Transcript Grade 2C

Prevention of Venous Thromboembolism
in Nonorthopedic Surgical Patients
----Antithrombotic Therapy and Prevention of
Thrombosis, 9th ed: American College of
Chest Physicians Evidence-Based Clinical
Practice Guidelines
Copyright: American College of Chest Physicians 2012©
Learning Objectives
• Describe a formal methodology for the evidencebased development of clinical practice guidelines
• Review select studies of venous thromboembolism
(VTE) prevention in surgical patients, as well as the
limitations of the studies
• Summarize recommendations for VTE prevention in
specific surgical populations
THERE IS NO LEVEL I EVIDENCE
VTE
• Thrombosis: the formation or presence of a blood
clot within a blood vessel
Merriam-Webster’s Medical Dictionary
• Embolism: obstruction or occlusion of a vessel by
a transported clot or vegetation, a mass of bacteria,
or other … material
Stedman’s Medical Dictionary
Deep Vein Thrombosis (DVT)
Pulmonary Embolism (PE)
Goldhaber SZ. N Engl J Med. 1998;339(2):93-104.
Pulmonary Angiography
Bliss et al. N Engl J Med. 2002;347(23):1876-1881.
CT Pulmonary Angiography
Goldhaber SZ. N Engl J Med. 1998;339(2):93-104.
Kearon SF. CMAJ. 2003;168:183-194.
Risk Factors: Virchow’s Triad
• Stasis
– Immobility
– Congestive heart failure
• Injury
– Surgery (especially major orthopedic and pelvic)
– Trauma
• Thrombophilia
– Cancer
– Oral contraceptives
– Hereditary states (factor V Leiden, PT mutations)
VTE Epidemiology
• Most common cause of preventable death in
hospitalized patients
• Risk of fatal perioperative PE ~0.8%
International Multicentre Trial. Lancet. 1975
• 150,000 to 200,000 deaths per year; ~1/3 in
perioperative patients
Horlander et al. Arch Intern Med. 2003;163:1711-1717.
• AHRQ: VTE prevention is number 1 priority to
improve safety in hospitals
Many Surgical Patients At-Risk
• 2003 Nationwide Inpatient Sample
• Adult surgical patients, LOS ≥2 days
• 7.8 million surgical discharges
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•
•
•
44% low risk
15% moderate risk
24% high risk
17% very high risk
• 4.4 million at risk for VTE
Anderson et al. Am J Hematol. 2007;82:777-782.
Million Women Study
• Population-based, prospective cohort study
• 947,454 middle-aged women in U.K. enrolled
between 1996-2001
• Mean follow-up 6.2 years
• 239,614 underwent surgery
– 5,419 readmitted for VTE within 12 weeks of inpatient
surgery (2.25%)
– 270 deaths from fatal PE
Sweetland et al. BMJ. 2009;339:b4583.
Additional Challenges
• Numerous comparisons
– LDUH, LMWH, fondaparinux, low-dose ASA, high-dose
ASA, ES and IPC vs no prophy
– Mechanical vs pharmacologic
– Add mechanical to pharmacologic
– 16 unique evidence profiles and still counting!
• Numerous surgical populations
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–
–
–
Abdomen and pelvis (vascular, bariatric)
Neurosurgery (craniotomy, spine)
Trauma (TBI, SCI, other major trauma)
Cardiac, thoracic, other…
VTE Consequences
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•
•
•
•
•
•
Leg swelling, discomfort (DVT)
Dyspnea, chest pain, hemoptysis, hypoxemia (PE)
Extended hospital LOS
Fatal PE (RV failure)
≥3 months of anticoagulant treatment
Postphlebitic syndrome
Chronic thromboembolic pulmonary HTN (~4%)
Pengo et al. N Engl J Med. 2004;350:2257-2264.
VTE Prevention
• Targets one or two legs of Virchow’s triad:
– Mechanical prophylaxis (stasis)
• Elastic compression stockings
• Intermittent pneumatic compression devices
VTE Prevention
• Targets one or two legs of Virchow’s triad:
– Mechanical prophylaxis (stasis)
• Elastic compression stockings
• Intermittent pneumatic compression devices
– Pharmacological prophylaxis (hypercoagulability)
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•
•
•
Unfractionated heparin
Low-molecular-weight heparins
Fondaparinux
Aspirin (?)
Guidelines Defined
“Systematically developed statements to assist
practitioners and patient decisions about
appropriate health care for specific
circumstances.”
Field MJ, Lohr KN (eds). Clinical Practice Guidelines: Directions for a New
Program. Institute of Medicine, Washington, DC: National Academy Press,
1990.
Guidelines and
Performance Measures
• Public reporting
– Cardiac surgery outcomes in New York State
• Pay for performance
– Reward “good” behavior
– CMS: several VTE prevention P4P measures
• Registries
– Accreditation
– Facilitate quality improvement
Case Scenario
• 50 year-old woman scheduled to undergo elective
laparoscopic cholecystectomy
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–
–
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PMH notable for moderate emphysema
No personal or family history of VTE
Medications: Spiriva®, albuterol
Stopped smoking 1 year ago
• What should we recommend for perioperative
VTE prophylaxis in this patient?
Conceptual Framework
• VTE pharmacoprophylaxis involves a tradeoff
between preventing thrombosis and causing bleeding
• When making tradeoffs, need to compare absolute
risks of thrombosis and bleeding
• In order to determine absolute risks (eg, number of
symptomatic DVTs prevented), need to know the
following:
– Baseline risk in control/comparison group
– Relative risk for intervention vs control
• When making tradeoffs, also need to assign values to
events being compared
Calculating Absolute Effects
Scenario
Any surgical
patient
Baseline
Risk of
sVTE
(%)
Baseline
Risk of
Major
Bleeding
(%)
?
?
RR VTE RR Bleed Number
Number
(UFH vs (UFH vs
of VTEs
of Bleeds
no
no
Prevented
Caused
Prophy) Prophy) (per 1000) (per 1000)
0.50
2.0
?
?
Calculating Absolute Effects
Scenario
Baseline
Risk of
sVTE
(%)
Baseline
Risk of
Major
Bleeding
(%)
RR VTE
(UFH vs
no
Prophy)
Moderate VTE/
Average Bleed
2
1
10
10
Moderate VTE/
High bleed
2
2
10
20
High VTE/
average bleed
4
1
20
10
High VTE/
high bleed
4
2
20
20
0.50
RR Bleed
(UFH vs
no
Prophy)
2.0
Number of
VTEs
Prevented
(per 1000)
Number of
Bleeds
Caused
(per 1000)
Estimating Baseline Risk
• Retrospective, observational study
• Large sample (n=8,216) of consecutively admitted
“general” surgical inpatients
• Tertiary center
• Measured clinically suspected, objectively
confirmed VTE over 30 days
• Risk stratification according to patient-specific
and procedure-specific characteristics
• Prophylaxis nonuniform but reported
Baseline Risk of VTE
Case Scenario
• 50-year-old woman scheduled to undergo elective
laparoscopic cholecystectomy
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–
–
–
PMH notable for moderate COPD
No personal or family history of VTE
Medications: Spiriva®, albuterol
Stopped smoking 1 year ago
• What should we recommend for perioperative
VTE prophylaxis in this patient?
Baseline Risk of VTE (Caprini Score)
4
Baseline Risk of VTE
Bahl et al. Ann Surg. 2010;251:344-350.
Baseline Risk of VTE
52%
0.1%
10%
37%
Bahl et al. Ann Surg. 2010;251:344-350.
IMT Results: Bleeding
Outcome
LDUH
N=2045
No Prophylaxis
N=2076
RR
4
5
0.81 (0.21 to 3.0)
Excessive intra-op
182
126
1.47 (1.18 to 1.82)
Wound hematoma
158
117
1.37 (1.09 to 1.73)
202/731
202/744
1.02 (0.86 to 1.20)
Fatal bleed
Transfusion
Calculating Absolute Effects
Scenario
Moderate
VTE-Risk
Patient
Baseline
Risk of
sVTE
RR VTE
(UFH vs
no
Prophy)
(%)
Baseline
Risk of
Major
Bleeding
(%)
RR
Bleed
(UFH vs
no
Prophy)
2.6
1.2
0.59
1.57
Number
Number
of VTEs
of Bleeds
Prevented Caused
(per 1000) (per 1000)
11
7
Evidence Synthesis:
Tradeoffs between desirable and
undesirable outcomes
Recommendation
For general surgical patients at moderate risk for
venous thromboembolism who are not at high risk
for perioperative bleeding, we suggest low-dose
unfractionated heparin (Grade 2B) over no
prophylaxis.
Recommendation
For general surgical patients at high risk for
venous thromboembolism who are not at high risk
for perioperative bleeding, we recommend use of
low-dose unfractionated heparin (Grade 1B) over
no prophylaxis.
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For general and abdominal-pelvic surgery patients at very low
risk for VTE (< 0.5%; Rogers score, < 7; Caprini score, 0)
No specific pharmacologic (Grade 1B) or mechanical (Grade 2C)
prophylaxis be used other than early ambulation.
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For general and abdominal-pelvic surgery patients at low risk
for VTE (~ 1.5%; Rogers score, 7-10; Caprini score, 1-2)
Suggest mechanical prophylaxis, preferably with intermittent
pneumatic compression (IPC), over no prophylaxis (Grade 2C).
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For general and abdominal-pelvic surgery patients at moderate
risk for VTE (~ 3.0%; Rogers score, > 10; Caprini score, 3-4)
who are not at high risk for major bleeding complications:
Suggest LMWH (Grade 2B), LDUH (Grade 2B), or mechanical
prophylaxis, preferably with IPC (Grade 2C), over no
prophylaxis.
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For general and abdominal-pelvic surgery patients at moderate
risk for VTE (3.0%; Rogers score, > 10; Caprini score, 3-4)
who are at high risk for major bleeding complications or those
in whom the consequences of bleeding are thought to be
particularly severe
Suggest mechanical prophylaxis, preferably with IPC, over no
prophylaxis (Grade 2C).
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For general and abdominal-pelvic surgery patients at high risk
for VTE (~ 6.0%; Caprini score, ≥ 5) who are not at high risk
for major bleeding complications
Recommend pharmacologic prophylaxis with LMWH (Grade
1B) or LDUH (Grade 1B) over no prophylaxis.
Suggest that mechanical prophylaxis with elastic stockings or
IPC should be added to pharmacologic prophylaxis (Grade 2C).
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For high-VTE-risk patients undergoing abdominal or pelvic
surgery for cancer who are not otherwise at high risk for major
bleeding complications
Recommend extended-duration pharmacologic prophylaxis (4
weeks) with LMWH over limited-duration prophylaxis (Grade
1B).
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For high-VTE-risk general and abdominal-pelvic surgery
patients who are at high risk for major bleeding complications
or those in whom the consequences of bleeding are thought to
be particularly severe
We suggest use of mechanical prophylaxis, preferably with
IPC, over no prophylaxis until the risk of bleeding diminishes
and pharmacologic prophylaxis may be initiated (Grade 2C).
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For general and abdominal-pelvic surgery patients at high risk
for VTE (6%; Caprini score, ≥ 5) in whom both LMWH and
unfractionated heparin are contraindicated or unavailable and
who are not at high risk for major bleeding complications
Suggest low-dose aspirin (Grade 2C), fondaparinux (Grade 2C),
or mechanical prophylaxis, preferably with IPC (Grade 2C),
over no prophylaxis.
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For general and abdominal-pelvic surgery patients, we suggest
that an inferior vena cava (IVC) filter should not be used for
primary VTE prevention (Grade 2C).
Patients Undergoing General, GI, Urologic, Gynecologic, Bariatric, Vascular,
Plastic, or Reconstructive Surgery
For general and abdominal-pelvic surgery patients, we suggest
that periodic surveillance with venous compression ultrasound
(VCU) should not be performed (Grade 2C).
Major Trauma
For major trauma patients, we suggest use of LDUH (Grade
2C), LMWH (Grade 2C), or mechanical prophylaxis, preferably
with IPC (Grade 2C), over no prophylaxis.
Patients With Major Trauma: Traumatic Brain Injury, Acute Spinal Injury,
and Traumatic Spine Injury
For major trauma patients at high risk for VTE (including
those with acute spinal cord injury, traumatic brain injury, and
spinal surgery for trauma), we suggest adding mechanical
prophylaxis to pharmacologic prophylaxis (Grade 2C) when not
contraindicated by lower extremity injury.
Patients With Major Trauma: Traumatic Brain Injury, Acute Spinal Injury,
and Traumatic Spine Injury
For major trauma patients, we suggest that periodic
surveillance with VCU should not be performed (Grade 2C).
Major Trauma
For major trauma patients in whom LMWH and LDUH are
contraindicated, we suggest mechanical prophylaxis, preferably
with IPC, over no prophylaxis (Grade 2C) when not
contraindicated by lower-extremity injury. We suggest adding
pharmacologic prophylaxis with either LMWH or LDUH when
the risk of bleeding diminishes or the contraindication to
heparin resolves (Grade 2C).
Major Trauma
For major trauma patients, we suggest that an IVC filter
should not be used for primary VTE prevention (Grade 2C).
Patients Undergoing Cardiac Surgery
For cardiac surgery patients with an uncomplicated
postoperative course, we suggest use of mechanical
prophylaxis, preferably with optimally applied IPC, over either
no prophylaxis (Grade 2C) or pharmacologic prophylaxis
(Grade 2C).
Patients Undergoing Cardiac Surgery
For cardiac surgery patients whose hospital course is prolonged
by one or more nonhemorrhagic surgical complications, we
suggest adding pharmacologic prophylaxis with LDUH
or LMWH to mechanical prophylaxis (Grade 2C).
Patients Undergoing Thoracic Surgery
For thoracic surgery patients at moderate risk for VTE who
are not at high risk for perioperative bleeding, we suggest
LDUH (Grade 2B), LMWH (Grade 2B), or mechanical
prophylaxis with optimally applied IPC (Grade 2C) over no
prophylaxis.
Remarks: Three of the seven authors favored a strong (Grade 1B)
recommendation in favor of LMWH or LDUH over no prophylaxis
in this group.
Patients Undergoing Thoracic Surgery
For thoracic surgery patients at high risk for VTE who are not
at high risk for perioperative bleeding, we suggest LDUH
(Grade 1B) or LMWH (Grade 1B) over no prophylaxis. In
addition, we suggest that mechanical prophylaxis with ES or
IPC should be added to pharmacologic prophylaxis (Grade 2C).
Patients Undergoing Thoracic Surgery
For thoracic surgery patients who are at high risk for major
bleeding, we suggest use of mechanical prophylaxis, preferably
with optimally applied IPC, over no prophylaxis until the risk
of bleeding diminishes and pharmacologic prophylaxis may be
initiated (Grade 2C).
Patients Undergoing Craniotomy
For craniotomy patients, we suggest that mechanical
prophylaxis, preferably with IPC, be used over no prophylaxis
(Grade 2C) or pharmacologic prophylaxis (Grade 2C).
Patients Undergoing Craniotomy
For craniotomy patients at very high risk for VTE (eg, those
undergoing craniotomy for malignant disease), we suggest
adding pharmacologic prophylaxis to mechanical prophylaxis
once adequate hemostasis is established and the risk of bleeding
decreases (Grade 2C).
Patients Undergoing Spinal Surgery
For patients undergoing spinal surgery, we suggest mechanical
prophylaxis, preferably with IPC, over no prophylaxis (Grade
2C), unfractionated heparin (Grade 2C), or LMWH (Grade
2C).
Patients Undergoing Spinal Surgery
For patients undergoing spinal surgery at high risk for VTE
(including those with malignant disease or those undergoing
surgery with a combined anterior-posterior approach), we
suggest adding pharmacologic prophylaxis to mechanical
prophylaxis once adequate hemostasis is established and the
risk of bleeding decreases (Grade 2C).
Endorsing Organizations
This guideline has received the endorsement of the
following organizations:
•
•
•
•
•
American Association for Clinical Chemistry
American College of Clinical Pharmacy
American Society of Health-System Pharmacists
American Society of Hematology
International Society of Thrombosis and Hemostasis
Acknowledgement of Support
The ACCP appreciates the support of the following organizations
for some part of the guideline development process:
Bayer Schering Pharma AG
National Heart, Lung, and Blood Institute (Grant No.R13 HL104758)
With educational grants from
Bristol-Myers Squibb and Pfizer, Inc.
Canyon Pharmaceuticals, and
sanofi-aventis U.S.
Although these organizations supported some portion of the development
of the guidelines, they did not participate in any manner with the scope,
panel selection, evidence review, development, manuscript writing,
recommendation drafting or grading, voting, or review. Supporters did not
see the guidelines until they were published.