Harmful or Physiologic: Diagnosing Fibrinolysis Shutdown in a Trauma Cohort With Rotational Thromboelastometry.

BACKGROUND: Despite its central role in early trauma coagulopathy, abnormal fibrinolysis continues to be poorly understood. Excessive fibrinolysis is a known contributor to mortality. Recent studies with thromboelastography (TEG) suggest decreased fibrinolysis (or shutdown) may be just as harmful. Considering the broad use of 2 different viscoelastic assays, which are not interchangeable, we proposed for the first time to define and characterize fibrinolysis shutdown using rotational thromboelastometry (ROTEM). METHODS: Retrospective cohort study of severely injured patients with admission ROTEM. Shutdown was defined by the best Youden index value of the maximum lysis. Fibrinolysis phenotypes were physiologic, hyperfibrinolysis, and shutdown. Multivariable logistic regression evaluated association between Injury Severity Score and the fibrinolysis phenotypes, and the association among shutdown phenotype with mortality, blood transfusion, and thrombotic events. RESULTS: Five hundred fifty patients were included. Maximum lysis <3.5% was selected to define shutdown. Predominant phenotype was physiologic (70.7%), followed by shutdown (25.6%) and hyperfibrinolysis (3.6%). Shutdown patients had higher Injury Severity Score, lower base excess, and required more transfusions than physiologic group. Shutdown was associated with acidosis (base excess: odds ratio [OR] for a 1 mEq/L increase, 0.93; 95% confidence interval [CI], 0.88-0.98; P = .0094) and the combination of clotting derangements, higher clot firmness (maximum clot formation: OR for a 2 mm increase, 1.8; 95% CI, 1.5-2.27; P < .0001), lower fibrinogen (OR for a 0.5 g/dL decrease, 1.47; 95% CI, 1.18-1.84; P = .0006), and poor clot formation dynamics (clot formation time: OR for a 5 seconds increase, 1.25; 95% CI, 1.15-1.36; P < .0001). Fibrinolysis shutdown was not independently associated with mortality (OR, 0.61; 95% CI, 0.28-1.33; P = .21), massive transfusion (OR, 2.14; 95% CI, 0.79-5.74; P = .1308), or thrombotic events (OR, 1.08; 95% CI, 0.37-3.15; P = .874). Shutdown was associated with increased 24-hour transfusion (OR, 2.24; 95% CI, 1.24-4.04; P = .007). CONCLUSIONS: Despite higher injury burden, evidence of shock, and greater need for blood transfusions, early fibrinolysis shutdown was not associated with mortality, suggesting that it could represent an adaptive physiologic response to life-threatening trauma.

Catecholamines as outcome markers in isolated traumatic brain injury: the COMA-TBI study.

BACKGROUND: Elevated catecholamine levels might be associated with unfavorable outcome after traumatic brain injury (TBI). We investigated the association between catecholamine levels in the first 24 h post-trauma and functional outcome in patients with isolated moderate-to-severe TBI. METHODS: A cohort of 174 patients who sustained isolated blunt TBI was prospectively enrolled from three Level-1 Trauma Centers. Epinephrine (Epi) and norepinephrine (NE) concentrations were measured at admission (baseline), 6, 12 and 24 h post-injury. Outcome was assessed at 6 months by the extended Glasgow Outcome Scale (GOSE) score. Fractional polynomial plots and logistic regression models (fixed and random effects) were used to study the association between catecholamine levels and outcome. Effect size was reported as the odds ratio (OR) associated with one logarithmic change in catecholamine level. RESULTS: At 6 months, 109 patients (62.6%) had an unfavorable outcome (GOSE 5-8 vs. 1-4), including 51 deaths (29.3%). Higher admission levels of Epi were associated with a higher risk of unfavorable outcome (OR, 2.04, 95% CI: 1.31-3.18, p = 0.002) and mortality (OR, 2.86, 95% CI: 1.62-5.01, p = 0.001). Higher admission levels of NE were associated with higher risk of unfavorable outcome (OR, 1.59, 95% CI: 1.07-2.35, p = 0.022) but not mortality (OR, 1.45, 95% CI: 0.98-2.17, p = 0.07). There was no relationship between the changes in Epi levels over time and mortality or unfavorable outcome. Changes in NE levels with time were statistically associated with a higher risk of mortality, but the changes had no relation to unfavorable outcome. CONCLUSIONS: Elevated circulating catecholamines, especially Epi levels on hospital admission, are independently associated with functional outcome and mortality after isolated moderate-to-severe TBI.

Inflammatory cytokine and chemokine profiles are associated with patient outcome and the hyperadrenergic state following acute brain injury.

BACKGROUND: Traumatic brain injury (TBI) elicits intense sympathetic nervous system (SNS) activation with profuse catecholamine secretion. The resultant hyperadrenergic state is linked to immunomodulation both within the brain and systemically. Dysregulated inflammation post-TBI exacerbates secondary brain injury and contributes to unfavorable patient outcomes including death. The aim of this study was to characterize the early dynamic profile of circulating inflammatory cytokines/chemokines in patients admitted for moderate-to-severe TBI, to examine interrelationships between these mediators and catecholamines, as well as clinical indices of injury severity and neurological outcome. METHODS: Blood was sampled from 166 isolated TBI patients (aged 45 ± 20.3 years; 74.7 % male) on admission, 6-, 12-, and 24-h post-injury and from healthy controls (N = 21). Plasma cytokine [interleukin (IL)-1ß, -2, -4, -5, -10, -12p70, -13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ] and chemokine [IL-8, eotaxin, eotaxin-3, IFN-γ-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, -4, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1ß, thymus activation regulated chemokine (TARC)] concentrations were analyzed using high-sensitivity electrochemiluminescence multiplex immunoassays. Plasma catecholamines [epinephrine (Epi), norepinephrine (NE)] were measured by immunoassay. Neurological outcome at 6 months was assessed using the extended Glasgow outcome scale (GOSE) dichotomized as good (>4) or poor (≤4) outcomes. RESULTS: Patients showed altered levels of IL-10 and all chemokines assayed relative to controls. Significant differences in a number of markers were evident between moderate and severe TBI cohorts. Elevated IL-8, IL-10, and TNF-α, as well as alterations in 8 of 9 chemokines, were associated with poor outcome at 6 months. Notably, a positive association was found between Epi and IL-1ß, IL-10, Eotaxin, IL-8, and MCP-1. NE was positively associated with IL-1ß, IL-10, TNF-α, eotaxin, IL-8, IP-10, and MCP-1. CONCLUSIONS: Our results provide further evidence that exaggerated SNS activation acutely after isolated TBI in humans may contribute to harmful peripheral inflammatory cytokine/chemokine dysregulation. These findings are consistent with a potentially beneficial role for therapies aimed at modulating the inflammatory response and hyperadrenergic state acutely post-injury.

Detailed description of all deaths in both the shock and traumatic brain injury hypertonic saline trials of the Resuscitation Outcomes Consortium.

OBJECTIVE: To identify causes and timing of mortality in trauma patients to determine targets for future studies. BACKGROUND: In trials conducted by the Resuscitation Outcomes Consortium in patients with traumatic hypovolemic shock (shock) or traumatic brain injury (TBI), hypertonic saline failed to improve survival. Selecting appropriate candidates is challenging. METHODS: Retrospective review of patients enrolled in multicenter, randomized trials performed from 2006 to 2009. Inclusion criteria were as follows: injured patients, age 15 years or more with hypovolemic shock [systolic blood pressure (SBP) ≤ 70 mm Hg or SBP 71-90 mm Hg with heart rate ≥ 108) or severe TBI [Glasgow Coma Score (GCS) ≤ 8]. Initial fluid administered was 250 mL of either 7.5% saline with 6% dextran 70, 7.5% saline or 0.9% saline. RESULTS: A total of 2061 subjects were enrolled (809 shock, 1252 TBI) and 571 (27.7%) died. Survivors were younger than nonsurvivors [30 (interquartile range 23) vs 42 (34)] and had a higher GCS, though similar hemodynamics. Most deaths occurred despite ongoing resuscitation. Forty-six percent of deaths in the TBI cohort were within 24 hours, compared with 82% in the shock cohort and 72% in the cohort with both shock and TBI. Median time to death was 29 hours in the TBI cohort, 2 hours in the shock cohort, and 4 hours in patients with both. Sepsis and multiple organ dysfunction accounted for 2% of deaths. CONCLUSIONS: Most deaths from trauma with shock or TBI occur within 24 hours from hypovolemic shock or TBI. Novel resuscitation strategies should focus on early deaths, though prevention may have a greater impact.

Fresh frozen plasma: red blood cells (1:2) coagulation effect is equivalent to 1:1 and whole blood.

BACKGROUND: Preemptive treatment of trauma-associated coagulopathy involves transfusion of fresh frozen plasma (FFP) at 1:1 ratio with red blood cells (RBCs), but the optimal ratio remains controversial. In combat theaters, fresh whole blood (FWB) is also an option. The objective of this study was to determine the effect of FFP:RBC ratios 1:1, 1:2, 1:3 and FWB on coagulation during resuscitation. MATERIALS AND METHODS: Thirty-six rats were randomized in the following six groups: Group 1: sham; Group 2: hemorrhage followed by sole lactated Ringer (LR) infusion; Group 3: FFP:RBC (1:1); Group 4: FFP:RBC (1:2); Group 5: FFP:RBC (1:3); Group 6: FWB transfusion. Another 25 animals were used for blood harvesting. Hemorrhage was induced by withdrawing 40% of total blood volume, mean arterial pressure (MAP) decreased to 45% of baseline, and laparotomy. Animals underwent LR infusion followed by blood product transfusion preset for each group. Blood samples were obtained at baseline and in the 105th minute for thromboelastometry and lactate. RESULTS: Hemorrhage caused a significant decrease in MAP and increase in lactate (P < 0.05). MAP was persistently low in group 2 despite fluid infusion (P < 0.05), but not in the other groups after 20 min of resuscitation. Mean clot formation time, alpha angle, and maximum clot firmness decreased significantly (P < 0.05) in group 2 (LR) and group 5 (1:3) compared with other groups. CONCLUSIONS: FFP:RBC in a 1:2 ratio optimally harnessed hemostatic resuscitation and prudent use of blood products compared with 1:1 and 1:3 ratios and to FWB transfusion.

Physical rehabilitation of the critically ill trauma patient in the ICU.

OBJECTIVES: To 1) review the existing evidence for early mobilization of the critically ill patients in the ICU with polytrauma; 2) provide intensivists with an introduction to the biomechanics, physiology, and nomenclature of injuries; 3) summarize the evidence for early mobilization in each anatomic area; and 4) provide recommendations for the mobilization of these patients. DATA SOURCES: A literature search of the MEDLINE and EMBASE databases for articles published in English between 1980 and 2011. STUDY SELECTION: Studies pertaining to physical therapy and rehabilitation in trauma patients were selected. Articles were excluded if they dealt with pediatrics, geriatrics, burn injuries, isolated hand injuries, chronic (i.e., not acute) injuries, nontraumatic conditions, and pressure/decubitus ulcers, were in a language other than English, were published only in abstract form, were letters to the editor, were case reports, or were published prior to 1980. DATA EXTRACTION: Reviewers extracted data and summarized results according to anatomical areas. DATA SYNTHESIS: Of 1,411 titles and abstracts, 103 met inclusion criteria. We found no articles specifically addressing the rehabilitation of polytrauma patients in the ICU setting or patients with polytrauma in general. We summarized the articles addressing the role of mobilization for specific injuries and treatments. We used this evidence, in combination with biologic rationale and physician and surgeon experience and expertise, to summarize the important considerations when providing physical therapy to these patients in the ICU setting. CONCLUSIONS: There is a paucity of evidence addressing the role of early mobilization of ICU patients with polytrauma and patients with polytrauma in general. Evidence for the beneficial role of early mobilization of specific injuries exists. Important considerations when applying a strategy of early physical therapy and mobilization to this distinctive patient group are summarized.

Reducing time-to-treatment decreases mortality of trauma patients with acute subdural hematoma.

OBJECTIVES: To determine if reducing prehospital time and time-to-craniotomy is associated with decreased mortality in trauma patients with acute subdural hematomas. BACKGROUND: Time-to-treatment is an important performance filter for trauma systems, yet very little evidence exists to support its use. Despite the biological rationale supporting the notion of the "Golden Hour" for trauma patients, no evidence exists to support it. Likewise, it remains controversial whether or not time-to-craniotomy is associated with survival in patients with subdural hematomas. Previous studies may have been affected by selection bias. METHODS: Retrospective cohort study of all trauma patients who arrived directly from the scene of injury. Study patients were all patients with acute subdural hematomas and without severe torso injuries, who required craniotomy at a Canadian level 1 trauma center from January 1 1996 to December 31 2007. The independent variables of interest were prehospital time and time-to-craniotomy. The primary outcome measure was in-hospital mortality. RESULTS: Of 12,105 trauma patients assessed, 149 patients met inclusion criteria. Overall, 40% (n = 60) patients died. On univariate analysis, there was a strong trend suggesting that patients arriving within the "Golden Hour after trauma" had decreased mortality (37% vs. 53%, P = 0.09). However, there was no difference in mortality for patients undergoing craniotomy within 4 hours and after 4 hours (42% vs. 36%, P = 0.4). On multivariate logistic regression, increased prehospital time was found to be associated with increased mortality (odds ratio 1.03 per minute, 95% CI 1.004-1.05, P = 0.024). Surprisingly, there was a trend showing that increased trauma room to craniotomy times were associated with lower mortality (odds ratio 0.995 per minute, 95% CI 0.99-1.0, P = 0.056). However, patients who quickly had their craniotomy seemed to have more severe neurological injury. CONCLUSION: Rapid transport of patients with traumatic subdural hematomas hospital is associated with decreased mortality.

Hypoperfusion in severely injured trauma patients is associated with reduced coagulation factor activity.

BACKGROUND: Recent studies have shown that acute traumatic coagulopathy is associated with hypoperfusion, increased plasma levels of soluble thrombomodulin, and decreased levels of protein C but with no change in factor VII activity. These findings led to the hypothesis that acute traumatic coagulopathy is primarily due to systemic anticoagulation, by activated protein C, rather than decreases in serine protease activity. This study was designed to examine the effect of hypoperfusion secondary to traumatic injury on the activity of coagulation factors. METHODS: Post hoc analysis of prospectively collected data on severely injured adult trauma patients presenting to a single trauma center within 120 minutes of injury. Venous blood was analyzed for activity of factors II, V, VII, VIII, IX, X, and XI. Base deficit from arterial blood samples was used as a marker of hypoperfusion. RESULTS: Seventy-one patients were identified. The activity of factors II, V, VII, IX, X, and XI correlated negatively with base deficit, and after stratification into three groups, based on the severity of hypoperfusion, a statistically significant dose-related reduction in the activity of factors II, VII, IX, X, and XI was observed. Hypoperfusion is also associated with marked reductions in factor V activity levels, but these appear to be relatively independent of the degree of hypoperfusion. The activity of factor VIII did not correlate with base deficit. CONCLUSIONS: Hypoperfusion in trauma patients is associated with a moderate, dose-dependent reduction in the activity of coagulation factors II, VII, IX, X, and XI, and a more marked reduction in factor V activity, which is relatively independent of the severity of shock. These findings suggest that the mechanisms underlying decreased factor V activity--which could be due to activated protein C mediated cleavage, thus providing a possible link between the proposed thrombomodulin/thrombin-APC pathway and the serine proteases of the coagulation cascade--and the reductions in factors II, VII, IX, X, and XI may differ. Preservation of coagulation factor activity in the majority of normally and moderately hypoperfused patients suggests that aggressive administration of plasma is probably only indicated in severely hypoperfused patients. Markers of hypoperfusion, such as base deficit, might be better and more readily available predictors of who require coagulation support than international normalized ratio or activated partial thromboplastin time.

Clotting factor deficiency in early trauma-associated coagulopathy.

BACKGROUND: Coagulopathic bleeding is a leading cause of in-hospital death after injury. A recently proposed transfusion strategy calls for early and aggressive frozen plasma transfusion to bleeding trauma patients, thus addressing trauma-associated coagulopathy (TAC) by transfusing clotting factors (CFs). This strategy may dramatically improve survival of bleeding trauma patients. However, other studies suggest that early TAC occurs by protein C activation and is independent of CF deficiency. This study investigated whether CF deficiency is associated with early TAC. METHODS: This is a prospective observational cohort study of severely traumatized patients (Injury Severity Score ≥ 16) admitted shortly after injury, receiving minimal fluids and no prehospital blood. Blood was assayed for CF levels, thromboelastography, and routine coagulation tests. Critical CF deficiency was defined as ≤ 30% activity of any CF. RESULTS: Of 110 patients, 22 (20%) had critical CF deficiency: critically low factor V level was evident in all these patients. International normalized ratio, activated prothrombin time, and, thromboelastography were abnormal in 32%, 36%, and 35%, respectively, of patients with any critically low CF. Patients with critical CF deficiency suffered more severe injuries, were more acidotic, received more blood transfusions, and showed a trend toward higher mortality (32% vs. 18%, p = 0.23). Computational modeling showed coagulopathic patients had pronounced delays and quantitative deficits in generating thrombin. CONCLUSIONS: Twenty percent of all severely injured patients had critical CF deficiency on admission, particularly of factor V. The observed factor V deficit aligns with current understanding of the mechanisms underlying early TAC. Critical deficiency of factor V impairs thrombin generation and profoundly affects hemostasis.

The natural history of trauma-related coagulopathy: implications for treatment.

BACKGROUND: Hemorrhage is a leading cause of death in trauma patients and coagulopathy is a significant contributor. Although the exact mechanisms of trauma-associated coagulopathy (TAC) are incompletely understood, hemostatic resuscitation strategies have been developed to treat TAC. Our study sought to identify which trauma patients develop TAC and the factors associated with its development, to describe the natural history of TAC, and to identify patients with TAC who may not require hemostatic resuscitation. METHODS: Patients with early coagulopathy (International Normalized Ratio >1.3) who were admitted directly from the scene within 1 hour of injury were identified in our institutional trauma registry. We analyzed these data for the presence of TAC, predictors of early and delayed TAC, and evolution of TAC during the first 24 hours of admission. RESULTS: Of 2,473 patients, 290 (12%) had early TAC (International Normalized Ratio >1.3) and 271 (11%) developed delayed TAC. Multivariate analysis identified female gender (odds ratio [OR] 1.25 [1.11-1.41]), lower pH (OR 0.08 [0.015-0.47]), lower hemoglobin (OR 0.96 [0.95-0.97]), lower temperature (OR 0.82 [0.70-0.95]), and blunt mechanism (OR 0.49 [0.33-0.71]) as factors significantly associated with development of early TAC. Progression of early TAC occurred in 64%, and these patients had more severe abdominal injury and received more emergency room crystalloid. Of patients with early TAC who did not receive fresh frozen plasma, only 49% developed worsening coagulopathy. Patients with isolated intracranial hemorrhage had higher rates of bleeding progression (75% vs. 20%, p < 0.005) in the presence of early TAC. CONCLUSIONS: TAC may appear in an early or delayed form and its presence and progression are associated with a number of identifiable factors. Although TAC commonly progresses, it also resolves spontaneously in many patients. Further research is required to identify which patients with TAC require hemostatic treatment, although those with intracranial hemorrhages seem to warrant aggressive therapy.

Prehospital resuscitation with hypertonic saline-dextran modulates inflammatory, coagulation and endothelial activation marker profiles in severe traumatic brain injured patients.

BACKGROUND: Traumatic brain injury (TBI) initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury. METHODS: Using a prospective, randomized controlled trial we investigated the impact of prehospital resuscitation of severe TBI (GCS < 8) patients using 7.5% hypertonic saline in combination with 6% dextran-70 (HSD) vs 0.9% normal saline (NS), on selected cellular and soluble inflammatory/coagulation markers. Serial blood samples were drawn from 65 patients (30 HSD, 35 NS) at the time of hospital admission and at 12, 24, and 48-h post-resuscitation. Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b) and degranulation (CD63, CD66b) molecules. Circulating concentrations of soluble (s)L- and sE-selectins (sL-, sE-selectins), vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1), pro/antiinflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL-10)], tissue factor (sTF), thrombomodulin (sTM) and D-dimers (D-D) were assessed by enzyme immunoassay. Twenty-five healthy subjects were studied as a control group. RESULTS: TBI provoked marked alterations in a majority of the inflammatory/coagulation markers assessed in all patients. Relative to control, NS patients showed up to a 2-fold higher surface expression of CD62L, CD11b and CD66b on polymorphonuclear neutrophils (PMNs) and monocytes that persisted for 48-h. HSD blunted the expression of these cell-surface activation/adhesion molecules at all time-points to levels approaching control values. Admission concentrations of endothelial-derived sVCAM-1 and sE-selectin were generally reduced in HSD patients. Circulating sL-selectin levels were significantly elevated at 12 and 48, but not 24 h post-resuscitation with HSD. TNF-alpha and IL-10 levels were elevated above control throughout the study period in all patients, but were reduced in HSD patients. Plasma sTF and D-D levels were also significantly lower in HSD patients, whereas sTM levels remained at control levels. CONCLUSIONS: These findings support an important modulatory role of HSD resuscitation in attenuating the upregulation of leukocyte/endothelial cell proinflammatory/prothrombotic mediators, which may help ameliorate secondary brain injury after TBI. TRIAL REGISTRATION: NCT00878631.

Permissive hypotension and desmopressin enhance clot formation.

BACKGROUND: Experimental studies of uncontrolled hemorrhage demonstrated that permissive hypotension (PH) reduces blood loss, but its effect on clot formation remains unexplored. Desmopressin (DDAVP) enhances platelet adhesion promoting stronger clots. We hypothesized PH and DDAVP have additive effects and reduce bleeding in uncontrolled hemorrhage. METHODS: Rabbits (n = 42) randomized as follows: sham; normal blood pressure (NBP) resuscitation; PH resuscitation-60% baseline mean arterial pressure; NBP plus DDAVP 1 hour before (DDAVP NBP) or 15 minutes after beginning of shock (DDAVP T1 NBP); and PH plus DDAVP 1 hour before (DDAVP PH) or 15 minutes after beginning of shock (DDAVP T1 PH). Fluid resuscitation started 15 minutes after aortic injury and ended at 85 minutes. Intraabdominal blood loss was calculated, aortic clot sent for electron microscopy. Activated partial thromboplastin time, platelet count, thromboelastometry, arterial blood gases, and complete blood count were performed at baseline and 85 minutes. Analysis of variance was used for comparison. RESULTS: NBP received more fluid volume and had greater intraabdominal blood loss. DDAVP, when administered preshock, significantly reduced blood loss in NBP and fluid requirement when given postshock. Platelets, arterial blood gas, complete blood count, and activated partial thromboplastin time were similar at 85 minutes. NBP delayed clot formation and worsened thrombodynamic potential on thromboelastometry, whereas PH and DDAVP improved. Electron microscopy showed lack of fibrin on NBP clots, whereas DDAVP and PH clots displayed exuberant fibrin/platelet aggregates. DDAVP NBP presented intermediate clots. CONCLUSION: PH reduced bleeding and improved hemostasis compared with normotensive resuscitation. DDAVP given preshock exerted similar effects with normotensive resuscitation.

Prolonged prothrombin time after recombinant activated factor VII therapy in critically bleeding trauma patients is associated with adverse outcomes.

BACKGROUND: In trauma patients with significant hemorrhage, it is hypothesized that failure to normalize prothrombin time (PT) after recombinant activated factor VII (rFVIIa) treatment predicts poor clinical outcomes and potentially indicates a need for additional therapeutic interventions. METHODS: To assess the value of PT to predict outcomes after rFVIIa or placebo therapy, we performed a post hoc analysis of data from 169 severely injured, critically bleeding trauma patients who had 1-hour postdose PT measurements from two randomized clinical trials. Baseline characteristics and outcome parameters were compared between subjects with 1-hour postdose PT >or=18 seconds and PT <18 seconds. RESULTS: In rFVIIa-treated subjects, prolonged postdose PT values >or=18 seconds were associated with significantly higher 24-hour mortality (60% vs. 3%; p < 0.001) and 30-day mortality, increased incidence of massive transfusion, and fewer intensive care unit-free days compared with postdose PT values <18 seconds. Recombinant rFVIIa-treated subjects with postdose PT >or=18 seconds had significantly lower baseline hemoglobin levels, fibrinogen levels, and platelet counts than subjects with postdose PT values <18 seconds even though they received similar amounts of blood products before rFVIIa dosing. Placebo-treated subjects with postdose PT >or=18 seconds had significantly increased incidence of massive transfusion, significantly decreased intensive care unit-free days, and significantly lower levels of fibrinogen and platelets at baseline compared with subjects with postdose PT values <18 seconds. CONCLUSIONS: The presence of prolonged PT after rFVIIa or placebo therapy was associated with poor clinical outcomes. Because subjects with postdosing PT >or=18 seconds had low levels of hemoglobin, fibrinogen, and platelets, this group may benefit from additional blood component therapy.

The treatment of bleeding is to stop the bleeding! Treatment of trauma-related hemorrhage.

BACKGROUND: The secret with any alternative to transfusion is to minimize the need for transfusion in the first place. This can be done by reducing the volume of blood loss. The volume of blood being lost can be reduced by direct methods where possible (i.e., hemostasis at the point of bleeding), or by improving the coagulation profile of the patient, thereby improving the extrinsic coagulation. Recombinant activated factor VII (rFVIIa) offers theoretical possibilities of improving the coagulation profile. STUDY DESIGN AND METHODS: The efficacy and safety of rFVIIa for the treatment of bleeding in patients with severe blunt and penetrating trauma has been investigated in two double-blind, placebo-controlled studies within a single trial-one on patients with blunt injury and the other in similar patients with penetrating injury. RESULTS: In patients with blunt trauma alive at 48 hours, treatment with rFVIIa effected a significant reduction in the primary endpoint of 48-hour red blood cell (RBC) transfusion requirement (p = 0.02), and the safety of the dosing regimen was established. Similar trends were observed in patients with penetrating injuries. Across both studies and treatment arms, the 48-hour mortality rate ranged from 16 to 19 percent. In the blunt trauma study, this equated to 13 patients from each arm who died before the benefits of treatment could be adequately assessed. Analysis of data for the 117 blunt trauma patients who survived at least 48 hours after receiving study treatment shows that, in addition to reducing RBC requirement, rFVIIa significantly reduced the need for massive transfusion over 48 hours (>20 RBC units) (relative risk reduction of 56% [95% confidence interval: 9%-79%]; p = 0.03), and the fresh-frozen plasma (p = 0.036), platelet (p = 0.023), and cryoprecipitate (p = 0.053) requirements within 48 hours, and was associated with a significant reduction in the 30-day risk of acute respiratory distress syndrome (ARDS) (p = 0.05) and multiple organ failure and/or ARDS (p = 0.05). CONCLUSION: Treatment with adjunctive rFVIIa significantly reduces transfusion requirements in the 48 hours after severe injury and these procoagulant effects may improve clinical outcome at 30 days.

Linking the chain of survival: trauma as a traditional role model for multisystem trauma and brain injury.

PURPOSE OF REVIEW: Trauma systems are central in the care of trauma patients and the concept of 'Critical Care Cascade' matches the concept of the 'Trauma Systems'. Both concepts aim to offer a model of continuum care from prehospital assistance to ICU discharge that can have a significant impact on outcome. In spite of the trauma system concept maturity, many controversies still remain unresolved. This text will review some of the relevant literature related to prehospital and early hospital care of trauma patients. RECENT FINDINGS: Effectiveness of trauma systems and outcome studies on prehospital and early hospital care have been published recently. Limitations, controversies and important points of those studies will be highlighted in this text. SUMMARY: Although there is a lack of definitive evidence to support many of the current recommendations for the acute care of trauma patients, the historical development of trauma systems, their long experience and even the existing controversies, can help to establish other critical pathways and can guide performance evaluations so necessary to improve outcomes.

Abnormal coagulation tests are associated with progression of traumatic intracranial hemorrhage.

BACKGROUND: Intracranial hemorrhage (ICH) is common in traumatic brain injury (TBI) and a major determinant of death and disability. ICH commonly increases in size and coagulopathy has been implicated in such progression. We investigated the association between coagulopathy diagnosed by routine laboratory tests and ICH progression. METHODS: Subgroup post hoc analysis from a randomized controlled trial including adult patients with blunt severe TBI (Glasgow Coma Scale score or=1.3, activated partial thromboplastin time >or=35, or platelet count (PLT)

Extravasation of intravenous computed tomography scan contrast in blunt abdominal and pelvic trauma.

BACKGROUND: Intravenous contrast extravasation (CE) on computed tomography (CT) scan in blunt abdominal trauma is generally regarded as an indication for the need for invasive intervention (either angiography or laparotomy). More recently, improvements in CT scan technology have increased the sensitivity in detecting CE, and, thus, we postulate that not all patients with this finding require intervention. METHODS: This study is a retrospective review of all patients who underwent a CT scan for blunt abdominal trauma between January 1999 and September 2003. Patterns of injury, associated injuries, management, and outcomes were examined for patients with CE. RESULTS: Seventy of 1,435 patients (4.8%) demonstrated CE. Mean age was 44 years and mean Injury Severity Score was 39. The location of CE was intra-abdominal in 25, pelvis/retroperitoneum in 39, and both areas in 3 patients. Six patients received supportive treatment for nonsurvivable head injury and were excluded from further analysis. Overall, 30 (47%) patients underwent immediate intervention (angiography or laparotomy) and 34 (53%) were managed nonoperatively. Of those who had initial nonoperative management, overall seven (20.5%) underwent intervention, with the remainder being managed without intervention. The success for nonoperative management was greater for those with pelvic/retroperitoneal CE (4 of 7: 57%) than for intra-abdominal extravasation (23 of 27: 85%). CONCLUSION: Although evidence of CE may suggest significant vascular injury, our data suggest that not all patients require invasive intervention. Further studies are needed to better define criteria for nonoperative management in patients with CE identified on their initial CT scan.

Early massive transfusion in trauma patients: Canadian single-centre retrospective cohort study.

PURPOSE: To determine associations between red blood cell (RBC) transfusion and early and late clinical outcomes in massively transfused adult trauma patients. METHODS: A retrospective cohort study (1992-2001) including 260 patients receiving >or=10 RBC units or=48 hr, the maximum SOFA score was associated with RBC units transfused before 48 hr (linear regression beta coefficient 0.075, P < 0.0001), lower nadir hemoglobin before 48 hr (0.034, P = 0.03), age (0.032, P = 0.015), and admission SOFA (0.59, P < 0.0001). The RBC units transfused by 48 hr were not associated with either hospital mortality (n = 35) among patients surviving >or=48 hr (independent predictors, age [logistic regression odds ratio (OR) 1.06, 95% confidence interval 1.03-1.10], ISS [OR 1.07, 1.02-1.13], and maximum SOFA score [OR 1.56, 1.27-1.93]) or 48-hr mortality (n = 117) (independent predictors, admission SOFA [1.65, 1.45-1.88] and later year of hospital admission [OR 1.15, 1.02-1.29]). CONCLUSIONS: Hospital mortality is high among massively transfused trauma patients. Among early survivors, 48-hr RBC transfusion volume is associated with increased organ dysfunction, but not hospital mortality. Also, it is not associated with 48-hr mortality. Future research should continue to explore methods to improve hemostasis and minimize the need for RBC transfusion.

Thromboelastography and rotational thromboelastometry for the surgical intensivist: A narrative review.

BACKGROUND: Viscoelastic tests (VETs), specifically thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are gaining popularity in the management of critically ill surgical patients with hemorrhage or thrombosis due to their comprehensive characterization of the coagulation process and point-of-care availability in comparison to conventional coagulation tests (CCTs). We review current evidence for VET use in patients in the surgical intensive care unit (SICU). METHODS: We searched PUBMED, EMBASE and the Cochrane Library through May 30, 2018 for articles that evaluated the use of VETs in patient populations and clinical scenarios germane to the surgical intensivist. Individual articles were critically evaluated for relevance and appropriate methodology using a structured technique. Information on patient characteristics, timing and methods of CCTs/VETs, and outcomes was collected and summarized in narrative form. RESULTS: Of 2,589 identified articles, 36 were included. Five (14%) were interventional studies and 31 (86%) were observational. Twenty-five (69%) evaluated TEG, 11 (31%) ROTEM and 18 (50%) CCTs. Investigated outcomes included quantitative blood loss (13 (36%)), blood product transfusion (9 (25%)), thromboembolic events (9 (25%)) and mortality (6 (17%)). We identified 12 clinical scenarios with sufficient available evidence, much of which was of limited quantity and poor methodological quality. Nonetheless, research supports the use of VETs for guiding early blood product administration in severe traumatic hemorrhage and for the prediction of abstract excess bleeding following routine cardiac surgery. In contrast, evidence suggests VET-based heparin dosing strategies for venous thromboembolism prophylaxis are not superior to standard dosing in SICU patients. CONCLUSION: While VETs have the potential to impact the care of critically ill surgical patients in many ways, current evidence for their use is limited, mainly because of poor methodological quality of most available studies. Further high-quality research, including several ongoing randomized controlled trials, is needed to elucidate the role of TEG/ROTEM in the SICU population. LEVEL OF EVIDENCE: Systematic review, level IV.