Venous Thromboembolism in Intensive Care Medicine Kenneth E. Wood, DO Professor of Medicine and Anesthesiology Director of Critical Care Medicine and Respiratory Care The Trauma and Life Support Center University of Wisconsin Hospital and Clinics

Venous Thromboembolism in ICU Pathophysiology of Thrombosis

Intensivists General Paradigm Pipes Stuff Flow

Hematology 101 for Intensivists = Biologically Active Conduit Clot Bleed Stuff Pipe Flow Stuff Coagulation fibrinolysis

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

ICU Venous Thromboembolism Adopted from Dalen CHEST 2002; 122:1440-56 X X X Catheter X X Sepsis X Burns X Stroke X MI/CHF X X X Trauma X X X Major Surgery Vessel Stasis Hypercoag ICU Risk Factors

Venous Thromboembolism in ICU Prophylaxis and DVT

Asymptomatic DVT ICU Admit 6.3% Fraisse Am J Resp CCM 2000; 161:1109-14 MICU-Resp fail/vent 19% Goldberg Am J Resp CCM 1996; 153:A94 MICU-Resp fail/vent 10.7% Schonhster Respiration 1998; 65:173-7 Respiratory ICU 7.5% Harris J Vas Surg 1997; 26:734-9 Surgical ICU % DVT Patient Population

Prospective Eval DVT Critically Ill Non-Prophylaxed 28% 85 Venogram Vent COPD Fraisse 2000 31% 390 US Medical Kapoor 1999 32% 104 US Medical Hirsch 1995 29% 60 Fib LS General Cade 1982 13% 23 Fib LS Respiratory Moser 1981 % DVT # Screen Control Study

Natural History of DVT 132 Surgical patients no prophylaxis 56% No PE (5) 44% PE (4) 42% Calf only (17) 23% propagation Popliteal/femoral (9) 35% Calf with spontaneous lysis (14) 30% DVT (40) 70% No DVT (92) Kakkar Lancet 1969; 6:230-32

DVT Prophylaxis Trials in Critically Ill Geerts J Crit Care 2002; 17:95-104 15% Nadroparin 28% Placebo Fraisse 00 11% UF Heparin 31% Placebo Kapoor 99 13% UF Heparin 29% Placebo Cade 82 % DVT Treatment % DVT Control Study

Femoral Catheter Associated DVT 11% US Med/Surg Jogut 00 9% Femoral 26% Tibial Venogram Med/Surg Durbec 97 7% Femoral 17% Tibial Venogram Med/Surg Durbec 97 25% US Med/Surg Trottier 95 14% US Trauma 8.5 Fr Meredith 93 % DVT Screen Population Study

Autopsy Studies PE Critically Ill Geerts J Crit Care 2002; 17:95-104 PE Autopsy Fatal Present ICU Setting Study 12% 27% Med/Surg Neuhaus 1978 0% 20% Respiratory Moser 1981 1% 10% Surgical Cullin 1986 3% 8% Surgical Willemsen 2000 2% 7% Medical Blosser 1998 -- 23% Medical Pingleton 1981

VTE Prophylaxis Pharmacologic Unfractionated heparin Low molecular weight heparin Vit K Antagonists Mechanical Graduated Compression Stockings Intermittent Pneumatic Compression Devices IVC filters

Thromboembolism Risk Surgical Patients  Prophylaxis Geerts CHEST 2004;126(3)Supplement: 338S-400S Surgery with multiple risk factors (age > 40 yr, cancer, prior VTE) Hip or knee arthroplasty, HFS Major trauma, SCI 0.2-5% 4-10% 10-20% 40-80% Highest Risk Surgery >60, 94 40-60 with additional risk factors (prior VTE, cancer, hypercoagulability) 0.4-1.0% 2-4% 4-8% 20-40% High Risk Minor surgery risk factors Surgery 40-60 no risk factors 0.1-0.4% 1-2% 2-4% 10-20 % Moderate Risk Minor Surgery < 40 no risk factors <0.01% 0.2% 0.4% 2% Low Risk Fatal Clinical Proximal Calf PE, % DVT, %

Collins NEJM 1988; 318:1162-73 0 30 40 50 60 70 20 10 C ontrol Heparin Screening DVT Fatal PE Percentage 60.5 20.3 1.9 0.6 Relative risk reduction 67% Relative risk reduction 68%

Significant Risk Factors and Odds Ratios for Venous Thromboembolism Developed From the National Trauma Data Bank Knudson Ann Surg 2004; 240:490-98 Odds Ratio (95% CI) Risk Factor (Number at Risk) 4.32 (3.91 – 4.77) *Major surgical procedure (n=73,974) 1.95 (1.62 – 2.34) Shock on admission (BP<90 mm Hg) (n=18,510) 7.93 (5.83 – 10.78) *Venous injury (n=1450) 10.62 (9.32 – 12.11) *Ventilator days > 3 (n=13,037) 2.59 (2.31 – 2.90) *Head injury (AIS score  3) (n=52,197) 3.39 (2.41 – 4.77) Spinal cord injury with paralysis (n=2852) 3.16 (2.85 – 3.51) *Lower extremity fracture (n=63,508) 2.93 (2.01 – 4.27) Pelvic fracture (n=2707) 2.29 (2.07 – 2.55) *Age  40y (n=178,851)

Anti-Xa Activity After Enoxaparin 40 mg SQ 1.0 Time (hours) Anti Xa activity (U/ml) 0 3 6 9 12 0 0.2 0.4 0.6 0.8 Ward (Group 2), n=13 ICU patients (Group 1), n=16 Priglinger CCM 2003; 31:1405-09

Venous Thromboembolism in ICU Pathophysiology of Pulmonary Embolism

Major Pulmonary Embolism mPAP - LVEDP PVR = CO Pulmonary Artery Pressure Q = Flow = Cardiac Output Incremental Resistance Mean Closing Pressure P 2 - P 1 Q = R mPAP - LVEDP CO = PVR

Major Pulmonary Embolism Pulmonary Artery Pressure Q = Flow = Cardiac Output Effect of Pulmonary Embolism Mean Closing Pressure Incremental Resistance

Venous Thromboembolism in ICU Pulmonary Embolism Diagnostics

Canadian Score for Pre-test Probability Wells Throm Haemost 2000; 83:416-420. Creating the Score 1.0 Malignancy (on treatment, treated in thep past 6 mo, or palliative 1.0 Hemoptysis 1.5 Previous DVT/PE 1.5 Immobilization or surgery in the previous 4 wk 1.5 Heart rate >100 beats/min 3.0 An alternative diagnosis is less likely than PE 3.0 Suspected DVT Points Criteria High 7 66.7 >6 points Moderate 53 20.5 3-6 points Low 40 3.6 0-2 points Interpretation of Risk Patients with this Score, % Mean Probability of PE, % Score Range Interpretation of the Score

Clinical Gestalt vs Prediction Rules “ Clinical gestalt of experienced clinicians and prediction rules used by physicians of varying experience have shown similar accuracy in discriminating among patients who have a low, moderate or high pretest probability of PE” Chandilal JAMA 2003; 290:2849-2858 Prediction Rules Clinical Gestalt 38% - 98% 46% - 91% High 16% - 46% 26% - 47% Moderate 3% - 28% 8% - 19% Low Rate Pulmonary Embolism Rate Pulmonary Embolism Pretest Prob

Diagnostic Approach to Pulmonary Embolism High Clinical Probability CT Angio Positive CT Diagnosis confirmed Negative CT Duplex Ultrasound Positive Negative Diagnosis Confirmed Pulmonary Angiography Positive Negative Diagnosis Excluded Diagnosis Confirmed Fedullo NEJM 2003; 349:1247-56

Diagnostic Strategies for Excluding Pulmonary Embolism with Upper 95% Confidence Limit of 3% or less and 3 month risk Marieke Ann Int Med 2003; 138:941-951 0.2 (0.8) Normal D-dimer low clinical probability 0.0 (1.8) Normal D-dimer 0.6 (1.2) Normal lung scan, normal legs 0.9 (2.3) Normal lung scan 0.8 (2.1) Normal pulmonary angiogram 3-month Risk for VTE complications (upper 95% CL) Diagnostic Strategy Initial Evaluation

Venous Thromboembolism in ICU Pulmonary Embolism Therapeutics

Massive Pulmonary Embolism Therapeutics Heparin Thrombolytics Embolectomy Vena Caval filters Standard Bolus Catheter Surgical

Thrombolytic Therapy-Randomized Trials Heparin Lysis 3.4% 3.4% 2.9% 2.2% 256 Konstantinides 2002 0% 0% -- 100% 8 Sanchez 1995 0% 0% 9% 4% 101 Goldhaber 1993 0% 3% 0% 0% 58 Levine 1990 -- 11% -- 0% 13 PIOPED 1990 0% 0% 0% 0% 30 Marini 1988 -- 0% -- 9% 20 Ly 1978 -- 0% -- 8% 30 Tibbutt 1974 15% 9% 19% 7% 160 UPET 1970 Recurrent Mortality Recurrent Mortality # Study