Thromboprophylaxis in ICU

VTE (DVT+PE) in critical care patients

• Common, often unrecognized & overlooked

• Significant morbidity & mortality

• PE, if not fatal can result in PHT

• DVT can give rise to PTS

• Risk & prevention poorly characterized

• Evidence based guidelines not available

• Existing guidelines not suitable

• Benefit/ Risk ratio different among groups

Overview

• Risks & Prevalence of VTE in critical care

• Available trials of Thromboprophylaxis

• Practical approach to prevention of VTE

VTE in critical care units: Risks

• Massive PE usually occurs without warning & often no potential to resuscitate

• In most deaths,not considered even cause

• ICU deaths ► Postmortem examination:

PE reported in 13% & caused death in 3%

“Vast majority of pts have a major risk factor & most have multiple risk factors”Geerts W, Selby R. Prevention of VTE in ICU. Chest 2003; 124: 357-363.

Risk factors for VTE in critically ill pts

*Factors present before ICU admission ߂• Recent Surgery,Trauma, Burns, Sepsis• Malignancy & its treatment• Immobilization/bed rest, stroke, spinal injury• Advanced age, Heart/ Respiratory failure• Previous VTE• Pregnancy, Puerperium, Estrogens* Some of these risk factors predate admission to the

ICU

Risk factors for VTE in critically ill patients

Additional factors acquired in ICU ߂• Immobilization• Central venous lines• Sepsis, surgical procedures• Pharmacologic sedation/ Paralysis• Mechanical Ventilation• Vasopressor, heart failure • Renal dialysis• Depletion of endogenous anticoagulants

ICU acquired DVT■ Majority of DVT occur in first 5 d of ICU care

Four Independent risk factors:• Personal or family H/O VTE• End-stage renal disease• Platelet transfusion• Vasopressor use

Cook D et al. DVT in medical-surgical critically ill patients. Crit Care Med. 2005;33:1565-1571

Prospective studies of DVT rates in critical care patients not receiving prophylaxis

SourceMoser

(1981)Cade

(1982)

Kapoor (1999)

Fraisse

(2000)

Cook (2005)

ICU setting

Respiratory ICU

General ICU

Medical ICU

Ventilated

COPDGeneral

ICU

DesignProspective

cohortBlinded

RCTBlinded

RCTBlinded M/C

RCTProspect

RCT

DVT Scre test

Fg LS for

3-6 dFg LS for

4-10 dSDU Venography DUS

Patients, No.

23 60 390 85 261

DVT % 13 29 31 28 10

Consequences of asymptomatic DVT

• Unsuspected DVT may be present prior to admission to ICU

• DUS documented DVT have greater frequency of PE (11.5% vs. 0%, p=0.01)

• Even small PE poorly tolerated by critically ill, reduced cardioresp reserve patients

Ibrahim EH et al. DVT during prolonged mechanical ventilation despite prophylaxis. Crit Care Med 2002.

Absolute risk of DVT in hospitalized patients*

Patient Group DVT Prevalence, %

Medical patients 10-20

General surgery 15-40

Major gynaecologic surgery 15-40

Major urologic surgery 15-40

Neurosurgery 15-40

Stroke 20-50

Hip or Knee Arthroplasty, Hip fracture surgery 40-60

Major trauma 40-80

Spinal cord injury 60-80

Critical Care Patients 10-80* Rates based on objective diagnostic testing for DVT in patients not receiving thromboprophylaxis.

Rationale for Thromboprophylaxis

• High prevalence of VTE

• Consequences of un-prevented VTE

• Efficacy & effectiveness of prophylaxis

Diagnosis of DVT

■ Clinical examination: often unreliable

■ Objective testing: Noninvasive & Invasive• Fibrinogen leg scanning or Fg uptake test• Impedance Plethysmography• Venous Doppler ultrasound (DUS) • d-dimer assays & Venography• Spiral CT scan, Nuclear scan, V/Q scan• Pulmonary angiogram, MR venography

Pharmacoprophylaxis: Anticoagulants

� Heparin & its derivatives:

• Unfractionated Heparin (UFH) or LDH

• Low molecular weight heparin (LMWH)

• Fondaparinux

Vitamin K antagonists: Warfarin

Direct thrombin inhibitors:

Argatroban, Ximelagatran

Mechanical methods of prophylaxis

Graduated compression stockings (GCS)� Intermittent pneumatic compression (IPS)� Venous foot pump� IVC filters�� Thrombolytic therapy for acute DVT

Thromboprophylaxis studies in ICU

• PE is a common preventable cause of death.

■ Highest ranked safety practice:

“Appropriate use of prophylaxis to prevent VTE in patients at risk”

• Thromboprophylaxis reduces adverse patient outcome & overall costs.Agency for healthcare research & quality:

Shojania KG et al. Making health care safer: A critical analysis of patient safety practices. Evidence report. 2003

Thromboprophylaxis trials in ICU patients

Intervention DVT, No./Total Patients (%)

Source Method of Diagnosis

Control Experimental Control Experiment

Cade (1982)

Fg LS for 4 -10 d

Placebo Heparin, 5,000 U SC

bid

NR/NR (29) NR/NR

(13)

Kapoor et al

(1999)

DUS on admission & every 3 d

Placebo Heparin, 5,000 U SC

bid

122/390 (31) 44/401

(11)

Fraisse et al

(2000)

Venography before day

21

Placebo Nadroparin, approx 70

AXa U/Kg SC qd

24/85

(28)

13/84

(15)

Goldhaber et al (2000)

DUS on days 3, 7, 10

& 14

Heparin, 5000 U SC bid

Enoxaparin, 30 mg SC bid

NR/NR (13) NR/NR (16)

Thromboprophylaxis use in ICU

• Number of studies have assessed use of Thromboprophylaxis in ICU

• Average compliance among 3654 patients was 69% (range 33-100%)

• Intensivists consider VTE an important Problem, worthy of preventive intervention

• 31% pts had no prophylaxis, & “accepted” compliance reported in only one study

Thromboprophylaxis utilization in ICU Source Type of ICU Admission

No.Prophylaxis

Use, %

Keane et at (1994) Medical 161 33

Peters et al (1997) Medical/Surgical 100 45

Ibrahimbacha et al (1998) Medical 145 53

Ibrahimbacha et al (1998) Medical 71 86

Levi et al (1998) Not reported 584, 598 64, 99

Ryskamp & Trottier (1998) Medical/Surgical 209 86

Cook et al (2000) Medical/Surgical 93 63

Gurkin et al (2000) Surgical 329 74

Rodriguez et al (2000) Medical 45 78

Thurm et al (2000) Medical 24 100

Cook et al (2001) Surgical 89 98

Lentine et al (2002) Medical 342 74

Mysliwiec et al ( 2002) Medical 116 84

Rocha & Tapson ( 2002) Medical 103 76

Prevention of VTE in critical care

• High risk of VTE in critically ill patients

• Policy for Thromboprophylaxis essential

• Both LDH & LMWH efficacious in reducing asymptomatic DVT

• Advantage of LMWH over LDH include its once daily dose & lower risk of HIT

• Effective & safe methods for other patient groups,likely to be relevant to ICU pts

ACCP guidelines: critical care

• Assessment & Review of VTE risk

• Thromboprophylaxis essential, ASAP

• Initiation & Selection of specific methods, should be based on risk

• Anticoagulant based prophylaxis more efficacious than mechanical

• Poor compliance with mech. methods

ACCP guidelines: critical care

• LDH: Low to Moderate thrombosis risk pts

• LMWH: High risk patients

• Mechanical Prophylaxis (GCS &/or IPC): High bleeding risk

patients

• Combined methods:

Greater protection, than either alone

• Sequential prophylaxis: Relevant patients

Principles of Thromboprophylaxis

• Should be reviewed daily & changed if necessary, depending on clinical status

• Should not be interrupted for procedures or Surgery, unless high bleeding risk

• Insertion/removal of epidural catheters to coincide with nadir of anticoagulant effect

Principles of Thromboprophylaxis

• Routine screening for asymptomatic DVT: Neither effective, nor cost effective

• Single proximal DUS for high risk patients:

■ Positive: Therapeutic intervention

■ Negative: Prophylaxis

• Should be continued at discharge from ICU

• Each ICU should have written policy

• Policy updated as new evidence emerges

Principles of thromboprophylaxis

• Compliance with policy should be enhanced:

■ Regular interactive education

■ Active involvement of pharmacist

■ Preprinted orders/ Reminders

■ Computer decision support systems

■ Consult hematology/ thrombosis service

• Adherence to policy assessed with audits

• Local quality improvement efforts

Initial Prophylaxis considerations in ICU pts.

Critical Care Admission

? Bleeding Risk

HIGH Mechanical prophylaxis (GCS &/ or IPC) Delay prophylaxis until high bleeding risk resolves Screen for proximal DVT with DUS in high risk patients.

USUAL Low dose heparin Low molecular weight heparin Combined anticoagulant and mechanical prophylaxis

Prophylaxis recommendations in ICU pts.

Bleeding Risk

Thrombosis Risk

Prophylaxis Recommendations

Low Moderate LDH ( heparin 5,000 U SC bid)

Low High LMWH ( 4,000-6,000 AXa U/d)

HighModerate GCS or IPC → LDH when bleeding

risk decreases

High High GCS or IPC → LMWH when bleeding risk decreases

Prevention of VTEEvidence based guidelines:

1. Mechanical methods be used primarily in pts at high risk of bleeding or as adjunct to anticoagulants, and ensure proper use & optimal compliance.

2. They recommend against use of aspirin alone as prophylaxis for any pt group.

3. For each antithrombotic agent, clinician should consider the manufacturers suggested dosing guidelines.

Evidence based guidelines4. Consider renal impairment when deciding

doses of antithrombotics, cleared by kidneys, particularly in elderly & pts at high risk for bleeding

5. In all pts undergoing neuraxial blocks, exercise special caution when using anticoagulants

Geerts WH, Pineo GF, Heit JA et al. Prevention of VTE: the seventh ACCP conference on antithrombotic & thrombolytic therapy. Chest 2004. 126: 338-400

Conclusion

• Careful studies of VTE in ICU patients has lagged behind other patients groups:

■ Marked heterogeneity among critically ill pts in their risks

■ Length of stay & Survival

■ Routine screening difficult & less reliable

• High thrombosis risk in ICU pts, warrant prophylaxis.

Conclusion

• More research required in this area• Guidance from ICU specific & other

studies• Routine use of thromboprophylaxis,

most effective strategy:■ Decrease the consequences of VTE ■ Improve patients outcome■ Reduce cost following critical illness

THANKS