Thromboprophylaxis in ICU

Dr. Rajnish K. Jain,

M.D.
Professor & Head,
Anaesthesiology & Critical Care,
BMHRC, BHOPAL
 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
߂ Factors present before ICU admission*
• 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

߂ Additional factors acquired in ICU

• 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
Moser Cade Kapoor Fraisse Cook
Source (1981) (1999) (2005)
(1982) (2000)

ICU Respiratory General Medical Ventilated General

setting ICU ICU ICU COPD ICU

Prospective Blinded Blinded Blinded M/C Prospect

Design
cohort RCT RCT RCT RCT

DVT Fg LS for Fg LS for

SDU Venography DUS
Scre test 3-6 d 4-10 d
Patients,
23 60 390 85 261
No.
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 Control Experimental Control Experiment

Diagnosis
Cade Fg LS for Placebo Heparin, NR/NR (29) NR/NR
(1982) 4 -10 d 5,000 U SC (13)
bid
Kapoor DUS on Placebo Heparin, 122/390 (31) 44/401
et al admission & 5,000 U SC (11)
(1999) every 3 d bid
Fraisse Venography Placebo Nadroparin, 24/85 13/84
et al before day approx 70 (28) (15)
(2000) 21 AXa U/Kg SC
qd
Goldha DUS on Heparin, Enoxaparin, NR/NR (13) NR/NR (16)
ber et al days 3, 7, 10 5000 U 30 mg SC bid
(2000) & 14 SC bid
 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 Prophylaxis
No. 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 USUAL
 Mechanical prophylaxis  Low dose heparin
(GCS &/ or IPC)  Low molecular weight
 Delay prophylaxis until heparin
high bleeding risk resolves  Combined anticoagulant
 Screen for proximal DVT
with DUS in high risk and mechanical
patients. prophylaxis
 Prophylaxis recommendations in ICU pts.
Bleeding Thrombosis
Prophylaxis Recommendations
Risk Risk
Low Moderate LDH ( heparin 5,000 U SC bid)

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

Moderate GCS or IPC → LDH when bleeding

High
risk decreases

GCS or IPC → LMWH when

High High
bleeding risk decreases
 Prevention of VTE
Evidence 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 guidelines
4. 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