Herb A. Phelan

Damage control resuscitation: the new face of damage control.

Juan C. Duchesne, MD, FACS, FCCP, Norman E. McSwain, Jr., MD, FACS, Bryan A. Cotton, MD, FACS, John P. Hunt, MD, MPH, FACS, Jeff Dellavolpe, MD, Kelly Lafaro, MD, MPH, Alan B. Marr, MD, FACS, Earnest A. Gonzalez, MD, FACS, Herb A. Phelan, MD, FACS, Tracy Bilski, MD, FACS, Patrick Greiffenstein, MD, James M. Barbeau, MD, JD, Kelly V. Rennie, MD, Christopher C. Baker, MD, FACS, Karim Brohi, MD, FRCS, FRCA, Donald H. Jenkins, MD, FACS, and Michael Rotondo, MD, FACS

Clinical and mechanistic drivers of acute traumatic coagulopathy.

BACKGROUND Acute traumatic coagulopathy (ATC) occurs after severe injury and shock and is associated with increased bleeding, morbidity, and mortality. The effects of ATC and hemostatic resuscitation on outcome are not well-explored. The PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study provided a unique opportunity to characterize coagulation and the effects of resuscitation on ATC after severe trauma. METHODS Blood samples were collected upon arrival on a subset of PROMMTT patients. Plasma clotting factor levels were prospectively assayed for coagulation factors. These data were analyzed with comprehensive PROMMTT clinical data. RESULTS There were 1,198 patients with laboratory results, of whom 41.6% were coagulopathic. Using international normalized ratio of 1.3 or greater, 41.6% of patients (448) were coagulopathic, while 20.5% (214) were coagulopathic using partial thromboplastin time of 35 or greater. Coagulopathy was primarily associated with a combination of an Injury Severity Score (ISS) of greater than 15 and a base deficit (BD) of less than −6 (p < 0.05). Regression modeling for international normalized ratio–based coagulopathy shows that prehospital crystalloid (odds ratio [OR], 1.05), ISS (OR, 1.03), Glasgow Coma Scale (GCS) score (OR, 0.93), heart rate (OR, 1.08), systolic blood pressure (OR, 0.96), BD (OR, 0.92), and temperature (OR, 0.84) were significant predictors of coagulopathy (all p < 0.03). A subset of 165 patients had blood samples collected and coagulation factor analysis performed. Elevated ISS and BD were associated with elevation of aPC and depletion of factors (all p < 0.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p < 0.04). Similar results were found for partial thromboplastin time–defined coagulopathy. CONCLUSION ATC is associated with the depletion of factors I, II, V, VII, VIII, IX, and X and is driven by the activation of the protein C system. These data provide additional mechanistic understanding of the drivers of coagulation abnormalities after injury. Further understanding of the drivers of ATC and the effects of resuscitation can guide factor-guided resuscitation and correction of coagulopathy after injury. LEVEL OF EVIDENCE Epidemiologic/prognostic study, level IV.

An evaluation of multidetector computed tomography in detecting pancreatic injury: results of a multicenter AAST study.

BACKGROUND Efforts to determine the suitability of low-grade pancreatic injuries for nonoperative management have been hindered by the inaccuracy of older computed tomography (CT) technology for detecting pancreatic injury (PI). This retrospective, multicenter American Association for the Surgery of Trauma-sponsored trial examined the sensitivity of newer 16- and 64-multidetector CT (MDCT) for detecting PI, and sensitivity/specificity for the identification of pancreatic ductal injury (PDI). METHODS Patients who received a preoperative 16- or 64-MDCT followed by laparotomy with a documented PI were enrolled. Preoperative MDCT scans were classified as indicating the presence (+) or absence (-) of PI and PDI. Operative notes were reviewed and all patients were confirmed as PI (+), and then classified as PDI (+) or (-). As all patients had PI, an analysis of PI specificity was not possible. PI patients formed the pool for further PDI analysis. As sensitivity and specificity data were available for PDI, multivariate logistic regression was performed for PDI patients using the presence or absence of agreement between CT and operative note findings as an independent variable. Covariates were age, gender, Injury Severity Score, mechanism of injury, presence of oral contrast, presence of other abdominal injuries, performance of the scan as part of a dedicated pancreas protocol, and image thickness < or =3 mm or > or =5 mm. RESULTS Twenty centers enrolled 206 PI patients, including 71 PDI (+) patients. Intravenous contrast was used in 203 studies; 69 studies used presence of oral contrast. Eight-nine percent were blunt mechanisms, and 96% were able to have their duct status operatively classified as PDI (+) or (-). The sensitivity of 16-MDCT for all PI was 60.1%, whereas 64-MDCT was 47.2%. For PDI, the sensitivities of 16- and 64-MDCT were 54.0% and 52.4%, respectively, with specificities of 94.8% for 16-MDCT scanners and 90.3% for 64-MDCT scanners. Logistic regression showed that no covariates were associated with an increased likelihood of detecting PDI for either 16- or 64-MDCT scanners. The area under the curve was 0.66 for the 16-MDCT PDI analysis and 0.77 for the 64-MDCT PDI analysis. CONCLUSION Sixteen and 64-MDCT have low sensitivity for detecting PI and PDI, while exhibiting a high specificity for PDI. Their use as decision-making tools for the nonoperative management of PI are, therefore, limited.

A randomized, double-blinded, placebo-controlled pilot trial of anticoagulation in low-risk traumatic brain injury: The Delayed Versus Early Enoxaparin Prophylaxis I (DEEP I) study.

BACKGROUND Our group has created an algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI), which stratifies patients into low, moderate, and high risk for spontaneous injury progression and tailors a prophylaxis regimen to each arm. We present the results of the Delayed Versus Early Enoxaparin Prophylaxis I study, a double-blind, placebo-controlled, randomized pilot trial on the low-risk arm. METHODS In this two-institution study, patients presenting within 6 hours of injury with prespecified small TBI patterns and stable scans at 24 hours after injury were randomized to receive enoxaparin 30 mg bid or placebo from 24 to 96 hours after injury in a double-blind fashion. An additional computed tomography scan was obtained on all subjects 24 hours after starting treatment (and therefore 48 hours after injury). The primary end point was the radiographic worsening of TBI; secondary end points were venous thromboembolism occurrence and extracranial hemorrhagic complications. RESULTS A total of 683 consecutive patients with TBI were screened during the 28 center months. The most common exclusions were for injuries larger than the prespecified criteria (n = 199) and preinjury anticoagulant use (n = 138). Sixty-two patients were randomized to enoxaparin (n = 34) or placebo (n = 28). Subclinical, radiographic TBI progression rates on the scans performed 48 hours after injury and 24 hours after start of treatment were 5.9% (95% confidence interval [CI], 0.7–19.7%) for enoxaparin and 3.6% (95% CI, 0.1–18.3%) for placebo, a treatment effect difference of 2.3% (95% CI, −14.42–16.5%). No clinical TBI progressions occurred. One deep vein thrombosis occurred in the placebo arm. CONCLUSION TBI progression rates after starting enoxaparin in small, stable injuries 24 hours after injury are similar to those of placebo and are subclinical. The next Delayed Versus Early Enoxaparin Prophylaxis studies will assess efficacy of this practice in a powered study on the low-risk arm and a pilot trial of safety of a 72-hour time point in the moderate-risk arm. LEVEL OF EVIDENCE Therapeutic study, level II.

Prehospital intravenous fluid is associated with increased survival in trauma patients.

BACKGROUND Delivery of intravenous crystalloid fluids (IVF) remains a tradition-based priority during prehospital resuscitation of trauma patients. Hypotensive and targeted resuscitation algorithms have been shown to improve patient outcomes. We hypothesized that receiving any prehospital IVF is associated with increased survival in trauma patients compared with receiving no prehospital IVF. METHODS Prospective data from 10 Level 1 trauma centers were collected. Patient demographics, prehospital IVF volume, prehospital and emergency department vital signs, lifesaving interventions, laboratory values, outcomes, and complications were collected and analyzed. Patients who did or did not receive prehospital IVF were compared. Tests for nonparametric data were used to assess significant differences between groups (p ⩽ 0.05). Cox regression analyses were performed to determine the independent influence of IVF on outcome and complications. RESULTS The study population consisted of 1,245 trauma patients; 45 were excluded owing to incomplete data; 84% (n = 1,009) received prehospital IVF, and 16% (n = 191) did not. There was no difference between the groups with respect to sex, age, and Injury Severity Score (ISS). The on-scene systolic blood pressure was lower in the IVF group (110 mm Hg vs. 100 mm Hg, p < 0.04) and did not change significantly after IVF, measured at emergency department admission (110 mm Hg vs. 105 mm Hg, p = 0.05). Hematocrit/hemoglobin, fibrinogen, and platelets were lower (p < 0.05), and prothrombin time/international normalized ratio and partial thromboplastin time were higher (p < 0.001) in the IVF group. The IVF group received a median fluid volume of 700 mL (interquartile range, 300–1,300). The Cox regression revealed that prehospital fluid administration was associated with increased survival (hazard ratio, 0.84; 95% confidence interval, 0.72–0.98; p = 0.03). Site differences in ISS and fluid volumes were demonstrated (p < 0.001). CONCLUSION Prehospital IVF volumes commonly used by PRospective Observational Multicenter Massive Transfusion Study (PROMMTT) investigators do not result in increased systolic blood pressure but are associated with decreased in-hospital mortality in trauma patients compared with patients who did not receive prehospital IVF. LEVEL OF EVIDENCE Therapeutic study, level IV.

The use of leukoreduced red blood cell products is associated with fewer infectious complications in trauma patients

BACKGROUND Clinical studies suggest that leukocytes in banked blood may increase infectious complications after transfusion. However, these investigations included few injured patients. Therefore, the effect of the use of leukoreduced red blood cell (RBC) products in this patient population is unknown. In addition, large numbers of RBC transfusions are frequently required in the treatment of patients with hemorrhagic shock, which may have a more profound effect on infectious risk. The purpose of this study was to determine the effect of prestorage leukoreduction on infectious complications in injured patients. METHODS A retrospective before-and-after cohort study was conducted at an urban level 1 trauma center. A policy of using leukoreduced RBC products commenced in January 2002. Patients treated from March 2002 through December 2003 received leukoreduced RBC products. Those transfused from March 2000 through December 2001 served as controls. Inclusion criteria were age >or=18 years, survival >or=2 days after admission, and transfusion of >or=2 U RBCs within 24 hours of admission. There were 240 patients in the leukoreduction group, and 438 patients in the control group. Multivariate logistic regression controlling for age, sex, injury severity, and number of transfusions was used to determine if leukoreduction status was an independent predictor of infectious complications. Subset analysis was performed on patients receiving massive transfusion (ie, >6 units in 24 hours; n = 168). RESULTS Patient demographics and injury severity characteristics were similar during both treatment periods. Overall, those patients receiving leukoreduced RBC products had a 45% reduction in nosocomial pneumonia (odds ratio [OR] .55; 95% confidence interval [CI] .33-.91) and a significant reduction in the development of any type of infection (OR .48; 95% CI .31-.73). In the massive-transfusion subset, the OR for development of any infection was .33 (95% CI, .15-.73), and the OR for the development of pneumonia was .29 (95% CI, .11.76) in those patients receiving leukoreduced RBC products. There were no differences in mortality within the overall- or massive-transfusion subset analyses. CONCLUSION Prestorage leukoreduction is associated with a reduction of infectious complications in injured patients. Furthermore, this protective effect appears more pronounced in patients receiving massive transfusion (>6 U packed RBCs).

Early resuscitation intensity as a surrogate for bleeding severity and early mortality in the PROMMTT study.

BACKGROUND The classic definition of massive transfusion, 10 or more units of red blood cells (RBCs) in 24 hours, has never been demonstrated as a valid surrogate for severe hemorrhage and can introduce survival bias. In addition, the definition fails to capture other products that the clinician may have immediately available, and may use, during the initial resuscitation. Assuming that units of resuscitative fluids reflect patient illness, our objective was to identify a rate of resuscitation intensity (RI) that could serve as an early surrogate of sickness for patients with substantial bleeding after injury. METHODS Adult patients surviving at least 30 minutes after admission and receiving one or more RBCs within 6 hours of admission from 10 US Level 1 trauma centers were enrolled in the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Total fluid units were calculated as the sum of the number of crystalloid units (1 L = 1 U), colloids (0.5 L = 1 U), and blood products (1 RBC = 1 U, 1 plasma = 1 U, 6 pack platelets = 1 U). Univariable and multivariable logistic regressions were used to evaluate associations between RI and 6-hour mortality, adjusting for age, center, penetrating injury, weighted Revised Trauma Score (RTS), and Injury Severity Score (ISS). RESULTS A total of 1,096 eligible patients received resuscitative fluids within 30 minutes, including 620 transfused with blood products. Despite varying products used, the total fluid RI was similar across all sites (3.2 ± 2.5 U). Patients who received four or more units of any resuscitative fluid had a 6-hour mortality rate of 14.4% versus 4.5% in patients who received less than 4 U. The adjusted odds ratio of 6-hour mortality for patients receiving 4 U or more within 30 minutes was 2.1 (95% confidence interval, 1.2–3.5). CONCLUSION Resuscitation with four or more units of any fluid was significantly associated with 6-hour mortality. This study suggests that early RI regardless of fluid type can be used as a surrogate for sickness and mortality in severely bleeding patients. LEVEL OF EVIDENCE Epidemiologic/prognostic study, level III.

Resuscitate early with plasma and platelets or balance blood products gradually: findings from the PROMMTT study.

BACKGROUND The trauma transfusion literature has yet to resolve which is more important for hemorrhaging patients, transfusing plasma and platelets along with red blood cells (RBCs) early in resuscitation or gradually balancing blood product ratios. In a previous report of PROMMTT results, we found (1) plasma and platelet:RBC ratios increased gradually during the 6 hours following admission, and (2) patients achieving ratios more than 1:2 (relative to ratios <1:2) had significantly decreased 6-hour to 24-hour mortality adjusting for baseline and time-varying covariates. To differentiate the association of in-hospital mortality with early plasma or platelet transfusion from that with delayed but gradually balanced ratios, we developed a separate analytic approach. METHODS Using PROMMTT data and multilevel logistic regression to adjust for center effects, we related in-hospital mortality to the early receipt of plasma or platelets within the first three to six transfusion units (including RBCs) and 2.5 hours of admission. We adjusted for the same covariates as in our previous report: Injury Severity Score (ISS), age, time and total number of blood product transfusions upon entry to the analysis cohort, and bleeding from the head, chest, or limb. RESULTS Of 1,245 PROMMTT patients, 619 were eligible for this analysis. Early plasma was associated with decreased 24-hour and 30-day mortality (adjusted odds ratios of 0.47 [p = 0.009] and 0.44 [p = 0.002], respectively). Too few patients (24) received platelets early for meaningful assessment. In the subgroup of 222 patients receiving no early plasma but continuing transfusions beyond Hour 2.5, achieving gradually balanced plasma and platelet:RBC ratios of 1:2 or greater by Hour 4 was not associated with 30-day mortality (adjusted odds ratios of 0.9 and 1.1, respectively). There were no significant center effects. CONCLUSION Plasma transfusion early in resuscitation had a protective association with mortality, whereas delayed but gradually balanced transfusion ratios did not. Further research will require considerably larger numbers of patients receiving platelets early. LEVEL OF EVIDENCE Therapeutic study, level IV.

Pharmacologic Venous Thromboembolism Prophylaxis after Traumatic Brain Injury: A Critical Literature Review

Despite the frequency and morbidity of venous thromboembolism (VTE) development after traumatic brain injury (TBI), no national standard of care exists to guide TBI caregivers for the use of prophylactic anticoagulation. Fears of iatrogenic propagation of intracranial hemorrhage patterns have led to a dearth of research in this field, and it is only relatively recently that studies dedicated to this question have been performed. These have generally been limited to retrospective and/or observational studies in which patients are classified in a binary fashion as having the presence or absence of intracranial blood. This methodology does not account for the fact that smaller injury patterns stabilize more rapidly, and thus may be able to safely tolerate earlier initiation of prophylactic anticoagulation than larger injury patterns. This review seeks to critically assess the literature on this question by examining the existing evidence on the safety and efficacy of pharmacologic VTE prophylaxis in the setting of elective craniotomy (as this is the closest model available from which to extrapolate) and after TBI. In doing so, we critique studies that approach TBI as a homogenous or a heterogenous study population. Finally, we propose our own theoretical protocol which stratifies patients into low, moderate, and high risk for the likelihood of natural progression of their hemorrhage pattern, and which allows one to tailor a unique VTE prophylaxis regimen to each individual arm.

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).