Download Anticoagulants and Neuraxial and Peripheral Nerve Blocks

Anticoagulants and Neuraxial
and Peripheral Nerve Blocks
Gholamreza moradi,
Cardiac Anesthesiologist,
Kermanshah University of Medical Sciences
 In 1997, the American Society of Regional Anesthesia and Pain Medicine
(ASRAPM) convened a panel of experts to discuss the increased number of
reports of epidural hematoma secondary to the then newly introduced low
molecular weight heparin (LMWH) enoxaparin.
 The same panel revised their guidelines in 2003 to include the newer
antiplatelet drugs.
 The third edition of the guidelines was published in 2010 partly to make
recommendations on the issue of anticoagulants and plexus and peripheral
nerve blockade.
PERIOPERATIVE DEEP VENOUS
THROMBOSIS
 Some 50% of DVTs after total joint surgery begin intraoperatively;the highest
incidence occurs during surgery and the first postoperative day. Almost 75% of
DVTs develop within the first 48 hr after surgery.
 Some of the risk factors for the development of DVTs are previous history of DVT or
pulmonary embolism,major surgery, age over 60, obesity, malignancy,increased
duration of surgery, prolonged immobilization,presence of varicose veins, and the
use of estrogen.
 B-mode compression ultrasonography with and without Doppler is the first-line
modality for confirming diagnosis in symptomatic patients. It is portable and the
most accurate noninvasive study of DVTs. Failure of the vein to compress is indirect
evidence that a thrombus is present.
PERIOPERATIVE PROPHYLAXIS OF DEEP
VENOUS THROMBOSIS IN TOTAL JOINT
SURGERY
 The prevention of DVT after total joint surgery includes intraoperative,
mechanical, and pharmacologic measures.
 The use of epidural hypotensive anesthesia is associated with improved
visualization of the operative field, less intraoperative blood loss, and shorter
duration of surgery.
 Mechanical devices decrease stasis by augmenting venous flow in the lower
legs,9 and appear to have a fibrinolytic effect through a reduction in
plasminogen activator inhibitor.(calf-length sleeve, thigh-length stockings, and
foot pump devices)
 The pharmacologic management of DVTs includes the use of aspirin, warfarin,
LMWH, thrombin inhibitors, and the newer drugs including rivaroxaban.
 For aspirin, most regimens use doses of 325 to 650 mg twice a day. The incidence
of DVT when aspirin alone is used in TKR ranges from 41% to 78%.
 For warfarin, the usual dosing regimen is 5 mg given the night of surgery, followed
by adjustment of the dose to maintain an international normalized ratio (INR) of
2.0 to 2.5. Higher INRs may result in hemarthromas.The incidence of DVT with
warfarin is 25% to 59%.
 Heparin is not widely used for postoperative prophylaxis after total joint surgery
probably because of the better bioavailability and predictability of LMWH.
 LMWH is an effective prophylaxis against DVT after total joint surgery,12–14 and
appears to be more effective than warfarin.The incidence of DVT in patients who
had total hip surgery is 5% with enoxaparin and 12% with warfarin.
 Dalteparin is also associated with lower incidence of DVTs after total hip
arthroplasty when compared to warfarin(13% versus 24%).
 Fondaparinux, a specific Xa inhibitor, is given for 5 to 9 days after surgery at a
daily dose of 2.5 mg. The drug reduces the incidence of venous
thromboembolism by 57%, comparable to enoxaparin.
RELEVANT PHARMACOLOGY
OF ANTICOAGULANTS
AND IMPLICATIONS FOR
NEURAXIAL BLOCKADE
ASRA RECOMMENDATIONS
FOR ANTIPLATELET THERAPY
AND NEURAXIAL BLOCK
 The ASRA concluded that neuraxial blocks may be performed in patients on
aspirin or NSAIDs.
 Neuraxial blocks in patients on COX-2 inhibitors are safe, although the
concomitant use of COX-2 inhibitors and warfarin may increase the risk of
bleeding.
 Aspirin and NSAIDs alone do not significantly increase the risk of spinal
hematoma. The combination of these drugs, however, increases the risk of
spontaneous hemorrhagic complications, bleeding at puncture sites, and spinal
hematoma.
 Case reports of intraspinal hematoma after aspirin and NSAIDs had complicating
factors such as concomitant administration of other anticoagulant, epidural
vascular abnormalities, and technical difficulties. The intake of different
antiplatelet medications has been identified as a major risk factor in the
development of spinal hematoma after neuraxial injections.
 In the pain clinic the interventional physician has to decide whether it is prudent
to continue the aspirin or NSAIDs before a neuraxial injection.
 If the indication forthe aspirin is not strong, such as routine daily aspirin in an
elderly but healthy patient, then the physician may choose to stop the
medication especially in cervical and thoracic injections. This is because in these
patients it is difficult to differentiate between new or old symptoms (numbness
and weakness) or between real and imagined pathology.
 Greater caution is advised in cervical and thoracic injections since the epidural
space is narrower in these levels, the presence of the spinal cord in the area, and
the fact that the studies on neuraxial injections in the presence of antiplatelet
therapy were done mostly in patients who had lumbar injections.
 ASRA recommended that clopidogrel be stopped for 7 days before a neuraxial
injection. If a neuraxial injection has to be performed at 5 days after discontinuation
of clopidogrel, then a PFA II or a P2Y12 assay must be performed. Platelet inhibition
of less than 10% in the P2Y12 assay signifies safe neuraxial injection.
 A delay of 10 to 14 days is recommended with ticlopidine.This is because the halflife of ticlopidine increases from 12 hr after a single dose to 4 to 5 days after a
steady state is reached.
 For patients on clopidogrel and aspirin, it is recommended that the clopidogrel be
stopped for 7 days and the patient placed on aspirin therapy. The aspirin is then
continued up to the time of injection, after which the patient is switched back on
clopidogrel after the block.
WARFARIN: PHARMACOLOGY
AND ASRA RECOMMENDATIONS
 Warfarin is an oral anticoagulant that interferes with the synthesis of the vitamin K–
dependent clotting factors II,VII, IX, and X. It also inhibits the anticoagulant protein
C. Both factor VII and protein C have short halflives(6–7 hr) and increase in the INR
is the result of the competing effects of reduced factor VII and protein C and the
washout of existing clotting factors.
 Prophylactic anticoagulation (INRs of 2.0–2.5) is reached 48 to 72 hr after the initial
dose. Maximal anticoagulation is reached in 4 to 5 days.
 An INR value of 1.4 or less is considered by ASRA as a safe value for placement or
removal of an epidural catheter. There is very little correlation between the INR
and factor VII during the early phase of warfarin therapy. At 12 to 14 hr after
warfarin, it is probably safe to remove the epidural catheter in the presence of an
elevated INR of up to 1.9 since the activity of factor VII were noted to correlate
with adequate hemostasis.
HEPARIN AND LMWH:
PHARMACOLOGY AND ASRA
RECOMMENDATIONS
 Heparins are glycosaminoglycans that consist of chains of alternating residues of dglucosamine and uronic acid,either glucuronic acid or iduronic acid.
Unfractionated heparin is a heterogeneous mixture of polysaccharide chains
ranging in molecular weight from 3000 to 30,000.A unique pentasaccharide
sequence, randomly distributed along the heparin chains, binds to antithrombin
(AT).The binding of the heparin pentasaccharide to AT causes a conformational
change in AT that accelerates its ability to inactivate thrombin, factor Xa, and
factor IXa. In addition,UFH releases tissue factor pathway inhibitor from
endothelium, enhancing its activity against factor Xa.
 The anticoagulant effect of subcutaneous heparin takes 1 to 2 hr but the effect of
intravenous heparin is immediate.
 The aPTT is used to monitor the effect of heparin; therapeutic anticoagulation is
achieved with a prolongation of the aPTT to greater than 1.5 times the baseline
value or a heparin level of 0.2 to 0.4 U/ml.
 For patients who are scheduled for vascular procedures and given intravenous UFH
during the surgery, it was noted that it was safe to perform preoperative neuraxial
blocks if some precautions are observed.
 In summary, the ASRA guidelines on the performance of neuraxial procedures in
patients who are anticoagulated with heparin are as follows:
 (1) the neuraxial technique should be avoided in patients with other
coagulopathies;
 (2) although the occurrence of bloody or difficult needle placement increases
the risk of hematoma, discussion with the surgeon of the risk/benefit ratio should
determine cancellation or noncancellation of the case;
 (3) the heparin administration should be delayed for 1 hr after needle placement;
 (4) indwelling neuraxial catheters should be removed 2 to 4 hr after the last
heparin dose, and the patient’s coagulation status is evaluated and
reheparinization occurs 1 hrafter catheter removal
 (5) minimal concentrations of local anesthetics should be used for early detection
of signs of spinal hematoma and the patient is monitored postoperatively for signs
of hematoma.
 Subcutaneous TID heparin is associated with increased bleeding. ASRA
recommended against neuraxial injections in patients on subcutaneous TID
heparin because of reports of increased bleeding and the absence of
prospective studies in this setting.
 There appears to be a continuing debate as to whether neuraxial procedures
should be performed in patients who undergo cardiopulmonary bypass. In these
patients the following precautions have been recommended:
 (1) neuraxial procedures should be avoided in patients with a known
coagulopathy,
 (2) surgery should be delayed 24 hr in the patient with a traumatic tap
 (3) the time from the neuraxial procedure to the systemic heparinization should
exceed 1 hr
 (4) heparinization and reversal should be monitored and controlled tightly
 (5) theepidural catheter should be removed when normal coagulation is
restored and the patient should be monitored closely for signs of spinal
hematoma after the catheter is removed.
LOW-MOLECULAR-WEIGHT HEPARIN
 Low-molecular-weight heparins are the fractionated forms of heparin with a
mean molecular weight of 5000.85 Similar to unfractionated heparin, LMWH
activates antithrombin,accelerating antithrombin’s interaction with thrombin
and factor Xa. LMWH, like unfractionated heparin, also releases tissue factor
pathway from the endothelium.
 The LMWHs have a longer half-life and doseindependent clearance compared
to heparin, resulting in a more predictable anticoagulant response.
 The plasma half-life of the LMWHs ranges from 2 to 4 hr after an intravenous
injection and 3 to 6 hr after a subcutaneous injection. It should be noted that
anti-Xa activity is still present 12 hr after injection of LMWH.
 The recommendations of the ASRA for patients receiving LMWH and neuraxial
anesthesia are as follows:
 Monitoring of the anti-Xa level is not recommended.
 The administration of antiplatelet or oral anticoagulant medications with
LMWHs may increase the risk of spinal hematoma.
 The presence of blood during needle placement and catheter placement
does not necessitate postponement of surgery. However, the initiation of LMWH
therapy should be delayed for 24 hr postoperatively.
 The first dose of LMWH prophylaxis after twice-daily enoxaparin should be given
no earlier than 24 hr postoperatively and only in the presence of adequate
hemostasis.
 It may be given 6 to 8 hr after a once-daily dosing of enoxaparin.
 In patients who are on LMWH, needle/catheter placement should occur at
least 12 hr after the last prophylactic dose of enoxaparin or 24 hr after
dalteparin (120 U/kg every 12 hr or 200 U/kg every 12 hr), or after higher doses
of enoxaparin (1 mg/kg every 12 hr; 1.5 mg/kg daily).
 There should be a 12-hr interval between the last prophylactic dose of
enoxaparin and removal of the epidural catheter.
 For higher doses of enoxaparin, a 24-hr delay is recommended.
 The LMWH may be administered 2 hr after the epidural catheter is removed.
FONDAPARINUX
 Fondaparinux is a synthetic anticoagulant that is a selective Xa
inhibitor.Because it is synthesized chemically, it exhibits batch-to-batch
consistency.
 The drug is rapidly absorbed, reaching a maximum concentration within 1.7
hr of dosing and has a half-life of 21 hr.
 It has 100% bioavailability. A dose of 2.5 mg is given subcutaneously 6 hr
after surgery, and subsequently once a day.
 The risk of spinal hematoma in patients on fondaparinux is not known at this
time, so ASRA recommended that neuraxial injections should involve singleneedle pass, atraumatic needle placements, and avoidance of intraspinal
catheters
HERBAL THERAPIES
 Garlic inhibits platelet aggregation and its effect on hemostasis appears to
last 7 days.
 Ginkgo inhibits platelet-activating factor and its effect lasts 36 hr, while the
effect of ginseng lasts 24 hr.
 Ginkgo inhibits platelet-activating factor and its effect lasts 36 hr, while the
effect of ginseng lasts 24 hr.
 In spite of their effect on platelet function, herbal drugs by themselves
appear to present no added significant risk in the development of spinal
hematoma in patients having epidural or spinal anesthesia.
 There appears to be no 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.
ANTICOAGULATION AND PERIPHERAL
NERVE BLOCKS
 ASRA recommended that the same guidelines on neuraxial injections be
followed for peripheral nerve blocks.
 This is especially important in deep plexus and noncompressible blocks (e.g.,
lumbar plexus block, deep cervical plexus blocks) or blocks near vascular areas
such as celiac plexus blocks or superior hypogastric plexus blocks.