Kenneth P. Steinberg, MD, FACP, Editor
Professor of Medicine, University of Washington School of Medicine
Dr. Steinberg reports no financial relationships in this field of study.
SOURCE: Kaplan D, et al. VTE incidence and risk factors in patients with severe sepsis and septic shock. Chest. 2015. doi:10.1378/chest.15-0287. [Epub ahead of print]
The purpose of this multicenter study was to prospectively determine the incidence of VTE among ICU patients with sepsis and septic shock, and to identify independent risk factors for VTE in these patients. Consecutively identified patients admitted to the ICU at three academic medical centers with a diagnosis of severe sepsis or septic shock were prospectively identified and enrolled within 72 hours of admission. All patients, or their legal surrogate, provided informed consent. The investigators used common, standard definitions for sepsis and septic shock. While the choice of VTE prophylaxis was left to the treating physicians, VTE thromboprophylaxis was recorded for all patients. Patients underwent compression ultrasonography (CUS) and were followed for the primary outcome: acute VTE of any type (including upper and lower extremity DVT and symptomatic PE) prior to ICU discharge. All-cause 28-day mortality was also recorded. Variables from univariate analyses that were associated with VTE (including CVC insertion, age, length of stay, and mechanical ventilation) were included in a multivariable logistic regression analysis to determine independent VTE predictors.
The authors prospectively studied 113 consecutively enrolled ICU patients with severe sepsis and septic shock. Over 50% of patients had shock requiring vasopressors, and more than 75% required mechanical ventilation. A CVC was placed as part of the ICU care for 61.1% of patients (n = 69/113). All-cause 28-day mortality was 21.2% (95% CI 14.1-30.0). Overall, 80.5% (n = 91/113) of patients had VTE chemoprophylaxis prescribed and SCDs were prescribed for the remainder of patients (19.5%, n = 22/113) not given anticoagulant-based VTE prophylaxis due to a contraindication, such as bleeding or coagulopathy. The authors state that all patients received VTE prophylaxis according to their hospitals’ guidelines.
The primary outcome of acute VTE of any type (including upper and lower extremity DVT and symptomatic PE) occurred in 42 patients (37.2%, 95% CI 28.3-46.8). Clinically significant VTE occurred in 88.1% of patients (n = 37/42). Isolated, asymptomatic, distal DVT, the clinical significance of which remains uncertain, occurred in 11.9% (n = 5/42) of patients. Among patients with a CVC, 23.2% (n = 16/69) had CVC-associated upper extremity DVT. Only 3 patients (2.7%) had a CUS performed at the request of their primary ICU team due to clinical suspicion of venous thrombosis and, in 2 of these 3 patients (66%), acute DVT was present.
Septic patients with clinically significant VTE had a significantly longer ICU length of stay compared to patients without VTE (18.2 ± 9.9 versus 13.4 ± 11.5 days, p < 0.05). ICU length of stay did not differ between patients with and without VTE (10.4 ± 3.3 vs. 13.4 ± 11.5, p = 0.57). All-cause, 28-day mortality was not statistically different between the two groups (p=0.18).
The incidence of VTE did not differ between patients receiving LMWH compared to UFH (33.3% vs. 41.3%, respectively; p = 0.43). Similarly, there was no difference in the incidence of VTE between patients receiving pharmacologic-based prophylaxis compared to SCDs (37.3% vs. 36.3%, respectively; p = 0.93). In univariate analyses, several factors were independently associated with VTE, including age, ICU length of stay, the need for mechanical ventilation upon admission, the presence of an indwelling CVC, and the duration of mechanical ventilation. In multivariable analyses, two factors remained as significant VTE risk factors: the presence of an indwelling CVC and the duration of mechanical ventilation. Even when patients with upper extremity DVT were excluded, CVC use remained a significant risk factor for isolated lower extremity DVT and PE.
Most previous studies of VTE in the ICU found much lower rates of VTE but this appears to be the first multicenter prospective study of VTE in patients with sepsis. More than a third of these patients (37.2%; 95% CI, 28.3 to 46.8) had a venous thromboembolism (VTE) despite receiving recommended thromboprophylaxis and 88% of these were clinically significant (defined by the researchers as pulmonary embolism, proximal deep vein thrombosis, and/or symptomatic distal deep vein thrombosis). Patients with specifical clinically significant VTE had longer length of stay, though mortality was not statistically different. The study found insertion of a central venous catheter (CVC) and longer duration of mechanical ventilation to be independent risk factors for VTE.
This study demonstrates a markedly higher incidence of VTE in patients with sepsis and septic shock than has previously been observed in studies of all ICU patients. This suggests that patients with sepsis may have a greater proclivity toward VTE. Two possible explanations may explain this predisposition. The systemic inflammatory response of sepsis accompanied by high levels of circulating cytokines may cause endothelial injury and an increased risk for VTE. It is also possible that thromboprophylaxis is less effective in patients with sepsis.
One concerning finding in the study was that only 3 of the patients had compression ultrasounds ordered due to a clinical suspicion of DVT; most of the DVTs were found with the protocolled screening. I agree with the authors that clinicians should have a high suspicion for VTE in patients with sepsis. I also agree that it is reasonable to minimize the risk factors for VTE identified in this study by targeting removal of CVCs when they are not necessary and decreasing duration of mechanical ventilation through standardized weaning protocols and early mobility. Hospitalists who take care of patients in the ICU, or even non-ICU patients with sepsis, should be aware of these observations and should take a lead role in making sure their hospitals have protocols for the use of thromboprophylaxis, removing unnecessary CVCs, and weaning from mechanical ventilation. But it is important to remember that this study demonstrates a correlation between sepsis and VTE and does not demonstrate that routine screening and treatment leads to improved outcomes. That is a hypothesis for a future study.