CONSENSUS STATEMENTS
Second Consensus Conference on Neuraxial Anesthesia and Anticoagulation
April 25-28, 2002
Regional
Anesthesia in the Anticoagulated Patient: Defining the
Risks - TOP
Introduction
Numerous studies have documented the safety
of neuraxial anesthesia and analgesia in the anticoagulated
patient. Patient management is based on appropriate
timing of needle placement and catheter removal relative
to the timing of anticoagulant drug administration.
Familiarity with the pharmacology of hemostasis-altering
drugs, the clinical studies involving patients undergoing
neuraxial blockade while receiving these medications,
as well as the case reports of spinal hematoma will
guide the clinician in management decisions.
New challenges in the management of the
anticoagulated patient undergoing neuraxial blockade
have arisen as medical standards for the prevention
of perioperative venous thromboembolism were established.
Likewise, as more efficacious anticoagulants and antiplatelet
agents have been introduced, patient management has
become more complex. In response to these patient safety
issues, the American Society of Regional Anesthesia
and Pain Medicine convened its Second Consensus Conference
on Neuraxial Anesthesia and Anticoagulation. It is important
to note that although the consensus statements are based
on a thorough evaluation of the available information,
in some cases, data are sparse. Variances from recommendations
contained in this document may be acceptable based on
the judgment of the responsible anesthesiologist. The
consensus statements are designed to encourage safe
and quality patient care, but cannot guarantee a specific
outcome. They are also subject to timely revision as
justified by evolution of information and practice.
Finally, the current information focuses on neuraxial
blocks and anticoagulants; the risk following plexus
and peripheral techniques remains undefined. Conservatively,
the Consensus Statements on Neuraxial Anesthesia and
Anticoagulation may be applied to plexus and peripheral
techniques. However, this may be more restrictive than
necessary.
The original manuscript developed from
the Consensus Conference held during the Annual Spring
Meeting on Regional Anesthesia, April 25-28, 2002 in
Chicago, Illinois is published in the May 2003 issue
of Regional Anesthesia and Pain Medicine (Reg Anesth
Pain Med 2003;28:172-97) . The full-length document,
used in conjunction with these abridged consensus statements,
provides the necessary background to a more complete
understanding of the clinical issues discussed at the
Consensus Conference.
Regional
Anesthesia in the Anticoagulated Patient - TOP
Anesthetic Management
of the Patient Receiving Thrombolytic Therapy
Patients receiving fibrinolytic/thrombolytic
medications are at risk of serious hemorrhagic events,
particularly those who have undergone an invasive procedure.
Consensus statements are based on the profound effect
on hemostasis, the use of concomitant heparin and/or
antiplatelet agents (which further increase the risk
of bleeding), and the potential for spontaneous neuraxial
bleeding with these medications.
Advances in fibrinolytic/ thrombolytic therapy have
been associated with an increased use of these drugs,
which will require further increases in vigilance.
Ideally, the patient should be queried prior to the
thrombolytic therapy for a recent history of lumbar
puncture, spinal or epidural anesthesia, or epidural
steroid injection to allow appropriate monitoring.
Guidelines detailing original contraindications for
thrombolytic drugs suggest avoidance of these drugs
for 10 days following puncture of noncompressible
vessels. - Preoperative evaluation should determine
whether fibrinolytic or thrombolytic drugs have been
used preoperatively, or have the likelihood of being
used intraoperatively or postoperatively. Patients
receiving fibrinolytic and thrombolytic drugs should
be cautioned against receiving spinal or epidural
anesthetics except in highly unusual circumstances.
Data are not available to clearly outline the length
of time neuraxial puncture should be avoided after
discontinuation of these drugs.
- In those patients who have received
neuraxial blocks at or near the time of fibrinolytic
and thrombolytic therapy, neurological monitoring
should be continued for an appropriate interval. It
may be that the interval of monitoring should not
be more than two hours between neurologic checks.
Furthermore, if neuraxial blocks have been combined
with fibrinolytic and thrombolytic therapy and ongoing
epidural catheter infusion, the infusion should be
limited to drugs minimizing sensory and motor block
to facilitate assessment of neurologic function.
- There is no definitive recommendation
for removal of neuraxial catheters in patients who
unexpectedly receive fibrinolytic and thrombolytic
therapy during a neuraxial catheter infusion. The
measurement of fibrinogen level (one of the last clotting
factors to recover) may be helpful in making a decision
about catheter removal or maintenance.
Regional
Anesthesia in the Anticoagulated Patient - TOP
Anesthetic Management
of the Patient Receiving Unfractionated Heparin
Anesthetic management of the heparinized
patient was established over two decades ago. Initial
recommendations have been supported by in-depth reviews
of case series, case reports of spinal hematoma and
the ASA Closed Claims Project.
- During subcutaneous (mini-dose) prophylaxis
there is no contraindication to the use of neuraxial
techniques. The risk of neuraxial bleeding may be
reduced by delay of the heparin injection until after
the block, and may be increased in debilitated patients
after prolonged therapy. Since heparin-induced thrombocytopenia
may occur during heparin administration, patients
receiving heparin for greater than four days should
have a platelet count assessed prior to neuraxial
block and catheter removal.
- Combining neuraxial techniques
with intraoperative anticoagulation with heparin during
vascular surgery seems acceptable with the following
cautions:
- Avoid the technique in
patients with other coagulopathies.
- Heparin administration should be
delayed for 1 hour after needle placement.
- Indwelling neuraxial catheters
should be removed 2-4 hours after the last heparin
dose and the patient's coagulation status is evaluated;
re-heparinization should occur one hour after
catheter removal.
- Monitor the patient postoperatively
to provide early detection of motor blockade and
consider use of minimal concentration of local
anesthetics to enhance the early detection of
a spinal hematoma.
- Although the occurrence of a bloody
or difficult neuraxial needle placement may increase
risk, there are no data to support mandatory cancellation
of a case. Direct communication with the surgeon
and a specific risk-benefit decision about proceeding
in each case is warranted.
- Currently, insufficient data and experience
are available to determine if the risk of neuraxial
hematoma is increased when combining neuraxial techniques
with the full anticoagulation of cardiac surgery.
Postoperative monitoring of neurologic function and
selection of neuraxial solutions that minimize sensory
and motor block is recommended to facilitate detection
of new/progressive neurodeficits.
- The concurrent use of medications that
affect other components of the clotting mechanisms
may increase the risk of bleeding complications for
patients receiving standard heparin. These medications
include antiplatelet medications, LMWH and oral anticoagulants.
Regional
Anesthesia in the Anticoagulated Patient - TOP
Anesthetic Management
of the Patient Receiving Low Molecular Weight Heparin
(LMWH)
Anesthesiologists in North America can
draw on the extensive European experience to develop
practice guidelines for the management of patients undergoing
spinal and epidural blocks while receiving perioperative
LMWH. All consensus statements contained herein respect
the labeled dosing regimens of LMWH as established by
the FDA. Although it is impossible to devise recommendations
that will completely eliminate the risk of spinal hematoma,
previous consensus recommendations have appeared to
improve outcome. Concern remains for higher dose applications,
where sustained therapeutic levels of anticoagulation
are present.
- Monitoring of the anti-Xa level is
not recommended. The anti-Xa level is not predictive
of the risk of bleeding and is, therefore, not helpful
in the management of patients undergoing neuraxial
blocks.
- Antiplatelet or oral anticoagulant
medications administered in combination with LMWH
may increase the risk of spinal hematoma. Concomitant
administration of medications affecting hemostasis,
such as antiplatelet drugs, standard heparin, or dextran
represents an additional risk of hemorrhagic complications
perioperatively, including spinal hematoma. Education
of the entire patient care team is necessary to avoid
potentiation of the anticoagulant effects.
- The presence of blood during needle
and catheter placement does not necessitate postponement
of surgery. However, initiation of LMWH therapy in
this setting should be delayed for 24 hours postoperatively.
Traumatic needle or catheter placement may signify
an increased risk of spinal hematoma, and it is recommended
that this consideration be discussed with the surgeon.
- Preoperative LMWH
- Patients on preoperative
LMWH thromboprophylaxis can be assumed to have
altered coagulation. In these patients needle
placement should occur at least 10-12 hours after
the LMWH dose.
- Patients receiving higher (treatment)
doses of LMWH, such as enoxaparin 1 mg/kg every
12 hours, enoxaparin 1.5 mg/kg daily, dalteparin
120 U/kg every 12 hours, dalteparin 200 U/kg daily,
or tinzaparin 175 U/kg daily will require delays
of at least 24 hours to assure normal hemostasis
at the time of needle insertion.
- Neuraxial techniques should be
avoided in patients administered a dose of LMWH
two hours preoperatively (general surgery patients),
because needle placement would occur during peak
anticoagulant activity.
- Postoperative LMWH
Patients with postoperative initiation of LMWH thromboprophylaxis
may safely undergo single-injection and continuous
catheter techniques. Management is based on total
daily dose, timing of the first postoperative dose
and dosing schedule.
- Twice daily dosing. This
dosage regimen may be associated with an increased
risk of spinal hematoma. The first dose of LMWH
should be administered no earlier than 24 hours
postoperatively, regardless of anesthetic technique,
and only in the presence of adequate (surgical)
hemostasis. Indwelling catheters should be removed
prior to initiation of LMWH thromboprophylaxis.
If a continuous technique is selected, the epidural
catheter may be left indwelling overnight and
removed the following day, with the first dose
of LMWH administered at least two hours after
catheter removal.
- Single daily dosing. This dosing
regimen approximates the European application.
The first postoperative LMWH dose should be administered
6-8 hours postoperatively. The second postoperative
dose should occur no sooner than 24 hours after
the first dose. Indwelling neuraxial catheters
may be safely maintained. However, the catheter
should be removed a minimum of 10-12 hours after
the last dose of LMWH. Subsequent LMWH dosing
should occur a minimum of 2 hours after catheter
removal.
Regional
Anesthesia in the Anticoagulated Patient - TOP
Regional Anesthetic
Management of the Patient on Oral Anticoagulants
The management of patients receiving warfarin
perioperatively remains controversial. Consensus statements
are based on warfarin pharmacology, the clinical relevance
of vitamin K coagulation factor levels/deficiencies,
and the case reports of spinal hematoma among these
patients.
- Caution should be used when performing
neuraxial techniques in patients recently discontinued
from chronic warfarin therapy. The anticoagulant therapy
must be stopped, (ideally 4-5 days prior to the planned
procedure) and the PT/INR measured prior to initiation
of neuraxial block. Early after discontinuation of
warfarin therapy, the PT/INR reflect predominantly
factor VII levels, and in spite of acceptable factor
VII levels, factors II and X levels may not be adequate
for normal hemostasis. Adequate levels of II, VII,
IX, and X may not be present until the PT/INT is within
normal limits.
- The concurrent use of medications that
affect other components of the clotting mechanisms
may increase the risk of bleeding complications for
patients receiving oral anticoagulants, and do so
without influencing the PT/INR. These medications
include aspirin and other NSAIDs, ticlopidine and
clopidogrel, unfractionated heparin and LMWH.
- For patients receiving an initial dose
of warfarin prior to surgery, the PT/INR should be
checked prior to neuraxial block if the first dose
was given more than 24 hours earlier, or a second
dose of oral anticoagulant has been administered.
- Patients receiving low dose warfarin
therapy during epidural analgesia should have their
PT/INR monitored on a daily basis, and checked before
catheter removal, if initial doses of warfarin are
administered more than 36 hours preoperatively. Initial
studies evaluating the safety of epidural analgesia
in association with oral anticoagulation utilized
mean daily doses of approximately 5 mg of warfarin.
Higher dose warfarin may require more intensive monitoring
of the coagulation status.
- As thromboprophylaxis with warfarin
is initiated, neuraxial catheters should be removed
when the INR is <1.5. This value was derived from
studies correlating hemostasis with clotting factor
activity levels greater than 40%.
- Neurologic testing of sensory and motor
function should be performed routinely during epidural
analgesia for patients on warfarin therapy. The type
of analgesic solution should be tailored to minimize
the degree of sensory and motor blockade. These checks
should be continued after catheter removal for at
least 24 hours, and longer if the INR was greater
than 1.5 at the time of catheter removal.
- An INR > 3 should prompt the physician
to withhold or reduce the warfarin dose in patients
with indwelling neuraxial catheters. We can make no
definitive recommendation for removal of neuraxial
catheters in patients with therapeutic levels of anticoagulation
during neuraxial catheter infusion.
- Reduced doses of warfarin should be
given to patients who are likely to have an enhanced
response to the drug.
Regional
Anesthesia in the Anticoagulated Patient - TOP
Anesthetic Management
of the Patient Receiving Antiplatelet Medications
Antiplatelet medications, including NSAIDs,
thienopyridine derivatives (ticlopidine and clopidogrel)
and platelet GP IIb/IIIa antagonists (abciximab, eptifibatide,
tirofiban) exert diverse effects on platelet function.
The pharmacologic differences make it impossible to
extrapolate between the groups of drugs regarding the
practice of neuraxial techniques.
- There is no wholly accepted test, including
the bleeding time, which will guide antiplatelet therapy.
Careful preoperative assessment of the patient to
identify alterations of health that might contribute
to bleeding is crucial. These conditions include a
history of easy bruisability/excessive bleeding, female
gender, and increased age.
- NSAIDs appear to represent no added
significant risk for the development of spinal hematoma
in patients having epidural or spinal anesthesia.
The use of NSAIDs alone does not create a level of
risk that will interfere with the performance of neuraxial
blocks.
- At this time, there do not seem to
be specific concerns as to the timing of single-shot
or catheter techniques in relationship to the dosing
of NSAIDs, postoperative monitoring, or the timing
of neuraxial catheter removal.
- The actual risk of spinal hematoma
with ticlopidine and clopidogrel and the GP IIb/IIIa
antagonists is unknown. Consensus management is based
on labeling precautions and the surgical, interventional
cardiology/radiology experience.
- Based on labeling and
surgical reviews, the suggested time interval
between discontinuation of thienopyridine therapy
and neuraxial blockade is 14 days for ticlopidine
and 7 days for clopidogrel.
- Platelet GP IIb/IIIa inhibitors
exert a profound effect on platelet aggregation.
Following administration, the time to normal platelet
aggregation is 24-48 hours for abciximab and 4-8
hours for eptifibatide and tirofiban. Neuraxial
techniques should be avoided until platelet function
has recovered. GP IIb/IIIa antagonists are contraindicated
within four weeks of surgery. Should one be administered
in the postoperative period (following a neuraxial
technique), the patient should be carefully monitored
neurologically.
- The concurrent use of other medications
affecting clotting mechanisms, such as oral anticoagulants,
unfractionated heparin, and LMWH, may increase the
risk of bleeding complications. Cyclooxygenase-2 inhibitors
have minimal effect on platelet function and should
be considered in patients who require anti-inflammatory
therapy in the presence of anticoagulation.
Regional
Anesthesia in the Anticoagulated Patient - TOP
Anesthetic Management
of the Patient Receiving Herbal Therapy
Herbal drugs, by themselves, appear to
represent no added significant risk for the development
of spinal hematoma in patients having epidural or spinal
anesthesia. This is an important observation since it
is likely that a significant number of our surgical
patients utilize alternative medications preoperatively
and perhaps during their postoperative course.
- The use of herbal medications alone
does not create a level of risk that will interfere
with the performance of neuraxial blocks. Mandatory
discontinuation of these medications, or cancellation
of surgery in patients in whom these medications have
been continued, is not supported by available data.
- Data on the combination of herbal therapy
with other forms of anticoagulation are lacking. However,
the concurrent use of other medications affecting
clotting mechanisms, such as oral anticoagulants or
heparin, may increase the risk of bleeding complications
in these patients.
- There is no wholly accepted test to
assess adequacy of hemostasis in the patient reporting
preoperative herbal medications.
- At this time, there do not seem to
be specific concerns as to the timing of neuraxial
block in relationship to the dosing of herbal therapy,
postoperative monitoring, or the timing of neuraxial
catheter removal.
Regional
Anesthesia in the Anticoagulated Patient - TOP
New Anticoagulants
(Direct Thrombin Inhibitors and Fondaparinux)
New antithrombotic drugs which target
various steps in the hemostatic system, such as inhibiting
platelet aggregation, blocking coagulation factors,
or enhancing fibrinolysis are continually under development.
The most extensively studied are antagonists of specific
platelet receptors and direct thrombin inhibitors. Many
of these antithrombotic agents have prolonged half-lives
and are difficult to reverse without administration
of blood components.
Thrombin Inhibitors
Recombinant hirudin derivatives, including desirudin,
lepirudin, and bivalirudin inhibit both free and clot-bound
thrombin. Argatroban, an L-arginine derivative, has
a similar mechanism of action. Although there are no
case reports of spinal hematoma related to neuraxial
anesthesia among patients who have received a thrombin
inhibitor, spontaneous intracranial bleeding has been
reported. Due to the lack of information available,
no statement regarding risk assessment and patient management
can be made. Identification of interventional cardiac
and surgical risk factors associated with bleeding following
invasive procedures may be helpful.
Fondaparinux
Fondaparinux produces its antithrombotic effect through
factor Xa inhibition. The FDA released fondaparinux
with a black box warning similar to that of the LMWHs
and heparinoids. The actual risk of spinal hematoma
with fondaparinux is unknown. Consensus statements are
based on the sustained and irreversible antithrombotic
effect, early postoperative dosing, and the spinal hematoma
reported during initial clinical trials. Close monitoring
of the surgical literature for risk factors associated
with surgical bleeding may be helpful in risk assessment
and patient management.
- Until further clinical experience is
available, performance of neuraxial techniques should
occur under conditions utilized in clinical trials
(single needle pass, atraumatic needle placement,
avoidance of indwelling neuraxial catheters). If this
is not feasible, an alternate method of prophylaxis
should be considered.
Regional Anesthesia in
the Anticoagulated Patient - TOP
Summary
Practice guidelines or recommendations
summarize evidence-based reviews. However, the rarity
of spinal hematoma defies a prospective-randomized study,
and there is no current laboratory model. As a result,
these consensus statements represent the collective
experience of recognized experts in the field of neuraxial
anesthesia and anticoagulation. They are based on case
reports, clinical series, pharmacology, hematology,
and risk factors for surgical bleeding. An understanding
of the complexity of this issue is essential to patient
management; a "cookbook" approach is not appropriate.
Rather, the decision to perform spinal or epidural anesthesia/analgesia
and the timing of catheter removal in a patient receiving
antithrombotic therapy should be made on an individual
basis, weighing the small, though definite risk of spinal
hematoma with the benefits of regional anesthesia for
a specific patient. Alternative anesthetic and analgesic
techniques exist for patients considered an unacceptable
risk. The patient's coagulation status should be optimized
at the time of spinal or epidural needle/catheter placement,
and the level of anticoagulation must be carefully monitored
during the period of epidural catheterization. Indwelling
catheters should not be removed in the presence of therapeutic
anticoagulation, as this appears to significantly increase
the risk of spinal hematoma. It must also be remembered
that identification of risk factors and establishment
of guidelines will not completely eliminate the complication
of spinal hematoma. Vigilance in monitoring is critical
to allow early evaluation of neurologic dysfunction
and prompt intervention. We must focus not only on the
prevention of spinal hematoma, but also optimization
of neurologic outcome.
References- TOP
Horlocker TT. Wedel DJ. Benzon H. Brown
DL. Enneking FK. Heit JA. Mulroy MF. Rosenquist RW.
Rowlingson J. Tryba M. Yuan CS. Regional anesthesia
in the anticoagulated patient: defining the risks (the
second ASRA Consensus Conference on Neuraxial Anesthesia
and Anticoagulation).Regional Anesthesia & Pain
Medicine. 28(3):172-97, 2003 May-Jun.
Consensus
Conference Participants - TOP
Terese T. Horlocker, M.D.
Professor
Department of Anesthesiology
Mayo Clinic
Rochester, MN
Honorio T. Benzon, M.D.
Professor
Chief of Pain Management Service
Department of Anesthesiology
Northwestern University Medical School
Chicago, IL
David L. Brown, M.D.
Professor and Head
Department of Anesthesia
University of Iowa College of Medicine
Iowa City, IA
F. Kayser Enneking, M.D.
Associate Professor
Department of Anesthesiology
University of Florida College of Medicine
Gainesville, FL
John A. Heit, M.D.
Professor
Director of Special Coagulation DNA-Diagnostic
Laboratory and Thrombophilia Center
Division of Cardiovascular Diseases and Division of
Hematology
Department of Internal Medicine
Mayo Clinic
Rochester, MN
Michael F. Mulroy, M.D.
Clinical Associate Professor
Department of Anesthesiology
Virginia Mason Medical Center
Seattle, WA
Richard W. Rosenquist, M.D.
Associate Professor
Director of Pain Medicine
Depar
