Article

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

Authors:
  • Regional Medical Center, Bayonet Point, Husdon, Florida
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Abstract

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.

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... 20 Trauma investigators have developed a decision rule to risk stratify patients with tICrH for early chemoprophylaxis (see figure 4). 21 While this rule has only been tested in a pilot trial of low-risk patients with stable CT images for early VTE prevention (prophylactic dose heparins, not full oral anticoagulation), it is useful to conceptualize risk of hematoma expansion in the setting of anticoagulant considerations. 21 It is also telling that the study of 62 patients had no clinically significant hematoma expansion at 48 hours after injury. ...
... 21 While this rule has only been tested in a pilot trial of low-risk patients with stable CT images for early VTE prevention (prophylactic dose heparins, not full oral anticoagulation), it is useful to conceptualize risk of hematoma expansion in the setting of anticoagulant considerations. 21 It is also telling that the study of 62 patients had no clinically significant hematoma expansion at 48 hours after injury. Ongoing changes in hemorrhage based on follow-up imaging may offer an important criterion for evaluating patients for treatment reinitiation. ...
... The Parkland Protocol (modified Berne Norwood criteria) categorizes traumatic brain injury (TBI) patterns as low, moderate or high risk for hematoma expansion when considering venous thromboembolism (VTE) prophylaxis. Reproduced with conditional permission from Phelan et al.21 Copyright 2012 Wolters Kluwer Health.copyright. ...
Article
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Anticoagulant-associated traumatic intracranial hemorrhage (tICrH) is a devastating injury with high morbidity and mortality. For survivors, treating clinicians face the dilemma of restarting oral anticoagulation with scarce evidence to guide them. Thromboembolic risk is high from the bleeding event, patients’ high baseline risks, that is, the pre-existing indication for anticoagulation, and the risk of immobility after the bleeding episode. This must be balanced with potentially devastating hematoma expansion or new hemorrhagic lesions. Retrospective evidence and expert opinion support restarting oral anticoagulants in most patients with tICrH, but timing is uncertain. Researchers have failed to make clear distinctions between tICrH and spontaneous intracranial hemorrhage (sICrH), which have differing natural histories. While both appear to benefit from restarting, sICrH has a higher rebleeding risk and similar or lower thrombotic risk. Clinical equipoise on restarting is also divergent. In sICrH, equipoise is centered on whether to restart. In tICrH, it is centered on when. Several prospective randomized clinical trials are ongoing or about to start to examine the risk–benefit of restarting. Most of them are restricted to patients with sICrH, with antiplatelet control groups. Most are also restricted to direct oral anticoagulants (DOACs), as they are associated with a lower overall risk of ICrH. There is some overlap with tICrH via subdural hematoma, and one trial is specific to restart timing with DOACs in only traumatic cases. This is a narrative review of the current evidence for restarting anticoagulation and restart timing after tICrH along with a summary of the ongoing and planned clinical trials.
... 2,3 Guidelines for patients with TBI lack high-level recommendations regarding the use of pharmaceutical VTE (pVTE) prophylaxis in patients with severe TBI, and randomized controlled trials (RCTs) on the effectiveness of pVTE prophylaxis are scarce. 4,5 This lack of high-level evidence could result in substantial variation in pVTE prophylaxis practices. Previous studies reported wide variation in incidence rates of deep venous thrombosis (DVT) and pulmonary embolism (PE), 6 but more recent studies suggest that the incidence rates of clinical VTE are low. ...
... acid, and extracranial surgery. The median length of hospital stay in patients receiving pVTE prophylaxis was 20 days (interquartile range [IQR], 11-36) versus 7 days (IQR, [3][4][5][6][7][8][9][10][11][12][13][14] in patients without pVTE prophylaxis. A similar pattern was noted for patients receiving pVTE prophylaxis during ICU stay versus patients receiving no pVTE prophylaxis or after ICU stay. ...
... Although higher incidences of VTE have been reported in previous studies in TBI, 6,17 others reported similar or even lower percentages compared with our study. 5,7 The discrepancy between higher incidences in other studies may be partly explained either by a lack of routine lower-limb screening with ultrasound for DVT or clinical under-reporting of DVT in our study. In our study, no conclusion on these outcomes (DVT and PE) could be drawn given that the statistical power was very low. ...
Article
The aims of this study are to describe the use of pharmaceutical venous thromboembolism (pVTE) prophylaxis in patients with traumatic brain injury (TBI) in Europe and study the association of pVTE prophylaxis with outcome. We included 2006 patients ≥18 years of age admitted to the intensive care unit from the CENTER-TBI study. VTE events were recorded based on clinical symptoms. Variation between 54 centers in pVTE prophylaxis use was assessed with a multi-variate random-effect model and quantified with the median odds ratio (MOR). The association between pVTE prophylaxis and outcome (Glasgow Outcome Scale-Extended at 6 months) was assessed at center level with an instrumental variable analysis and at patient level with a multi-variate proportional odds regression analysis and a propensity-matched analysis. A time-dependent Cox survival regression analysis was conducted to determine the effect of pVTE prophylaxis on survival during hospital stay. The association between VTE prophylaxis and computed tomography (CT) progression was assessed with a logistic regression analysis. Overall, 56 patients (2%) had a VTE during hospital stay. The majority, 1279 patients (64%), received pVTE prophylaxis, with substantial between-center variation (MOR, 2.7; p < 0.001). A moderate association with improved outcome was found at center level (odds ratio [OR], 1.2 [0.7-2.1]) and patient level (multi-variate adjusted OR, 1.4 [1.1-1.7], and propensity adjusted OR, 1.5 [1.1-2.0]), with similar results in subgroup analyses. Survival was higher with the use of pVTE prophylaxis (p < 0.001). We found no clear effect on CT progression (OR, 0.9; CI [0.6-1.2]). Overall, practice policies for pVTE prophylaxis vary substantially between European centers, whereas pVTE prophylaxis may contribute to improved outcome. Trial registration number is NCT02210221 at ClinicalTrials.gov, registered on August 6, 2014 (first patient enrollment on December 19, 2014).
... The estimated incidence of VTE in TBI patients with chemoprophylaxis is 0 to 14 per cent when initiated after a stable head CT scan. [5][6][7][8] A meta-analysis of early (<72 hours) versus late (>72 hours) chemoprophylaxis initiation suggested that early chemoprophylaxis reduces the risk of VTE. 6 However, that study estimated the risk of bleed progression at 3.6 to 60 per cent (pooled rate of 18%). 6 Because of the risk of progressive bleeding, previous studies have waited 48 to 72 hours postinjury and for a stable head CT to initiate chemoprophylaxis. ...
... 5,7 However, a study comparing chemoprophylaxis with placebo in low-risk patients with TBI demonstrated a similar rate of ICH progression when initiated 24 hours after injury and with a stable head CT, with none of the observed instances of ICH progression being clinically significant. 8 The current Trauma Quality Improvement Project (TQIP) chemoprophylaxis recommendation is to initiate chemoprophylaxis at 24 hours and with stable head CT in patients at low risk of ICH progression, at 72 hours and with a stable head CT in moderate-risk patients, and to consider inferior vena cava (IVC) placement in high-risk patients. 9 The optimal chemoprophylactic agent is also a topic of deliberation. ...
... The 4.7 per cent incidence of VTE found in the assay-guided group was within the range of estimates for VTE rates with chemoprophylaxis in the literature of 0 to 14 per cent. [5][6][7][8] The incidence observed in the assay-guided group in this study was higher than that found in the DEEP I study which reported a 0 per cent incidence in the LMWH cohort. 8 However, this finding is due to the overall low severity of TBI in the study populations. ...
Article
This study evaluated the safety of early anti-factor Xa assay–guided enoxaparin dosing for chemoprophylaxis in patients with TBI. We hypothesized that assay-guided chemoprophylaxis would be comparable in the risk of intracranial hemorrhage (ICH) progression to fixed dosing. An observational analysis of adult patients with blunt traumatic brain injury (TBI) was performed at a Level I trauma center from August 2016 to September 2017. Patients in the assay-guided group were treated with an initial enoxaparin dose of 0.5 mg/kg, with peak anti-factor Xa activity measured four hours after the third dose. Prophylactic range was defined as 0.2 to 0.5 IU/mL with a dose adjustment of ± 10 mg based on the assay result. The assay-guided group was compared with historical fixed-dose controls and to a TBI cohort from the most recent Trauma Quality Improvement Project dataset. Of 179 patients included in the study, 85 were in the assay-guided group and 94 were in the fixed-dose group. Compared with the fixed-dose group, the assay-guided group had a lower Glasgow Coma Score and higher Injury Severity Score. The proportion of severe (Abbreviated Injury Score, head ≥3) TBI, ICH progression, and venous thromboembolism rates were similar between all groups. The assay-guided and fixed-dose groups had chemoprophylaxis initiated earlier than the Trauma Quality Improvement Project group. The assay-guided group had the highest percentage of low molecular weight heparin use. Early initiation of enoxaparin anti-factor Xa assay–guided venous thromboembolism chemoprophylaxis has a comparable risk of ICH progression to fixed dosing in patients with TBI. These findings should be validated prospectively in a multicenter study.
... 6 Recently, the pendulum of thought for pVCFs in trauma has swung in the other direction, favoring earlier and more aggressive chemoprophylaxis. [7][8][9][10][11] Some have argued that pVCF has been overused and the paradigm shift to VTE prophylaxis without IVC filters is the future of trauma care. 12 Therefore, to evaluate whether the use of pVCFs has led to decreased rates of VTE and improved mortality, our institutional use of pVCFs was examined. ...
... More neurosurgeons are willing to initiate anticoagulation within 24-48 hours after computed tomography scanning has confirmed the stability of intracranial hemorrhage. [7][8][9][10][11]22 In our study, patients receiving pVCFs received them on the basis that they would be unable to be anticoagulated for greater than 48 hours. Acceptance of early VTE prophylaxis in traumatic brain injury has markedly decreased the number of patients considered for pVCFs. ...
Article
The role of prophylactic vena cava filters (pVCFs) in trauma patients remains controversial. After 20 years of data collection and experience, we reviewed our venous thromboembolism guideline for the efficacy of pVCFs in preventing pulmonary embolism (PE). A retrospective cohort study was performed using our Level I trauma center registry from January 1997 thru December 2016. This population was then divided by the presence of pVCFs. Univariate analysis was performed comparing the incidence of PEs, deep vein thrombosis, and mortality between those with and without a pVCF. There were 35,658 patients identified, of whom 2 per cent (n = 847) received pVCFs. The PE rate was 0.4 per cent in both groups. The deep vein thrombosis rate for pVCFs was 3.9 per cent compared with 0.6 per cent in the no-VCF group (P < 0.0001). Given that there was no difference in the rates of PEs between the cohorts, the subset of patients with a PE were analyzed by their risk factors. Only ventilator days > 3 were associated with a higher risk in the no-pVCF group (0.2 vs 1.5%, P = 0.033). pVCFs did not confer benefit reducing PE rate. In addition, despite their intended purpose, pVCFs cannot eliminate PEs in high-risk trauma patients, suggesting a lack of utility for prophylaxis in this population.
... Intracranial Hemorrhage (ICH) proportions were available in the manuscript for 16 of the 22 cohorts and showed a mean proportion of 85.8 per cent. [12][13][14][15][16][17][18][19][20][21] Glasgow Coma Scale score values were available in the manuscript for 11 of the 22 cohorts with a mean value of 9.3. 15,18,19,[21][22][23][24][25] Trait Comparisons between PE Patients and Those at Risk for DVT The individual cohort ISS and age results for patients with PE are shown in Table 2 and values for patients at risk for DVT are shown in Tables 3 and 4. For patients at risk for DVT, the test for heterogeneity, using cohort size, was not significant for ISS (P 4 0.2146) or age (P 4 0.7644). ...
... [12][13][14][15][16][17][18][19][20][21] Glasgow Coma Scale score values were available in the manuscript for 11 of the 22 cohorts with a mean value of 9.3. 15,18,19,[21][22][23][24][25] Trait Comparisons between PE Patients and Those at Risk for DVT The individual cohort ISS and age results for patients with PE are shown in Table 2 and values for patients at risk for DVT are shown in Tables 3 and 4. For patients at risk for DVT, the test for heterogeneity, using cohort size, was not significant for ISS (P 4 0.2146) or age (P 4 0.7644). Other data used for comparisons of patients with PE and those at risk for DVT are displayed in Table 5. ...
Article
We delineated the incidence of trauma patient pulmonary embolism (PE) and risk conditions by performing a systematic literature review of those at risk for deep vein thrombosis (DVT). The PE proportion was 1.4 per cent (95% confidence interval 5 1.2-1.6) in at-risk patients. Of 10 conditions, PE was only associated with increased age (P < 0.01) or leg injury (P < 0.01; risk ratio 5 1.6). As lower extremity DVT (LEDVT) proportions increased, mortality proportions (P = 0.02) and hospital stay (P = 0.0002) increased, but PE proportions did not (P = 0.13). LEDVT was lower with chemoprophylaxis (CP) (4.9%) than without CP (19.1%; P < 0.01). PE was lower with CP (1.0%) than without CP (2.2%; P = 0.0004). Mortality was lower with CP (6.6%) than without CP (11.6%; P = 0.002). PE was similar with (1.2%) and without (1.9%; P = 0.19) mechanical prophylaxis (MP). LEDVT was lower with MP (8.5%) than without MP (12.2%; P = 0.0005). PE proportions were similar with (1.3%) and without (1.5%; P = 0.24) LEDVTsurveillance. Mortality was higher with LEDVTsurveillance (7.9%) than without (4.8%; P < 0.01). A PE mortality of 19.7 per cent (95% confidence interval 5 18-22) 3 a 1.4 per cent PE proportion yielded a 0.28 per cent lethal PE proportion. As PE proportions increased, mortality (P = 0.52) and hospital stay (P = 0.13) did not. Of 176 patients with PE, 76 per cent had no LEDVT. In trauma patients at risk for DVT, PE is infrequent, has a minimal impact on outcomes, and death is a black swan event. LEDVTsurveillance did not improve outcomes. Because PE was not associated with LEDVT and most patients with PE had no LEDVT, preventing, diagnosing, and treating LEDVT may be ineffective PE prophylaxis.
... A trial randomized 62 patients with small TBI patterns and stable brain CT scans at 24 h after injury to receive enoxaparin 30 mg bid or placebo 24 to 96 h after injury. [24] The rates of radiographic progression of TBI on CT scans performed 24 h after the start of treatment were 5.9% (95% CI, 0.7%-19.7%) for enoxaparin and 3.6% (95% CI, 0.1%-18.3%) ...
... for placebo. [24] In an observational study where 49.5% of 812 TBI patients received pharmacologic prophylaxis, lower VTE risk was found in the pharmacologic prophylaxis group (risk ratio, 0.194; 95% CI, 0.049-0.760). [25] The lack of clear recommendations on the timing of pharmacologic prophylaxis in TBI leads to inconsistent and variable prophylaxis practices. ...
Article
OBJECTIVES: Patients with traumatic brain injury (TBI) have an increased risk for venous thromboembolism (VTE). The current guidelines recommend pharmacologic prophylaxis, but its timing remains unclear. METHODS: In this retrospective cohort study, patients with moderate-to-severe TBI admitted to a tertiary care intensive care unit between 2016 and 2019 were categorized into two groups according to the timing of pharmacologic prophylaxis: early if prophylaxis was given within 72 h from hospital admission and late if after 72 h. RESULTS: Of the 322 patients in the cohort, 46 (14.3%) did not receive pharmacological prophylaxis, mainly due to early brain death; 152 (47.2%) received early pharmacologic prophylaxis and 124 (38.5%) received late prophylaxis. Predictors of late pharmacologic prophylaxis were lower body mass index, intracerebral hemorrhage (odds ratio [OR], 3.361; 95% confidence interval [CI], 1.269–8.904), hemorrhagic contusion (OR, 3.469; 95% CI, 1.039–11.576), and lower platelet count. VTE was diagnosed in 43 patients on a median of 10 days after trauma (Q1, Q3: 5, 15): 6.6% of the early prophylaxis group and 26.6% of the late group (P < 0.001). On multivariable logistic regression analysis, the predictors of VTE were Acute Physiology and Chronic Health Evaluation II score, subarachnoid hemorrhage, and late versus early pharmacologic prophylaxis (OR, 3.858; 95% CI, 1.687–8.825). The late prophylaxis group had higher rate of tracheostomy, longer duration of mechanical ventilation and stay in the hospital, lower discharge Glasgow coma scale, but similar survival, compared with the early group. CONCLUSIONS: Late prophylaxis (>72 h) was associated with higher VTE rate in patients with moderate-to-severe TBI, but not with higher mortality.
... 24 Those trauma centers that provide pharmacologic prophylaxis within 24 hours after TBI have significantly lower rates of VTE with no difference in rates of late neurosurgical intervention. 23,[25][26][27][28][29][30] Even in the setting of combat related penetrating TBI, initiating pharmacologic prophylaxis 24 hours after injury for those patients with a stable CT was safe, with similar progression rates regardless of pharmacologic prophylaxis. 29 The majority of TBI patients with a stable CT may be initiated on enoxaparin within 24 hours, and nearly all TBI patients should receive pharmacologic prophylaxis within 72 hours of the time of injury. ...
... 29 The majority of TBI patients with a stable CT may be initiated on enoxaparin within 24 hours, and nearly all TBI patients should receive pharmacologic prophylaxis within 72 hours of the time of injury. 23,28,31 Spinal Trauma ...
Article
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This algorithm was designed to provide comprehensive and clear guidance aimed at reducing the VTE rate after trauma. Although there are multiple factors that will lead to deviations from the presented algorithm, most trauma patients should be initiated on early and higher doses of enoxaparin that often should be adjusted by anti-Xa levels. For most trauma patients, pharmacologic prophylaxis should continue uninterrupted throughout the hospital stay and at times after discharge. Avoiding preventable and non–evidence-based delays to the initiation and missed doses of pharmacologic prophylaxis should be a best-practice focus of all trauma centers, and it has clearly been associated with decreased rates of VTE events.
... A number of authors have posited a mandatory 24-to 72-hour period of documented stability of intracranial bleeds before beginning thromboprophylaxis. [3][4][5][6] Hence, early discrimination of SDHs from ESDEs has important clinical implications. ...
Article
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Background and purpose: Extravasation of iodinated contrast into subdural space following contrast-enhanced radiographic studies results in hyperdense subdural effusions, which can be mistaken as acute subdural hematomas on follow-up noncontrast head CTs. Our aim was to identify the factors associated with contrast-enhancing subdural effusion, characterize diffusion and washout kinetics of iodine in enhancing subdural effusion, and assess the utility of dual-energy CT in differentiating enhancing subdural effusion from subdural hematoma. Materials and methods: We retrospectively analyzed follow-up head dual-energy CT studies in 423 patients with polytrauma who had undergone contrast-enhanced whole-body CT. Twenty-four patients with enhancing subdural effusion composed the study group, and 24 randomly selected patients with subdural hematoma were enrolled in the comparison group. Postprocessing with syngo.via was performed to determine the diffusion and washout kinetics of iodine. The sensitivity and specificity of dual-energy CT for the diagnosis of enhancing subdural effusion were determined with 120-kV, virtual monochromatic energy (190-keV) and virtual noncontrast images. Results: Patients with enhancing subdural effusion were significantly older (mean, 69 years; 95% CI, 60-78 years; P < .001) and had a higher incidence of intracranial hemorrhage (P = .001). Peak iodine concentration in enhancing subdural effusions was reached within the first 8 hours of contrast administration with a mean of 0.98 mg/mL (95% CI, 0.81-1.13 mg/mL), and complete washout was achieved at 38 hours. For the presence of a hyperdense subdural collection on 120-kV images with a loss of hyperattenuation on 190-keV and virtual noncontrast images, when considered as a true-positive for enhancing subdural effusion, the sensitivity was 100% (95% CI, 85.75%-100%) and the specificity was 91.67% (95% CI, 73%-99%). Conclusions: Dual-energy CT has a high sensitivity and specificity in differentiating enhancing subdural effusion from subdural hematoma. Hence, dual-energy CT has a potential to obviate follow-up studies.
... The BTF guidelines have no recommendations on the timing, dosing, and preferred agents in DVT prophylaxis. Indeed, no national standard of care exists to guide TBI caregivers in the initiation and use of prophylactic anticoagulation, specifically chemoprophylaxis, despite the frequency and morbidity of DVT events after TBI. 25 This variance in adherence to the guidelines may be attributed to the fear of an increase in intracerebral hemorrhage after chemoprophylaxis in TBI patients; however preliminary trials 26 have indicated no significant worsening of TBI after chemoprophylaxis. We hope future TBI guidelines will use new evidence to encourage stronger adherence to the BTF recommendations. ...
Article
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Background: The Brain Trauma Foundation has developed treatment guidelines for the care of patients with acute traumatic brain injury. The Adam Williams Initiative is a program established to provide education and resources to encourage hospitals across the United States to incorporate the guidelines into practice. Objective: To explore the relationship in hospitals between participation in the Adam Williams Initiative and adherence to the Brain Trauma Foundation guidelines for patients with acute traumatic brain injury. Method: Hospitals that participated in the Adam Williams Initiative entered data into an online tracking system of patients with traumatic brain injury for at least 2 years after the initial site training. Data included baseline hospital records and daily records on hospital care of patients with traumatic brain injury, including blood pressure, intracranial pressure, cerebral perfusion pressure, oxygenation, and other data relevant to the 15 key metrics in the Brain Trauma Foundation guidelines. Results: The 16 hospitals funded by the Adam Williams Initiative had good overall adherence to the 15 key metrics of the recommendations detailed in the Brain Trauma Foundation guidelines. Variability in results was primarily due to data collection methods and analysis. Conclusions: The Adam Williams Initiative helps promote adherence to the Brain Trauma Foundation guidelines for hospital care of patients with traumatic brain injury by providing a platform for developing and standardizing best practices. Participation in the initiative is associated with high adherence to clinical guidelines, a situation that may subsequently improve care and outcomes for patients with traumatic brain injury.
... A randomized, controlled trial including 62 low risk patients showed the safety of this protocol for this group: no progression of brain hemorrhage with the use of low-molecular-weight heparin at 24 h post-injury and one DVT with the use of placebo at 24 h post-injury. 33 However, more evidence is needed before this protocol can be widely accepted for the guidelines. ...
Article
Our aim was to describe current approaches and to quantify variability between European intensive care units (ICUs) in patients with traumatic brain injury (TBI). Therefore, we conducted a provider profiling survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The ICU Questionnaire was sent to 68 centers from 20 countries across Europe and Israel. For this study, we used ICU questions focused on 1) hemoglobin target level (Hb-TL), 2) coagulation management, and 3) deep venous thromboembolism (DVT) prophylaxis. Seventy-eight participants, mostly intensivists and neurosurgeons of 66 centers, completed the ICU questionnaire. For ICU-patients, half of the centers (N = 34; 52%) had a defined Hb-TL in their protocol. For patients with TBI, 26 centers (41%) indicated an Hb-TL between 70 and 90 g/L and 38 centers (59%) above 90 g/L. To treat trauma-related hemostatic abnormalities, the use of fresh frozen plasma (N = 48; 73%) or platelets (N = 34; 52%) was most often reported, followed by the supplementation of vitamin K (N = 26; 39%). Most centers reported using DVT prophylaxis with anticoagulants frequently or always (N = 62; 94%). In the absence of hemorrhagic brain lesions, 14 centers (21%) delayed DVT prophylaxis until 72 h after trauma. If hemorrhagic brain lesions were present, the number of centers delaying DVT prophylaxis for 72 h increased to 29 (46%). Overall, a lack of consensus exists between European ICUs on blood transfusion and coagulation management. The results provide a baseline for the CENTER-TBI study, and the large between-center variation indicates multiple opportunities for comparative effectiveness research.
... 49 Phelan et al. reportó los resultados de un estudio de cohorte randomizado que utilizaba un protocolo institu- cional en el que si un paciente no cumplía criterios espe- cíficos de severidad y no se encontraba deterioro en la TC a repetición luego de 24 horas posterior al trauma (cri- terio de Bernee Norwood modificados) se iniciaba ya sea heparina de bajo peso molecular (30 mg cada 12 horas) o placebo; este estudio no identificó ningún caso en el que ocurriera una progresión clínica de TCE luego de la pro- filaxis farmacológica (progresión radiológica en TC de 5.9% en pacientes que recibieron HBPM versus 3.6% en el grupo placebo). 54 ...
Article
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Resumen Los pacientes que reciben anticoagulación y que presentan lesiones traumáticas craneales están en riesgo aumentado de presentar fenómenos hemorrágicos a nivel intracraneal. La mortalidad en esta clase de pacientes es elevada lo que los convierte en una población que amerita un cuidadoso abordaje y seguimiento. Usualmente los pacientes que observamos en servicios de urgencia son traumas craneales leves pero la evolución del paciente anticoagulado en algunos casos es impredecible. Ac-tualmente, han sido publicados diversos estudios con relación a anticoagulación y lesión traumática cerebral. Presentamos una concisa revisión de la literatura enfocada a médicos neurólogos y neurocirujanos. Palabras clave: Anticoagulación, trauma craneal, neurotrauma. Abstract Patients receiving anticoagulation and those with traumatic cranial lesions are at increased risk of hemorrhagic phenomena at the intracranial level. Mortality in this class of patients is high, which makes them a population that deserves a careful approach and follow-up. Usually the patients we observe in emergency services are mild cranial traumas but the evolution of the anticoagulated patient in some cases is unpredictable. Currently, several studies have been published in relation to anticoa-gulation and traumatic brain injury. We present a concise review of the literature focused on neurologists and neurosurgeons.
... And one patient in the placebo group developed deep vein thrombosis (DVT). 24 A recent meta-analysis of clinical trials and observational trials recommended that use of pharmacological prophylaxis was safe when initiated within 24 to 48 hours of TBI with periodic intracranial imaging to rule out hemorrhage. 25 As per BTF guidelines, use of pharmacological prophylaxis with low molecular weight heparin or low-dose unfractionated heparin in combination with mechanical prophylaxis is to be considered when the benefit is found to outweigh the risk of cerebral bleed. 9 Periodic ultrasonographic examination to rule out DVT is recommended in high-risk patients. ...
Article
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Traumatic brain injury (TBI) is a significant public health problem. It is the leading cause of death and disability despite advancements in its prevention and treatment. Treatment of a patient with head injury begins on the site of trauma and continues even during her/his transportation to the trauma care center. Knowledge of secondary brain injuries and timely management of those in the prehospital period can significantly improve the outcome and decrease mortality after TBI. Intensive care management of TBI is guided by Brain Trauma Foundation guidelines (4th edition). Seventy percent of blunt trauma patients will also suffer from some degree of head injury. The management of these extracranial injuries may influence the neurological outcomes. Damage control tactics may improve early mortality (control hemorrhage) and delayed mortality (minimize systemic inflammation and organ failure). Neuromonitoring plays an important role in the management of TBI because it is able to assess multiple aspects of cerebral physiology and guide therapeutic interventions intended to prevent or minimize secondary injury. Bedsides, multimodality monitoring predominantly comprises monitoring modalities for cerebral blood flow, cerebral oxygenation, and cerebral electrical activity. Establishing a reliable prognosis early after injury is notoriously difficult. However, TBI is a much more manageable injury today than it has been in the past, but it remains a major health problem.
... Furthermore, there was no association between early prophylaxis and increased risk of late neurosurgical interventions or death. Phelan and colleagues 25 showed that, in patients with TBI who had repeat head computed tomography showing stable intracranial hemorrhage, pharmacologic prophylaxis could be initiated as early as 24 hours after injury. These studies suggest that LMWH should be the preferred pharmacologic prophylaxis for patients with severe TBI. ...
Article
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Background: Venous thromboembolism (VTE) is a common and serious complication seen in patients with trauma. Guidelines recommend the routine use of pharmacologic prophylaxis; however, compliance rates vary widely. The aim of this study was to describe the clinical practice related to VTE prophylaxis in the first 24 hours after injury at our level 1 Canadian trauma centre and the impact of a thrombosis consultation service. Methods: We performed a retrospective review of the health records of adult patients with trauma admitted between Jan. 1, 2012, and June 30, 2013. The rate of VTE was ascertained. The use of an initial prophylactic regimen, potential contraindications to prophylaxis and involvement of the thrombosis service were determined. Results: A total of 633 patients were included, 459 men and 174 women with a mean age of 47.4 years. The mean Injury Severity Score was 15.8. The overall VTE rate was 2.8%. A total of 514 patients (81.2%) received VTE prophylaxis, mechanical in 302 (47.7%) and pharmacologic in 231 (36.5%) (19 patients received both types). The thrombosis service was involved in the care of 164 patients (25.9%). Patients seen by the thrombosis service were more likely to receive VTE prophylaxis than those not seen by the service (145 [88.4%] v. 369 [78.7%], p < 0.01). Conclusion: Compliance with VTE prophylaxis administration was suboptimal, and opportunities for improvement exist. The involvement of a thrombosis consultation service appears to improve compliance with VTE prophylaxis, and augmented use of this service may improve clinical outcomes.
... The Neurocritical Care Society suggests that an ideal start time for VTE CP is sometime less than 72 h after a hemorrhage, but admits that the existing literature is limited with no definitive guidelines [15]. One study recommends initiating prophylaxis 24 h after a stable intracranial hemorrhage (ICH), but this study is limited by a small sample size, and remaining studies that recommend starting up to 4 days after a stable ICH are limited by lack of randomization or a comparator group [15,17]. Therefore, we performed a post hoc analysis starting at five days after injury to see if delays beyond this conservative initiation point were associated with increased risk of VTE. ...
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Background Utilization of intracranial pressure monitors (ICPMs) has not been consistently shown to improve mortality in patients with severe traumatic brain injury (TBI). A single-center analysis concluded that venous thromboembolism (VTE) chemoprophylaxis (CP) posed no significant bleeding risk in patients following ICPM implementation; however, there is still debate about the optimal use and timing of CP in patients with ICPMs for fear of worsening intracranial hemorrhage. We hypothesized that ICPM use is associated with increased time to VTE CP and thus increased VTE in patients with severe TBI.MethodsA retrospective analysis of the Trauma Quality Improvement Program (2010–2016) was performed to compare severe TBI patients with and without ICPMs. A multivariable logistic regression analysis was completed.ResultsFrom 35,673 patients with severe TBI, 12,487 (35%) had an ICPM. Those with ICPMs had a higher rate of VTE CP (64.3% vs. 49.4%, p < 0.001) but a longer median time to CP initiation (5 vs. 4 days, p < 0.001) as well as a longer hospital length of stay (LOS) (18 vs. 9 days, p < 0.001) compared to those without ICPMs. After adjusting for covariates, ICPM use was found to be associated with a higher risk of VTE (9.2% vs 4.3%, OR = 1.75, CI = 1.42–2.15, p < 0.001).Conclusions Compared to patients without ICPMs, those with ICPMs had a longer delay to initiation of CP leading to an increase in VTE. In addition, there was a nearly two-fold higher associated risk for VTE in patients with ICPMs even when controlling for known VTE risk factors. Improved adherence to initiation of CP in the setting of ICPMs may help decrease the associated risk of VTE with ICPMs.
... The timing of initiating thromboprophylaxis and dosage is not universally agreed upon. Several different studies have concluded that a period of 24 h after stable computerized tomography (CT) imaging of the brain is appropriate to start prophylaxis [12][13][14]. However, two other studies suggest the period of safety is after 48 and 72 h, respectively [15,16]. ...
Article
Purpose of review: The traumatically injured patient is at high risk for developing venous thromboembolism. Clinical practice guidelines developed by the American College of Chest Physicians and the Eastern Association for the Surgery of Trauma recognize the importance of initiating thromboprophylaxis, but the guidelines lack specific recommendations regarding the timing and dose of pharmacologic thromboprophylaxis. We review the literature regarding initiation of thromboprophylaxis in different injuries, the use of inferior vena cava filters, laboratory monitoring, dosing regimens, and the use of antiplatelet therapy. Recent findings: Use of pharmacologic thromboprophylaxis with invasive intracranial monitors is not associated with increased bleeding complications. The initiation of low-molecular-weight heparin (LMWH) prophylaxis 48 h postinjury in blunt solid organ injury is not associated with an increase in the rate of failed nonoperative management. Antiplatelet therapy in conjunction with LMWH may help to prevent venous thromboembolism. Summary: In the setting of blunt traumatic brain and solid organ injury, initiation of pharmacologic thromboprophylaxis 48 h after injury is not associated with increased bleeding complications. There is no consensus or clear data showing which dosing regimen of LMWH is most effective or whether routine laboratory measurements are beneficial for determining effective thromboprophylaxis.
... Other studies suggest similar efficacy and safety when prophylaxis was started within 24 to 36 hours 316 of blunt traumatic brain injury [42]. A randomized double-blind placebo-controlled study by Phelan et al 317 evaluated the clinical difference between enoxaparin (30 mg twice daily) PVTE-Px started within 24-96 hours 318 versus placebo in patients with TBI [43]. Sixty-two patients presenting with prespecified small TBI patterns and 319 stable scans at 24 hours after injury were included. ...
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Background: Pharmacological venous thromboembolism prophylaxis (PVTE-Px) in trauma care is challenging and frequently delayed until post injury bleeding risk is perceived to be sufficiently low; yet data for optimal initiation time is lacking. This study assessed practice pattern of PVTE-Px initiation time and dose in traumatic brain injury (TBI), spinal cord injury (SCI), and non-operative (NOR) solid organ injuries. Methods: Multicenter, cross sectional, observational, survey-based study involving intensivists, trauma surgeons, general surgeons, spine orthopedics, and neurosurgeons practicing in trauma centers. The data of demographics, PVTE-Px timing and dose, and five clinical case scenarios were obtained. Analyses were stratified by early initiators vs. late initiators and logistic regression models were used to identify factors associated with early initiation of PVTE-Px. Results: Of 102 physicians (29 % response rate), most respondents were intensivists (63.7%) and surgeons (who are general and trauma surgeons) (22.5%); majority were consultants (58%), practicing at level 1 trauma centers (40.6%) or academic teaching hospitals (45.1%). A third of respondents (34.2%) indicated that decision to initiate PVTE-Px in TBI and SCI was made by a consensus between surgical, critical care, and neurosurgical services. For patients with NOR solid organ injuries, 34.2% of respondents indicated trauma surgeons initiated the decision on PVTE-Px timing. About 53.7% of the respondents considered their PVTE-Px practice as appropriate, half used combined mechanical and PVTE-Px (57.1%), 52% preferred enoxaparin (40 mg once daily), and only 6.5% used anti-Xa level to guide enoxaparin prophylactic dose. Responses to clinical cases varied. For TBI and TBI with intracranial pressure monitor , 40.3% and 45.6% of the respondents were early initiators with stable repeated head computed tomography [CT], respectively. For SCI, most respondents were early initiators without repeated CT spine (36.8%). With regards to NOR solid organ injuries [gunshot wound to the liver and grade IV splenic injuries], 49.1% and 36.4% of respondents were early initiators without a repeat CT abdomen. Conclusions: Variations were observed in PVTE-Px initiation time influenced by trauma type. Our findings suggested enoxaparin is preferred in a standard prophylactic dose. More robust data from randomized trials are needed and the use of clinicians judgment is recommended.
... Moreover, a significant proportion of surgeons (trauma and general surgeons) would initiate PVTE-Px early in TBI and TBI with ICP monitor within 24 h which is consistent with most former literature. [41][42][43][44] This finding is relatively in line with the ACS-TQIP recommendations for VTE prophylaxis in TBI patients. [13] These guidelines subcategorize patients into low, moderate, and high risk of hemorrhagic progression. ...
... [41] Other studies suggest similar efficacy and safety when prophylaxis was started within 24-36 h of blunt traumatic brain injury. [ [41][42][43][44] This finding is relatively in line with the ACS-TQIP recommendations for VTE prophylaxis in TBI patients. [13] These guidelines subcategorize patients into low, moderate, and high risk of hemorrhagic progression. ...
... Fear of ICH progression often delays the initiation of enoxaparin, although increasingly it is administered early after brain trauma. [23][24][25][26][27][28][29][30][31][32] Prospective data established that enoxaparin 24 hours after admission was safe for some patients with TBI. 24 25 Subsequently, the decision to initiate pharmacological prophylaxis was based on whether or not ICH progression was observed on the follow-up CT. 26 31 32 If ICH progression was noted, exposure to pharmacological prophylaxis predicted further progression. ...
Article
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Background We sought to compare enoxaparin dosing for venous thromboembolism (VTE) prophylaxis in trauma patients with and without traumatic brain injury (TBI) to better understand the time and dose required to reach target anti-Xa levels. Our hypothesis was that patients with TBI have significant delays in the initiation of adequate pharmacological prophylaxis and require a higher enoxaparin dose than currently recommended. Methods The medical records of trauma patients who received enoxaparin dosing based on anti-Xa trough levels between August 2014 and October 2016 were reviewed. Patients were included if their anti-Xa trough level reached the target range (0.1 IU/mL to 0.2 IU/mL). Results A total of 163 patients had anti-Xa levels within the target range of which 41 (25.2%) had TBI. Patients with TBI had longer delays before initiating enoxaparin (7.5 days vs. 1.5 days after admission, p<0.01) and were more likely to receive unfractionated heparin prior to enoxaparin (46.3% vs. 11.5%, p<0.01). Anti-Xa levels reached the target range later in patients with TBI (11 days vs. 5 days after admission, p<0.01). Enoxaparin 40 mg two times per day was the median dose required to reach the target anti-Xa levels for both cohorts. VTE rates were higher among patients with TBI (22.0% vs. 9.0%, p=0.03). Four patients (9.8%) had progression of their intracranial hemorrhage prior to receiving enoxaparin, although none progressed during enoxaparin administration. Conclusion Among patients with TBI who reached target anti-Xa levels, 11 days after admission were required to reach a median enoxaparin dose of 40 mg two times per day. Unfractionated heparin was used as pharmacological prophylaxis in about half of these patients. The delay in reaching the target anti-Xa levels and the use of unfractionated heparin likely contribute to the higher VTE rate in patients with TBI. Level of evidence Level III, therapeutic.
... However, a recent study demonstrated that the risk of DVT formation is increased irrespective of time of initiation of pharmacologic prophylaxis [25]. Currently, the Delayed Versus Early Enoxaparin Prophylaxis (DEEP) studies are underway in Texas [26]. These studies follow an algorithm designed to study the safety and efficacy of enoxaparin prophylaxis after TBI. ...
Article
Background The literature on upper extremity deep venous thrombosis (UEDVT) is not as abundant as that on lower extremities. This study aimed to identify the risk factors for UEDVT, associated mortality and morbidity in trauma patients and the impact of pharmacological prophylaxis therein.MethodsA 3-year retrospective review of patients admitted to a Level 1 trauma center was conducted. Patients aged 18 years or older who had experienced a traumatic event and had undergone an upper extremity ultrasound (UEUS) were included in the study. Multiple logistic regression was used to identify independent risk factors that contributed to UEDVT.ResultsA total of 6,607 patients were admitted due to traumatic injuries during the study period, of whom 5.6% (373) had at least one UEUS during their hospitalization. Fifty-six (15%) were diagnosed with an UEDVT, as well as three non-fatal pulmonary emboli (PE) and four (7.1%) deaths, p = 0.03. Pharmacological prophylaxis with low-molecular-weight heparin (LMWH) or unfractionated heparin showed a protective effect against UEDVT; among the patients positive for UEDVT, 14 of 186 patients (7.5%) received LMWH, while 42 of 195 (21.5%) did not receive LMWH (p < 0.001). Multiple logistic regression revealed that the presence of upper extremity fractures, peripherally inserted central catheter (PICC) lines, and traumatic brain injury (TBI) were independent risk factors for UEDVT.ConclusionsUEDVT are associated with a higher mortality. The presence of upper extremity fractures, PICC lines, and TBI were independent risk factors for UEDVTs. Further, pharmacological prophylaxis reduces the risk of UEDVT.
Article
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Background: Pharmacologic thromboprophylaxis with low molecular weight heparin (LMWH) increases the risk of intracra-nial rebleeding if started too early in patients with traumatic brain injuries. The risk of thromboembolic complications increases progressively to 20% after ten days even with mechanical thromboprophylaxis measures such as calf compressions and graded elastic stockings.
Article
Background: Patients suffering from traumatic brain injury (TBI) are at increased risk of venous thromboembolism (VTE). However, initiation of pharmacological venous thromboprophylaxis (VTEp) may cause further intracranial hemorrhage. We reviewed the literature to determine the postinjury time interval at which VTEp can be administered without risk of TBI evolution and hematoma expansion. Methods: MEDLINE and EMBASE databases were searched. Inclusion criteria were studies investigating timing and safety of VTEp in TBI patients not previously on oral anticoagulation. Two investigators extracted data and graded the papers' levels of evidence. Randomized controlled trials were assessed for bias according to the Cochrane Collaboration Tool and Cohort studies were evaluated for bias using the Newcastle-Ottawa Scale. We performed univariate meta-regression analysis in an attempt to identify a relationship between VTEp timing and hemorrhagic progression and assess study heterogeneity using an I 2 statistic. Results: Twenty-one studies were included in the systematic review. Eighteen total studies demonstrated that VTEp postinjury in patients with stable head computed tomography scan does not lead to TBI progression. Fourteen studies demonstrated that VTEp administration 24 to 72 hours postinjury is safe in patients with stable injury. Four studies suggested that administering VTEp within 24 hours of injury in patients with stable TBI does not lead to progressive intracranial hemorrhage. Overall, meta-regression analysis demonstrated that there was no relationship between rate of hemorrhagic progression and VTEp timing. Conclusions: Literature suggests that administering VTEp 24 to 48 hours postinjury may be safe for patients with low-hemorrhagic-risk TBIs and stable injury on repeat imaging.
Chapter
This chapter focuses on the clinical indications for DVT prophylaxis, treatment options, clinical presentation of deep vein thrombosis, and long-term outcomes of prophylaxtic treatment utilizing both retrospective and prospective data ranging from 1975 to 2017.
Article
Introduction: Patients with spinal trauma are at high-risk for venous-thromboembolism(VTE). Guidelines recommend prophylactic anticoagulation but they are unclear on timing of initiation of thromboprophylaxis. The aim of our study was to assess the impact of early vs late initiation of venous thromboprophylaxis in patients with spinal trauma who underwent operative intervention. Methods: We performed a 2-year (2013-14) review of patients with isolated spine trauma (S-AIS≥3 and no other injury in another body region with AIS>2) who underwent operative intervention and received thromboprophylaxis post-operatively. Patients were divided into two groups based on the timing of initiation of thromboprophylaxis: early(<48 hours) and late(≥48 hours); and were matched in a 1:1 ratio using propensity-score-matching(PSM) for demographics, admission vitals, injury parameters, type of operative intervention, hospital course, and type of prophylaxis(LMWH vs UFH). Outcomes were rates of deep-venous thrombosis(DVT) and/or pulmonary embolism(PE), red-cell transfusions, the rate of operative interventions for spinal cord decompression and mortality after initiation of thromboprophylaxis. Results: 9585 patients underwent operative intervention and received anticoagulants, of which 3554 patients (early:1772, late:1772) were matched. Matched groups were similar in demographics, injury parameters, ED-Vitals, hospital LOS, rates of IVC filter placement and time to operative procedure. Patients who received thromboprophylaxis within 48 hours of operative intervention, unlike those who did not, were less likely to develop DVT (2.1% vs. 10.8%, p<0. 01). However, the rate of PE was similar in both groups (p=0.75). Additionally, there was no difference in post-prophylaxis red cell transfusion requirements (p=0.61), rate of post-prophylaxis decompressive procedure on the spinal cord (p=0.27), and mortality (p=0.53). Conclusion: Early VTE prophylaxis is associated with decreased rates of DVT in patients with operative spinal trauma without increasing the risk of bleeding and mortality. VTE prophylaxis should be initiated within 48-hours of surgery to reduce the risk of DVT in this high-risk patient population. Level of evidence: Level III, Therapeutic studies.
Chapter
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Neuromonitoring refers to the use of various modalities to monitor the integrity of the nervous system. Unlike the other body systems that have been easy to monitor, evaluation of structural integrity and function of the nervous system has been difficult. However, over last two decades, there has been a significant upward trend in development of newer devices for neuromonitoring. The modalities of neuromonitoring are used in operation theaters as well as in the intensive care unit (ICU). In this chapter, we touch upon all the modalities of neuromonitoring as well as the evidence supporting their effectiveness.
Article
Background Traumatic intracranial hemorrhage (TICH) and its progression have historically resulted in poor prognosis and functional disability. Such outcomes can impact the daily lives and financial condition of patients' families as well as add burden to the health care system. This review examines the diverse therapeutic intervention that were observed in randomized clinical trials (RCT) on various outcomes. Many demographic and clinical risk factors have been identified for poor prognosis after a TICH. Among the many therapeutic strategies studied, few found to have some beneficial effect in minimizing the progression of hemorrhage and reducing the overall mortality. Methods A literature review was conducted of all relevant sources using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to include articles that were RCTs for patients aged 18 years and above to include a total of 19 articles. Results Across studies, many therapies have been assessed; however, only few findings including infusion of tranexamic acid (TXA), use of β-blocker, and early operative evacuation of TICH yielded favorable results. Use of steroid and blood transfusion to target higher hemoglobin levels showed evidence of adversely impacting the outcome. Conclusion Of the many therapeutic strategies available for TICH, very few therapies have proven to be beneficial
Article
Background: Venous thromboembolism is a common complication of traumatic brain injury with an estimated incidence of 25% when chemoprophylaxis is delayed. The timing of initiating prophylaxis is controversial given the concern for hemorrhage expansion. Objective: To determine the safety of initiating venous thromboembolic event (VTE) chemoprophylaxis within 24 h of presentation. Methods: We performed a retrospective analysis of patients with traumatic intracranial hemorrhage presenting to a level I trauma center. Patients receiving early chemoprophylaxis (<24 h) were compared to the matched cohort of patients who received heparin in a delayed fashion (>48 h). The primary outcome of the study was radiographic expansion of the intracranial hemorrhage. Secondary outcomes included VTE, use of intracranial pressure (ICP) monitoring, delayed decompressive surgery, and all-cause mortality. Results: Of 282 patients, 94 (33%) received chemoprophylaxis within 24 h of admission. The cohorts were evenly matched across all variables. The primary outcome occurred in 18% of patients in the early cohort compared to 17% in the delayed cohort ( P = .83). Fifteen patients (16%) in the early cohort underwent an invasive procedure in a delayed fashion; this compares to 35 patients (19%) in the delayed cohort ( P = .38). Five patients (1.7%) in our study had a VTE during their hospitalization; 2 of these patients received early chemoprophylaxis ( P = .75). The rate of mortality from all causes was similar in both groups. Conclusion: Early (<24 h) initiation of VTE chemoprophylaxis in patients with traumatic intracranial hemorrhage appears to be safe. Further prospective studies are needed to validate this finding.
Article
Background: Enoxaparin was shown to have a neuroprotective effect in animal models as well as a human study following traumatic brain injury. This study was conducted to assess the effect of enoxaparin on the clinical outcome of severe traumatic brain injury (TBI) and its safety. Methods: This study is a randomized double-blinded placebo-controlled trial. The inclusion criteria were age 16-70, a closed head injury, a postresuscitation Glasgow Coma Scale (GCS) between 5 and 8, and a latency time between the injury and entering the study of less than 5 h. The patients were randomized into enoxaparin and placebo groups. In the enoxaparin group, 0.5 mg/kg enoxaparin was injected subcutaneously every 6 h in six total doses. The two groups were compared for the occurrence of intracranial hematoma (ICH) and for clinical neurological outcome, assessed by the Glasgow Outcome Scale. Results: Twenty-seven patients were assigned to the placebo group and 26 to the enoxaparin group. The two groups were similar regarding baseline characteristics, including age, sex, postresuscitation GCS, and best motor response. The occurrence of new ICH or an ICH size increase was insignificantly more frequent in the enoxaparin group than the placebo group (26.9% vs. 7.4%, P = 0.076). The favorable outcome rate in the enoxaparin group was significantly higher than in the placebo group (57.7% vs. 25.9%, P = 0.019). Conclusions: This study showed that the early administration of enoxaparin could lead to favorable outcomes in severe TBI patients without significantly increasing cerebral hemorrhagic complications.
Article
Background Inferior vena cava filters (IVCF) for venous thromboembolic prophylaxis in high-risk trauma patients is a controversial practice. Utilization of IVCF prophylaxis was evaluated at a level 1 trauma center. Daily cost of IVCF prophylaxis, time to IVCF, duration between IVCF and chemoprophylaxis, and number of patients needed to treat (NNT) to prevent pulmonary embolism (PE) was calculated. Methods A retrospective review of prophylactic IVCF over a 5-year period (2010-2014). Demographic, physiologic, injury, procedural, and outcome data were abstracted from the administrative trauma database. Medicare fees and days without chemoprophylaxis were used to determine daily IVCF cost. NNT was calculated using PE events in a cohort without IVCF. Results Over the 5-year period, 146 patients with mean age 56.3 y (SD ± 24.2), 67.8% male, underwent prophylactic IVCF. Predominant mechanisms of injuries were falls (45.9%) and motor vehicle accidents (20.5%) with median Injury Severity Score of 25 (intraquartile range [IQR] 16-29) and head Abbreviated Injury Score of 3 (IQR 3-5). Most common operative interventions required in 24.7% were orthopedic (25.3%) and neurosurgical (21.9%). Median time to IVCF was 78 h (IQR 48-144). Most common IVCF indications were closed head injury (48.6%) and spinal injuries (30.8%). Median time to administration of chemoprophylaxis was 96 h after IVCF (IQR 24-192) in 57.5%. Median IVCF cost was $759/d (IQR $361-$1897) compared with $4.32 for chemoprophylaxis. PE occurred in 0.26% without IVCF. PE did not occur with prophylactic IVCF. Estimated NNT was 379 (95% CI 265, 661). Conclusions Prophylactic IVCF placement is a costly practice with relatively low benefit. Anticipated time without chemoprophylaxis and patient criteria should be considered before routine IVCF placement.
Article
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Objective: We hypothesized that low molecular weight heparin (LMWH) is superior to unfractionated heparin (UH) for venous thromboembolism (VTE) prophylaxis in patients with severe traumatic brain injuries (TBI). Summary background data: Pharmacological VTE prophylaxis with LMWH or UH is the current standard of care in TBI. Clinical work suggests that LMWH may be more effective than UH for VTE prophylaxis in trauma patients. Experimental work shows that heparinoids may have neuroprotective properties. Methods: ACS TQIP database study including patients with blunt severe TBI (AIS ≥ 3), those that received LMWH or UH VTE prophylaxis. Patients with severe extracranial injuries (AIS ≥ 3), death within 72 hours, or hospital stay <48 hours were excluded. Demographic and clinical data on admission was collected, as well as head, thorax, and abdomen AIS, and timing of prophylaxis (within 48 hours, 49-72 hours, and >72 hours). Outcomes included VTE complications, mortality, and unplanned return to the operating room. Multivariate analysis was performed to compare outcomes between patients receiving LMWH and UH. Results: Overall, 20,417 patients met the criteria for inclusion in the study, 10,018 (49.1%) received LMWH and 10,399 (50.9%) UH. Multivariate analysis showed that LMWH was an independent protective factor against mortality and thromboembolic complications, regardless of timing of prophylaxis initiation. The type of prophylaxis had no effect on the need for unplanned return to the operating room. Conclusions: LMWH prophylaxis in severe TBI is associated with better survival and lower thromboembolic complications than UH.
Chapter
Venous thromboembolism prophylaxis after traumatic brain injury and spinal cord injury is both necessary and problematic. Here, we discuss the type, dose, and timing of pharmacologic prophylaxis as well as the practice of prophylactic vena cava filtration. The discussions entail brief literature about each practice, the author’s practice patterns, and the recommendations of national organizations.
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Traumatic brain injury (TBI) is associated with both hypercoagulable and hypocoagulable states; however, the causes of each are still not well understood. These coagulopathies are further complicated by TBI patients who are injured while on antithrombotic medications. This chapter compiles data from the most recent peer-reviewed publications and drug references on the pathophysiology of coagulopathy in TBI patients, predictors of outcomes, the impact of preinjury antithrombotic medication use, reversal agents, monitoring parameters, and when to restart antithrombotic medications post-TBI. Direct-acting oral anticoagulants (DOACs) and their impact on TBI management are discussed in detail.
Article
Background: Appropriate venous thromboembolism (VTE) chemoprophylaxis in trauma and emergency general surgery (EGS) patients is crucial. Objective: The purpose of this study is to review the recent literature and offer recommendations for VTE chemoprophylaxis in trauma and EGS patients. Methods: We conducted a literature search from 2000 to 2021 for articles investigating VTE chemoprophylaxis in adult trauma and EGS patients. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Results: Our search resulted in 34 articles. Most studies showed low-molecular-weight heparin (LMWH) is similar to unfractionated heparin (UFH) for VTE prevention; however, LMWH was more commonly used. Adjusted chemoprophylaxis dosing did not change the VTE rate but the timing did. Direct oral anticoagulants (DOACs) have been shown to be safe and effective in trauma and traumatic brain injury (TBI)/spinal cord injury (SCI). Studies showed VTE prophylaxis in EGS can be inconsistent and improves with guidelines that lower VTE events. Conclusions: There may be no benefit to receiving LMWH over UFH in trauma patients. In addition, different drugs under the class of LMWH do not change the incidence of VTE. Adjusted dosing of enoxaparin does not seem to affect VTE incidence. The use of DOACs in the trauma TBI and SCI setting has been shown to be safe and effective in reducing VTE. One important consideration with VTE prophylaxis may be the timing of prophylaxis initiation, specifically as it relates to TBI, with a higher likelihood of developing VTE as time progresses. EGS patients are at a high risk of VTE. Improved compliance with clinical guidelines in this population is correlated with decreased thrombotic events.
Article
Importance There is a lack of evidence regarding the effectiveness and safety of pharmacologic venous thromboembolism (VTE) prophylaxis among patients who undergo neurosurgical interventions for traumatic brain injury (TBI). Objective To measure the association between timing of VTE prophylaxis after urgent neurosurgical intervention for TBI and thromboembolic and intracranial complications. Design, Setting, and Participants This retrospective cohort study included adult patients (aged ≥16 years) who underwent urgent neurosurgical interventions (craniotomy/craniectomy or intracranial monitor/drain insertion within 24 hours after admission) for TBI at level 1 and 2 trauma centers participating in the American College of Surgeons Trauma Quality Improvement Program between January 1, 2012, and December 31, 2016. Data were analyzed from January to August 2020. Exposures Timing of pharmacologic VTE prophylaxis initiation after urgent neurosurgical intervention (prophylaxis delay) measured in days (24-hour periods). Main Outcomes and Measures The primary outcome was VTE (deep vein thrombosis or pulmonary embolism). Secondary outcomes were repeated neurosurgery (neurosurgical reintervention after initiation of VTE prophylaxis) and mortality. Hierarchical logistic regression models were used to evaluate the association between prophylaxis delay and each outcome at the patient level and were adjusted for patient baseline and injury characteristics. Results The study included 4951 patients (3676 [74%] male; median age, 50 years [IQR, 31-64 years]) who underwent urgent neurosurgical intervention for TBI at 304 trauma centers. The median prophylaxis delay was 3 days (IQR, 1-5 days). After adjustment for patient baseline and injury characteristics, prophylaxis delay was associated with increased odds of VTE (adjusted odds ratio [aOR], 1.08 per day; 95% CI, 1.04-1.12). Earlier initiation of prophylaxis was associated with increased risk of repeated neurosurgery. During the first 3 days, each additional day of prophylaxis delay was associated with a 28% decrease in odds of repeated neurosurgery (aOR, 0.72 per day; 95% CI, 0.59-0.88). After 3 days, each additional day of prophylaxis delay was associated with an additional 15% decrease in odds of repeated neurosurgery (aOR, 0.85 per day; 95% CI, 0.80-0.90). Earlier prophylaxis was associated with greater mortality among patients who initially underwent intracranial monitor/drain procedures, such that each additional day of prophylaxis delay was associated with decreased odds of death (aOR, 0.94 per day; 95% CI, 0.89-0.99). Conclusions and Relevance In this cohort study of patients who underwent urgent neurosurgical interventions for TBI, early pharmacologic VTE prophylaxis was associated with reduced risk of thromboembolism. However, earlier initiation of prophylaxis was associated with increased risk of repeated neurosurgery. These findings suggest that although timely initiation of prophylaxis should be prioritized, caution should be used particularly during the first 3 days after the index procedure, when this risk appears to be highest.
Article
Introduction: Peer victimization is a common experience in early adolescence often associated with psychosocial issues, following some youth into adulthood. Preliminary findings from a longitudinal study on peer victimization and protective factors were measured in rural elementary youth. Bullying is often seen as a schoolonly issue but research findings suggest the importance of systems outside the school setting as important protective factors for intervention. Methods: Preliminary data were collected through online questionnaires focused on direct, relational, and electronic victimization. Protective factors, including parent and community support, were also measured. Participants include 307 children (52.8 percent female; 80.4 percent White; mean age = 10) attending the fourth and fifth grade at four rural, South Dakota public school districts. Results: Overall, 91.2 percent of the sample reported at least one peer victimization experience during the first wave of data collection. Traditional victimization results include 57.7 percent citing direct and 89.5 percent relational. Electronic victimization was 25.3 percent. Participants reported high levels of community (94.8 percent) and parent (68.3 percent) support. Community support was significantly, negatively correlated with all types of victimization but parent support was only significant in relation to direct victimization. Conclusions: Findings provide an important baseline of the prevalence of direct, relational, and electronic victimization among rural young adolescents and the importance of community and parent support. Results demonstrate the need for a community wide approach including, health care providers, to take an active role to prevent and assist affected youth.
Article
Introduction Timing to start of chemoprophylaxis for venous thromboembolism (VTE) in patients with traumatic brain injury (TBI) remains controversial. We hypothesize that early administration is not associated with increased intracranial hemorrhage. Methods A retrospective study of adult patients with TBI following blunt injury was performed. Patients with penetrating brain injury, any moderate/severe organ injury other than the brain, need for craniotomy/craniectomy, death within 24 hours of admission, or progression of bleed on 6 hour follow-up head computed tomography scan were excluded. Patients were divided into early (≤24 hours) and late (>24 hours) cohorts based on time to initiation of chemoprophylaxis. Progression of bleed was the primary outcome. Results 264 patients were enrolled, 40% of whom were in the early cohort. The average time to VTE prophylaxis initiation was 17 hours and 47 hours in the early and late groups, respectively ( P < .0001). There was no difference in progression of bleed (5.6% vs. 7%, P = .67), craniectomy/-craniotomy rate (1.9% vs. 2.5%, P = .81), or VTE rate (0% vs. 2.5%, P = .1). Conclusion Early chemoprophylaxis is not associated with progression of hemorrhage or need for neurosurgical intervention in patients with TBI and a stable head CT 7 hours following injury.
Article
Background Venous thromboembolism (VTE) is recognized as a factor of morbidity and mortality in trauma patients suffering from severe blunt traumatic brain injury (TBI). The administration of pharmacological prophylaxis is broadly accepted as an effective therapy to prevent VTE events in trauma patients. Regardless of its ascertained efficacy, the risk of hematoma progression complicates the therapy in patients suffering from TBI: therefore, the optimal time to start prophylactic anticoagulation in these patients remains controversial. Methods All primary admissions to our level-1-trauma center between January 2012 and December 2016 were screened for severe blunt TBI with a head Abbreviated Injury Scale (AIS) ≥ 3. Patients who died within the first 24 h were excluded. Basic demographic results, thromboembolic events and progression of the intracranial hematoma were extracted from the patient’s records. The patients were categorized into 4 groups according to start of VTE chemoprophylaxis: early ( < 24 h after hospitalization), intermediate (24–48 h), late ( > 48 h) and no therapy (no prophylactic anticoagulation within the first five days of hospitalization). A total of 292 patients with severe TBI were analyzed (early: n = 93, intermediate: n = 90, late: n = 74, no therapy: n = 35). The overall rate of intracranial bleeding progression was 13.6% after prophylactic anticoagulation was started. Results No statistically significant differences were found in the frequency of intracranial bleeding progression comparing the different time groups (early 12.9% vs. intermediate 11.1% vs. late 17.6%; adj. p = 0.13). In patients with VTE chemoprophylaxis, no thromboembolic events were recorded. Male gender, age, head AIS and subarachnoidal hemorrhage were identified as independent risk factors associated with intracranial hematoma progression. Conclusion The early administration of VTE chemoprophylaxis within 24 h after admission in patients with severe TBI did not increase the risk of intracranial bleeding progression.
Article
Background: Venous thromboembolism (VTE) is a cause of considerable morbidity and mortality in hospitalized patients. An evidence-based algorithm was developed and implemented at our institution to guide perioperative VTE prophylaxis management. Objective: We evaluated compliance with prescription of risk-appropriate VTE prophylaxis and administration of prescribed VTE prophylaxis in neurosurgery patients. Methods: This was a retrospective analysis of post-operative neurosurgery patients at a single institution with subsequent diagnosis of acute VTE during their inpatient stay. Descriptive statistics were used to characterize pharmacologic VTE prophylaxis and prescribing patterns. Results: The incidence of VTE in our neurosurgery population was 248/13,913 (1.8%). Of the 123 patients, the median time to VTE diagnosis was 96 (IQR: 58-188) hours after surgery. 108 (87.8%) patients were prescribed risk-appropriate VTE prophylaxis, among whom 61 (56.5%) received all doses as prescribed. Fifty-three (43.1%) patients missed at least one dose of prescribed prophylaxis and median missed doses was 3 (IQR: 0-3). The median time to first dose of pharmacologic VTE prophylaxis was 42 hours (IQR: 28-51). Over half (n=63, 51.2%) of the VTE risk assessments contained at least one error, of which 15 (12.2%) would have resulted in a change in recommendation. Conclusion: Our evidence-based VTE prophylaxis algorithm was not accurately completed in more than half of patient cases. A substantial proportion of patients who developed VTE had a defect in their VTE prophylaxis management during their inpatient stay. Research to improve optimal VTE prevention practice in neurosurgery patients is needed.
Article
Background: Traumatic brain injury (TBI) continues to be a deadly injury. Universally accepted guidelines regarding the use of venous thromboembolism (VTE) chemoprophylaxis in trauma patients presenting with TBI have not been established. The purpose of this review is to identify and review the current literature and present the evidence for anticoagulant chemoprophylaxis regimens in patients with TBI. Methods: A search of five databases including PubMed, Web of Science, Google Scholar, JAMA Network, and Cochrane Journals was conducted for studies evaluating the safety and efficacy of venous thromboembolism prophylaxis regimens according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA). The GRADE Working Group criteria was used for quality of evidence assessment. Results: Seventeen studies were included in this review: one randomized controlled trial, two prospective observational studies, ten retrospective reviews, and five systematic reviews. Most studies demonstrated that early chemoprophylactic administration is associated with a decreased incidence of VTE in patients with TBI without an increase in intracranial bleed. Conclusion: For patients with TBI resulting in intracranial hemorrhages, administration of VTE chemoprophylaxis is warranted for those patients with stable repeat CT scans. Early chemoprophylaxis, at 24-72 hours is associated with reduced VTE incidence without a corresponding increase or exacerbation of intracranial hemorrhage in patients with TBI who have a stable repeat head CT scan. More studies are needed to establish guidelines for the safety and efficacy of VTE prophylaxis protocols in adult patients with TBI. Level of evidence: Level III; Systematic Review.
Article
Objectives Patients with spontaneous intracerebral hemorrhage (sICH) have a nearly fourfold greater risk for venous thromboembolism (VTE) than those with acute ischemic stroke, and VTE after sICH is associated with high risk for in-hospital mortality. The benefit from prophylactic heparin for VTE remains uncertain because its safety is not documented. In this study, we used an updated meta-analysis to evaluate the safety of heparin for the prevention of VTE in patients with sICH. Methods Electronic databases Medline and Embase from January 1990 to November 2017 and the Cochrane Library were searched using these keywords: intracerebral hemorrhage, stroke, hemorrhagic stroke, subarachnoid hemorrhage, heparin, heparinoids, low-molecular-weight heparin, anticoagulants, prophylactic, low dose, prevention, deep venous thrombosis, pulmonary embolism, venous thrombosis, randomized controlled trial, controlled clinical trial, and outcome. We evaluated the quality of included studies according to the bias risk in the Cochrane Handbook for Systematic Reviews of Interventions v.5.1.0. All statistical analyses were performed with RevMan v.5 software (Cochrane Collaboration, London, United Kingdom). Tests of heterogeneity were conducted with the Mantel-Haenszel method. Results Nine studies involving 4,055 patients with sICH met the inclusion criteria in this meta-analysis. Of these studies, only one met all specific criteria and had a low probability of bias, whereas eight studies met only some of the criteria and had a moderate probability of bias. In comparison with non-heparin treatments, low-molecular-weight heparin or unfractionated heparin was associated with a nonsignificant increase in any hematoma enlargement, a nonsignificant reduction in extracranial hemorrhage, a nonsignificant increase in mortality, a nonsignificant increase in the number of modified Rankin Scale scores of 3 to 5, and a nonsignificant increase in numbers of Glasgow Outcome Scale scores of 2 to 3. Conclusion Prophylactic heparin was associated with a nonsignificant increase in any hematoma enlargement and mortality, a nonsignificant reduction in extracranial hemorrhage, and a nonsignificant increase in the incidence of major disability in patients with sICH. It is probably safe to administer heparin to prevent VTE in patients with sICH.
Article
Background The purpose of this study was to evaluate the optimal timing and type of pharmacological venous thromboembolism prophylaxis (VTEp) in patients with severe blunt head trauma with acute subdural hematomas (ASDH). Methods Matched cohort study using ACS-TQIP database (2013–2016) including patients with isolated ASDH. Outcomes of matched patients receiving early prophylaxis (EP, ≤48 h) and late prophylaxis (LP, >48 h) were compared with univariable and multivariable regression analysis. Results In 1,660 matched cases VTE complications (3.1% vs 0.5%, p < 0.001) were more common in the LP compared to the EP group. Multivariable regression analysis identified EP as an independent protective factor for VTE complications (OR 0.169, p < 0.001) but not mortality (p = 0.260). The adjusted risk for delayed craniectomy was not associated with EP compared to LP (p = 0.095). LMWH was independently associated with a lower mortality (OR 0.480, p = 0.008) compared to UH. Conclusions Early VTEp (≤48 h) does not increase the risk for craniectomies and is independently associated with fewer VTE complications in patients with isolated ASDH. LMWH was independently associated with a lower mortality compared to UH.
Article
Background Enoxaparin is the recommended agent for deep vein thrombosis (DVT) chemoprophylaxis in trauma patients. Current literature suggests weight-based dosing is superior to standard dosing for adequate chemoprophylaxis. Literature regarding the use of weight-based enoxaparin in the setting of traumatic brain injury (TBI) however is limited. Methods A retrospective analysis of adult trauma patients admitted between January 1, 2018 to February 28, 2019 was performed. Sixty-six patients with TBI receiving weight-based enoxaparin met inclusion criteria. Incidence of intracranial hemorrhage (ICH) expansion was the primary endpoint. Newly diagnosed venous thromboembolism (VTE) and death were secondary endpoints. Results Two patients, out of sixty-six, had progression of their TBI requiring surgical intervention. Newly diagnosed VTE occurred in one patient. No deaths were due to ICH expansion or VTE. Conclusions Use of weight-based enoxaparin dosing in the setting of TBI shows promise without an increased incidence of ICH expansion when compared to other studies. Level of Evidence and Study Type: Level IV, Therapeutic.
Chapter
Several recent national guidelines and reviews conclude that pharmacologic, in addition to mechanical, thromboprophylaxis appears to be safe among TBI patients with stabilized hemorrhagic patterns. Despite this, there are many issues concerning efficiency and safety in severe TBI, especially in patients with coagulopathies.
Article
Introduction Venous thromboembolism (VTE) prophylaxis in pediatric patients is controversial and is mainly dependent on protocols derived from adult practices. Our study aimed to compare outcomes among pediatric trauma patients who received low molecular weight heparin (LMWH) compared to those who received unfractionated heparin (UFH). Methods We performed 2 years (2015-2016) retrospective analysis of the Pediatrics ACS-TQIP database. Pediatric trauma patients (age ≤ 17) who received thromboprophylaxis with either LMWH or UFH were included. Patients were stratified into three age groups. Analysis of each subgroup and the entire cohort was performed. Outcome measures included VTE events (deep vein thrombosis [DVT] and pulmonary embolism [PE]), hospital and ICU length of stay (LOS) among survivors, and mortality. Propensity score matching was used to match the two cohorts LMWH vs UFH. Results A matched cohort of 1,678 pediatric trauma patients were analyzed. A significant difference in survival, DVT events, and in-hospital LOS was seen in the age groups above 9 years. Overall, the patients who received LMWH had lower mortality (1.4% vs 3.6%, p < 0.01), DVT (1.7% vs 3.7%, p < 0.01), and hospital LOS among survivors (7 days vs 9 days, p < 0.01) compared to those who received UFH. There was no significant difference in the ICU LOS among survivors and the incidence of PE between the two groups. Conclusion LMWH is associated with increased survival, lower rates of DVT, and decreased hospital LOS compared to UFH among pediatric trauma patients age 10-17 years. Level of Evidence Level III Prophylactic. Study Type Prophylactic.
Article
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Resumen Los pacientes que reciben anticoagulación y que presentan lesiones traumáticas craneales están en riesgo aumentado de presentar fenómenos hemorrágicos a nivel intracraneal. La mortalidad en esta clase de pacientes es elevada lo que los convierte en una población que amerita un cuidadoso abordaje y seguimiento. Usualmente los pacientes que observamos en servicios de urgencia son traumas craneales leves pero la evolución del paciente anticoagulado en algunos casos es impredecible. Ac-tualmente, han sido publicados diversos estudios con relación a anticoagulación y lesión traumática cerebral. Presentamos una concisa revisión de la literatura enfocada a médicos neurólogos y neurocirujanos. Palabras clave: Anticoagulación, trauma craneal, neurotrauma. Abstract Patients receiving anticoagulation and those with traumatic cranial lesions are at increased risk of hemorrhagic phenomena at the intracranial level. Mortality in this class of patients is high, which makes them a population that deserves a careful approach and follow-up. Usually the patients we observe in emergency services are mild cranial traumas but the evolution of the anticoagulated patient in some cases is unpredictable. Currently, several studies have been published in relation to anticoa-gulation and traumatic brain injury. We present a concise review of the literature focused on neurologists and neurosurgeons. Keywords: Anticoagulation, cranial trauma, neurotrauma.
Chapter
Computed tomography (CT) is the key tool to diagnose intracranial haemorrhage following craniocerebral trauma. MRI provides additional information in cases when this seems appropriate such as a more detailed clarification of traumatic neurological disabilities, differentiation between oedema and ischaemia or imaging of shear damage to the neuronal fibre pathways. Most common is subarachnoid haemorrhage (SAH), followed by subdural (SDH) and epidural haemorrhage (EDH). Besides trauma, SAH may also emerge spontaneously due to rupture of an aneurysm, most likely at the Willis circle. In contrast to spontaneous subarachnoidal bleeding, traumatic SAH does not normally occur at the Sylvian fissure or the basal cisterns, but rather at the cortical, surface sulci and in the interhemispheric gap. As a consequence, the distribution pattern may cause clarification by CT angiography. Subdural haematomas are common concomitant injuries of craniocerebral trauma, especially within elderly patients. They impress computer tomographically as falciform hyperdense bleeding, which can spread along the interhemispheric gap or the falx cerebri and are, therefore, able to cross the adhesion points of the dura and calotte, in contrast to epidural haematomas. Because of their mostly venous origin, neurologic symptoms are commonly subacute. Despite the very early stage of SDH up to 1 h, SDH loses density with time but may show several bleeding events, making it variable in density, especially in CT follow-ups. Epidural haematomas are rather rare, but often dramatic consequences of craniocerebral trauma are associated with skull fractures in up to 90% of cases. They emerge especially temporally at the coup site and are mostly of arterial origin with subsequent secondary complications, such as mass effects. In acute diagnostics, the CT shows a biconvex and hyperdense bleeding, which does not cross the sutures. EDHs with surgical decompression in time have a good outcome, which is why quick and correct diagnosis is of extraordinary importance. A clinically symptom-free interval between the time of injury and the start of mass effects can aggravate diagnosis. Contusions are one of the most common complications of SHT and occur when the gyri collide with the cranial calotte or dura mater. They manifest themselves as multiple hyperdense lesions with perifocal oedema, preferably at the frontobase and in the temporal lobe, and are often associated with other intracranial haemorrhages, especially SAB. Their peculiarity is that they tend to haemorrhagic progression in up to 50% of cases. Contrast extravasation can predict this. According to this background, control CTs play an important role and can be prognostically decisive. An intravenous administration of KM should be weighed up accordingly in follow-up examinations. Diffuse axonal damage occurs primarily on the basis of high-speed trauma with associated rapid head rotation. The axonal integrity is destroyed. Since a haemorrhagic component is often absent or can be extremely discreet, the detection with CT is often not possible, and instead, MRI is the imaging method of choice. DAI lesions are most frequently found in descending order at the medullary cortex border, the corpus callosum and in the brainstem. DAI is associated with a very unfavourable prognosis, especially in severe SHT, and is a frequent cause of persistent disabilities up to maximum forms such as apallic syndrome. At present, however, there is still no clear evidence of an increase in risk of patients under anticoagulation after mild craniocerebral trauma, especially for the endpoint of compulsory therapy, if the data situation is unsatisfactory. For a final evaluation, a significantly more mature study situation on patients under anticoagulation with mild SHT is required. This should only be possible with very large numbers of patients in a multicentre approach. In order to be able to cope with the presumably increasing incidence of SHT with increasing age in the future, a continuous reduction in the radiation exposure of the CT and a better availability of the MRT will be necessary. Further positive effects may arise from the establishment of dual-energy CT in SHT diagnostics. It is possible that the virtual native representation will help in the assessment of the course after KM administration. In addition, it may even be possible to identify active bleeding components in haematomas.
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This article discusses the prevention of venous thromboembolism (VTE) and is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh risks, burden, and costs. Grade 2 suggestions imply that individual patient values may lead to different choices (for a full discussion of the grading, see the "Grades of Recommendation" chapter by Guyatt et al). Among the key recommendations in this chapter are the following: we recommend that every hospital develop a formal strategy that addresses the prevention of VTE (Grade 1A). We recommend against the use of aspirin alone as thromboprophylaxis for any patient group (Grade 1A), and we recommend that mechanical methods of thromboprophylaxis be used primarily for patients at high bleeding risk (Grade 1A) or possibly as an adjunct to anticoagulant thromboprophylaxis (Grade 2A). For patients undergoing major general surgery, we recommend thromboprophylaxis with a low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH), or fondaparinux (each Grade 1A). We recommend routine thromboprophylaxis for all patients undergoing major gynecologic surgery or major, open urologic procedures (Grade 1A for both groups), with LMWH, LDUH, fondaparinux, or intermittent pneumatic compression (IPC). For patients undergoing elective hip or knee arthroplasty, we recommend one of the following three anticoagulant agents: LMWH, fondaparinux, or a vitamin K antagonist (VKA); international normalized ratio (INR) target, 2.5; range, 2.0 to 3.0 (each Grade 1A). For patients undergoing hip fracture surgery (HFS), we recommend the routine use of fondaparinux (Grade 1A), LMWH (Grade 1B), a VKA (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B], or LDUH (Grade 1B). We recommend that patients undergoing hip or knee arthroplasty or HFS receive thromboprophylaxis for a minimum of 10 days (Grade 1A); for hip arthroplasty and HFS, we recommend continuing thromboprophylaxis > 10 days and up to 35 days (Grade 1A). We recommend that all major trauma and all spinal cord injury (SCI) patients receive thromboprophylaxis (Grade 1A). In patients admitted to hospital with an acute medical illness, we recommend thromboprophylaxis with LMWH, LDUH, or fondaparinux (each Grade 1A). We recommend that, on admission to the ICU, all patients be assessed for their risk of VTE, and that most receive thromboprophylaxis (Grade 1A).
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Traumatic brain injury (TBI) patients are known to be at high risk for venous thromboembolic events (VTEs). The Brain Trauma Foundation Guidelines (2007) state that low-molecular-weight heparin or unfractionated heparin should be used to prevent VTE complications, but suggest that there is an increased risk of expansion of intracranial hemorrhages (ICH) with VTE prophylaxis. In addition, it is unclear which treatment regimen (i.e., medication, dose, and timing) provides the best risk:benefit ratio in TBI patients. We reviewed all moderate-to-severe TBI patients admitted over a 5-year period to: (1) examine the occurrence of VTEs and their timing; (2) examine the symptomatic expansion of ICH while on VTE prophylaxis; and (3) compare the efficacy of two prophylactic agents: enoxaparin and dalteparin. Two-hundred eighty-seven patients were included. VTE prophylaxis was started 48-72 h post-trauma in all individuals who had no confounding coagulopathy, when two consecutive computed tomography (CT) scans revealed hemorrhage stability. VTEs occurred in 7.3% of treated patients, mostly within 2 weeks after trauma. Proximal VTEs occurred in 3.1% of treated patients. No significant difference in VTE rates was seen between enoxaparin (7.0%) and dalteparin (7.5%; p = 0.868). Moreover, the group treated with dalteparin was more severely injured (higher Injury Severity Score [p = 0.002]), had lower Glasgow Coma Scale (GCS) scores (p = 0.003), and had more inferior vena cava (IVC) filters placed (p = 0.007). The two groups did not show significant differences in the development of VTE when controlled for ISS and IVC filters (p = 0.819). Importantly, only one patient suffered a symptomatic expansion of ICH while on VTE prophylaxis, at 15 days post-trauma. These results suggest that current regimens of VTE prophylaxis used in our TBI population provide a relatively high level of protection against VTEs, and an extremely low risk of expanding ICH. They also suggest that there was no difference in VTE between dalteparin- and enoxaparin-treated patients.
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The identification of trauma patients at risk for the development of deep venous thrombosis (DVT) at the time of admission remains difficult. The purpose of this study is to validate the risk assessment profile (RAP) score to stratify patients for DVT prophylaxis. All patients admitted from November 1998 thru May 1999 were evaluated for enrollment. We prospectively assigned patients as low risk or high risk for DVT using the RAP score. High-risk patients received both pharmacologic and mechanical prophylaxis. Low-risk patients received none. Surveillance duplex Doppler scans were performed each week of hospitalization or if symptoms developed. Hospital charges for prophylaxis were used to determine the savings in the low-risk group. Statistical differences between the risk groups for each factor of the RAP and development of DVT were determined by the chi-squared test, with significance at a probability value of less than .05. There were 102 high-risk (64%) and 58 low-risk (36%) individuals studied. Eleven of the high-risk group (10.8%) experienced the development of DVT (asymptomatic, 64%). None of the low-risk group was diagnosed with DVT. Five of the 16 RAP factors were statistically significant for DVT. Eliminating prophylaxis and Doppler scans in low-risk patients resulted in a total savings of $18,908 in hospital charges. The RAP score correctly identified trauma patients at increased risk for the development of DVT. Despite prophylaxis, the high-risk group warrants surveillance scans. Withholding prophylaxis in low-risk patients can reduce hospital charges without risk.
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Pi (pi) and kappa (kappa) statistics are widely used in the areas of psychiatry and psychological testing to compute the extent of agreement between raters on nominally scaled data. It is a fact that these coefficients occasionally yield unexpected results in situations known as the paradoxes of kappa. This paper explores the origin of these limitations, and introduces an alternative and more stable agreement coefficient referred to as the AC1 coefficient. Also proposed are new variance estimators for the multiple-rater generalized pi and AC1 statistics, whose validity does not depend upon the hypothesis of independence between raters. This is an improvement over existing alternative variances, which depend on the independence assumption. A Monte-Carlo simulation study demonstrates the validity of these variance estimators for confidence interval construction, and confirms the value of AC1 as an improved alternative to existing inter-rater reliability statistics.
Article
Background Patients with traumatic intracranial hemorrhagic injuries (IHIs) are at high risk for venous thromboembolism (VTE). The safety of early anticoagulation for IHI has not been established.Hypothesis Enoxaparin can be safely administered to most patients with IHI for VTE prophylaxis.Setting Level I trauma center.Design Prospective, single-cohort, observational study.Patients and Methods One hundred fifty (85%) of 177 patients with blunt IHI received enoxaparin beginning approximately 24 hours after hospital admission until discharge. Brain computed tomographic (CT) scans were performed at admission, 24 hours after admission, and at variable intervals thereafter based on clinical course. Patients were excluded for coagulopathy, heparin allergy, expected brain death or discharge within 48 hours, and age younger than 14 years. Complications of enoxaparin prophylaxis were defined as Marshall CT grade progression of IHI, expansion of an existing IHI, or development of a new hemorrhagic lesion on follow-up CT after beginning enoxaparin use.Results Thirty-four patients (23%) had CT progression of IHI. Twenty-eight CT scans (19%) worsened before enoxaparin therapy and 6 (4%) worsened after beginning enoxaparin use. No differences between operative patient (2/24, 8%) and nonoperative patient (4/126, 3%) complications were identified (P = .23). Study group mortality was 7% (10/150). All 6 patients who developed progression of IHI after initiation of enoxaparin therapy survived hospitalization. A deep vein thrombosis was identified in 2 (2%) of 106 patients.Conclusion Enoxaparin can be safely used for VTE prophylaxis in trauma patients with IHI when started 24 hours after hospital admission or after craniotomy.
Article
We have created a theoretical algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI) known as the Parkland Protocol, which stratifies patients into low-, medium-, and high-risk categories for spontaneous progression of hemorrhage. This prospective study characterizes the incidence and timing of radiographic progression of the TBI patterns in these categories. Inclusion criterion was presentation with intracranial blood between February 2010 and March 2011; exclusion was receipt of only one computed tomographic scan of the head during the inpatient stay or preinjury warfarin. At admission, all patients were preliminarily categorized per the Parkland Protocol as follows: low risk (LR), patients meeting the modified Berne-Norwood criteria; moderate risk (MR), injuries larger than the modified Berne-Norwood criteria without requiring a neurosurgical procedure; high risk (HR), any patient with a craniotomy/monitor. A total of 245 patients with intracranial hemorrhage were enrolled during the 13-month study period. Of patients preliminarily classified as LR at admission (n = 136), progression was seen in 25.0%. Spontaneous worsening was seen in 7.4% of LR patients at 24 hours after injury, and no LR patients progressed at 72 hours after injury. In patients initially classified as MR at admission (n = 42), progression was seen in 42.9%, with 91.5% of patients demonstrating stable computed tomographic head scans at 72 hours after injury. In patients initially classified as HR (n = 67), 64.2% demonstrated spontaneous progression of their TBI patterns, with 10.5% continuing to progress at 72 hours after injury. Most repeat scans were performed as routinely scheduled studies (81-91%). Increases in the incidence of spontaneous worsening were seen as severities of injury progressed from the Parkland Protocol's LR to MR to HR arms. The time frames for these spontaneous worsenings seem to be such that the protocol's theoretical recommendations for venous thromboembolism prophylaxis are worth pursuing as future points of investigation.
Article
Published formulas for the large sample variance of the kappa statistic that are appropriate for the case of different sets of raters for different Ss, when each set of raters is selected at random from a larger pool of available raters, are determined to be incorrect. New formulas are derived and checked by Monte Carlo simulation. Kappa is shown to be identical, except for terms that go to zero as the number of Ss increases, to the intraclass correlation coefficient resulting from applying a one-way ANOVA to the data. (10 ref) (PsycINFO Database Record (c) 2012 APA, all rights reserved)
Article
Introduced the statistic kappa to measure nominal scale agreement between a fixed pair of raters. Kappa was generalized to the case where each of a sample of 30 patients was rated on a nominal scale by the same number of psychiatrist raters (n = 6), but where the raters rating 1 s were not necessarily the same as those rating another. Large sample standard errors were derived.
Article
Timing and type of chemoprophylaxis (CP) that should be used in patients with traumatic brain injury (TBI) remains unclear. We reviewed our institutions experience with low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in TBI. The charts of all TBI patients with a head abbreviated injury severity score >2 (HAIS) and an intensive care unit length of stay >48 hours admitted during a 42-month period between 2006 and 2009 were reviewed. CP was initiated after intracranial hemorrhage was considered stable. We reviewed all operative notes and radiologic reports in these patients to analyze the rate of significant intracranial hemorrhagic complications, deep venous thrombosis, or pulmonary embolus. A total of 386 patients with TBI were identified; 158 were treated with LMWH and 171 were treated with UFH. HAIS was significantly different between the LMWH (3.8 ± 0.7) and UFH (4.1 ± 0.7) groups; the time to initiation of CP was not. The UFH group had a significantly higher rate of deep venous thrombosis and pulmonary embolus. Progression of ICH that occurred after the initiation of CP was significantly higher in the UFH-treated patients (59%) when compared with those treated with LMWH (40%). Two patients in the UFH group required craniotomy after the initiation of CP. LMWH is an effective method of CP in patients with TBI, providing a lower rate of venous thromboembolic and hemorrhagic complications when compared with UFH. A large, prospective, randomized study would better evaluate the safety and efficacy of LMWH in patients suffering blunt traumatic brain injury.
Article
Patients with traumatic brain injury (TBI) are at high risk for venous thromboembolism (VTE), but physicians are cautious with chemical prophylaxis in these patients because of concern about exacerbating intracranial hemorrhage. We hypothesized that early use of chemical thromboprophylaxis would reduce VTE incidence without increasing intracranial hemorrhage. Records of all patients admitted with a TBI to a Level I trauma center from 2006 to 2008 were reviewed. TBI was defined as intracranial hemorrhage, hematoma, contusion, or diffuse axonal injury with a head Abbreviated Injury Scale score >2. Patients were excluded if they were discharged or died within 72 hours of admission. Chemical prophylaxis was defined as subcutaneous or intravenous unfractionated heparin or low molecular weight heparin before any VTE diagnosis. Progression of TBI was defined by worsening CT findings. VTE was defined as deep venous thrombosis or pulmonary embolus confirmed by radiology reports. Primary outcomes were progression of hemorrhage and VTE events. Eight hundred and twelve of the 1,258 patients admitted to the trauma center with a TBI met study criteria. Chemical thromboprophylaxis was given to 49.5% (n = 402). Mean head Abbreviated Injury Scale score was 3.4 in both groups. One hundred and sixty-nine patients started prophylaxis within 48 hours and 242 patients began within 72 hours. Patients receiving chemical prophylaxis had a lower incidence of VTE (1% versus 3%; p = 0.019). Although not statistically significant, they also had a lower rate of injury progression, 3% versus 6% (p = 0.055). Use of chemical thromboprophylaxis in TBI patients with a stable or improved head CT after 24 hours substantially reduces the incidence of VTE and does not increase the risk of progression of intracranial hemorrhage.
Article
Patients with traumatic brain injuries (TBIs) are at high risk for venous thromboembolic sequelae; however, prophylaxis is often delayed because of the perceived risk of intracranial hemorrhagic exacerbation. The goal of this study was to determine whether enoxaparin for early venous thromboembolism (VTE) prophylaxis is safe for hemodynamically stable patients with TBIs. This is a retrospective cohort study from a Level I Trauma Center of patients with TBIs receiving early (0-72 hours) or late (>72 hours) VTE prophylaxis. Inclusion criteria included evidence of acute intracranial hemorrhagic injury (IHI) on admission computed tomography, head/neck abbreviated injury score≥3, age≥16 years, and hospital length of stay≥72 hours. Exclusion criteria included intracranial pressure monitor/ventriculostomy, current systemic anticoagulation, pregnancy, coagulopathy, history of DVT, ongoing intra-abdominal hemorrhage 24 hours postadmission, and preexisting inferior vena cava filter. Progression of IHI defined as lesion expansion/new IHI on repeat computed tomography. Totally, 669 patients were identified: 268 early (40.1%) and 401 late (59.9%), with a mean injury severity score of 27.8±10.2 and 29.4±11, respectively. Head neck abbreviated injury score of 3 (47% vs. 34%), 4 (42% vs. 46%), 5 (11% vs. 19%), and 6 (0% vs. 1%) were reported for the early and late treatment groups, respectively. Mean time to prophylaxis was 2.77 days±0.49 days and 5.31 days±1.97 days. IHI progression before prophylaxis was 9.38% versus 17.41% (p<0.001) and after prophylaxis was 1.46% versus 1.54% (p>0.9). Proportions of proximal DVT were 1.5% versus 3.5% (p=0.117) and pulmonary embolism were 1.5% versus 2.2% (p=0.49). There were no differences in injury severity score, age, and pelvic and/or long bone fractures. We found no evidence that early VTE prophylaxis increases the rate of IHI progression in hemodynamically stable patients with TBIs. The natural rate of IHI progression observed is comparable with previous studies. Although not powered to detect differences in the incidence of DVT and pulmonary embolism, the data trend toward increased proportions of both VTE outcomes in the late group.
Article
Pharmacologic thromboprophylaxis (PTP) may exacerbate intracranial hemorrhage (ICH) in patients with traumatic brain injury (TBI). We examined risk factors for hemorrhage progression in patients with blunt TBI and hypothesized that PTP would increase ICH progression in a subset of these patients. We retrospectively studied patients with TBI admitted to our level I trauma center during 19 months. Progression of hemorrhage was examined in two populations: patients with a stable initial follow-up (F/U) computed tomography (CT) and patients with hemorrhage progression on initial F/U CT. Risk factors potentially associated with hemorrhage progression were analyzed using logistic regression. Timing of PTP was defined two ways: exposed to PTP versus not exposed; early (<72 hours), late (>or=72 hours), or no PTP. Three hundred forty patients with TBI were reviewed and hemorrhage progression occurred in 32.4% (n = 110) of patients of which 59.1% were considered clinically significant. In patients with ICH progression on initial F/U CT, predictors of subsequent hemorrhage progression include exposure to PTP (odds ratio [OR]: 13.07, p = 0.01), extradural/subdural hemorrhage (OR: 5.15, p = 0.03), Glasgow Coma Score 3-8 (OR: 4.64, p = 0.03), and body mass index >or=25 (OR = 4.32, p = 0.03). PTP was not significantly associated with hemorrhage progression in patients with a stable initial F/U CT. These findings suggest that PTP use is associated with a 13-fold increased odds of further hemorrhage progression in patients whose F/U CT within 1 day of admission showed ICH progression; 16% of this risk can be attributed to receiving PTP. Conversely, PTP may be safe in a subgroup of patients with TBI with no ICH progression on initial F/U CT.
Article
Deep venous thrombosis (DVT) is common among trauma patients. If left untreated it may result in lethal pulmonary thromboembolism. Previous studies have suggested that intracranial hemorrhage serves as an independent risk factor for the development of DVT. These studies were not able to exclude anticoagulation therapy as a confounding variable in their analysis. Our objective was to determine the association of traumatic brain injury (TBI) to the formation of DVT irrespective of the use of anticoagulation therapy. All patients admitted to an academic level I Trauma Center between 2000 and 2007 with blunt or penetrating injuries were selected for inclusion in this study. Patients who died or who were discharged within 24 hours of admission were excluded in the analysis. TBI was defined as any intraparenchymal hemorrhage or extra-axial intracranial bleeding identified on radiographic imaging or both. Anticoagulation therapy was defined as the uninterrupted use of either subcutaneous lovenox or heparin. Risk ratios and 95% confidence intervals compared the risk of DVT among patients with and without TBI according to the initiation of anticoagulation therapy (no therapy, <24 hours, 24-48 hours, and >48 hours) adjusted for age, gender, race, injury severity, mechanism of injury, spinal injury, and lower extremity fracture. Irrespective of the time of initiation of pharmacologic prophylaxis, TBI is independently associated with the formation of DVT. A threefold to fourfold increased risk of DVT formation is consistent across all prophylaxis groups among patients with TBI. The incidence of DVT among injured patients with TBI is significantly higher than those patients without head injury independent of anticoagulation therapy. Rigorous surveillance to detect DVT among trauma patients with TBI should be undertaken and where appropriate alternate means for pulmonary thromboembolism prevention used.
Article
To determine the safety of early enoxaparin for venous thromboembolism (VTE) prophylaxis in patients with blunt traumatic brain injury (TBI). Prospective observational study of patients with TBI who received enoxaparin within 48 hours after admission. Brain computed tomography (CT) scans were obtained at the time of admission, at 24 hours, and at variable intervals thereafter based on clinical course. Patients were excluded from the study for intracerebral contusions >/=2 cm, multiple contusions within one brain region, subdural or epidural hematomas >/=8 mm, increased size or number of lesions on follow-up CT, persistent intracranial pressure >20 mm Hg, or neurosurgeon or trauma surgeon reluctance to initiate early pharmacologic VTE prophylaxis. Bleeding complications were defined as CT progression of hemorrhage by Marshall CT Classification or radiologists' report, regardless of any neurologic deterioration. Main outcomes measured were intracranial bleeding complications, discharge Glasgow Outcome Score, and hospital mortality. Five hundred twenty-five patients were studied. Eighteen patients (3.4%) had progressive hemorrhagic CT changes after receiving enoxaparin, 12 of whom had no change in treatment, neurologic status, or outcome. Six patients (1.1%) had a change in treatment or potential outcome, including three who required subsequent craniotomy. Twenty-one patients (4.0%) died, and pharmacologic prophylaxis may have contributed to one death (0.2%). Discharge Glasgow Outcome Scores were 445 (84.8%) good recovery, 19 (3.6%) moderate disability, 36 (6.8%) severe disability, 4 (0.8%) persistent vegetative state, and 21 (4.0%) dead. Enoxaparin should be considered as an option for early VTE prophylaxis in selected patients with blunt TBI. Early enoxaparin should be strongly considered in those patients with TBI with additional high risk traumatic injuries.
Article
There are few data in the literature on venous thromboembolic (VTE) prophylaxis for the traumatic population with intracranial hemorrhage (ICH). We reviewed our institutional experience and compared the incidence of deep vein thrombosis and pulmonary embolism in patients with ICH receiving either early prophylaxis (< 72 hours from admission) or late prophylaxis (> 72 hours from admission), and the respective incidences in progression of intracranial hemorrhage. We identified 124 patients for this study. There were 29 patients (23%) who received early (< 72 hours) pharmacological VTE prophylaxis and 53 patients (43%) received late (> 72 hours) prophylaxis. In the study, 42 patients had intermittent pneumatic compression devices and received no pharmacological VTE prophylaxis. Among those with pharmacological VTE prophylaxis, 10 patients (8%) developed VTE (9 deep vein thrombosis and 1 pulmonary embolism). Three patients with pharmacological VTE prophylaxis developed ICH progression, with one being clinically significant. Our institutional review demonstrated that it seems safe to initiate early pharmacological VTE prophylaxis in blunt head trauma with stable ICH. Nevertheless, further prospective randomized studies are needed to fully elucidate the safety and efficacy in the timing of prophylaxis for blunt head trauma with ICH.
Article
This paper presents a general statistical methodology for the analysis of multivariate categorical data arising from observer reliability studies. The procedure essentially involves the construction of functions of the observed proportions which are directed at the extent to which the observers agree among themselves and the construction of test statistics for hypotheses involving these functions. Tests for interobserver bias are presented in terms of first-order marginal homogeneity and measures of interobserver agreement are developed as generalized kappa-type statistics. These procedures are illustrated with a clinical diagnosis example from the epidemiological literature.
Article
Venous thromboembolism (VTE) is a frequent and potentially life-threatening complication after trauma. The purpose of this study is to investigate the effectiveness of enoxaparin in preventing deep venous thrombosis (DVT) and pulmonary embolism (PE) after injury in patients who are at high risk for developing VTE. A prospective single-cohort observational study was initiated for seriously injured blunt trauma patients admitted to a Level I trauma center during a 7-month period. Patients were eligible for the study if time hospitalized was > or = 72 hours, Injury Severity Score (ISS) was > or = 9, enoxaparin was started within 24 hours after admission, and one or more of the following high risk criteria were met: age > 50 years, ISS > or = 16, presence of a femoral vein catheter, Abbreviated Injury Score (AIS) > or = 3 for any body region, Glasgow Coma Scale (GCS) Score < or = 8, presence of major pelvic, femur, or tibia fracture, and presence of direct blunt mechanism venous injury. Patients with closed head injuries and nonoperatively treated solid abdominal organ injuries were also potential participants. The primary outcomes measured were thromboembolic events--either a documented lower extremity DVT by duplex color-flow doppler ultrasonography or a PE documented by rapid infusion CT pulmonary angiography or conventional pulmonary angiography. There were 118 patients enrolled in the study. Two patients (2%) developed DVT, one of which was proximal to the calf (95% confidence interval, 0% to 6%). Two of 12 patients (17%) with splenic injuries who received enoxaparin failed initial nonoperative management. There were no other bleeding complications, and no clinical evidence or documented episodes of PE. One patient died from multiple system organ failure. Enoxaparin is a practical and effective method for reducing the incidence of VTE in high risk, seriously injured patients. This study supports further investigation into the safety of enoxaparin prophylaxis in patients with closed head injuries and nonoperatively treated solid abdominal organ injuries.
Article
Prophylaxis for venous thromboembolism (VTE) in head injured patients has avoided heparin products because of concern for exacerbating intracranial bleeding. The purpose of this study was to evaluate the safety of unfractionated heparin (UFH) for VTE prophylaxis after traumatic brain injury. We retrospectively evaluated the early use of UFH in patients sustaining a severe closed head injury (Abbreviated Injury Scale score > 3) from January 1, 2000, through December 31, 2000. Two groups were formed on the basis of the timing of UFH administration: within 72 hours of admission (Early group), or after the third day of hospitalization (Late group), if at all. Intracranial bleeding related to UFH administration was assessed by computed tomographic scan of the head and/or clinical examination. Sixty-four of 76 patients with intracranial blood on admission head computed tomographic scan fulfilled study criteria. Seventy-three percent (n = 47) were in the Early group and 27% (n = 17) were in the Late group. None of the Early group had an increase in intracranial bleeding or deterioration on neurologic examination as a result of UFH administration. However, there was no statistical difference in VTE events between the two groups. Early use of UFH in the severe head injured patient does not increase bleeding complications.
Article
Although there are alternative methods and drugs for preventing venous thromboembolism (VTE), it is not clear which modality is most suitable and efficacious for patients with severe (stable or unstable) head/spinal injures. The aim of this study was to compare intermittent pneumatic compression devices (IPC) with low-molecular-weight heparin (LMWH) for preventing VTE. We prospectively randomized 120 head/spinal traumatized patients for comparison of IPC with LMWH as a prophylaxis modality against VTE. Venous duplex color-flow Doppler sonography of the lower extremities was performed each week of hospitalization and 1 week after discharge. When there was a suspicion of pulmonary embolism (PE), patients were evaluated with spiral computed tomography. Patients were analyzed for demographic features, injury severity scores, associated injuries, type of head/spinal trauma, complications, transfusion, and incidence of deep venous thrombosis (DVT) and PE. Two patients (3.33%) from the IPC group and 4 patients (6.66%) from the LMWH group died, with their deaths due to PE. Nine other patients also succumbed, unrelated to PE. DVT developed in 4 patients (6.66%) in the IPC group and in 3 patients (5%) in the LMWH group. There was no statistically significant difference regarding a reduction in DVT, PE, or mortality between groups ( p = 0.04, p > 0.05, p > 0.05, respectively). IPC can be used safely for prophylaxis of VTE in head/spinal trauma patients.
Article
Venous thromboembolism is a preventable cause of death in the severely injured patient. Low-molecular-weight heparins (LMWHs) have been recommended as effective, safe prophylactic agents. However, LMWH use remains controversial in patients at risk for bleeding, those with traumatic brain injury, and those undergoing multiple invasive or operative procedures. We hypothesized that a protocol utilizing once-daily LMWH prophylaxis in high-risk trauma patients, regardless of the need for invasive procedures, is feasible, safe, and effective. From August 1998 to August 2000, all patients admitted to our American College of Surgeons-verified Level I trauma facility following injury were evaluated for deep venous thrombosis (DVT) risk and prospectively followed. Patients at high risk for DVT, including those with stable intracranial injuries, were placed on our institutional protocol and prospectively followed. Patients on the protocol received daily injections of the LMWH, dalteparin; DVT screening was performed with duplex ultrasonography within 48 hours of admission and after 7 to 10 days after injury. Regimen compliance, bleeding complications, DVT rates, and pulmonary embolus (PE) rates were analyzed. During the 2-year study period, 6247 trauma patients were admitted; 743 were considered at high risk for DVT. Most of the patients were men (72%), with a mean age of 38.7 years (range 15-89 years) and a mean injury severity score (ISS) of 19.5. Compliance with the daily regimen was maintained in 74% of patients. DVT was detected in 3.9% and PE in 0.8%. The wound complications rate was 2.7%, and the need for unexplained transfusions was 3%. There were no exacerbations of head injury following dalteparin initiation due to bleeding. There were 16 patient deaths; none was caused by PE or late hemorrhage. Once-daily dosing of prophylactic LMWH dalteparin is feasible, safe, and effective in high-risk trauma patients. Our protocol allows one to "operate through" systemic prophylaxis and ensures timely prophylaxis for brain-injured and multisystem trauma patients.
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