Ronald Chang

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage

BACKGROUND Plasma‐based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large‐animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. METHODS We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. “Early plasma” was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. RESULTS Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71–1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within‐group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20–9.35). CONCLUSION Although early plasma transfusion was not associated with improved in‐hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in‐hospital survival in those with multifocal intracranial hemorrhage.

Choice of Fluid Therapy in the Initial Management of Sepsis, Severe Sepsis, and Septic Shock.

ABSTRACT Sepsis results in disruption of the endothelial glycocalyx layer and damage to the microvasculature, resulting in interstitial accumulation of fluid and subsequently edema. Fluid resuscitation is a mainstay in the initial treatment of sepsis, but the choice of fluid is unclear. The ideal resuscitative fluid is one that restores intravascular volume while minimizing edema; unfortunately, edema and edema-related complications are common consequences of current resuscitation strategies. Crystalloids are recommended as first-line therapy, but the type of crystalloid is not specified. There is increasing evidence that normal saline is associated with increased mortality and kidney injury; balanced crystalloids may be a safer alternative. Albumin is similar to crystalloids in terms of outcomes in the septic population but is costlier. Hydroxyethyl starches appear to increase mortality and kidney injury in the critically ill and are no longer indicated in these patients. In the trauma population, the shift to plasma-based resuscitation with decreased use of crystalloid and colloid in the treatment of hemorrhagic shock has led to decreased inflammatory and edema-mediated complications. Studies are needed to determine if these benefits also occur with a similar resuscitation strategy in the setting of sepsis.

Plasma Resuscitation Improved Survival in a Cecal Ligation and Puncture Rat Model of Sepsis

Background: The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-h survival in a rat sepsis model. Methods: Adult male Sprague–Dawley rats (375–425 g) were subjected to 35% cecal ligation and puncture (CLP) (t = 0 h). Twenty-two hours post-CLP and prior to resuscitation (t = 22 h), animals were randomized to resuscitation with normal saline (NS, 10 cc/kg/h) or pooled rat fresh frozen plasma (FFP, 3.33 cc/kg/h). Resuscitation under general anesthesia proceeded for the next 6 h (t = 22 h to t = 28 h); lactate was checked every 2 h, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t = 22 h) and after resuscitation (t = 28 h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-to-dry weight ratio. Fisher exact test was used to analyze the primary outcome of 48-h survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-tailed alpha level of <0.05 was used for all statistical tests. Results: Thirty-three animals were studied: 14 FFP, 14 NS, and 5 sham. Post-CLP but preresuscitation (t = 22 h) variables between FFP and NS animals were similar and significantly deranged compared with sham animals. FFP significantly increased 48-h survival compared to NS (n = 8 [57%] vs n = 2 [14%]), attenuated the post-resuscitation (t = 28 h) levels of epinephrine (mean 2.2 vs 7.0 ng/mL), norepinephrine, (3.8 vs 8.9 ng/mL), IL-6 (3.8 vs 18.7 ng/mL), and syndecan-1 (21.8 vs 31.0 ng/mL) (all P < 0.05), improved the post-resuscitation PO2 to FiO2 ratio (353 vs 151), and reduced the pulmonary wet-to-dry weight ratio (5.28 vs 5.94) (all P < 0.05). Conclusion: Compared to crystalloid, plasma resuscitation increased 48-h survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.

Remote Damage Control Resuscitation in Austere Environments

Hemorrhage is the leading cause of preventable military and civilian trauma death. Damage control resuscitation with concomitant mechanical hemorrhage control has become the preferred in-hospital treatment of hemorrhagic shock. In particular, plasma-based resuscitation with decreased volumes of crystalloids and artificial colloids as part of damage control resuscitation has improved outcomes in the military and civilian sectors. However, translation of these principles and techniques to the prehospital, remote, and austere environments, known as remote damage control resuscitation, is challenging given the resource limitations in these settings. Rapid administration of tranexamic acid and reconstituted freeze-dried (lyophilized) plasma as early as the point of injury are feasible and likely beneficial, but comparative studies in the literature are lacking. Whole blood is likely the best fluid therapy for traumatic hemorrhagic shock, but logistical hurdles need to be addressed. Rapid control of external hemorrhage with hemostatic dressings and extremity tourniquets are proven therapies, but control of noncompressible hemorrhage (ie, torso hemorrhage) remains a significant challenge.

Multicenter retrospective study of noncompressible torso hemorrhage: Anatomic locations of bleeding and comparison of endovascular versus open approach

BACKGROUND Rational development of technology for rapid control of noncompressible torso hemorrhage (NCTH) requires detailed understanding of what is bleeding. Our objectives were to describe the anatomic location of truncal bleeding in patients presenting with NCTH and compare endovascular (ENDO) management versus open (OPEN) management. METHODS This is a retrospective study of adult trauma patients with NCTH admitted to four urban Level I trauma centers in the Houston and San Antonio metropolitan areas in 2008 to 2012. Inclusion criteria include named axial torso vessel disruption, Abbreviated Injury Scale chest or abdomen score of 3 or higher with shock (base excess, <-4) or truncal operation in 90 minutes or less, or pelvic fracture with ring disruption. Exclusion criteria include isolated hip fractures, falls from standing, or prehospital cardiopulmonary resuscitation. After dichotomizing into OPEN, ENDO, and resuscitative thoracotomy (RT) groups based on the initial approach to control NCTH, a mixed-effects Poisson regression with robust error variance (controlling for age, mechanism, Injury Severity Score, shock, hypotension, and severe head injury as fixed effects and site as a random effect) was used to test the hypothesis that ENDO was associated with reduced in-hospital mortality in NCTH patients. RESULTS Five hundred forty-three patients with NCTH underwent ENDO (n = 166, 31%), OPEN (n = 309, 57%), or RT (n = 68, 12%). Anatomic bleeding locations were 25% chest, 41% abdomen, and 31% pelvis. ENDO was used to treat relatively few types of vascular injuries, whereas OPEN and RT injuries were more diverse. ENDO patients had more blunt trauma (95% vs. 34% vs. 32%); severe injuries (median Injury Severity Score, 34 vs. 27 vs. 21), and increased time to intervention (median, 298 vs. 92 vs. 51 minutes) compared with OPEN and RT. Mortality was 15% versus 20% versus 79%. ENDO was associated with decreased mortality compared to OPEN (relative risk, 0.58; 95% confidence interval, 0.46-0.73). CONCLUSION Although ENDO may reduce mortality in NCTH patients, significant group differences limit the generalizability of this finding. LEVEL OF EVIDENCE Therapeutic, level V.BACKGROUND Rational development of technology for rapid control of noncompressible torso hemorrhage (NCTH) requires detailed understanding of what is bleeding. Our objectives were to describe the anatomic location of truncal bleeding in patients presenting with NCTH and compare endovascular (ENDO) management versus open (OPEN) management. METHODS This is a retrospective study of adult trauma patients with NCTH admitted to four urban Level I trauma centers in the Houston and San Antonio metropolitan areas in 2008 to 2012. Inclusion criteria include named axial torso vessel disruption, Abbreviated Injury Scale chest or abdomen score of 3 or higher with shock (base excess, <−4) or truncal operation in 90 minutes or less, or pelvic fracture with ring disruption. Exclusion criteria include isolated hip fractures, falls from standing, or prehospital cardiopulmonary resuscitation. After dichotomizing into OPEN, ENDO, and resuscitative thoracotomy (RT) groups based on the initial approach to control NCTH, a mixed-effects Poisson regression with robust error variance (controlling for age, mechanism, Injury Severity Score, shock, hypotension, and severe head injury as fixed effects and site as a random effect) was used to test the hypothesis that ENDO was associated with reduced in-hospital mortality in NCTH patients. RESULTS Five hundred forty-three patients with NCTH underwent ENDO (n = 166, 31%), OPEN (n = 309, 57%), or RT (n = 68, 12%). Anatomic bleeding locations were 25% chest, 41% abdomen, and 31% pelvis. ENDO was used to treat relatively few types of vascular injuries, whereas OPEN and RT injuries were more diverse. ENDO patients had more blunt trauma (95% vs. 34% vs. 32%); severe injuries (median Injury Severity Score, 34 vs. 27 vs. 21), and increased time to intervention (median, 298 vs. 92 vs. 51 minutes) compared with OPEN and RT. Mortality was 15% versus 20% versus 79%. ENDO was associated with decreased mortality compared to OPEN (relative risk, 0.58; 95% confidence interval, 0.46–0.73). CONCLUSION Although ENDO may reduce mortality in NCTH patients, significant group differences limit the generalizability of this finding. LEVEL OF EVIDENCE Therapeutic, level V.

Abnormalities of laboratory coagulation tests versus clinically evident coagulopathic bleeding: Results from the prehospital resuscitation on helicopters study (PROHS)

Background. Laboratory‐based evidence of coagulopathy (LC) is observed in 25–35% of trauma patients, but clinically‐evident coagulopathy (CC) is not well described. Methods. Prospective observational study of adult trauma patients transported by helicopter from the scene to nine Level 1 trauma centers in 2015. Patients meeting predefined highest‐risk criteria were divided into CC+ (predefined as surgeon‐confirmed bleeding from uninjured sites or injured sites not controllable by sutures) or CC‐. We used a mixed‐effects, Poisson regression with robust error variance to test the hypothesis that abnormalities on rapid thrombelastography (r‐TEG) and international normalized ratio (INR) were independently associated with CC+. Results. Of 1,019 highest‐risk patients, CC+ (n=41, 4%) were more severely injured (median ISS 32 vs 17), had evidence of LC on r‐TEG and INR, received more transfused blood products at 4 hours (37 vs 0 units), and had greater 30‐day mortality (59% vs 12%) than CC‐ (n=978, 96%). The overall incidence of LC was 39%. 30‐day mortality was 22% vs 9% in those with and without LC. In two separate models, r‐TEG K‐time >2.5 min (RR 1.3, 95% CI 1.1–1.7), r‐TEG mA <55 mm (RR 2.5, 95% CI 2.0–3.2), platelet count <150 x 109/L (RR 1.2, 95% CI 1.1–1.3), and INR >1.5 (RR 5.4, 95% CI 1.8–16.3) were independently associated with CC+. A combined regression model was not generated because too few patients underwent both r‐TEG and INR. Conclusion. CC was rare compared to LC. CC was associated with poor outcomes and impairment of both clotting factor and platelet‐mediated coagulation components.

Early chemoprophylaxis is associated with decreased venous thromboembolism risk without concomitant increase in intraspinal hematoma expansion after traumatic spinal cord injury

BACKGROUND After traumatic spinal cord injury (SCI), there is increased risk of venous thromboembolism (VTE), but chemoprophylaxis (PPX) may cause expansion of intraspinal hematoma (ISH). METHODS Single-center retrospective study of adult trauma patients from 2012 to 2015 with SCI. Exclusion criteria: VTE diagnosis, death, or discharge within 48 hours. Patients were dichotomized based on early (⩽48 hours) heparinoid and/or aspirin PPX. Intraspinal hematoma expansion was diagnosed intraoperatively or by follow-up radiology. We used multivariable Cox proportional hazards to estimate the effect of PPX on risk of VTE and ISH expansion controlling for age, injury severity score (ISS), complete SCI, and mechanism as static covariates and operative spine procedure as a time-varying covariate. RESULTS Five hundred one patients with SCI were dichotomized into early PPX (n = 260 [52%]) and no early PPX (n = 241 [48%]). Early PPX patients were less likely blunt injured (91% vs 97%) and had fewer operative spine interventions (65% vs 80%), but age (median, 43 vs 49 years), ISS (median 24 vs 21), admission ISH (47% vs 44%), and VTE (5% vs 9%) were similar. Cox analysis found that early heparinoids was associated with reduced VTE (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.16–0.84) and reduced pulmonary embolism (PE) (HR, 0.20; 95% CI, 0.06–0.69). The estimated number needed to treat with heparinoids was 10 to prevent one VTE and 13 to prevent one PE at 30 days. Early aspirin was not associated with reduced VTE or PE. Seven patients (1%) had ISH expansion, of which four were on PPX at the time of expansion. Using heparinoid and aspirin as time-varying covariates, neither heparinoids (HR, 1.90; 95% CI, 0.32–11.41) nor aspirin (HR, 3.67; 95% CI, 0.64–20.88) was associated with ISH expansion. CONCLUSION Early heparinoid therapy was associated with decreased VTE and PE risk in SCI patients without concomitant increase in ISH expansion. LEVEL OF EVIDENCE Therapeutic, level IV.