Use of Antithrombotic Agents In The Presence Of Neuraxial Anesthesia

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1 Use of Antithrombotic Agents In The Presence Of Neuraxial Anesthesia Insertion, removal or presence of a catheter in selected sites can place a patient who is antithrombotic agent at risk for a local bleeding complication, including a neurologic injury such as paraplegia causing bleeding and development of a spinal hematoma. The timing of epidural relative to the prior administration time of an is critically important, and removal of the catheter must occur when the patient is the magnitude of any antithrombotic effects in the blood is minimal and associated with a low risk of bleeding. Prior to manipulation (insertion or removal) of a catheter in the epidural space, it is the responsibility of the nurse and/or physician who is responsible for the management of the epidural catheter (= the anesthesiology pain service or a health care provided designated by the anesthesiology pain service) to determine if the patient is y antithrombotic therapy (heparin, low molecular weight heparin, other Factor Xa inhibitors, direct thrombin inhibitor, warfarin, aspirin, GPIIb/IIIa antagonists, ADP P2Y12 receptor inhibitor, NSAIDs, etc.). For all patients who are antithrombotic agent, the planned time of catheter removal or insertion should occur when the planned pharmacological effect is minimal and below the threshold associated with causing bleeding. The management of catheter removal should be based on a directly discussion between the primary care team and the acute perioperative pain service (pager ). As a general rule, the patient must either be off antithrombotic therapy or the effect of the antithrombotic agent should be negligible at the time of catheter insertion or removal. The attached guidelines make specific timing recommendations. These precautions do not apply to most peripheral nerve block catheters. Should a once daily parenteral be in use, adjust the administration time to 2100 when possible. Procedures involving closed areas such as the selected ocular, pericardial, spinal or CNS regions are considered high risk for major bleeding in a patient on antithrombotic therapy. If the risk of bleeding associated with a procedure or the need for neuraxial anesthesia outweighs the estimated risk of acute thrombosis, holding the antithrombotic agent for a longer period of time before the procedure should be considered. References: 1. Geerts WH, Bergquist D, Pineo GF, et al. Prevention of Venous Thromboembolism. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8 th edition). CHEST 2008;133:Page 382S 2. Various chapters from The American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9 th edition) published in 2012 were also reviewed. 3. Horlocker TT, et al. Regional Anesthesia in the patient tithrombotic or thrombolytic therapy. American Society of regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition) Regional Anesthesia and Pain Medicine, 2010;35(1): Horlocker TT. Regional Anaesthesia in the patient tithrombotic and antiplatelet therapy. Brit J Anaesth 2011;107:i96-i Gogarten W, Vandermeulen E, Van Aken H, et al. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Eur J Anaesthesiol 2010;27: Manchikanti, L et al. Assessment of Bleeding Risk of Interventional Techniques: A Best Evidence Synthesis of Practice Patterns and Perioperative Management of Anticoagulant and Antithrombotic Therapy. Pain Physician 2013; 16:SE261-SES UW Medicine Pharmacy services: Suggestions for peri-procedural management of edoxaban. Suggestion based on ASRA 2015 Updates. 8. SAVAYSATM (edoxaban) prescribing information. Parsippany, NJ: Daiichi Sankyo Co., LTD;

2 Recommendations For Timing Of Epidural Catheter Manipulation Relative To Use Of Antithrombotic Agents ANTICOAGULANTS 1 PROPHYLAXIS Dosing Unfractionated Heparin 5,000 units q12hrs or q8 hrs Low Molecular Weight Heparin Enoxaparin 30mg SC q12h Enoxaparin 40mg SC Dalteparin 5,000 units SC Dalteparin 2,500 units SC Fondaparinux 2.5mg Timing of spinal needle insertion or epidural catheter placement in a patient who has been given an minimum of 1 4 Pre-operative LMWH is not recommended with neuraxial procedures. 2 minimum of 7 4 Catheter manipulation in the presence of anticoagulation PARENTERAL Agents Timing of epidural catheter removal (If could not be avoided while catheter in place) 5,000 units SC q 1 - No time restrictions apply 3 For doses over 10,000 units daily, assess on a patient to patient basis Caution with use. Avoid concurrent use of twice daily LMWH Once daily dose is permitted; avoid any. Can change to twice daily LMWH once catheter is removed. UFH or once daily prophylactic LMWH while the catheter is in A minimum of 1 between the last dose and catheter removal is recommended. Best if catheter removed just before the next dose, when the effect is at a minimum. Twice daily LMWH can be initiated after catheter is removed. In the event fondaparinux was consider waiting hours or Minimum time between epidural catheter insertion or removal and administration of 2

3 THERAPEUTIC Dosing Unfractionated Heparin (IV or SC) Low Molecular Weight Heparin Enoxaparin 1mg/kg SC q12h Enoxaparin 1.5mg/kg SC Dalteparin 100units/kg SC q12h Dalteparin 200units/kg SC placement until the aptt is less than 40 seconds and/or greater or equal to post stopping IV infusion or greater than 1 post SC dose minimum of 2 4 Caution; avoid any Contraindicated when an epidural catheter in Can start LMWH once catheter is removed. Avoid removal during treatment. Hold infusion removal. Consider getting an aptt (send priority one).target aptt less than 40 seconds and greater or equal to post stopping IV infusion or greater than1 post SC dose manipulation receiving therapeutic anticoagulation. Use of UFH is preferred over use of LMWH while the catheter is in. If LMWH was started and an epidural is in place, hold LMWH and wait 24 hours to reach a low effect before removal. Fondaparinux 5mg, 7.5mg, 10mg minimum of 7 4 Bivalirudin Hold infusion 4-6 hours. Delay until thrombin time (TT) has normalized to baseline In the event fondaparinux was consider waiting hours or In the event bivaluridin was consider waiting 4- then draw TT. Removing the catheter can occur when TT has normalized. 3

4 Warfarin Dabigatran Rivaroxaban Apixaban Edoxaban Stop warfarin 5 days prior to Assess INR the day prior to catheter placement Consider 2.5 mg PO Vitamin. K if INR greater than 1.5. If more urgent reversal needed with insertion in next 1, can consider 1mg IV Vitamin K. INR Target is less than or equal to 1.2. Contact the anticoagulation service ( ) for assistance. Stop dabigatran 3 to 5 days prior to - CrCl greater or equal to 50 ml/min: 3 days - CrCl less than50 ml/min: 4 to 5 das Stop rivaroxaban at least 2-3 days prior to Consider stopping at least 4 days prior if patient has impaired renal function or age greater than 65. -CrCl 60ml/min or greater: 2 days -CrCl 30-59ml/min: 3 days -CrCl: 15-29ml/min: 4 days Stop apixaban at least 3 days prior to -CrCl greater than 50ml/min: 3 days -CrCl less than or equal to 50ml/min: 4 days Stop edoxaban at least 3 days prior to No specific recommendations for renal dose adjustments. In general, edoxaban is not patients with CrCL > 95 ml/min. ORAL Agents Do not initiate until the catheter has been removed. If an place after warfarin started, the catheter should be removed before the INR exceeds 1.5. Check the INR (Send STAT or Priority one) prior to removal. In the event dabigatran was started and an epidural is in place, consider waiting hours or longer before removing the In the event rivaroxaban was consider waiting 18 hours or In the event apixaban was started and an epidural is in place, consider waiting 12-2 or catheter In the event edoxaban was started and an epidural is in place, consider waiting 1 or longer before removing the catheter after last administration. 2 Can start warfarin any time after the catheter has been removed. Warfarin NOT a catheter in Dabigatran NOT a catheter in Rivaroxaban NOT a catheter in No specific recommendations. Consider 48 hours Apixaban NOT a catheter in after catheter removal. Edoxaban NOT catheter in 1. Additional details in the ASRA guidelines are provided in selected situations such as pregnancy, vascular or cardiac surgery. 2. A neuraxial technique is contraindicated in a patient who received LMWH/Fondaparinux/Direct Thrombin Inhibitor pre-operatively. Indwelling catheters should be removed prior to starting, but may be safely maintained if the patient is receiving prophylactic LMWH. 3. Consider measuring the aptt in individuals who may have a therapeutic effect when given 5,000 units of unfractionated heparin subcutaneously such as individuals who are age 80 or older or who weight below 50kg. If the aptt is above 40 seconds, consider removing the catheter at the time the next dose is due to be given, and avoid administering the next dose for 2 to before restarting. 4. Longer hold periods may be required in patients with impaired renal function or who have a high risk of bleeding and who are at a low risk for thrombosis. SC = Subcutaneous; IV = Intravenous; INR = International Normalized Ration; aptt = activated partial thromboplastin time; h = hours; mg = milligrams; kg = Kilograms. 4

5 ANTIPLATELET Minimum time between last dose of antiplatelet agent and when catheter placement can occur Catheter manipulation in the presence of antiplatelet therapy PARENTERAL Agents Timing of epidural catheter removal (If antiplatelet could not be avoided while catheter in place) Abciximab 48 hours treatment. A minimum of 48 hours between discontinuation of abciximab Eptifibatide 8 hours* CONTRAINDICATED while catheter in place treatment. A minimum of 8 hours between discontinuation of eptifibatide Tirofiban 8 hours* treatment. A minimum of 8 hours between discontinuation of tirofiban Aspirin/NSAIDs Aggrenox (dipyridamole + aspirin Dipyridamole Clopidogrel ORAL Agents 7 days treatment. A minimum of 7 days between discontinuation of clopidogrel Prasugrel 7-10 days treatment. A minimum of 7-10 days between discontinuation of prasugrel Ticagrelor 5 days treatment. A minimum of 5 days between discontinuation of ticagrelor Cilostazol 4 treatment. A minimum of 4 between discontinuation of cilostazol Ticlopidine 10 days CONTRAINDICATED while catheter in place treatment. A minimum of 10 days between discontinuation of ticlopidine Vorapaxar Anagrelide Pentosan treatment. placement has not A minimum amount of time to safely remove a catheter has not been. A minimum amount of time to safely remove a catheter has not been. Minimum time between epidural catheter insertion or removal and administration of antiplatelet agent 5 hours * Longer hold periods may be required in patients with impaired renal function or who have high risk of bleeding and who are at a low risk for thrombosis Approved by UCDHS Pharmacy & Therapeutics Committee 6/

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