Regional Anesthesia and Anticoagulants recorded

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Regional Anesthesia and Anticoagulants: What’s New?:

Regional Anesthesia and Anticoagulants: What’s New? John T. Fitzgerald, BSN Webster University

Objectives:

Objectives Review current recommendations for regional anesthesia for patients on anticoagulant and antiplatelet therapy Discuss implications of newer anticoagulants on regional anesthesia Discuss the use of Ultrasound-Guided peripheral nerve blocks in prevention of vascular injury

Disclosure:

Disclosure I am not being compensated by any of the makers of products discussed in the following presentation

Review of Clotting Cascade:

Review of Clotting Cascade Intrinsic Pathway (Contact Activation) Negatively charged surface Extrinsic Pathway (Tissue Factor) TF from damaged cell contact with Factor VII Lead to activation of Final Common pathway Prothrombin → Thrombin Fibrinogen → Fibrin

American Society of Regional Anesthesia Guidelines:

American Society of Regional Anesthesia Guidelines “Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy” American Society for Regional Anesthesia and Pain Medicine Evidence Based Guidelines (3rd Edition) 2010 Consensus Statements with recommendations for providers preforming neuraxial and peripheral regional anesthetic/analgesic blockade

Strength of Recommendations:

Strength of Recommendations Level of Evidence A, Randomized Control Trials B, Observational Studies C, Case Reports and Expert opinion Strength of Recommendation 1, General Agreement 2, Conflicting Evidence 3, Not Recommended

What are we worried about?:

What are we worried about? Epidural Hematoma Actual incidence unknown One Literature review showed… 1 in 150,000 epidural less than 1 in 220,000 spinal Symptoms Motor and sensory dysfunction Bowel bladder dysfunction Back pain

Case Study from BrJA:

Case Study from BrJA 80 year-old woman undergoing total knee arthroplasty LMWH 10h prior to surgery for DVT prophylaxis CSE performed atraumatic , no bloody tap LMWH for DVT prphylaxis 24h after initial dose 14 hours after catheter placement Accidental dose of Plavix

Case Study from BrJA:

Case Study from BrJA Right leg weakness(non-operative leg) noted one day post-op Attributed to epidural Right leg weakness continued 3 day post op and after epidural removal Weakness continued to develop 48h delay until MRI assessment (not avail at hospital) Laminectomy performed, weakness still present at 1 month after hematoma evacuation

Slide 12:

Axial T2 weighted images at the T12 (a) and L1 (b) levels demonstrate a large epidural haematoma returning low signal (black arrows in a and b). Tam N L K et al. Br. J. Anaesth. 2006;96:262-265

Epidural Hematoma:

Epidural Hematoma Treatment Laminectomy and evacuation of blood Timely Decompression Good outcome in 50% of patients if surgery within 8 hours of diagnosis Shorter time between diagnosis and surgery → better outcome

The Drugs:

The Drugs Antiplatelet Agents NSAIDs Aspirin Thienopyridine derivatives Anticoagulants Heparin and LMWH Warfarin Factor Xa Inhibitors Direct Thrombin Inhibitors Thrombolytics Herbal Medications

Antiplatelet Agents:

Antiplatelet Agents Patients taking Antiplatelet agents for Coronary Stents refer to ACC/AHA recommendations When to preform Elective surgery if Antiplatelets need to be discontinued? BMS 4-6 weeks DES 12 months Should Aspirin be continued?

NSAIDs/Aspirin:

NSAIDs/Aspirin Aspirin Irreversibly acetylates p latelet Cyclooxygenase (COX) Inhibits formation of Thromboxane A2 Inhibits platelet activation for life of the platelet (7-10 days) NSAIDS Also inhibit COX, but duration determined by drug half-life No addition risk with NSAIDS including Aspirin for neuraxial anesthesia when used alone (1A) Neuraxial anesthesia not recommended if concurrent therapy with other anticoagulants (2C)

Platelets Pic:

Platelets Pic

Thienopyridines:

Thienopyridines

Thienopyridines:

Thienopyridines Inhibit activation of platelet by ADP D iscontinue prior to surgery or neuraxial technique ( 1C ) Clopidogrel – 7 Days Ticlopidine – 14 Days Based on labeling and cardiology/radiological experince Prasugrel – 7 Days prior to surgery

Glycoprotein IIb/IIIa Antagonists:

Glycoprotein IIb / IIIa Antagonists Glycoprotein IIb / IIIa receptor Final common pathway to platelet aggregation “Bridge Therapy” for Acute Coronary Syndrome ASRA recommendations ( 1C ) Abciximab 24-48 hours Eptifibatide and Tirobifan 4-8 hours Labeling instructions Avoid puncture of noncompressable sites and epidural

Platelets Pic:

Platelets Pic

Unfractionated Heparin:

Unfractionated Heparin Increases activity of Anti-thrombin III Inhibits Thrombin ( IIa ) Also inhibits factors Xa , IXa , XIa , XIIa Inquire if patient on other medications that affect coagualtion (1B) N o contraindication to neuraxial technique with subq 5000u BID dosing (1C) Recommend delay dosing until after regional >10000 U/day safety not established (2C)

Unfractionated Heparin:

Unfractionated Heparin Combination of Epidural and IV heparin during vascular surgery may be acceptable with recommendations (1A) Avoid with other coagulopathies Delay heparin 1 hour after needle Remove catheters 2-4 hours after last dose Wait 1 hour after removal for re-dose of heparin Communicate with surgeon, assess risk/benefit

Low Molecular Weight Heparin:

Low Molecular Weight Heparin LOVENOX ® http ://www.lovenox.com/hcp/dosing/surgery-dvt-prophylaxis.aspx

Low Molecular Weight Heparin:

Low Molecular Weight Heparin LOVENOX® http ://www.lovenox.com/hcp/dosing/surgery-dvt-prophylaxis.aspx

Low Molecular Weight Heparin:

Low Molecular Weight Heparin Avoid Neuraxial if on LMWH and other medications affecting hemostasis (1A) Blood during neuraxial placement. Discussion with surgeon, delay initiation of for LMWH 24 hours post op (2C) Preop Delay neuraxial at least 12 hrs after last dose (1C) Delay 24 hrs for higher dosing regimen (1C) Patients receiving LMWH 2 hours preop , recommend against neuraxial (1A)

Low Molecular Weight Heparin:

Low Molecular Weight Heparin Postop Single daily dose (1C) Neuraxial catheters may be maintained First post op dose 6-8 hours Second post op dose 24 hours after first dose Remove catheter 10-12 hours after last dose, next dose 2 hours after catheter removal Twice daily dose ( 1C ) Increased risk of spinal hematoma First dose 24 hours postop, only if adequate hemostasis Catheters removed 2 hours before first dose

Heparin Reversal:

Heparin Reversal Protamine 100% reversal of unfractionated heparin 66% reversal of LMWH Only fully reverses Anti- IIa activity A nti- Xa activity remains

Warfarin:

Warfarin Indirectly interferes with vitamin K dependent clotting factors Greater than 40% activity of each factor required for normal hemostasis, INR < 1.4

Warfarin:

Warfarin Discontinue Warfarin 4-5 days before procedure. Check INR < 1.5 before neuraxial placement or removal of catheter (1B) Concurrent use of other medications that affect clotting not recommended (1A) Low dose with catheter, monitor INR daily (2C)

Thrombolytics:

Thrombolytics

Newer Anticoagulants:

Newer Anticoagulants ASRA Guidelines mention briefly Thrombin Inhibitors Hirudin derivatives ( Desirudin , Lepirudin , Bivalirudi ) Argatroban Recommend against use of neuraxial technique for patients on Thrombin inhibitors (2C)

Fondaparinux (Arixtra):

Fondaparinux ( Arixtra ) Arixtra FDA approved 2001 Indirect Factor Xa inhibitor DVT prophylaxis for Hip/Knee replacement surgery Binds to/increases Antithrombin III activity ATIII activity selective for factor Xa

Fondaparinux (Arixtra):

Fondaparinux ( Arixtra ) Limited clinical experience Half-Life 21 hours Actual risk of neuraxial technique unknown Indwelling catheters not recommended

Rivaroxaban (Xarelto):

Rivaroxaban ( Xarelto ) Direct Factor Xa inhibitor FDA Approved July 2011 for DVT prophylaxis for hip surgery

Rivaroxaban (Xarelto):

Rivaroxaban ( Xarelto ) Renal and Gut clearance 13 hr half life in elderly Remove epidural 18 hrs after last dose Next dose 6 hrs after catheter removal

Dabigatran Etexilate (Pradaxa):

Dabigatran Etexilate ( Pradaxa ) Direct Thrombin Inhibitor FDA approved October 2010 for A-Fib anticoagulation European studies use for DVT prophylaxis

Dabigatran Etexilate (Pradaxa):

Dabigatran Etexilate ( Pradaxa ) Does not require INR testing Half-life 17 hours DC Prior to surgery 1-2 days CrCl > 50mL/min 3-5 days CrCl < 50mL/min Consider longer times for Spinal or Epidural puncture

Herbal Medications:

Herbal Medications Garlic Ginkgo Ginseng Various affects on platelet pathways Reports of increase in bleeding, but there are no recommendations to discontinue before surgery or neuraxial anesthesia (1C) Effects of administration along with other anticoagulants?

Peripheral Nerve Blocks:

Peripheral Nerve Blocks Major risk during regional anesthesia on patient with anticoagulants is bleeding. Significant blood loss is possible but expandable nature of neurovascular sheath v. epidural space may limit neurological damage Are peripheral nerve blocks less risky if site is compressible?

Peripheral Nerve Blocks:

Peripheral Nerve Blocks ASRA recommends that guidelines for neuraxial block be applied to peripheral blocks (1C) Actual data on peripheral nerve blocks and hematoma limited Most data is from experience in cath lab.

Ultrasound Guided:

Ultrasound Guided Strong evidence that US helps prevent unintended vascular puncture. Should Ultrasound Guided peripheral nerve block be standard of care?

Ultrasound Guided:

Ultrasound Guided

Conclusion:

Conclusion

References:

References Ben-David B. Complications of regional anesthesia: an overview. Anesthesiol Clin North America . 2002;20(3):665. http://search.ebscohost.com.library3.webster.edu/login.aspx?direct=true&db=mnh&AN=12298311&site=ehost-live . Horlocker TT, Wedel DJ. Anticoagulation and neuraxial block: historical perspective, anesthetic implications, and risk management. Reg Anesth Pain Med. 1998;23:129Y134. N . L. K. Tam, C. Pac- Soo , and P. M. Pretorius. Epidural haematoma after a combined spinal–epidural anaesthetic in a patient treated with clopidogrel and dalteparin Br. J. Anaesth . (February 2006) 96(2): 262-265 first published online December 16, 2005 doi:10.1093/ bja /aei297 Vandermeulen E, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesthesia And Analgesia [serial online]. December 1994;79(6):1165-1177. Available from: MEDLINE with Full Text, Ipswich, MA. Accessed September 2, 2011 American College of Cardiology Foundation, , American Heart Association Task Force on Practice Guidelines, , American Society of Echocardiography, , American Society of Nuclear Cardiology, , Heart Rhythm Society, , Society of Cardiovascular Anesthesiologists, , Society for Cardiovascular Angiography and Interventions, , Society for Vascular Medicine, , Society for Vascular Surgery, , Fleisher, Lee A., Beckman, Joshua A., Brown, Kenneth A., Calkins, Hugh, Chaikof , Elliot L., Fleischmann, Kirsten E., Freeman, William K., Froehlich, James B., Kasper, Edward K., Kersten , Judy R., Riegel , Barbara, Robb, John F. 2009 ACCF/AHA Focused Update on Perioperative Beta Blockade Incorporated Into the ACC/AHA 2007 Guidelines on Perioperative Cardiovascular Evaluation and Care for Noncardiac Surgery . J Am Coll Cardiol 2009 54: e13-118 Prasugrel Prescribing information. http://pi.lilly.com/us/effient.pdf Xarelto . http://www.xareltohcp.com/xarelto-medical-info.html . Updated July 18, 2011. Accessed Aug 3, 2011 Pradaxa . http://www.pradaxapro.com. Updated May 1, 2011. Accessed Aug 3, 2011 Gayle JA, Kaye AD, Kaye AM, Shah R. Anticoagulants: newer ones, mechanisms, and perioperative updates. Anesthesiol Clin . 2010;28(4):667-679. http://search.ebscohost.com.library3.webster.edu/login.aspx?direct=true&db=mnh&AN=21074744&site=ehost-live . Horlocker TT, Wedel DJ, Rowlingson JC, Enneking FK. Executive summary: regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med . 2010;35(1):102-105. http://search.ebscohost.com.library3.webster.edu/login.aspx?direct=true&db=mnh&AN=20048659&site=ehost-live . Krombach JW, Dagtekin O, Kampe S. Regional anesthesia and anticoagulation. Curr Opin Anaesthesiol . 2004;17(5):427-433. http://search.ebscohost.com.library3.webster.edu/login.aspx?direct=true&db=mnh&AN=17023901&site=ehost-live . Llau JV, Ferrandis R. New anticoagulants and regional anesthesia. Curr Opin Anaesthesiol . 2009;22(5):661-666. http://search.ebscohost.com.library3.webster.edu/login.aspx?direct=true&db=mnh&AN=19568169&site=ehost-live . Antonakakis J, Ting P, Sites B. Ultrasound-guided regional anesthesia for peripheral nerve blocks: an evidence-based outcome review. Anesthesiology Clinics [serial online]. June 2011;29(2):179-191. Niesen A, Hebl J. Multimodal clinical pathways, perineural catheters, and ultrasound-guided regional anesthesia: the anesthesiologist's repertoire for the 21st century. Minnesota Medicine [serial online]. March 2011;94(3):31-34.

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