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Pharmacy Times
Neuraxial anesthesia (NA) may be used in various settings: intraoperatively to provide anesthesia, postoperatively for pain control, in the peripartum period, and in managing chronic pain. For patients receiving anticoagulant therapy, a clinician’s greatest concern is the risk for hemorrhagic complications. Bleeding in the closed space of the spinal canal can result in an expanding hematoma, which increases the pressure on the spinal cord and may lead to spinal cord ischemia and infarction.
Bleeding is most common in the vessels in the prominent venous plexus of the epidural space; however, it can occur in the subdural space as well. This type of bleeding is called spinal epidural hematoma (SEH), and the risk is greatest when a patient’s coagulation system is abnormal, either when a needle is placed in the neuraxial space or when a continuous neuraxial catheter is removed.
The timing of neuraxial intervention must be coordinated with anticoagulant discontinuation and resumption. In general, patients receiving more than 1 medication affecting hemostasis should not receive NA.
The American Society of Regional Anesthesia and Pain Medicine (ASRA) is the current guiding consensus on the management of regional anesthesia and concurrent anticoagulation.1 The decision to use NA must outweigh the risk for SEH.
HEPARIN, LOW-MOLECULARWEIGHT HEPARINS, AND FONDAPARINUX
Three major risk factors for SEH associated with heparin have been identified in the literature: (1) a <60-minute time interval between the administration of heparin and lumbar puncture, (2) traumatic needle placement, and (3) concomitant use of other antithrombotics (eg, aspirin).2,3
ASRA has recommended that neuraxial blocks be avoided when coagulopathy is known to be present. Also, the time interval between instrumentation to systemic heparinization should exceed 60 minutes, systemic therapeutic heparin should be discontinued 2 to 4 hours prior to neuraxial catheter removal, and epidural catheters should be removed when normal coagulation is restored.
When prophylactic/subcutaneous heparin is being used, standard twice-daily dosing is not contraindicated. In patients receiving >10,000 U per day or 3×—daily dosing, safety has not been established. The risk for SEH may be reduced by delaying heparin injection until after the block or by holding the dose prior to removal of the catheter.
Low-molecular-weight heparins (LMWHs) have been shown to increase the risk for SEH. ASRA recommends once-daily thromboprophylaxis and delay of catheter insertion for 10 to 12 hours after the LMWH dose (for higher [treatment] doses of LMWH, 24 hours is necessary). After catheter insertion, oncedaily dosing should be delayed 6 to 8 hours, and twice-daily treatment dosing should be administered no earlier than 24 hours postoperatively.
More caution should be used with fondaparinux, as the risk for SEH is unknown. Until further information is available, ASRA recommends techniques only under conditions used in available controlled, clinical trials: single-needle pass, nontraumatic needle placement, and avoidance of indwelling neuraxial catheters.
WARFARIN AND TARGET-SPECIFIC ORAL ANTICOAGULANTS
Ideally, warfarin should be stopped 4 to 5 days before NA intervention. For removal of a neuraxial catheter, an international normalized ratio (INR) of <1.5 is ideal; however, for an INR of 1.5 to 3.0, neuraxial catheters may be removed only if other drugs affecting hemostasis were not used in combination with warfarin. If the INR is >3, the warfarin dose must be reduced or held until the INR is <3. For immediate catheter removal, fresh-frozen plasma may be used. The use of warfarin may resume immediately after NA because the anticoagulant effect is not immediate.
ASRA has not published guidelines for the use of target-specific oral anticoagulant agents on the basis that there is insufficient evidence to provide safe intervals for the use of NA. Pharmacokinetic and pharmacodynamic data may be helpful in providing some guidance. The American Heart Association (AHA) recommends that patients specifically on rivaroxaban discontinue anticoagulation 3 days prior to NA (5 days if the creatinine clearance [CrCl] is <50 mL/min) and wait 24 hours before redosing. The AHA also recommends discontinuation of dabigatran use in patients 5 days prior to NA (7 days if the CrCl is <50 mL/min) and waiting 24 hours before redosing.4
Dr. Resseguie is an advanced practice anticoagulation pharmacist for the Brigham & Women’s Hospital Anticoagulation Management Service in Boston, Massachusetts. Dr. Adams is a clinical pharmacy specialist at Brigham & Women’s Hospital in Boston, Massachusetts.
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