ABSTRACT
Progression of intracranial hemorrhage (PICH) is a significant cause of secondary brain injury in patients with traumatic brain injury (TBI). Previous studies have implicated a variety of mediators that contribute to PICH. We hypothesized that patients with PICH would display either a hypocoagulable state, hyperfibrinolysis, or both. We conducted a prospective study of adult trauma patients with isolated TBI. Blood was obtained for routine coagulation assays, platelet count, fibrinogen, thrombelastography, markers of thrombin generation, and markers of fibrinolysis at admission and 6, 12, 24, and 48 h. Univariate analyses were performed to compare baseline characteristics between groups. Linear regression models were created, adjusting for baseline differences, to determine the relationship between individual assays and PICH. One hundred forty-one patients met entry criteria, of whom 71 had hemorrhage progression. Patients with PICH had a higher Injury Severity Score and Abbreviated Injury Scale score (head), a lower Glasgow Coma Scale score, and lower plasma sodium on admission. Patients with PICH had higher D-dimers on admission. After adjusting for baseline differences, elevated D-dimers remained significantly associated with PICH compared to patients without PICH at admission. Hypocoagulation was not significantly associated with PICH in these patients. The association between PICH and elevated D-dimers early after injury suggests that fibrinolytic activation may contribute to PICH in patients with TBI.
Subject(s)
Brain Injuries, Traumatic/blood , Brain Injuries, Traumatic/diagnostic imaging , Disease Progression , Fibrinolysis/physiology , Intracranial Hemorrhages/blood , Intracranial Hemorrhages/diagnostic imaging , Adult , Aged , Brain Injuries, Traumatic/complications , Female , Fibrinogen/metabolism , Glasgow Coma Scale/trends , Humans , Intracranial Hemorrhages/etiology , Male , Middle Aged , Prospective Studies , Thrombelastography/trendsABSTRACT
BACKGROUND: Research within the field of surgical education has been expanding rapidly in order to guide future curricula. However, education studies often have minimal IRB oversight and evolving concerns exist regarding issues of informed consent of trainees. METHODS: We conducted an electronic, single center, anonymous survey of general surgery residents. The survey study was IRB approved and subjects were provided with information and opt-out sheets. RESULTS: The response rate was 43.5% (37/85). Approximately 76% of residents felt that education research was important and that they should participate. If a faculty member conducted the study, 18% of residents would feel coerced to participate and 21% would feel uncomfortable refusing to participate. The majority (81%) felt uncomfortable with peers viewing their identifiable records and a sizeable minority (24%) were uncomfortable with peers viewing de-identified records. CONCLUSION: Surgical residents believe that educational research is important, but researchers should be cognizant of unintended consequences on resident autonomy and confidentiality.
Subject(s)
Confidentiality , General Surgery/education , Internship and Residency , Research Subjects , Female , Humans , Male , Oregon , Pilot Projects , Surveys and Questionnaires , Young AdultABSTRACT
INTRODUCTION: Alcohol consumption has been shown to alter coagulation. However, thromboelastography with platelet mapping (TEG PM) to evaluate platelet function has not been studied. METHODS: A prospective, non-randomized study of healthy volunteers was conducted. Baseline TEG PM were collected. Subjects consumed alcoholic or non-alcoholic beverages for 2â¯h. Repeat TEG PM was collected. RESULTS: Fifty-four volunteers entered either the experimental group (EG, 17 women and 16 men) or control group (CG, 11 women and 10 men). After 2â¯h of alcohol or non-alcoholic drink consumption the median breath alcohol level was 0.08 [IQR 0.05, 0.12] in the EG and 0.00 in the CG. After consumption of alcohol, male EG subjects demonstrated higher median Adenosine Diphosphate (ADP) inhibition of platelet function (15.7% [3.9, 39.3] vs 8.2% [0, 30.1), pâ¯=â¯0.035), but female subjects did not. There was no evidence of increased arachidonic acid (AA) platelet inhibition in the EG compared to CG. Clot strength (TEG maximum amplitude) was not different between groups. CONCLUSION: After consumption of alcohol, healthy male volunteers demonstrate ADP platelet inhibition by TEG PM.
Subject(s)
Alcohol Drinking , Blood Platelets/drug effects , Platelet Function Tests , Adenosine Diphosphate/pharmacology , Adult , Case-Control Studies , Female , Healthy Volunteers , Humans , Male , Prospective Studies , ThrombelastographyABSTRACT
Splenectomy increases lifetime risk of thromboembolism (VTE) and is associated with long-term infectious complications, primarily, overwhelming post-splenectomy infection (OPSI). Our objective was to evaluate risk of VTE and infection at index hospitalization post-splenectomy. Retrospective review of all patients who received a laparotomy in the NTDB. Propensity score matching for splenectomy was performed, based on ISS, abdominal abbreviated injury score >3, GCS, sex and mechanism. Major complications, VTE, and infection rates were compared. Multiple logistic regression models were utilized to evaluate splenectomy-associated complications. 93,221 laparotomies were performed and 17% underwent splenectomy. Multiple logistic regression models did not demonstrate an association between splenectomy and major complications (OR 0.96, 95% CI 0.91-1.03, p = 0.25) or VTE (OR 1.05, 95% CI 0.96-1.14, p = 0.33). Splenectomy was independently associated with infection (OR 1.07, 95% CI 1.00-1.14, p = 0.045). Subgroup analysis of patients with infection demonstrated that splenectomy was most strongly associated with pneumonia (OR 1.41, 95% CI 1.26-1.57, p < 0.001). Splenectomy is not associated with higher overall complication or VTE rates during index hospitalization. However, splenectomy is associated with a higher rate of pneumonia.
Subject(s)
Infections/etiology , Laparotomy , Pneumonia/etiology , Postoperative Complications/etiology , Splenectomy/adverse effects , Wounds and Injuries/surgery , Databases, Factual , Female , Hospitalization , Humans , Infections/epidemiology , Injury Severity Score , Logistic Models , Male , Pneumonia/epidemiology , Postoperative Complications/epidemiology , Propensity Score , Retrospective Studies , Risk Factors , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiologyABSTRACT
BACKGROUND: Altered coagulation function after trauma can contribute to development of venous thromboembolism (VTE). Severe trauma impairs coagulation function, but the trajectory for recovery is not known. We hypothesized that enhanced, early recovery of coagulation function increases VTE risk in severely injured trauma patients. STUDY DESIGN: Secondary analysis was performed on data from the Pragmatic Randomized Optimal Platelet and Plasma Ratio (PROPPR) trial, excluding patients who died within 24 hours or were on pre-injury anticoagulants. Patient characteristics, adverse outcomes, and parameters of platelet function and coagulation (thromboelastography) were compared from admission to 72 hours between VTE (n = 83) and non-VTE (n = 475) patients. A p value < 0.05 indicates significance. RESULTS: Despite similar patient demographics, VTE patients exhibited hypercoagulable thromboelastography parameters and enhanced platelet function at admission (p < 0.05). Both groups exhibited hypocoagulable thromboelastography parameters, platelet dysfunction, and suppressed clot lysis (low clot lysis at 30 minutes) 2 hours after admission (p < 0.05). The VTE patients exhibited delayed coagulation recovery (a significant change compared with 2 hours) of K-value (48 vs 24 hours), α-angle (no recovery), maximum amplitude (24 vs 12 hours), and clot lysis at 30 minutes (48 vs 12 hours). Platelet function recovery mediated by arachidonic acid (72 vs 4 hours), ADP (72 vs 12 hours), and collagen (48 vs 12 hours) was delayed in VTE patients. The VTE patients had lower mortality (4% vs 13%; p < 0.05), but fewer hospital-free days (0 days [interquartile range 0 to 8 days] vs 10 days [interquartile range 0 to 20 days]; p < 0.05) and higher complication rates (p < 0.05). CONCLUSIONS: Recovery from platelet dysfunction and coagulopathy after severe trauma were delayed in VTE patients. Suppressed clot lysis and compensatory mechanisms associated with altered coagulation that can potentiate VTE formation require additional investigation.
Subject(s)
Anticoagulants/therapeutic use , Blood Coagulation Disorders/complications , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Wounds and Injuries/complications , Adult , Blood Coagulation Tests , Female , Humans , Injury Severity Score , Male , Middle Aged , Recovery of Function , Thrombelastography , Trauma Centers , Venous Thromboembolism/diagnostic imagingABSTRACT
Importance: Prophylactic enoxaparin is used to prevent venous thromboembolism (VTE) in surgical and trauma patients. However, VTE remains an important source of morbidity and mortality, potentially exacerbated by antithrombin III or anti-Factor Xa deficiencies and missed enoxaparin doses. Recent data suggest that a difference in reaction time (time to initial fibrin formation) greater than 1 minute between heparinase and standard thrombelastogram (TEG) is associated with a decreased risk of VTE. Objective: To evaluate the effectiveness of TEG-adjusted prophylactic enoxaparin dosing among trauma and surgical patients. Design, Setting, and Participants: This randomized clinical trial, conducted from October 2012 to May 2015, compared standard dosing (30 mg twice daily) with TEG-adjusted enoxaparin dosing (35 mg twice daily) for 185 surgical and trauma patients screened for VTE at 3 level I trauma centers in the United States. Main Outcomes and Measures: The incidence of VTE, bleeding complications, anti-Factor Xa deficiency, and antithrombin III deficiency. Results: Of the 185 trial participants, 89 were randomized to the control group (median age, 44.0 years; 55.1% male) and 96 to the intervention group (median age, 48.5 years; 74.0% male). Patients in the intervention group received a higher median enoxaparin dose than control patients (35 mg vs 30 mg twice daily; P < .001). Anti-Factor Xa levels in intervention patients were not higher than levels in control patients until day 6 (0.4 U/mL vs 0.21 U/mL; P < .001). Only 22 patients (11.9%) achieved a difference in reaction time greater than 1 minute, which was similar between the control and intervention groups (10.4% vs 13.5%; P = .68). The time to enoxaparin initiation was similar between the control and intervention groups (median [range] days, 1.0 [0.0-2.0] vs 1.0 [1.0-2.0]; P = .39), and the number of patients who missed at least 1 dose was also similar (43 [48.3%] vs 54 [56.3%]; P = .30). Rates of VTE (6 [6.7%] vs 6 [6.3%]; P > .99) were similar, but the difference in bleeding complications (5 [5.6%] vs 13 [13.5%]; P = .08) was not statistically significant. Antithrombin III and anti-Factor Xa deficiencies and hypercoagulable TEG parameters, including elevated coagulation index (>3), maximum amplitude (>74 mm), and G value (>12.4 dynes/cm2), were prevalent in both groups. Identified risk factors for VTE included older age (61.0 years vs 46.0 years; P = .04), higher body mass index (calculated as weight in kilograms divided by height in meters squared; 30.6 vs 27.1; P = .03), increased Acute Physiology and Chronic Health Evaluation II score (8.5 vs 7.0; P = .03), and increased percentage of missed doses per patient (14.8% vs 2.5%; P = .05). Conclusions and Relevance: The incidence of VTE was low and similar between groups; however, few patients achieved a difference in reaction time greater than 1 minute. Antithrombin III deficiencies and hypercoagulable TEG parameters were prevalent among patients with VTE. Low VTE incidence may be due to an early time to enoxaparin initiation and an overall healthier and less severely injured study population than previously reported. Trial Registration: clinicaltrials.gov Identifier: NCT00990236.
Subject(s)
Anticoagulants/administration & dosage , Enoxaparin/administration & dosage , Thrombelastography , Venous Thromboembolism/prevention & control , Adult , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Prospective Studies , Trauma Centers , Treatment Outcome , United StatesABSTRACT
Lactated Ringer's (LR) and normal saline (NS) are both used for resuscitation of injured patients. NS has been associated with increased resuscitation volume, blood loss, acidosis, and coagulopathy compared with LR. We sought to determine if pre-hospital LR is associated with improved outcome compared with NS in patients with and without traumatic brain injury (TBI). We included patients receiving pre-hospital LR or NS from the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Patients with TBI (Abbreviated Injury Scale [AIS] head ≥3) and without TBI (AIS head ≤2) were compared. Cox proportional hazards models including Injury Severity Score (ISS), AIS head, AIS extremity, age, fluids, intubation status, and hospital site were generated for prediction of mortality. Linear regression models were generated for prediction of red blood cell (RBC) and crystalloid requirement, and admission biochemical/physiological parameters. Seven hundred ninety-one patients received either LR (n = 117) or NS (n = 674). Median ISS, AIS head, AIS extremity, and pre-hospital fluid volume were higher in TBI and non-TBI patients receiving LR compared with NS (p < 0.01). In patients with TBI (n = 308), LR was associated with higher adjusted mortality compared with NS (hazard rate [HR] = 1.78, confidence interval [CI] 1.04-3.04, p = 0.035). In patients without TBI (n = 483), no difference in mortality was demonstrated (HR = 1.49, CI 0.757-2.95, p = 0.247). Fluid type had no effect on admission biochemical or physiological parameters, 6-hour RBC, or crystalloid requirement in either group. LR was associated with increased mortality compared with NS in patients with TBI. These results underscore the need for a prospective randomized trial comparing pre-hospital LR with NS in patients with TBI.
Subject(s)
Brain Injuries, Traumatic/diagnosis , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/mortality , Isotonic Solutions/pharmacology , Outcome Assessment, Health Care , Sodium Chloride/pharmacology , Abbreviated Injury Scale , Adult , Aged , Female , Humans , Injury Severity Score , Isotonic Solutions/administration & dosage , Isotonic Solutions/adverse effects , Middle Aged , Prospective Studies , Ringer's Lactate , Sodium Chloride/administration & dosage , Sodium Chloride/adverse effects , Young AdultABSTRACT
BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial has demonstrated that damage-control resuscitation, a massive transfusion strategy targeting a balanced delivery of plasma-platelet-red blood cell in a ratio of 1:1:1, results in improved survival at 3 hours and a reduction in deaths caused by exsanguination in the first 24 hours compared with a 1:1:2 ratio. In light of these findings, we hypothesized that patients receiving 1:1:1 ratio would have improved survival after emergency laparotomy. METHODS: Severely injured patients predicted to receive a massive transfusion admitted to 12 Level I North American trauma centers were randomized to 1:1:1 versus 1:1:2 as described in the PROPPR trial. From these patients, the subset that underwent an emergency laparotomy, defined previously in the literature as laparotomy within 90 minutes of arrival, were identified. We compared rates and timing of emergency laparotomy as well as postsurgical survival at 24 hours and 30 days. RESULTS: Of the 680 enrolled patients, 613 underwent a surgical procedure, 397 underwent a laparotomy, and 346 underwent an emergency laparotomy. The percentages of patients undergoing emergency laparotomy were 51.5% (174 of 338) and 50.3% (172 of 342) for 1:1:1 and 1:1:2, respectively (p = 0.20). Median time to laparotomy was 28 minutes in both treatment groups. Among patients undergoing an emergency laparotomy, the proportions of patients surviving to 24 hours and 30 days were similar between treatment arms; 24-hour survival was 86.8% (151 of 174) for 1:1:1 and 83.1% (143 of 172) for 1:1:2 (p = 0.29), and 30-day survival was 79.3% (138 of 174) for 1:1:1 and 75.0% (129 of 172) for 1:1:2 (p = 0.30). CONCLUSION: We found no evidence that resuscitation strategy affects whether a patient requires an emergency laparotomy, time to laparotomy, or subsequent survival. LEVEL OF EVIDENCE: Therapeutic study, level IV.
Subject(s)
Blood Transfusion/methods , Emergencies , Exsanguination/prevention & control , Laparotomy/methods , Resuscitation/methods , Wounds and Injuries/therapy , Adult , Combined Modality Therapy , Exsanguination/mortality , Female , Hospital Mortality , Humans , Injury Severity Score , Male , Middle Aged , North America/epidemiology , Survival Analysis , Treatment Outcome , Wounds and Injuries/mortalityABSTRACT
IMPORTANCE: Incorporating deliberate practice (DP) into residency curricula may optimize education. DP includes educationally protected time, continuous expert feedback, and a focus on a limited number of technical skills. It is strongly associated with mastery level learning. OBJECTIVE: Determine if a multidisciplinary breast rotation (MDB) increases DP opportunities. DESIGN: Beginning in 2010, interns completed the 4-week MDB. Three days a week were spent in surgery and surgical clinic. Half-days were in breast radiology, pathology, medical oncology, and didactics. The MDB was retrospectively compared with a traditional community rotation (TCR) and a university surgical oncology service (USOS) using rotation feedback and resident operative volume. Data are presented as mean ± standard deviation. SETTING: Oregon Health and Science University in Portland, Oregon; an academic tertiary care general surgery residency program. PARTICIPANTS: General surgery residents at Oregon Health and Science University participating in either the MDB, TCR or USOS. RESULTS: A total of 31 interns rated the opportunity to perform procedures significantly higher for MDB than TCR or USOS (4.6 ± 0.6 vs 4.2 ± 0.9 and 4.1 ± 1.0, p < 0.05). MDB was rated higher than TCR on quality of faculty teaching and educational materials (4.5 ± 0.7 vs 4.1 ± 0.9 and 4.0 ± 1.2 vs 3.5 ± 1.0, p < 0.05). Interns operated more on the MDB than on the USOS and were more focused on breast resections, lymph node dissections, and port placements than on the traditional surgical rotation or USOS. CONCLUSIONS: The MDB incorporates multidisciplinary care into a unique, disease-specific, and educationally focused rotation. It is highly rated and affords a greater opportunity for DP than either the USOS or TCR. DP is strongly associated with mastery learning and this novel rotation structure could maximize intern education in the era of limited work hours.
Subject(s)
Internship and Residency/methods , Specialties, Surgical/education , Breast Neoplasms/surgery , Female , Humans , OregonABSTRACT
BACKGROUND: Compared with lyophilized plasma (LP) buffered with other acids, LP with ascorbic acid (AA) attenuates systemic inflammation and DNA damage in a combat relevant polytrauma swine model. We hypothesize that increasing concentrations of AA in transfused LP will be safe, will be hemodynamically well tolerated, and will attenuate systemic inflammation following polytraumatic injury and hemorrhage in swine. METHODS: This prospective, randomized, blinded study involved 52 female swine. Forty animals were subjected to our validated polytrauma model and resuscitated with LP. Baseline control sham (n = 6), operative control sham (n = 6), low-AA (n = 10), medium-AA (n = 10), high-AA (n = 10) groups, and a hydrochloric acid control (HCL, n = 10) were randomized. Hemodynamics, thrombelastography, and blood chemistries were assessed. Inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], C-reactive protein, and IL-10) and DNA damage were measured at baseline, 2 hours, and 4 hours after liver injury. Significance was set at p < 0.05, with a Bonferroni correction for multiple comparisons. RESULTS: Hemodynamics, shock, and blood loss were similar between groups. All animals had robust procoagulant activity 2 hours following liver injury. Inflammation was similar between groups at baseline, and AA groups remained similar to HCL following liver injury. IL-6 and tumor necrosis factor α were increased at 2 hours and 4 hours compared with baseline within all groups (p < 0.008). DNA damage increased at 2 hours compared with baseline in all groups (p < 0.017) and further increased at 4 hours compared with baseline in HCL, low-, and high-AA groups (p < 0.005). C-reactive protein was similar between and within groups. IL-10 increased at 2 hours compared with baseline in low- and high-AA groups and remained elevated at 4 hours compared with baseline in the low-AA group (all, p < 0.017). CONCLUSION: Concentrations of AA were well tolerated and did not diminish the procoagulant activity of LP. Within our tested range of concentrations, AA can safely be used to buffer LP.
Subject(s)
Blood Transfusion , Animals , Ascorbic Acid , Cytokines/blood , DNA Damage , Female , Freeze Drying , Hemodynamics , Plasma/chemistry , Prospective Studies , Swine , ThrombelastographyABSTRACT
BACKGROUND: Traumatic diaphragmatic injury (TDI) is a rarely diagnosed injury in trauma. Previous studies have been limited in their evaluation of TDI because of small population size and center bias. Although injuries may be suspected based on penetrating mechanism, blunt injuries may be particularly difficult to detect. The American College of Surgeons National Trauma Data Bank is the largest trauma database in the United States. We hypothesized that we could identify specific injury patterns associated with blunt and penetrating TDIs. METHODS: We examined demographics, diagnoses, mechanism of injury, and outcomes for patients with TDI in 2012 as this is the largest and most recent dataset available. Comparisons were made using chi-square or independent samples t test. RESULTS: There were a total of 833,309 encounters in the National Trauma Data Bank in 2012. Three thousand eight hundred seventy-three patients had a TDI (.46%). Of those, 1,240 (33%) patients had a blunt mechanism and 2,543 (67%) had a penetrating mechanism. Patients with blunt TDI were older (44 ± 19 vs 31 ± 13 years, P < .001), had a higher injury severity score (33 ± 14 vs 24 ± 15, P < .001), and a higher mortality rate (19.8% vs 8.8%, P < .001). Compared with patients with penetrating injuries, those with blunt TDI were more likely to have injuries to the thoracic aorta (2.9% vs .5%, P < .001), lung (48.7% vs 28.1, P < .001), bladder (5.9% vs .7%, P < .001), and spleen (44.8% vs 29.1%, P < .001). Penetrating TDI was associated with liver and hollow viscus injuries. CONCLUSIONS: Diaphragmatic injury is an uncommon but significant diagnosis in trauma patients. Blunt injuries may be more likely to be occult; however, a pattern of associated injuries to the aorta, lung, spleen, and bladder should prompt further workup for TDI.
Subject(s)
Abdominal Injuries/epidemiology , Diaphragm/injuries , Multiple Trauma , Registries , Thoracic Injuries/epidemiology , Traumatology/statistics & numerical data , Wounds, Nonpenetrating/epidemiology , Abdominal Injuries/diagnosis , Adult , Databases, Factual , Female , Humans , Incidence , Injury Severity Score , Male , Retrospective Studies , Thoracic Injuries/diagnosis , United States/epidemiology , Wounds, Nonpenetrating/diagnosisABSTRACT
BACKGROUND: Cirrhosis may be a risk factor for mortality following blunt splenic injury (BSI) and it predicts the need for an operative intervention. METHODS: We performed a case-control study at 3 level 1 trauma centers. Comparisons were made with chi-square test, Wilcoxon rank-sum test, and binary logistic regression, and stratified by propensity for splenectomy. Data are presented as odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Mortality was 27% (21/77) and cirrhosis was a strong risk factor for death (OR 8.8, 95% CI 3.7 to 21.1). Compared with controls, cirrhosis was an independent risk factor for splenectomy (OR 5.4, 95% CI 2.5 to 11.5), and only splenic injury grade was associated with splenectomy (OR 2.2, 95% CI 1.3 to 3.6). Only admission model for end-stage liver disease was independently associated with mortality after an operation (OR 1.7, 95% CI 1.1 to 2.8). After propensity score matching, we found no association between splenectomy and mortality in cirrhotic patients. CONCLUSION: Cirrhosis dramatically increases mortality and the odds of an operative intervention in BSI patients with pre-existing cirrhosis, and BSI requires vigilant attention and early intervention should be considered.
Subject(s)
Abdominal Injuries/complications , Liver Cirrhosis/etiology , Spleen/injuries , Splenectomy/trends , Wounds, Nonpenetrating/complications , Abdominal Injuries/mortality , Abdominal Injuries/surgery , Adult , Female , Follow-Up Studies , Humans , Liver Cirrhosis/mortality , Male , Middle Aged , Prospective Studies , Spleen/surgery , Survival Rate/trends , United States/epidemiology , Wounds, Nonpenetrating/mortality , Wounds, Nonpenetrating/surgeryABSTRACT
BACKGROUND: The management of severe traumatic brain injury (TBI) frequently involves invasive intracranial monitoring or cranial surgery. In our institution, intracranial procedures are often deferred until an international normalized ratio (INR) of less than 1.4 is achieved. There is no evidence that a moderately elevated INR is associated with increased risk of bleeding in patients undergoing neurosurgical intervention (NI). Thrombelastography (TEG) provides a functional assessment of clotting and has been shown to better predict clinically relevant coagulopathy compared with INR. We hypothesized that in patients with TBI, an elevated INR would result in increased time to NI and would not be associated with coagulation abnormalities based on TEG. METHODS: A secondary analysis of prospectively collected data was performed in trauma patients with intracranial hemorrhage that underwent NI (defined as cranial surgery or intracranial pressure monitoring) within 24 hours of arrival. Time from admission to NI was recorded. TEG and routine coagulation assays were obtained at admission. Patients were considered hypocoagulable based on INR if their admission INR was greater than 1.4 (high INR). Manufacturer-specified values were used to determine hypocoagulability for each TEG variable. RESULTS: Sixty-one patients (median head Abbreviated Injury Scale [AIS] score, 5) met entry criteria, of whom 16% had high INR. Demographic, physiologic, and injury scoring data were similar between groups. The median time to NI was longer in patients with high INR (358 minutes vs. 184 minutes, p = 0.027). High-INR patients were transfused more plasma than patients with an INR of 1.4 or less (2 U vs. 0 U, p = 0.01). There was no association between an elevated INR and hypocoagulability based on TEG. CONCLUSION: TBI patients with an admission INR of greater than 1.4 had a longer time to NI. The use of plasma transfusion to decrease the INR may have contributed to this delay. A moderately elevated INR was not associated with coagulation abnormalities based on TEG. Routine plasma transfusion to correct a moderately elevated INR before NI should be reexamined. LEVEL OF EVIDENCE: Diagnostic study, level III.
Subject(s)
Brain Injuries/blood , International Normalized Ratio , Abbreviated Injury Scale , Adult , Aged , Brain Injuries/surgery , Cerebral Hemorrhage/blood , Cerebral Hemorrhage/surgery , Female , Humans , Intracranial Pressure , Male , Middle Aged , Prospective Studies , Thrombelastography , Time Factors , Young AdultABSTRACT
Mutations in myosin heavy chain (MyHC) can cause hypertrophic cardiomyopathy (HCM) that is characterized by hypertrophy, histopathology, contractile dysfunction, and sudden death. The signaling pathways involved in the pathology of HCM have not been elucidated, and an unresolved question is whether blocking hypertrophic growth in HCM may be maladaptive or beneficial. To address these questions, a mouse model of HCM was crossed with an antihypertrophic mouse model of constitutive activated glycogen synthase kinase-3beta (caGSK-3beta). Active GSK-3beta blocked cardiac hypertrophy in both male and female HCM mice. However, doubly transgenic males (HCM/GSK-3beta) demonstrated depressed contractile function, reduced sarcoplasmic (endo) reticulum Ca(2+)-ATPase (SERCA) expression, elevated atrial natriuretic factor (ANF) expression, and premature death. In contrast, female HCM/GSK-3beta double transgenic mice exhibited similar cardiac histology, function, and survival to their female HCM littermates. Remarkably, dietary modification from a soy-based diet to a casein-based diet significantly improved survival in HCM/GSK-3beta males. These findings indicate that activation of GSK-3beta is sufficient to limit cardiac growth in this HCM model and the consequence of caGSK-3beta was sexually dimorphic. Furthermore, these results show that blocking hypertrophy by active GSK-3beta in this HCM model is not therapeutic.