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Erschienen in: Intensive Care Medicine 3/2017

27.12.2016 | Original

Venous thromboembolic events in critically ill traumatic brain injury patients

verfasst von: Markus B. Skrifvars, Michael Bailey, Jeffrey Presneill, Craig French, Alistair Nichol, Lorraine Little, Jacques Duranteau, Olivier Huet, Samir Haddad, Yaseen Arabi, Colin McArthur, D. James Cooper, Rinaldo Bellomo, For the EPO-TBI investigators and the ANZICS Clinical Trials Group

Erschienen in: Intensive Care Medicine | Ausgabe 3/2017

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Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.
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Literatur
1.
Zurück zum Zitat Phelan HA (2013) Venous thromboembolism after traumatic brain injury. Semin Thromb Hemost 39:541–548CrossRefPubMed Phelan HA (2013) Venous thromboembolism after traumatic brain injury. Semin Thromb Hemost 39:541–548CrossRefPubMed
2.
Zurück zum Zitat Abdel-Aziz H, Dunham CM, Malik RJ, Hileman BM (2015) Timing for deep vein thrombosis chemoprophylaxis in traumatic brain injury: an evidence-based review. Crit Care 19:96CrossRefPubMedPubMedCentral Abdel-Aziz H, Dunham CM, Malik RJ, Hileman BM (2015) Timing for deep vein thrombosis chemoprophylaxis in traumatic brain injury: an evidence-based review. Crit Care 19:96CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Lier H, Bottiger BW, Hinkelbein J, Krep H, Bernhard M (2011) Coagulation management in multiple trauma: a systematic review. Intensive Care Med 37:572–582CrossRefPubMed Lier H, Bottiger BW, Hinkelbein J, Krep H, Bernhard M (2011) Coagulation management in multiple trauma: a systematic review. Intensive Care Med 37:572–582CrossRefPubMed
4.
Zurück zum Zitat Ho KM, Burrell M, Rao S, Baker R (2010) Incidence and risk factors for fatal pulmonary embolism after major trauma: a nested cohort study. Br J Anaesth 105:596–602CrossRefPubMedPubMedCentral Ho KM, Burrell M, Rao S, Baker R (2010) Incidence and risk factors for fatal pulmonary embolism after major trauma: a nested cohort study. Br J Anaesth 105:596–602CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Allen CJ, Murray CR, Meizoso JP, Ginzburg E, Schulman CI, Lineen EB, Namias N, Proctor KG (2016) Surveillance and early management of deep vein thrombosis decreases rate of pulmonary embolism in high-risk trauma patients. J Am Coll Surg 222:65–72CrossRefPubMed Allen CJ, Murray CR, Meizoso JP, Ginzburg E, Schulman CI, Lineen EB, Namias N, Proctor KG (2016) Surveillance and early management of deep vein thrombosis decreases rate of pulmonary embolism in high-risk trauma patients. J Am Coll Surg 222:65–72CrossRefPubMed
6.
Zurück zum Zitat Geerts WH, Code KI, Jay RM, Chen E, Szalai JP (1994) A prospective study of venous thromboembolism after major trauma. N Engl J Med 331:1601–1606CrossRefPubMed Geerts WH, Code KI, Jay RM, Chen E, Szalai JP (1994) A prospective study of venous thromboembolism after major trauma. N Engl J Med 331:1601–1606CrossRefPubMed
7.
Zurück zum Zitat 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–S36 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–S36
8.
Zurück zum Zitat 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 386:2499–2506CrossRefPubMed 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 386:2499–2506CrossRefPubMed
9.
Zurück zum Zitat 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 16:39CrossRefPubMedPubMedCentral 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 16:39CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Corwin HL, Gettinger A, Fabian TC, May A, Pearl RG, Heard S, An R, Bowers PJ, Burton P, Klausner MA, Corwin MJ, EPO Critical Care Trials Group (2007) Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med 357:965–976CrossRefPubMed Corwin HL, Gettinger A, Fabian TC, May A, Pearl RG, Heard S, An R, Bowers PJ, Burton P, Klausner MA, Corwin MJ, EPO Critical Care Trials Group (2007) Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med 357:965–976CrossRefPubMed
11.
Zurück zum Zitat 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 312:36–47CrossRefPubMedPubMedCentral 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 312:36–47CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D, Investigators C (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098CrossRefPubMed Singh AK, Szczech L, Tang KL, Barnhart H, Sapp S, Wolfson M, Reddan D, Investigators C (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098CrossRefPubMed
13.
Zurück zum Zitat Ekeh AP, Dominguez KM, Markert RJ, McCarthy MC (2010) Incidence and risk factors for deep venous thrombosis after moderate and severe brain injury. J Trauma 68:912–915PubMed Ekeh AP, Dominguez KM, Markert RJ, McCarthy MC (2010) Incidence and risk factors for deep venous thrombosis after moderate and severe brain injury. J Trauma 68:912–915PubMed
14.
Zurück zum Zitat Ortel TL (2010) Acquired thrombotic risk factors in the critical care setting. Crit Care Med 38:S43–S50CrossRefPubMed Ortel TL (2010) Acquired thrombotic risk factors in the critical care setting. Crit Care Med 38:S43–S50CrossRefPubMed
15.
Zurück zum Zitat Reiff DA, Haricharan RN, Bullington NM, Griffin RL, McGwin G Jr, Rue LW 3rd (2009) Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis. J Trauma 66:1436–1440CrossRefPubMed Reiff DA, Haricharan RN, Bullington NM, Griffin RL, McGwin G Jr, Rue LW 3rd (2009) Traumatic brain injury is associated with the development of deep vein thrombosis independent of pharmacological prophylaxis. J Trauma 66:1436–1440CrossRefPubMed
16.
Zurück zum Zitat Knudson MM, Ikossi DG, Khaw L, Morabito D, Speetzen LS (2004) Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank. Ann Surg 240:490–496 (discussion 496-498)CrossRefPubMedPubMedCentral Knudson MM, Ikossi DG, Khaw L, Morabito D, Speetzen LS (2004) Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank. Ann Surg 240:490–496 (discussion 496-498)CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat 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 15:501CrossRefPubMedPubMedCentral 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 15:501CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group, Cook D, Meade M et al (2011) Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 364:1305–1314CrossRef PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group, Cook D, Meade M et al (2011) Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 364:1305–1314CrossRef
19.
Zurück zum Zitat Garcia-Olivares P, Guerrero JE, Galdos P, Carriedo D, Murillo F, Rivera A (2014) PROF-ETEV study: prophylaxis of venous thromboembolic disease in critical care units in Spain. Intensive Care Med 40:1698–1708CrossRefPubMed Garcia-Olivares P, Guerrero JE, Galdos P, Carriedo D, Murillo F, Rivera A (2014) PROF-ETEV study: prophylaxis of venous thromboembolic disease in critical care units in Spain. Intensive Care Med 40:1698–1708CrossRefPubMed
20.
Zurück zum Zitat Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW (2008) Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation 117:93–102CrossRefPubMed Ageno W, Becattini C, Brighton T, Selby R, Kamphuisen PW (2008) Cardiovascular risk factors and venous thromboembolism: a meta-analysis. Circulation 117:93–102CrossRefPubMed
21.
Zurück zum Zitat Tracy RP (2002) Hemostatic and inflammatory markers as risk factors for coronary disease in the elderly. Am J Geriatr Cardiol 11(93–100):107 Tracy RP (2002) Hemostatic and inflammatory markers as risk factors for coronary disease in the elderly. Am J Geriatr Cardiol 11(93–100):107
22.
Zurück zum Zitat Kasjanovova D, Adameckova D, Gratzlova J, Hegyi L (1993) Sex-related and age-related differences in platelet function in vitro: influence of hematocrit. Mech Ageing Dev 71:103–109CrossRefPubMed Kasjanovova D, Adameckova D, Gratzlova J, Hegyi L (1993) Sex-related and age-related differences in platelet function in vitro: influence of hematocrit. Mech Ageing Dev 71:103–109CrossRefPubMed
23.
Zurück zum Zitat Gleerup G, Winther K (1995) The effect of ageing on platelet function and fibrinolytic activity. Angiology 46:715–718CrossRefPubMed Gleerup G, Winther K (1995) The effect of ageing on platelet function and fibrinolytic activity. Angiology 46:715–718CrossRefPubMed
24.
Zurück zum Zitat Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A, Salvetti A (2001) Age-related reduction of NO availability and oxidative stress in humans. Hypertension 38:274–279 (Dallas, Tex: 1979) CrossRefPubMed Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A, Salvetti A (2001) Age-related reduction of NO availability and oxidative stress in humans. Hypertension 38:274–279 (Dallas, Tex: 1979) CrossRefPubMed
25.
Zurück zum Zitat Martinelli I, Bucciarelli P, Mannucci PM (2010) Thrombotic risk factors: basic pathophysiology. Crit Care Med 38:S3–S9CrossRefPubMed Martinelli I, Bucciarelli P, Mannucci PM (2010) Thrombotic risk factors: basic pathophysiology. Crit Care Med 38:S3–S9CrossRefPubMed
26.
Zurück zum Zitat Franchini M, Targher G, Montagnana M, Lippi G (2008) The metabolic syndrome and the risk of arterial and venous thrombosis. Thromb Res 122:727–735CrossRefPubMed Franchini M, Targher G, Montagnana M, Lippi G (2008) The metabolic syndrome and the risk of arterial and venous thrombosis. Thromb Res 122:727–735CrossRefPubMed
27.
Zurück zum Zitat Nunez JM, Becher RD, Rebo GJ, Farrah JP, Borgerding EM, Stirparo JJ, Lauer C, Kilgo P, Miller PR (2015) Prospective evaluation of weight-based prophylactic enoxaparin dosing in critically Ill trauma patients: adequacy of antixa levels is improved. Am Surg 81:605–609PubMed Nunez JM, Becher RD, Rebo GJ, Farrah JP, Borgerding EM, Stirparo JJ, Lauer C, Kilgo P, Miller PR (2015) Prospective evaluation of weight-based prophylactic enoxaparin dosing in critically Ill trauma patients: adequacy of antixa levels is improved. Am Surg 81:605–609PubMed
28.
Zurück zum Zitat Ko A, Harada MY, Barmparas G, Chung K, Mason R, Yim DA, Dhillon N, Margulies DR, Gewertz BL, Ley EJ (2016) Association between enoxaparin dosage adjusted by anti-factor Xa trough level and clinically evident venous thromboembolism after trauma. JAMA Surg 151:1006–1013CrossRefPubMed Ko A, Harada MY, Barmparas G, Chung K, Mason R, Yim DA, Dhillon N, Margulies DR, Gewertz BL, Ley EJ (2016) Association between enoxaparin dosage adjusted by anti-factor Xa trough level and clinically evident venous thromboembolism after trauma. JAMA Surg 151:1006–1013CrossRefPubMed
30.
Zurück zum Zitat 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 41:1209–1219CrossRefPubMed 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 41:1209–1219CrossRefPubMed
Metadaten
Titel
Venous thromboembolic events in critically ill traumatic brain injury patients
verfasst von
Markus B. Skrifvars
Michael Bailey
Jeffrey Presneill
Craig French
Alistair Nichol
Lorraine Little
Jacques Duranteau
Olivier Huet
Samir Haddad
Yaseen Arabi
Colin McArthur
D. James Cooper
Rinaldo Bellomo
For the EPO-TBI investigators and the ANZICS Clinical Trials Group
Publikationsdatum
27.12.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Intensive Care Medicine / Ausgabe 3/2017
Print ISSN: 0342-4642
Elektronische ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-016-4655-2

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