥3, age >14 years, “isolated” TBI, and need for intracranial pressure monitoring were prospectively enrolled at a single, large urban tertiary care facility. Outcome was measured by mortality and extended Glasgow Outcome Scale (GOSE) at 12 months. Continuous, automated, digital data were collected every 6 seconds for 72 hours after admission, and 5-minute means of systolic blood pressure (SBP) were recorded. We calculated SBP as pressure × time dose (PTD) to describe the cumulative amplitude and duration of episodes above and below clinical thresholds. The extent and duration of the insults were calculated as percent time (%time), PTD, and PTD per day (PTD/D) of defined thresholds (SBP: <90 mm Hg, <100 mm Hg, <110 mm Hg, and <120 mm Hg; mean arterial pressure: <60 mm Hg and <70 mm Hg; heart rate: >100 bpm and >120 bpm; and SpO2: <88% and <92%) for the first 12 hours, 24 hours, and 48 hours of intensive care unit admission. We analyzed their ability to predict mortality and GOSE by receiver operator characteristics. RESULTS: Mean age was 33.9 (range, 16–83) years, mean admission Glasgow Coma Scale score 6.4 ± 3, and mean head Abbreviated Injury Scale score 4.2 ± 0.72. The 30-day mortality rate was 13.3%. Of the 45 patients in whom GOSE at 12 months was available, 28 (62%) had good neurologic outcomes (GOSE score >4). Traditional markers of poor outcome (admission SBP, admission Glasgow Coma Scale, and Marshall score) were not different between groups with good or poor outcome. PTD, PTD/D, and %time SBP <110 mm Hg and SBP <120 mm Hg predicted mortality at 12 hours, 24 hours, and 48 hours (p < 0.04). Percent time SBP <110 mm Hg in the first 24 hours was predictive of 12-month GOSE (p = 0.02). PTD/D SBP <120 mm Hg in the first 24 hours and PTD and PTD/D in the first 48 hours were also predictive of 12-month GOSE (p < 0.05). CONCLUSIONS: Within the first 48 hours of intensive care unit admission, hypotension was found to be predictive of mortality and functional outcomes at higher thresholds than traditionally defined. Systemic blood pressure targets closer to 120 mm Hg may be more efficacious in minimizing secondary insults and particularly useful in settings without invasive intracranial monitoring capabilities. LEVEL OF EVIDENCE: III, prognostic study.

Isolated severe traumatic brain injuries sustained during combat operations: demographics, mortality outcomes, and lessons to be learned from contrasts to civilian counterparts.

BACKGROUND Severe traumatic brain injuries occurring in the context of modern military conflict are entities about which little has been reported. We reviewed the epidemiology of these injuries from the Joint Trauma Theater Registry (JTTR), contrasting these results with civilian counterparts from the National Trauma Databank (NTDB). METHODS Isolated severe brain injuries (defined as head abbreviated injury scale [AIS] ≥3 and no other body region AIS>2) were queried from the JTTR over a period from 2003 to 2007. The demographics and outcomes of these injuries were reviewed. These results were then contrasted to findings of similar patients, age 18 years to 55 years, over the same period from the NTDB using propensity score matching derived from age, gender, systolic blood pressure, Glasgow Coma Scale, and AIS. RESULTS JTTR review identified 604 patients meeting study criteria, with a mean age of 25.7 years. Glasgow Coma Scale was ≤8 in 27.8%, and 98.0% were men. Hypotension at presentation was noted in 5.5%. Blast (61.9%) and gunshot wound (19.5%) mechanisms accounted for the majority of combat injuries. Intracranial pressure monitoring was used in 15.2%, and 27.0% underwent some form of operative cranial decompression, lobectomy, or debridement. When compared with matched civilian NTDB counterparts, JTTR patients were significantly more likely to undergo intracranial pressure monitoring (13.8% vs. 1.7%; p<0.001) and operative neurosurgical intervention (21.5% vs. 7.2%; p<0.001). Mortality was also significantly better among military casualties overall (7.7% vs. 21.0%; p<0.001; odds ratio, 0.32 [0.16-0.61]) and particularly after penetrating mechanisms of injury (5.6% vs. 47.9%; p<0.001; odds ratio, 0.07 [0.02-0.20]) compared with propensity score-matched NTDB counterparts. CONCLUSION Patients sustaining severe traumatic brain injury during military operations represent a unique population. Comparison with civilian counterparts has inherent limitations but reveals higher rates of neurosurgical intervention performed after penetrating injuries and a corresponding improvement in survival. Many factors likely contribute to these findings, which highlight the need for additional research on the optimal management of penetrating brain injury.

Basic endovascular skills for trauma course: bridging the gap between endovascular techniques and the acute care surgeon.

BACKGROUND The use of catheter-based skills is increasing in the field of vascular trauma. Virtual reality simulation (VRS) is a well-established means of endovascular skills training, and potentially lifesaving skills such as resuscitative endovascular balloon occlusion of the aorta (REBOA) may be obtained through VRS. METHODS Thirteen faculty members in the Division of Trauma and Critical Care performed REBOA six times on the Vascular Intervention System Training Simulator–C after a didactic and instructional session. Subjects were excluded if they had taken a similar endovascular training course, had additional training in endovascular surgery, or had performed this procedure in the clinical setting. Performance metrics included procedural time; accurate placement of guide wire, sheath, and balloon; correct sequence of steps; economy of motion; and safe use of endovascular tools. A precourse and postcourse test and questionnaire were performed by each subject. RESULTS Significant improvements in knowledge (p = 0.0013) and procedural task times (p < 0.0001) were observed at the completion of the course. No correlation was observed with endovascular experience in residency, number of central and arterial catheters placed weekly, or other parameters. All trainees strongly agreed that the course was beneficial, and the majority would recommend this training to other acute care surgeons. CONCLUSION Damage control endovascular procedures can be effectively taught using VRS. Significant improvements in procedural time and knowledge can be achieved regardless of endovascular experience in residency, years since residency, or other parameters. Novice interventionalists (acute care surgeons) can add a specific skill set (REBOA) to their existing core competencies, which has the potential to improve the survival and/or outcomes of severely injured patients.

Major hepatic necrosis: a common complication after angioembolization for treatment of high-grade liver injuries.

BACKGROUND The management of high-grade liver injuries often involves a combination of operative and nonoperative strategies. Angioembolization (AE) is frequently used in the management of these injuries. Morbidity in patients with high-grade hepatic injuries remains high despite improvements in mortality with a multimodality approach. Major hepatic necrosis (MHN) is a morbid, but underappreciated complication of AE in this patient population. This study will examine the risk factors and outcomes of patients with high-grade liver injures managed with AE who developed the complication of MHN. METHODS Patients admitted to the R Adams Cowley Shock Trauma Center between January 2002 and December 2007 with high-grade blunt or penetrating liver injuries (grades III-VI) were identified from the trauma registry and the medical records were retrospectively reviewed. Demographic and injury specific data, complications, and admission physiologic variables were collected. Patients who had therapeutic AE, either preoperatively or postoperatively, and went on to develop liver-related complications including MHN were reviewed. RESULTS There were 538 patients with high-grade liver injuries admitted during a 5-year period. One hundred and sixteen patients (22%) underwent angiography, and 71 (13%) had a therapeutic AE. Sixteen patients (22.5%) had grade III injuries, 44 (62%) had grade IV injuries, and 11 (15.5%) had grade V injuries. Overall mortality in this group was 14% with eight patients (11.3%) dying as a result of their liver injury. Complication rates were 18.8%, 65.9%, and 100% in the patients with grades III, IV, and V injuries, respectively, for an overall complication rate of 60.6%. Thirty patients (42.2%) went on to develop MHN. Patients who developed MHN were compared with those who did not. Baseline characteristics, Injury Severity Score, and hemodynamic parameters at admission were no different between the two groups. Patients with MHN had higher grade injuries, required significantly more blood product transfusions, and had a significantly longer length of stay (all p < 0.001). Patients who developed MHN were more likely to have undergone operative intervention (96.7% vs. 41.5%, p < 0.001), with 87% having a damage control laparotomy. Other liver-related complications occurred more frequently in the patients that developed MHN (60.0% vs. 34.1%, p = 0.03). However, mortality was not different in the two groups. CONCLUSION High-grade liver injuries pose significant challenges to those who care for trauma patients. Many patients can be successfully managed nonoperatively, but there are still patients that require laparotomy. AE is the logical augmentation of damage control techniques for controlling hemorrhage. However, given the nature and severity of these injuries, these therapies are not without complications. MHN was found to be a common complication in our study. It tended to occur in high-grade injures, was associated with higher complication rates, longer hospital length of stay, and higher transfusion requirements. Management of MHN can be challenging. Factors that still need to be elucidated are the role of perihepatic packing and timing of second look operation.

Ultrasound-guided peripheral intravenous access in the intensive care unit

PURPOSE Central venous catheters continue to be a popular means of maintaining vascular access in surgical intensive care units despite well-described complications. With edema, obesity, and difficult to visualize veins potentially affecting the surgically ill, inability to obtain peripheral intravenous (PIV) access may hinder the clinicians ability to avoid the use of central lines. With ultrasound gaining increased popularity for obtaining vascular access, we evaluated its utility in ultrasonagraphically placing PIV catheters for the purposes of either avoiding central venous access or removing central venous catheters. MATERIALS AND METHODS We performed a retrospective cohort review of our requests for ultrasound-guided PIV access in the intensive care unit between September 2007 and February 2008. RESULTS Over a 6-month period, 77 requests for ultrasound-guided PIV access were made for 59 surgical, trauma, and cardiothoracic intensive care unit patients. Reasons for inability to obtain PIVs through standard means included edema (95%), obesity (42%), IV drug abuse history (8%), and emergency access (4%). Of the 148 PIV lines that were requested, 147 PIV catheters were successfully placed (99%). Of these, 105 PIV catheters were placed on the first attempt (71%). Complications of PIVs included IV infiltration (3.4%), inadvertent removal (2.7%), and phlebitis/cellulitis (0.7%). As a result of placing these PIV catheters, 40 central lines were discontinued and 34 central lines were avoided. The average number of line days at the time of central venous catheter removal was 11 ± 11 days. CONCLUSION(S) In intensive care unit patients who do not require central venous lines, ultrasound-guided PIV access can have a high placement success rate and can result in fewer central line days and/or less reliance on central venous catheters for access-only purposes.