SCCM Resource Library-Timing of VTE Chemoprophylaxis With Major Orthopedic Surgery of Traumatic Femoral and Tibial Fractures

Video Transcription

My name is Kristen Salatolo and it's a privilege to present our study entitled Timing of VTE Chemoprophylaxis with Major Orthopedic Surgery of Traumatic  Femoral and Tibial Fractures. Lower extremity long bone fractures are the most common traumatic injuries and also place patients in the highest risk group  for developing a venous thromboembolism or VTE. Current clinical practice is to prevent the formation of VTEs with mechanical or pharmacological  prophylaxis. However, pharmacological thromboprophylactic agents carry a small but significant increased risk of bleeding. In 2021, the AAST critical care  committee provided a series of recommendations for VTE prophylaxis in trauma patients. Chief among them is that early initiation is standard of care  but it must be balanced with the risk of bleeding. There are absolute indications for holding chemoprophylaxis for surgery. These are active hemorrhage and  spiner head surgery. Outside of these events, there are almost no data demonstrating whether perioperative chemoprophylaxis leads to greater  development of bleeds. Because the safety of administering VTE chemoprophylaxis is not supported by appropriately powered studies and remains contentious, we  sought to determine the safety and efficacy of perioperative administration as measured by the incidence of clinically significant bleeding events  and development of VTEs in patients with femoral and tibial fractures. This was a retrospective study conducted at five level 1 trauma centers over  approximately two years and included nearly 900 trauma patients with lower extremity long bone fractures requiring surgery. Patients were excluded for  moderate or severe head or spine injuries, chronic pre-injury anticoagulant use, or if they did not receive low molecular weight heparin or  unfractionated heparin for VTE chemoprophylaxis. Key exposure and outcomes were defined as follows. Patients were considered to have  received perioperative administration of VTE chemoprophylaxis if doses were not held for surgery or if doses were initiated within 12 hours post-op.  Patients were not considered to have received perioperative administration of VTE chemoprophylaxis if the doses were held for surgery or if it was initiated  more than 12 hours post-op. The primary outcome was the incidence of a clinically significant hemorrhage or CSH that developed within 24 hours post-op.  That was actionable as outlined in the slide. We also performed a sensitivity analysis examining clinically significant hemorrhages within a 48 hour  post-op period. The study was powered 80% with 612 patients. The main effect of perioperative therapy on clinically significant hemorrhage was examined with  a multivariable mixed effect model for repeated measures, or MMRM, which considers multiple surgeries and events. We also used MMRM modeling to examine  several relevant subgroups which are presented in a forest plot later in the presentation. The subgroups were as follows. Fracture location, patients that  had one orthopedic surgery, patients that had more than one orthopedic surgery, and then the subgroup of patients who started VTE chemoprophylaxis prior to  surgery. Here we compared patients that had interrupted versus continued doses. And in the subgroup of patients who started VTE chemoprophylaxis after  surgery. Here we compared timing as within or more than 12 hours post-op. There were 878 patients. 43% had a hip fracture, 30% had a femur fracture, and  27% had a tibia fracture. The 878 patients had 917 long bone surgeries. 96% had one long bone surgery and 4% had multiple surgeries. Most patients were at  least 65 years old. The majority were white and female. Three-quarters of patients were injured in a fall. Nearly a quarter were on pre-injury  antiplatelets, and 12% had a normal GCS less than 15. Patients were evenly distributed by trauma center. The median time to surgery was 18 hours and the  median length of stay was 5 days. Most patients, or 68%, did not receive a perioperative dose of VTE chemoprophylaxis. The remaining 32% of  patients received a perioperative dose, although most of these were categorized as such because they initiated therapy within 12 hours post-op. The median time  to start VTE chemoprophylaxis was 26 hours. This reflects the typical practice in the United States where VTE chemoprophylaxis is not initiated until  after surgery, whereas in Europe it is more traditional to begin prophylaxis prior to surgery. Overall, 9% of patients developed the primary outcome of a  clinically significant hemorrhage. Before adjustment, there was no difference in bleeding events by timing of prophylaxis, with 7% in the perioperative group  versus 10% in the no perioperative group. The majority of patients that developed a bleed had a two-point drop in hemoglobin, resulting in blood  transfusion. Next, we determined what variables to adjust for in our regression models. There were no demographic or clinical differences by receipt of  perioperative VTE chemoprophylaxis, except total hours in surgery was shorter with perioperative therapy. 76 patients developed a bleed. There were  several clinical and demographic differences in patients who developed a clinically significant hemorrhage versus those who did not. In patients who  developed a clinically significant hemorrhage, they were older, more likely to have a fall injury, more likely to have an abnormal ED neuro exam, and be on  pre-injury antiplatelets. There were also differences in the incidence of bleed by fracture type. Patients with femur fractures were more likely to have a  bleed than those without a femur fracture, whereas patients with tibial fractures were less likely to develop a bleed than patients without tibial  fractures. As shown in the figure, patients with tibial fractures had the lowest incidence of bleed at 4% followed by hip fracture at 8.6% and femoral  shaft fractures at 15.5%. There was no association between perioperative VTE chemoprophylaxis and bleed in any of the fracture groups. There was also no  significant interaction, p equals 0.39, and so the results are presented in aggregate with adjustment for fracture type. This slide presents the main study  findings. The MMRM model adjusted for covariates that differed in univariate analyses as shown in this table. After adjustment, perioperative VTE  chemoprophylaxis was not associated with clinically significant hemorrhage. The odds ratio was 0.8 with a p-value of 0.45. An abnormal GCS, femur fracture, and  longer time in surgery were associated with increased odds of CSH after adjustment. The results of the subgroup analyses are shown here as a forest  plot. Each row represents a subgroup analysis. The gray horizontal bar demonstrates the model's odds ratio and 95% confidence interval, and the red  dotted line is an odds ratio of 1 or no difference. As shown, there were no subgroups that demonstrated an association between perioperative VTE  chemoprophylaxis and clinically significant hemorrhage. Secondary outcomes were no different except patients who received perioperative  therapy had a shorter hospital length of stay. The sensitivity analysis examining bleeds within 48 hours was also not significant with an adjusted odds ratio  of 1.05. The VTE rate was low irrespective of timing of chemoprophylaxis, but similar to what has recently been reported in the literature. There were  eight total VTEs and all patients survived. Six VTEs occurred in patients who had initiation delayed more than 12 hours post-op, one VTE occurred in a  patient whose chemoprophylaxis was interrupted for surgery, and one VTE was in a patient whose therapy was given early and continuously. To our knowledge,  this large multi-center cohort study is the first to provide direct evidence that patients with lower extremity long bone fractures who did not otherwise  have a high risk of bleeding have similar odds of developing a clinically significant hemorrhage whether VTE chemoprophylaxis is given in the  perioperative period or not. These results were not only adequately powered but were robust based on the sensitivity analysis and the subgroup  analysis. Prior evidence was insufficient and led to soft recommendations to continue VTE chemoprophylaxis perioperatively. Regarding development of  VTEs, receipt of perioperative VTE chemoprophylaxis was not significantly associated with VTE. However, seven of the eight VTEs occurred in patients with  delayed initiation or interruption, and the study was not powered for the secondary outcome. In conclusion, these results of this study demonstrate early  and continuous VTE chemoprophylaxis is safe and effective with major orthopedic surgery for long bone fractures. This study was performed by the Injury  Outcomes Network, which is a collaborative group of level one trauma centers. I'd like to acknowledge the work of the co-authors and co-PIs of the  study, as well as our clinical research coordinators, without which the study could not have been performed. Thank you very much.

Video Summary

The study examined the timing of venous thromboembolism (VTE) chemoprophylaxis in patients with lower extremity long bone fractures. Current practice is to use mechanical or pharmacological prophylaxis, but pharmacological agents carry a small risk of bleeding. The study aimed to determine the safety and efficacy of perioperative administration of VTE chemoprophylaxis. The results showed that perioperative administration of VTE chemoprophylaxis did not increase the risk of clinically significant bleeding. There was no association between perioperative VTE chemoprophylaxis and bleeding in any fracture group. Additionally, the study found that perioperative administration of VTE chemoprophylaxis was not significantly associated with VTE.

Asset Subtitle

Pharmacology, Trauma, Cardiovascular, 2022

Asset Caption

INTRODUCTION: Lower-extremity fractures represent 40% of traumatic injuries and are considered in the highest-risk group for developing a venous thromboembolism (VTE). Debate surrounds which operations are safe to continue VTE chemoprophylaxis without interruption. The study objective was to determine the safety and efficacy of perioperative administration of VTE chemoprophylaxis in patients with major orthopedic surgery. METHODS: This multicenter, retrospective cohort study included 880 adults with femoral or tibial fractures admitted between 1/1/2018 and 3/1/2020 to six trauma centers. Exclusions were head or spinal injury (AIS ≥2), pre-injury chronic anticoagulation, or no administration of LMWH or UFH for VTE chemoprophylaxis. Perioperative administration was defined as initiation preoperatively without interruption for surgery, or initiation within 12 hours postoperatively. The primary outcome was incidence of clinically significant postoperative hemorrhage (CSH), defined as overt hemorrhage resulting in blood transfusion, wound dehiscence, compartment syndrome, return to OR, or ≥2g/dl decrease in hemoglobin. Mixed repeated measures models evaluated differences in CSH based on perioperative therapy. RESULTS: There were 925 long bone surgeries. Of these, 48% (n=443) had perioperative therapy (n=222 initiated within 12h postop, n=221 not held for surgery). The remaining 52% of surgeries did not receive perioperative therapy (initiated > 12h postop, n=466; interrupted, n=15; discontinued postop, n=1). There were 176 patients with 185 CSH, nearly all resulting in ≥2g/dl drop in hemoglobin requiring blood transfusion (96%). The incidence of CSH was similar based on perioperative therapy or not (21% vs. 19%, p=0.64). After adjustment, there were similar odds of CSH by perioperative therapy (p=0.67). Covariates significantly associated with CSH were age ≥65y, GCS < 15, female sex, total hours in surgery, and pre-injury antiplatelet use. The incidence of VTEs were similar with perioperative therapy or not (1.1% vs. 1.9%, p=0.36). However, VTEs were more frequent when chemoprophylaxis was interrupted (4.4% vs. 0.2%, p < 0.001), as were CSH (33.7% vs. 14.4%, p < 0.001). CONCLUSIONS: These data suggest early and continuous VTE chemoprophylaxis is safe and effective with major orthopedic surgery for long bone fractures.

Meta Tag

Content Type Presentation

Knowledge Area Pharmacology

Knowledge Area Trauma

Knowledge Area Cardiovascular

Knowledge Level Advanced

Membership Level Select

Tag Anticoagulation

Tag Thromboembolism

Tag Burns

Tag Hemorrhage

Year 2022

Keywords

venous thromboembolism

chemoprophylaxis

lower extremity long bone fractures

perioperative administration

bleeding risk

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