Venous thromboembolic events in critically ill traumatic brain injury patients
To estimate the prevalence, risk factors, prophylactic treatment and impact on mortality for venous thromboembolism (VTE) in patients with moderate to severe traumatic brain injury (TBI) treated in the intensive care unit.
A post hoc analysis of the erythropoietin in traumatic brain injury (EPO-TBI) trial that included twice-weekly lower limb ultrasound screening. Venous thrombotic events were defined as ultrasound-proven proximal deep venous thrombosis (DVT) or clinically detected pulmonary embolism (PE). Results are reported as events, percentages or medians and interquartile range (IQR). Cox regression analysis was used to calculate adjusted hazard ratios (HR) with 95% confidence intervals (CI) for time to VTE and death.
Of 603 patients, 119 (19.7%) developed VTE, mostly comprising DVT (102 patients, 16.9%) with a smaller number of PE events (24 patients, 4.0%). Median time to DVT diagnosis was 6 days (IQR 2–11) and to PE diagnosis 6.5 days (IQR 2–16.5). Mechanical prophylaxis (MP) was used in 91% of patients on day 1, 97% of patients on day 3 and 98% of patients on day 7. Pharmacological prophylaxis was given in 5% of patients on day 1, 30% of patients on day 3 and 57% of patients on day 7. Factors associated with time to VTE were age (HR per year 1.02, 95% CI 1.01–1.03), patient weight (HR per kg 1.01, 95% CI 1–1.02) and TBI severity according to the International Mission for Prognosis and Analysis of Clinical Trials risk of poor outcome (HR per 10% increase 1.12, 95% CI 1.01–1.25). The development of VTE was not associated with mortality (HR 0.92, 95% CI 0.51–1.65).
Despite mechanical and pharmacological prophylaxis, VTE occurs in one out of every five patients with TBI treated in the ICU. Higher age, greater weight and greater severity of TBI increase the risk. The development of VTE was not associated with excess mortality.
KeywordsErythropoietin Deep venous thrombosis Pulmonary embolism Traumatic brain injury Venous thromboembolism
- 7.Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, Joint Section on Neurotrauma and Critical Care, AANS/CNS, Bratton SL, Chestnut RM, Ghajar J, McConnell Hammond FF, Harris OA, Hartl R, Manley GT, Nemecek A, Newell DW, Rosenthal G, Schouten J, Shutter L, Timmons SD, Ullman JS, Videtta W, Wilberger JE, Wright DW (2007) Guidelines for the management of severe traumatic brain injury. V. Deep vein thrombosis prophylaxis. J Neurotrauma 24(Suppl 1):S32–S36Google Scholar
- 8.Nichol A, French C, Little L, Haddad S, Presneill J, Arabi Y, Bailey M, Cooper DJ, Duranteau J, Huet O, Mak A, McArthur C, Pettila V, Skrifvars M, Vallance S, Varma D, Wills J, Bellomo R, EPO-TBI Investigators, ANZICS Clinical Trials Group (2015) Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet 386:2499–2506CrossRefPubMedGoogle Scholar
- 9.Nichol A, French C, Little L, Presneill J, Cooper DJ, Haddad S, Duranteau J, Huet O, Skrifvars M, Arabi Y, Bellomo R, EPO-TBI Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group (2015) Erythropoietin in traumatic brain injury: study protocol for a randomised controlled trial. Trials 16:39CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Robertson CS, Hannay HJ, Yamal JM, Gopinath S, Goodman JC, Tilley BC, Epo Severe TBITI, Baldwin A, Rivera Lara L, Saucedo-Crespo H, Ahmed O, Sadasivan S, Ponce L, Cruz-Navarro J, Shahin H, Aisiku IP, Doshi P, Valadka A, Neipert L, Waguspack JM, Rubin ML, Benoit JS, Swank P (2014) Effect of erythropoietin and transfusion threshold on neurological recovery after traumatic brain injury: a randomized clinical trial. JAMA 312:36–47CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Presneill J, Little L, Nichol A, French C, Cooper DJ, Haddad S, Duranteau J, Huet O, Skrifvars M, Arabi Y, Bellomo R, EPO-TBI Investigators, ANZICS Clinical Trials Group (2014) Statistical analysis plan for the Erythropoietin in Traumatic Brain Injury trial: a randomised controlled trial of erythropoietin versus placebo in moderate and severe traumatic brain injury. Trials 15:501CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Tracy RP (2002) Hemostatic and inflammatory markers as risk factors for coronary disease in the elderly. Am J Geriatr Cardiol 11(93–100):107Google Scholar
- 30.Beitland S, Sandven I, Kjærvik LK, Sandset PM, Sunde K, Eken T (2015) Thromboprophylaxis with low molecular weight heparin versus unfractionated heparin in intensive care patients: a systematic review with meta-anlaysis and trial sequential analysis. Intensive Care Med 41:1209–1219CrossRefPubMedGoogle Scholar