This nested case–control study of general trauma population revealed that long bone open fracture in extremities, spinal injury, central vein catheter placement, and any surgery were risk factors for PE. Bone fixation was the most frequent surgery, and delayed bone fixation also could be a risk factor for PE.
Long bone open fractures in upper and lower extremities emerged as high risk trauma for PE. Lower extremity fracture is an established risk factor for PE; however, in previous studies, upper extremity fracture has not been risk factor for PE 3,8,10,21. Whether open or closed fracture was a risk factor for PE was also unknown. In this study, long bone open fracture in the lower extremities was the most relevant trauma with PE, and long bone open fracture in the upper extremities was the second most relevant trauma. The possible underlying pathophysiology may be that open fracture has greater soft tissue damage involving the venous endothelium and has more bleeding from open wounds, resulting in more severe coagulopathy, than closed fracture 25–27. Venous stasis caused by immobility could also play a role in patients with lower extremity fracture 28. Open fracture in the extremities could be related to occurrence of PE.
We confirmed that spinal injury 9,12,21,29−31, central vein catheter placement 6,32,33, and surgery 3,10,12,21 were risk factors for PE, which is consistent with previous studies. Spinal injury is related to venous stasis because of long-term immobility. Vascular-related procedures such as central vein catheter placement and surgery could be related to endothelial injury and hypercoagulability.
Head, thoracic, and abdominal trauma were not risk factors for PE in this study, although whether these injury sites are risk factors for PE has been controversial in previous studies 3,4,7,9,11. Compared with this study, previous studies were limited by small sample size and uncontrolled potential confounders such as comorbidities, severity, and surgery. Regarding head trauma, recent studies focusing on the timing of post-traumatic PE showed that head trauma was associated with late onset of PE 16,34−36. Our cohort might have captured only early PE.
Early definitive surgery for bone fracture could reduce risk for PE. Previous studies showed that delayed definitive surgery for bone fracture (after 24 to 48 h) led to pulmonary complications such as pneumonia and acute respiratory distress syndrome because post-traumatic and post-surgical inflammation act as “two hit model” 22,37−39. However, few studies have showed an association between timing of definitive surgery and post-traumatic PE because it is a relatively infrequent complication 40. A subgroup analysis in this study showed that bone fixation during 24–120 h after injury was associated with a higher risk for PE. Our study suggests that early total care is better than damage control orthopedics regarding PE among patients with bone fracture.
In this study, patients with spinal injury, open fracture in the extremities, central vein catheter placement, and any surgery were at high risk of post-traumatic PE. Patients with these characteristics should be probably treated with pharmacological prophylaxis as soon as bleeding risk is adequately controlled.
The current study has several important limitations that warrant discussion. First, neither mechanical nor pharmacological prophylaxis was recorded in this database and could be potential confounding factors. Therefore, we performed a sensitivity analysis among ICU patients because prophylaxis is well adhered to in ICU in Japan (see Supplementary Table S4). The sensitivity analysis showed similar results, four of five risk factors for PE in the main analysis were independently associated with PE. Second, because they were risk factors for PE in previous studies, pneumonia and sepsis also could be potential confounding factors 13,32,41. However, we did not include these complications to logistic regression analyses because we did not have onset-time data of complications in our database. Third, we did not include patients who did not survive < 48 hours to exclude the impact of early trauma deaths. Some patients with PE might have been lost in our study. However, because VTE prophylaxis such as anticoagulants could not have been used in early phase of trauma care, these patients were presumably small number and their deaths were unpreventable. Fourth, there might be an information bias. The diagnosis of PE was based on the reports of the physician in charge, and it might have been an underdiagnosis. However, the incidence of PE among patients with eligible criteria was 0.5% (772/155,525) in this study, which is consistent with previous studies (0.1–2.6%) 3,5–7,9−11,40. Diagnosis was likely to have been correct. Moreover, physicians in Japan, compared with those in other countries, have relatively easier access to the use of computed tomography, because there are many computed tomography scanners in Japan 42.