Program Information

1. Program Information

2. Venous Thromboembolism (VTE) in ICU Chee M. Chan, MD Pulmonary and Critical Care Medicine Washington Hospital Center Washington, D.C.

3. VTE in ICU • Pathophysiology of thrombosis • Prophylaxis and DVT • Pathophysiology of pulmonary embolism • Pulmonary embolism diagnostics • Pulmonary embolism therapeutics

4. Secondary Development Risk Factors Prophylaxis Thrombolytics LMWH Lepirudin VTE Overview PrimaryPresentation Hemodynamic Instability Respiratory Failure Diagnostics Cardiac Echo Spiral CT Doppler US D-dimer Angiogram Therapeutics UF Heparin Warfarin Argatroban

5. Pathophysiology of Thrombosis

6. Vessel Injury Stasis Hyper-coagulability Inherited Acquired Venous Thromboembolism “ The detachment of larger or smaller fragments from the end of the softening thrombus are carried along by the current of blood and driven in remote vessels. This gives rise to the very frequent process upon which I have bestowed the name EMBOLIA.” Virchow, 1846

7. Virchow’s Triad • Hypercoagulable (25%) • Stasis • Vessel damage

8. Intensivists’ General Paradigm Pipes Stuff Flow

9. Clot Bleed Stuff Pipe = Biologically ActiveConduit Stuff Flow Coagulation Fibrinolysis Hematology 101 for Intensivists

10. Bleed Clot Stuff Pipe = Biologically Active Conduit Stuff Flow (stasis) Coagulation Fibrinolysis Hematology 101 for Intensivists

11. Bleed Clot Pathogenesis of VTE Thrombogenic Stimuli • Endothelial damage • Exposure of tissue factor/subendothelial matrix • Hypoxia  receptors for leukocytes • Activation by inflammatory cytokines (IL-1, TNF) • Express tissue factor • Internalize thrombomodulin ( Protein C activation) • Release PAI-1 • Activation of coagulation • Inflammation (IL-1, TNF) • Monocytes  tissue factor and tethered leukocytes • Internalize thrombomodulin • Shedding endothelial protein C receptor • Coagulation cascade activation Adapted from Wertz. Lung Biol Health Dis. 2003

12. Bleed Clot Pathogenesis of VTE Thrombogenic Stimuli • Blood flow (stasis) • Systemic • Immobilization pools blood in calf venous sinuses • Increased blood viscosity • Local • Hypoxia of valve cusps produces tissue factor and activates coagulation • Accumulation of clotting factors in venous sinuses of calf or valve cusp pockets Adapted from Wertz Lung Biology Health Disease 2003

13. ICU VTE Risk Factors Adopted from Dalen. CHEST 2002; 122:1440-1456.

14. DVT Recurrence PE Post-phlebitic syndrome DVT Prophylaxis in ICU • Most preventable cause of hospital associated death in medical patients  PE • Valvular damage • Symptomatic proximal DVT can be an extension of distal DVT that was previously asymptomatic • Significant number of fatal PEs NOT preceded by symptomatic DVT

15. ICU Issues and VTE • VTE are frequently unrecognized in critically ill patients • High risk • Unable to express symptoms • Physical signs masked by critical illness • Pulmonary embolism can result in: • Failure to wean from the ventilator • Increased ICU length of stay • Death

16. Asymptomatic DVT ICU Admit

17. Prospective Eval DVT Critically Ill Non-Prophylaxed

18. Natural History of DVT 132 surgical patients, no prophylaxis 70% No DVT (92) 30% DVT (40) 35% calf with spontaneous lysis (14) 42% calf only (17) 23% propagation Popliteal/femoral (9) 56% No PE (5) 44% PE (4) Kakkar. Lancet. 1969; 6:230-232.

19. 69% lower extremity ortho 61% pelvic fractures 80% femoral fractures 77% tibial fractures Incidence of VTEMajor Trauma W/out Prophylaxis • Lower leg DVT 58%, proximal DVT 18% • Vast majority clinically not apparent Incidence Geerts. N Engl J Med. 1994;331:1601-1606. 50% face, chest, abdomen 54% major head injury 62% spinal injury

20. DVT Prophylaxis Trials in Critically Ill Geerts. J Crit Care. 2002;17:95-104.

21. Femoral Catheter-associated DVT

22. Pulmonary Embolism in Patients with Upper Extremity Catheter DVT • 86 consecutive patients catheter DVT • 15% high probability (PE) V/Q scan (13/86) • 31% PE patients symptomatic (4/13) • 15% PE patient mortality (2/13) despite full anticoagulation •  DVT polyvinyl chloride or polyethylene Monreal. Thromb Haemost. 1994;72:548-5.50

23. Autopsy Studies PE Critically Ill Geerts. J Crit Care. 2002;17:95-104.

24. VTE Prophylaxis Pharmacologic Unfractionated heparin Low molecular weight heparin Vitamin K Antagonists Mechanical Graduated compression stockings Intermittent pneumatic compression devices IVC filters

25. Thromboembolism RiskSurgical Patients  Prophylaxis Geerts. Chest. 2004;126 Suppl:338S-400S.

26. Control Heparin 70 60.5 60 Relative risk reduction 67% 50 Relative risk reduction 68% 40 Percentage 30 20.3 20 10 1.9 0.6 0 Fatal PE Screening DVT Collins. N Engl J Med. 1988;318:1162-1173.

27. Trauma and VTE • Patients recovering from major trauma have the highest risk for developing VTE among all hospitalized patients. (Geerts. N Engl J Med. 1994;331:1601-1606.) • Without prophylaxis, multisystem or major trauma patients have a DVT risk exceeding 50%. (Kudsk. Am J Surg. 1989;158:515-519.) • PE is the third leading cause of death in trauma patients who survive beyond the first day. (Acosta. J Am Coll Surg. 1998;186:528-533.)

28. Risk Factors for VTE The following display the significant risk factors and odds ratios for VTE developed from the National Trauma Data Bank. Knudson. Ann Surg. 2004;240:490-498.

29. INJURED PATIENT • High Risk Factors • (Odds ratio for VTE = 2–3) • Age ³40 • Pelvic fx • Lower extremity fx • Shock • Spinal cord injury • Head injury (AIS ³3) • Very High Risk Factors • (Odds ratio for VTE = 4–10) • Major operative procedure • Venous injury • Ventilator days >3 • 2 or more high risk factors Does the patient have contraindication for heparin? Does the patient have contraindication for heparin? No Yes Yes No LMWH* and mechanical compression Mechanical Compression and serial CFDI OR temporary IVC filter Mechanical compression LMWH* * Prophylactic dose Knudson. Ann Surg. 2004;240:490-498.

30. Mechanical prophylaxis Graduated compression stockings (GCS) Intermittent pneumatic compression devices (IPC) Delayed prophylaxis until high risk bleeding abates Screen for proximal DVT with Doppler US in high risk patients Low dose unfractionated heparin (LDUH) Low molecular weight heparin (LMWH) Combination of LMWH and mechanical prophylaxis for high risk patients Assess Bleeding Risk High Low Critical Care Patient Adapted from Albers. Chest. 2008;133 Suppl:381S-453S.

31. Critical Care Patient Adapted from Albers. Chest. 2008;133 Suppl:381S-453S.

32. Anti-Xa Activity After Enoxaparin 40 mg SQ 1.0 Ward (Group 2), n=13 ICU patients (Group 1), n=16 0.8 0.6 Anti-Xa activity (U/ml) 0.4 0.2 0 12 6 9 3 0 Time (hours) Priglinger. Crit Care Med. 2003; 31:1405-1409.

33. Vena Caval Filters • 5 filter types -- all equal efficacy • Pulmonary embolism 2.6%-3.8% • Deep venous thrombosis 6%-32% • Insertion site thrombosis 23%-36% • Inferior caval thrombosis 3.6%-11.2% • Postphlebitic syndrome 14%-41% Streiff. Blood. 2000; 95:3669-3677.

34. ACCP Recommendations • ACCP recommendations for thromboprophylaxis in ICU patients • All ICU patients -> assessed for VTE prophylaxis • All ICU patients -> routine thromboprophylaxis • Moderate risk -> LMWH or LDUH prophylaxis • High risk -> LMWH prophylaxis • Bleeding risk high -> mechanical prophylaxis • When bleeding risks decreases -> chemical Adopted from Albers. Chest. 2008

35. Summary • VTE is common in critically ill patients. • Modifiable risk factors are limited in the ICU • In the ICU population, VTE occurrence ranges from 13-33%. • With use of prophylaxis, VTE risk can be decreased to 10-15%. • DVT prophylaxis is essential.