Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic therapy
- Executive Summary
These Guidelines deal with the cornerstone recommendations of Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy.
1. Administration of thromboprophylaxis
1.1 For each of the antithrombotic agents, we suggest that clinicians follow the FDA-approved dosing guidelines (Conditional)
2. Direct Oral Anticoagulants (DOAC)
2.1 Management of neuraxial block or deep plexus/peripheral block in the patient receiving a High dose of Apixaban (Eliquis)
2.1.1 We suggest that a high dose of apixaban be discontinued at least 72 hours prior to neuraxial block or deep plexus/peripheral block. Consider checking apixaban or aXa plasma level if <72 hours (Conditional)
2.1.2 We suggest that a residual apixaban plasma level <30 ng/mL or a residual aXa activity plasma level ≤0.1 IU/mL is acceptable prior to neuraxial block or deep plexus/peripheral block (Conditional)
2.1.3 We suggest that needle placement/catheter removal occurs at least 24 hours prior to the first postoperative dose (Conditional)
2.2 Management of neuraxial block or deep plexus/peripheral block in the patient receiving a Low dose of Apixaban (Eliquis)
2.2.1 We suggest that a low dose of apixaban be discontinued for at least 36 hours prior to neuraxial block or deep plexus/peripheral block. Consider checking apixaban or aXa plasma level if <36 hours (Conditional)
2.2.2 We suggest that a residual apixaban plasma level <30 ng/mL or a residual aXa activity plasma level ≤0.1 IU/mL is acceptable prior to neuraxial block or deep plexus/peripheral block (Conditional)
2.2.3 We suggest that needle placement/catheter removal occurs at least 6 hours prior to the first postoperative dose (Conditional)
2.3 Management of neuraxial block or deep plexus/peripheral block in the patient receiving a high dose of edoxaban (Savaysa)
2.3.1 We suggest that a high dose of edoxaban be discontinued for at least 72 hours prior to neuraxial block or deep plexus/peripheral block. Consider checking edoxaban or aXa activity plasma level if <72 hours (Conditional)
2.3.2 We suggest that a residual edoxaban plasma level <30 ng/mL or a residual aXa activity plasma level ≤0.1 IU/mL is acceptable prior to neuraxial block or deep plexus/peripheral block (Conditional)
2.3.3 We suggest that needle placement/catheter removal occurs at least 24 hours prior to the first (postoperative) dose (Conditional)
2.4 Management of the patient receiving a Low dose of Edoxaban (Savaysa)
There is no FDA-approved medical indication for low-dose edoxaban.
2.5 Management of neuraxial block or deep plexus/peripheral block in the patient receiving High dose of Rivaroxaban (Xarelto)
2.5.1 We suggest that a high dose of rivaroxaban be discontinued for at least 72 hours prior to neuraxial block or deep plexus/peripheral block. Consider checking rivaroxaban or aXa activity plasma level if <72 hours (Conditional)
2.5.2 We suggest that a residual rivaroxaban plasma level <30 ng/mL or a residual aXa activity plasma level ≤0.1 IU/mL is acceptable prior to neuraxial block or deep plexus/peripheral block (Conditional)
2.5.3 We suggest that needle placement/catheter removal occurs at least 24 hours prior to the first postoperative dose (Conditional)
2.6 Management of neuraxial block or deep plexus/peripheral block in the patient receiving a Low dose of Rivaroxaban (Xarelto)
2.6.1 We suggest that a low dose of rivaroxaban be discontinued for at least 24 hours (30 hours if CrCl <30 mL/min) prior to neuraxial block or deep plexus/peripheral block. Consider checking rivaroxaban or aXa activity plasma level if <24 hours (Conditional)
2.6.2 We suggest that a residual rivaroxaban plasma level <30 ng/mL or a residual aXa activity plasma level ≤0.1 IU/mL 1 is acceptable prior to neuraxial block or deep plexus/peripheral block (Conditional)
2.6.3 We suggest that needle placement/catheter removal occurs at least 6 hours prior to the first postoperative dose (Conditional)
2.7 Management of neuraxial block or deep plexus/peripheral block in the patient receiving a High dose of Dabigatran (Pradaxa)
2.7.1 We suggest that a high dose of dabigatran be discontinued for at least 72 hours in patients with a CrCl ≥50 mL/min prior to neuraxial block or deep plexus/peripheral block. Consider checking dabigatran plasma level if <72 hours (Conditional)
2.7.2 We suggest that a high dose of dabigatran be discontinued for 120 hours in patients with a CrCl 30–49 mL/min prior to neuraxial block or deep plexus/peripheral block. Consider checking dabigatran plasma level if <120 hours (Conditional)
2.7.3 We suggest against the performance of neuraxial or deep plexus/peripheral blocks in patients with a CrCl <30 mL/min unless a dabigatran plasma level is obtained and <30 ng/mL (Conditional)
2.7.4 Prior to neuraxial block or deep plexus/peripheral block we suggest that a residual dabigatran plasma level <30 ng/mL is acceptable (Conditional)
2.7.5 We suggest that needle placement/catheter removal occurs at least 24 hours prior to the first postoperative dose (Conditional)
2.8 Management of neuraxial block or deep plexus/peripheral block in the patient receiving a Low dose of Dabigatran (Pradaxa)
2.8.1 We suggest that a low dose of dabigatran be discontinued for at least 48 hours prior to neuraxial block or deep plexus/peripheral block. Consider checking dabigatran plasma level if <48 hours (Conditional)
2.8.2 We suggest that a residual dabigatran plasma level <30 ng/mL is acceptable prior to neuraxial block or deep plexus/peripheral block (Conditional)
2.8.3 We suggest against the performance of neuraxial or deep plexus/peripheral blocks in patients with a CrCl <30 mL/min unless a dabigatran plasma level is obtained and <30 ng/mL (Conditional)
2.8.4 We suggest that needle placement/catheter removal occurs at least 6 hours prior to the first postoperative dose (Conditional)
3. Use of Direct oral anticoagulant (DOAC) antidotes to facilitate placement of neuraxial block or deep plexus/peripheral block
3.1 Suggest against the use of idarucizumab, andexanet alfa, prothrombin complex concentrates (PCC), or activated prothrombin complex concentrates (aPCC) to reverse DOAC anticoagulant activity to enable the safe performance of a neuraxial intervention in routine patients (Conditional)
4. Intravenous and Subcutaneous Unfractionated Heparin
Management of neuraxial block or deep plexus/peripheral block in the patient receiving Unfractionated Heparin
4.1 We recommend daily review of the patient’s medical record to determine the concurrent use of medications that affect other pathways of hemostasis. These medications include antiplatelet medications, LMWH, and oral anticoagulants (Strong)
4.2 Since heparin-induced thrombocytopenia may occur during heparin administration, we recommend that patients receiving intravenous or subcutaneous UFH for >4 days have a platelet count assessed (Strong)
4.3 Intravenous heparin
4.3.1 Discontinue Intravenous heparin infusion for a minimum of 4–6 hours and coagulation status be assessed and normal prior to neuraxial block or deep plexus/peripheral block (Strong)
4.3.2 Delay intravenous heparin administration for a minimum of 1 hour after needle placement (Strong)
4.3.3 It is not recommended to maintain neuraxial or deep plexus catheters in the setting of continuous intravenous heparin administration. In the event of unanticipated heparinization, we recommend monitoring the patient with an indwelling catheter to allow for early detection of motor deficits and consider use of minimal concentration of local anesthetics to enhance early detection of a neuraxial hematoma (Strong)
4.3.4 Although the occurrence of a bloody or difficult neuraxial needle placement may increase the risk of hematoma, 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 recommended (Strong)
Heparinization during cardiopulmonary bypass
4.3.5 It is not recommended to maintain neuraxial or deep plexus/peripheral catheters in the setting of full anticoagulation during cardiac surgery. If unanticipated heparinization occurs, we suggest postoperative monitoring of neurological status and consider use of minimal concentration of local anesthetics to enhance early detection of neuraxial hematoma (Conditional)
4.4 Subcutaneous heparin
4.4.1 Preoperative low-dose UFH for thromboprophylaxis (5000 U two times per day or three times per day). We suggest needle placement occur a minimum of 4–6 hours after heparin administration or coagulation status be assessed and normal (Conditional)
4.4.2 Preoperative high dose UFH
7500–10 000 U two times per day or a daily dose of ≤20 000 U
We suggest neuraxial block occur a minimum of 12 hours after subcutaneous heparin administration and confirmation of normal coagulation status (Conditional)
>10 000 U subcutaneously per dose, or >20 000 U total daily dose
We suggest neuraxial block occur a minimum of 24 hours after subcutaneous heparin administration and confirmation of normal coagulation status (Conditional)
4.4.3 Postoperative low-dose UFH
There is no contraindication to maintaining neuraxial catheters in the presence of low-dose UFH. We suggest catheter removal occurs a minimum of 4–6 hours after heparin administration. Subsequent heparin administration may occur immediately after catheter removal (Conditional)
4.4.4 Postoperative high-dose UFH
The safety of indwelling neuraxial catheters in patients receiving doses >5000 U at a time or >15 000 U of UFH daily has not been established. We suggest that the risk and benefits be assessed on an individual basis and that techniques to facilitate detection of new/progressive neurological deficits (eg, enhanced neurological monitoring occur and neuraxial solutions to minimize sensory and motor block) be applied (Conditional)
5. Low molecular weight heparin (LMWH)
5.1 Management of neuraxial block or deep plexus/peripheral block in the patient receiving low molecular weight heparin
5.1.1 The aXa level is Not predictive of the risk of bleeding, although it may be useful in monitoring efficacy of therapy with high-dose regimens. We recommend against the routine use of aXa level monitoring (Strong)
5.1.2 Heparin-induced thrombocytopenia may occur during LMWH administration; therefore, we recommend that patients receiving LMWH for >4 days have a platelet count assessed prior to needle placement (Strong)
5.1.3 The presence of blood during needle and catheter placement does not necessitate postponement of surgery. We suggest that initiation of LMWH therapy in this setting should be delayed for 24 hours postoperatively and that this consideration be discussed with the surgeon (Strong)
5.2 Preoperative LMWH
5.2.1 In patients receiving low-dose LMWH, we recommend delay of at least 12 hours prior to needle/catheter placement (Stong)
5.2.2 In patients receiving high (therapeutic) doses of LMWH, we recommend delay of at least 24 hours prior to needle/catheter placement (Stong)
5.3 Postoperative LMWH
5.3.1 We recommend against concomitant administration of medications affecting hemostasis, such as antiplatelet drugs, standard heparin, or dextran, regardless of LMWH dosing regimen when there is an indwelling neuraxial catheter (Strong)
5.3.2 Twice-daily low dose. We recommend the first dose of LMWH be administered the following day and at least 12 hours after needle/catheter placement. Indwelling catheters should be removed prior to initiation of LMWH. Administration of LMWH should be delayed for 4 hours after catheter removal (Strong)
5.3.3 Single daily low dose. We recommend the first postoperative LMWH dose should be administered at least 12 hours after needle/catheter placement. Indwelling neuraxial catheters do not appear to represent increased risk and may be maintained. The catheter should be removed 12 hours after the last dose of LMWH. Subsequent LMWH dosing should occur at least 4 hours after catheter removal (Strong)
5.3.4 Single or twice-daily high ( therapeutic ) dosing. High-dose LMWH may be resumed 24 hours after non-high-bleeding-risk surgery and 48–72 hours after high-bleeding-risk surgery. We recommend that indwelling neuraxial catheters be removed 4 hours prior to the first postoperative dose and the first postoperative dose should be at least 24 hours after needle/catheter placement, whichever is greater (Strong)
6. Antiplatelet Medications
Management of neuraxial block or deep plexus/peripheral block in the patient taking NSAIDs
6.1 NSAIDs appear to represent no added risk for the development of major bleeding after regional anesthetic techniques. NSAIDs (including aspirin) do not create a level of risk that will interfere with the performance of neuraxial or deep plexus/peripheral blocks. In patients receiving these medications, we do not identify specific concerns as to the timing of single-injection or catheter techniques, postoperative monitoring, or the timing of neuraxial catheter removal. (Strong)
6.2 Management of neuraxial block or deep plexus/peripheral block in the patient taking Thienopyridines (Clopidogrel, Prasugrel)
6.2.1 Based on labeling and surgical/procedural experience, the suggested time interval between discontinuation of thienopyridine therapy and needle placement is 5–7 days for clopidogrel, and 7–10 days for prasugrel (Conditional)
6.2.2 Neuraxial and deep plexus/peripheral catheters should not be maintained with prasugrel due to the rapid onset. However, since the antiplatelet effect is not immediate with clopidogrel, they may be maintained for 1–2 days, provided a loading dose of the antiplatelet agent is not administered (Conditional)
6.2.3 Thienopyridine therapy may be resumed immediately after needle placement/catheter removal, provided a loading dose of the drugs is not administered. If a loading dose is administered, we suggest a time interval of 6 hours between catheter removal and administration (Conditional)
6.3 Management of neuraxial block or deep plexus/peripheral block in the patient taking Ticagrelor
6.3.1 Based on labeling and surgical/procedural experience, the recommended time interval between discontinuation of ticagrelor therapy and needle placement is 5 days (Conditional)
6.3.2 Neuraxial catheters should not be maintained with ticagrelor due to the rapid onset (Conditional)
6.3.3 Ticagrelor therapy may be resumed immediately after needle placement/catheter removal, provided a loading dose of the drug is not administered. If a loading dose is administered, we suggest a time interval of 6 hours between catheter removal and administration (Conditional)
6.4 Management of neuraxial block or deep plexus/peripheral block in the patient taking platelet GP IIb/IIa inhibitors
6.4.1 The 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. We recommend that needle placement should be avoided until platelet function—as impacted by the GP IIb/IIIa inhibitor—has recovered. Caution in patients on dual therapy who may still have residual NSAID effect (Strong)
6.4.2 Postoperative. Although GP IIb/IIIa antagonists are contraindicated within 4 weeks of surgery, should one be emergently administered in the postoperative period following a neuraxial or deep plexus/peripheral technique, we recommend the neuraxial infusion should be limited to drugs minimizing sensory and motor block to facilitate assessment of neurological function and that the patient be carefully monitored neurologically (Strong)
6.4.3 Timing of catheter removal is based on ongoing risk of thromboembolism and need for continued antithrombotic therapy and the potential for spinal bleeding during catheter maintenance and removal (Conditional)
6.5 Management of neuraxial block or deep plexus/peripheral block in the patient taking Cilostazol
6.5.1 The risk of serious bleeding in the presence of residual cilostazol effect is unknown. Based on the elimination half-life, we suggest that needle placement be avoided for 2 days after discontinuation of cilostazol (Conditional)
6.5.2 We suggest that neuraxial and deep plexus/peripheral catheters be removed prior to reinstitution of cilostazol therapy postoperatively (Conditional)
6.5.3 We suggest that the first postoperative dose of cilostazol be administered 6 hours after neuraxial or deep plexus/peripheral catheter removal (Conditional)
6.6 Management of neuraxial block or deep plexus/peripheral block in the patient taking Cangrelor
6.6.1 The risk of serious bleeding in the presence of residual cangrelor effect is unknown. Based on the elimination half-life, we suggest that needle placement be avoided for 3 hours after discontinuation of cangrelor (Conditional)
6.6.2 We suggest that neuraxial and deep plexus/peripheral catheters be removed prior to reinstitution of cangrelor therapy postoperatively (Conditional)
6.6.3 We suggest that the first postoperative dose of cangrelor be administered 8 hours after neuraxial or deep plexus/peripheral catheter removal (Conditional)
7. Parenteral Direct Thrombin Inhibitors
Management of neuraxial block or deep plexus/peripheral block in the patient taking parenteral Thrombin inhibitors (Argatroban, Bivalirudin, and Desirudin)
7.1 In patients receiving parenteral thrombin inhibitors, we suggest against the performance of neuraxial techniques (Conditional)
Parenteral anti-Xa agents
7.2 Management of neuraxial block or deep plexus/peripheral block in the patient receiving Fondaparinux
Low-dose fondaparinux (2.5 mg once per day)
7.2.1 We suggest holding low-dose fondaparinux (2.5 mg once per day) for 36 hours (young patients) to 42 hours (elderly patients) in healthy patients with normal renal function (Conditional)
7.2.2 We suggest holding fondaparinux for a minimum of 58 hours in patients with moderate renal insufficiency (CrCl 30–50 mL/min) (Conditional)
7.2.3 We suggest not performing neuraxial or deep plexus/peripheral blocks in patients with severe renal impairment (CrCl <30 mL/min) due to the 72 hours half-life (Conditional)
7.2.4 We suggest testing aXa activity calibrated to fondaparinux if placing the needle prior to these recommended times is considered (aXa ≤0.1 IU/mL) (Conditional)
High-dose fondaparinux (5–10 mg once per day)
7.2.5 We suggest holding high-dose fondaparinux (5-10 mg once per day) for a minimum of 70 hours (in young patients) and for a minimum of 105 hours (in elderly patients) with normal renal function (Conditional)
7.2.6 We suggest testing aXa activity calibrated to fondaparinux if placing needle prior to the recommended times is considered (aXa ≤0.1 IU/mL) (Conditional)
7.2.7 We suggest that neuraxial catheters be removed at least 6 hours prior to the first postoperative dose (Conditional)
8. Fibrinolytic and Thrombolytic drugs
Management of neuraxial block or deep plexus/peripheral block in the patient receiving Thrombolytic therapy
8.1 In patients scheduled to receive thrombolytic therapy, we recommend that the patient be queried, and the medical record reviewed 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 non-compressible vessels (Strong)
8.2 In patients who have received fibrinolytic and thrombolytic drugs, we recommend against needle placement for at least 48 hours. Documentation of normalization of clotting studies (including fibrinogen) is suggested (Strong)
8.3 In those patients who have received neuraxial blocks at or near the time of fibrinolytic and thrombolytic therapy, we recommend that frequent neurological monitoring (eg, every 2 hours) should be continued for at least 48 hours after the last dose. If neuraxial blocks have been combined with fibrinolytic and thrombolytic therapy and ongoing epidural catheter infusion, we recommend the infusion should be limited to drugs minimizing sensory and motor block to facilitate assessment of neurological function (Strong)
9. Vitamin K antagonists (warfarin)
Management of neuraxial block or deep plexus/peripheral block in the patient on Warfarin
9.1 We recommend that the anticoagulant therapy be stopped 5 days prior to the planned procedure, and the INR be measured and normalized (normal range of the local laboratory) prior to needle placement. (Strong)
9.2 In patients receiving an initial dose of warfarin prior to surgery, we suggest the INR should be checked prior to needle placement if the first dose was given >24 hours earlier, or if a second dose of oral anticoagulant has been administered (Conditional)
9.3 In patients receiving low-dose warfarin therapy during epidural analgesia, we suggest that their INR be monitored daily (Conditional)
9.4 We suggest that neuraxial catheters be removed when the INR is <1.5 (Conditional)
9.5 In patients with INR >1.5 but <3, the increased risk of maintaining a neuraxial catheter remains unknown. We suggest indwelling catheters may be maintained or removed with caution, closely following the INR and duration of warfarin therapy. (Conditional)
9.6 In patients with an INR >3, we recommend that the warfarin dose be held or reduced in patients with indwelling neuraxial catheters (Strong)
9.7 Neurological testing of sensory and motor function should be performed routinely during epidural analgesia for patients on warfarin therapy. To facilitate neurological evaluation, we recommend that the type of analgesic solution be tailored to minimize the degree of sensory and motor blockade (Strong)
9.8 We suggest that neurological assessment be continued for at least 48 hours following catheter removal (Conditional)
10. Herbal medications
Management of neuraxial block or deep plexus/peripheral block in patients using Herbal therapy
10.1 The use of herbal medications does not create a level of risk that will interfere with the performance of neuraxial blocks. We recommend against the mandatory discontinuation of these medications or avoidance of regional anesthetic techniques in patients on these medications (Strong)
11. Management of neuraxial block in the anticoagulated parturient
11.1 Given the limited pharmacological data on antithrombotic agents in pregnancy and in the absence of a large series of neuraxial techniques in the pregnant population receiving prophylaxis or treatment for venous thromboembolism, we suggest that the recommendations included in this document be applied to parturients (Conditional)
11.2 However, in circumstances involving select high-risk parturients receiving VTE prophylaxis, and requiring urgent interventions for maternal or fetal indications, the risk of general anesthesia may be greater than neuraxial anesthesia, and exceptions/modifications of these recommendations may be appropriate (Conditional)
12. Antithrombotic therapy in pregnancy
Management of deep plexus/peripheral block in the anticoagulated patient
12.1 For patients undergoing deep plexus or deep peripheral block, we recommend that guidelines for neuraxial block be similarly applied (Strong)
12.2 For patients undergoing other plexus or peripheral techniques, we suggest performance, catheter maintenance, and catheter removal be based on site compressibility, vascularity, and consequences of bleeding, should it occur (Conditional)