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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
߂Factors 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
Source Moser Cade Kapoor Fraisse Cook
(1981) (1982) (1999) (2000) (2005)

ICU Respiratory General Medical Ventilated General


setting ICU ICU ICU COPD ICU

Design Prospectivec Blinded Blinded Blinded M/C ProspectR


ohort RCT RCT RCT CT

DVT Scre Fg LS for Fg LS for 4- SDU Venography DUS


test 3-6 d 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 4 Placebo Heparin, 5,000 NR/NR (29) NR/NR
(1982) -10 d U SC bid (13)

Kapoor et DUS on Placebo Heparin, 5,000 122/390 (31) 44/401


al (1999) admission & U SC bid (11)
every 3 d
Fraisse et Venography Placebo Nadroparin, 24/85 13/84
al (2000) before day 21 approx 70 AXa (28) (15)
U/Kg SC qd

Goldhabe DUS on days Heparin, Enoxaparin, 30 NR/NR (13) NR/NR (16)


r et al 3, 7, 10 & 14 5000 U mg SC bid
(2000) 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)

High Moderate GCS or IPC → LDH when bleeding


risk decreases

High High GCS or IPC → LMWH when


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
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