Eileen M. Bulger

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.

Cytomegalovirus Reactivation in Critically-Ill Immunocompetent Patients

CONTEXT Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons, but the incidence and association of CMV reactivation with adverse outcomes in critically ill persons lacking evidence of immunosuppression have not been well defined. OBJECTIVE To determine the association of CMV reactivation with intensive care unit (ICU) and hospital length of stay in critically ill immunocompetent persons. DESIGN, SETTING, AND PARTICIPANTS We prospectively assessed CMV plasma DNAemia by thrice-weekly real-time polymerase chain reaction (PCR) and clinical outcomes in a cohort of 120 CMV-seropositive, immunocompetent adults admitted to 1 of 6 ICUs at 2 separate hospitals at a large US tertiary care academic medical center between 2004 and 2006. Clinical measurements were assessed by personnel blinded to CMV PCR results. Risk factors for CMV reactivation and association with hospital and ICU length of stay were assessed by multivariable logistic regression and proportional odds models. MAIN OUTCOME MEASURES Association of CMV reactivation with prolonged hospital length of stay or death. RESULTS The primary composite end point of continued hospitalization (n = 35) or death (n = 10) by 30 days occurred in 45 (35%) of the 120 patients. Cytomegalovirus viremia at any level occurred in 33% (39/120; 95% confidence interval [CI], 24%-41%) at a median of 12 days (range, 3-57 days) and CMV viremia greater than 1000 copies/mL occurred in 20% (24/120; 95% CI, 13%-28%) at a median of 26 days (range, 9-56 days). By logistic regression, CMV infection at any level (adjusted odds ratio [OR], 4.3; 95% CI, 1.6-11.9; P = .005) and at greater than 1000 copies/mL (adjusted OR, 13.9; 95% CI, 3.2-60; P < .001) and the average CMV area under the curve (AUC) in log(10) copies per milliliter (adjusted OR, 2.1; 95% CI, 1.3-3.2; P < .001) were independently associated with hospitalization or death by 30 days. In multivariable partial proportional odds models, both CMV 7-day moving average (OR, 5.1; 95% CI, 2.9-9.1; P < .001) and CMV AUC (OR, 3.2; 95% CI, 2.1-4.7; P < .001) were independently associated with a hospital length of stay of at least 14 days. CONCLUSIONS These preliminary findings suggest that reactivation of CMV occurs frequently in critically ill immunocompetent patients and is associated with prolonged hospitalization or death. A controlled trial of CMV prophylaxis in this setting is warranted.

Management of severe head injury: Institutional variations in care and effect on outcome

ObjectiveThe purpose of this study was three-fold: a) to examine variations in care of patients with severe head injury in academic trauma centers across the United States; b) to determine the proportion of patients who received care according to the Brain Trauma Foundation guidelines; and c) to correlate the outcome from severe traumatic brain injury with the care received. DesignRetrospective data collection for consecutive patients with closed head injury and long bone fracture admitted over an 8-month period. SettingThirty-four academic trauma centers in the United States PatientsAll patients admitted with a presenting Glasgow Coma Scale score ≤8. Measurements and Main ResultsVariations in care were assessed, including prehospital intubation, intracranial pressure monitoring, use of osmotic agents, hyperventilation, and computed tomography scan utilization. Aggressive centers were defined as those placing intracranial pressure monitors in >50% of patients meeting the Brain Trauma Foundation criteria for intracranial pressure monitoring. The primary outcome variables were mortality, functional status at discharge, and length of stay. Kaplan-Meier survival analysis was performed for aggressive vs. nonaggressive centers. A Cox proportional hazard model was used to evaluate the association between type of center and mortality rate. Length of stay was evaluated by using linear regression. ResultsThere was considerable variation in the rates of prehospital intubation, intracranial pressure monitoring, intracranial pressure-directed therapy, and head computed tomography scan utilization across centers. Management at an aggressive center was associated with a significant reduction in the risk of mortality (hazard ratio, 0.43; 95% confidence interval, 0.27–0.66). There was no statistically significant difference in functional status at the time of discharge for survivors. Adjusted length of stay for survivors at aggressive centers was shorter, compared with the length of stay at nonaggressive centers: −6 days (95% confidence interval, −14 to 2 days). ConclusionConsiderable national variation in the care of severely head-injured patients persists. An “aggressive” management strategy is associated with decreased mortality rate for patients with severe head injury, with no significant difference in functional status at discharge among survivors.

Rib fractures in the elderly.

BACKGROUND We sought to ascertain the extent to which advanced age influences the morbidity and mortality after rib fractures (fxs), to define the relationship between number of rib fractures and morbidity and mortality, and to evaluate the influence of analgesic technique on outcome. METHODS A retrospective cohort study involving all 277 patients > or = 65 years old with rib fxs admitted to a Level I trauma center over 10 years was undertaken. The control group consisted of 187 randomly selected patients, 18 to 64 years old, with rib fxs admitted over the same time period. Outcomes included pulmonary complications, number of ventilator days, length of intensive care unit and hospital stay (LOS), disposition, and mortality. The specific analgesic technique used was also examined. RESULTS The two groups had similar mean number of rib fxs (3.6 elderly vs. 4.0 young), mean chest Abbreviated Injury Scores (3.0 vs. 3.0), and mean Injury Severity Score (20.7 vs. 21.4). However, mean number of ventilator days (4.3 vs. 3.1), intensive care unit days (6.1 vs. 4.0), and LOS (15.4 vs. 10.7 days) were longer for the elderly patients. Pneumonia occurred in 31% of elderly versus 17% of young (p < 0.01) and mortality was 22% for the elderly versus 10% for the young (p < 0.01). Mortality and pneumonia rates increased as the number of rib fxs increased with and odds ratio for death of 1.19 and for pneumonia of 1.16 per each additional rib fracture (p < 0.001). The use of epidural analgesia in the elderly (LOS >2 days) was associated with a 10% mortality versus 16% without the use of an epidural (p = 0.28). In the younger group (LOS >2 days), mortality with and without the use of an epidural was 0% and 5%, respectively. CONCLUSION Elderly patients who sustain blunt chest trauma with rib fxs have twice the mortality and thoracic morbidity of younger patients with similar injuries. For each additional rib fracture in the elderly, mortality increases by 19% and the risk of pneumonia by 27%. As the number of rib fractures increases, there is a significant increase in morbidity and mortality in both groups, but with different patterns for each group. Further prospective study is needed to determine the utility of epidural analgesia in this population.

Out-of-Hospital Hypertonic Resuscitation Following Severe Traumatic Brain Injury: A Randomized Controlled Trial

CONTEXT Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI). OBJECTIVE To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients. INTERVENTION A single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting. MAIN OUTCOME MEASURE Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4). RESULTS The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, -4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, -4.0% to 9.7%]; P = .67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline/dextran, 75.7% with hypertonic saline, and 75.1% with normal saline (P = .88). CONCLUSION Among patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00316004.

Out-of-hospital Hypertonic Resuscitation After Traumatic Hypovolemic Shock A Randomized, Placebo Controlled Trial

Objective: To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. Background: Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. Methods: Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age ≥ 15 years with hypovolemic shock (systolic blood pressure ⩽ 70 mm Hg or systolic blood pressure 71–90 mm Hg with heart rate ≥ 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern. Results: A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival—HSD: 74.5% (0.1; 95% confidence interval [CI], −7.5 to 7.8); HS: 73.0% (−1.4; 95% CI, −8.7–6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality—HSD: 10% (5.2; 95% CI, 0.4–10.1); HS: 12.2% (7.4; 95% CI, 2.5–12.2); and NS: 4.8%, P < 0.01]. Conclusion: Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial. Clinical Trial Registration: Clinical Trials.gov, NCT00316017

Skeletal muscle predicts ventilator-free days, ICU-free days, and mortality in elderly ICU patients

IntroductionAs the population ages, the number of injured elderly is increasing. We sought to determine if low skeletal muscle mass adversely affected outcome in elderly patients following trauma.MethodsPatients ≥ 65 years of age with an admission abdominal computed tomography scan and requiring intensive care unit (ICU) stay at a Level I trauma center in 2009–2010 were reviewed. Muscle cross-sectional area at the 3rd lumbar vertebra was quantified and muscle index, a normalized measure of muscle mass, was calculated and related to clinical parameters including ventilator-free days, ICU-free days, and mortality. Using previously established sex-specific, muscle index cut-points, patients were then categorized as sarcopenic or non-sarcopenic and differences in clinical outcomes between these two groups were also compared. We also examined muscle index as a continuous variable relative to the same clinical outcomes.ResultsThere were 149 severely injured elderly patients (median age 79 years) enrolled in this study of which 71% were sarcopenic. Of the patients who were sarcopenic, 9% were underweight, 44% normal weight, and 47% overweight/obese as per body mass index (BMI) classifications. The overall mortality rate was 27% and univariate analysis demonstrated higher mortality among those who were sarcopenic (32% vs. 14%, P = 0.018). After controlling for age, sex, and injury severity, multiple logistic regression demonstrated that increased muscle index was significantly associated with decreased mortality (OR per unit muscle index = 0.93, 95% CI: 0.875-0.997, P = 0.025). In addition, multivariate linear regression showed that sarcopenia, but not muscle index, was associated with decreased ventilator-free (P = 0.004) and ICU-free days (P = 0.002). Neither BMI, serum albumin nor total adipose tissue on admission were indicative of survival, ventilator-free or ICU-free days.ConclusionsSarcopenia is highly prevalent in the elderly population with traumatic injuries. Traditional measures of nutritional assessment, such as BMI and serum albumin, do not accurately predict outcome in the injured elderly. Sarcopenia, however, represents a potential new predictor for mortality, discharge disposition, and ICU utilization. Measurement of muscularity allows for the early identification of at-risk patients who may benefit from aggressive and multidisciplinary nutritional and rehabilitative strategies.

Mass casualty triage: an evaluation of the data and development of a proposed national guideline.

Mass casualty triage is a critical skill. Although many systems exist to guide providers in making triage decisions, there is little scientific evidence available to demonstrate that any of the available systems have been validated. Furthermore, in the United States there is little consistency from one jurisdiction to the next in the application of mass casualty triage methodology. There are no nationally agreed upon categories or color designations. This review reports on a consensus committee process used to evaluate and compare commonly used triage systems, and to develop a proposed national mass casualty triage guideline. The proposed guideline, entitled SALT (sort, assess, life-saving interventions, treatment and/or transport) triage, was developed based on the best available science and consensus opinion. It incorporates aspects from all of the existing triage systems to create a single overarching guide for unifying the mass casualty triage process across the United States.

Safety and efficacy of video-assisted retroperitoneal debridement for infected pancreatic collections: a multicenter, prospective, single-arm phase 2 study.

BACKGROUND The feasibility of video-assisted retroperitoneal debridement (VARD) for infected pancreatic walled-off necrosis is established. We provide prospective data on the safety and efficacy of VARD. DESIGN Multicenter, prospective, single-arm phase 2 study. SETTING Six academic medical centers. PATIENTS We evaluated 40 patients with pancreatic necrosis who had infection determined using Gram stain or culture. INTERVENTIONS Percutaneous drains were placed at enrollment, and computed tomographic scans were repeated at 10 days. Patients who had more than a 75% reduction in collection size were treated with drains. Other patients were treated with VARD. Crossover to open surgery was performed for technical reasons and/or according to surgeon judgment. MAIN OUTCOME MEASURES Efficacy (ie, successful VARD treatment without crossover to open surgery or death) and safety (based on mortality and complication rates). Patients received follow-up care for 6 months. RESULTS We enrolled 40 patients (24 men and 16 women) during a 51-month period. Median age was 53 years (range, 32-82 years). Mean (SD) Acute Physiology and Chronic Health Evaluation II score at enrollment was 8.0 (5.1), and median computed tomography severity index score was 8. Of the 40 patients, 24 (60%) were treated with minimally invasive intervention (drains with or without VARD). Nine patients (23%) did not require surgery (drains only). For 31 surgical patients, VARD was possible in 60% of patients. Most patients (81%) required 1 operation. In-hospital 30-day mortality was 2.5% (intent-to-treat). Bleeding complications occurred in 7.5% of patients; enteric fistulas occurred in 17.5%. CONCLUSIONS This prospective cohort study supports the safety and efficacy of VARD for infected pancreatic walled-off necrosis. Of the patients, 85% were eligible for a minimally invasive approach. We were able to use VARD in 60% of surgical patients. The low mortality and complication rates compare favorably with open debridement. An unexpected finding was that a reduction in collection size of 75% according to the results of computed tomographic scans at 10 to 14 days predicted the success of percutaneous drainage alone.

Trauma patients receiving CPR: predictors of survival.

OBJECTIVE To determine whether prehospital clinical assessments are associated with the survival of traumatic cardiopulmonary arrest (TCPA) patients and to test recently issued clinical guidelines for prehospital cessation of resuscitative efforts published by the National Association of Emergency Physicians and the American College of Surgeons Committee on Trauma. METHODS A retrospective cohort study was done of all TCPA patients who had transported to a Level I trauma center by a municipal EMS provider between January 1, 1994 and April 1, 2001. Data regarding mechanism of injury, clinical assessments and care provided by EMS and the emergency department (ED), hospital care, survival, and neurologic outcome was collected. RESULTS 184 patients met exclusion criteria, with 14 (7.6%) surviving to discharge. Pupillary response to light, presence of a prehospital pulse or respiratory effort, a sinus electrocardiogram, and a Glascow Coma Scale greater than three were all significantly associated with survival but were not exclusive. 28.6% of patients admitted to the trauma center from the ED survived. There were frequent discrepancies between prehospital and ED clinical assessments. Several survivors met criteria for non-treatment according to the proposed clinical guidelines. CONCLUSIONS +/- Prehospital clinical assessments are not reliable for the triage of TCPA patients. Patients should be transported to the ED for further evaluation and care. The guidelines should not adopted until more thorough studies are conducted.