Anticoagulation and Regional Blocks.pptx

Anticoagulants and Regional Anaesthesia

1. Anticoagulation And Regional Anesthesia Dr. Pankaj Baral Moderator: Prof. Dr. Ashish Ghimire

2. Anticoagulation and Neuraxial /Peripheral Anesthesia Mudit Kaushal , MD, Ryan E. Rubin, MD, MPH, Alan D. Kaye, MD, PhD, DABA, DABPM, DABIPP, Karina Gritsenko , MD. Anesthesiology Clin 35 (2017) e21–e39

3. Anticoagulant Reversal and Anesthetic Considerations Joseph Meltzer, MD, Joseph R. Guenzer , MD Anesthesiology Clin 35 (2017) 191–205

4. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Fourth Edition) Terese T. Horlocker , MD , Erik Vandermeuelen , MD , Sandra L. Kopp, MD , Wiebke Gogarten , MD, Lisa R. Leffert , MD , and Honorio T. Benzon , MD ( Reg Anesth Pain Med 2018;43: 263–309) REGIONAL ANESTHESIA AND ACUTE PAIN

5. OBJECTIVES To understand the mechanisms of action of the most popular anticoagulants and novel anticoagulants (NAGs ). To review the management of patients on antithrombotic therapies for neuraxial techniques

6. POTENTIAL ADVANTAGES OF REGIONAL ANESTHETIC TECHNIQUES Smaller incidence of cardiac dysrhythmias venous thromboembolic events ( VTE) Pulmonary complications postoperatively

7. CONCLUSION: Neuraxial analgesia may be safe in the complex care of this delicate population, which may be an effective technique to avoid the potentially undesirable long-term effects on cognitive and motor development that are linked with poorly treated postoperative pain.

8. CONCLUSION: Epidural anesthesia /general anesthesia combination improves postoperative pain and side effects without increasing the risk of flap thrombosis.

9. CONCLUSION: Electing for regional anesthetic in the ambulatory surgery setting has been associated with a relative risk reduction of 77% in postoperative nausea and vomiting when compared with elective general anesthesia .

10. CONCLUSION: Spinal analgesia reduced early neuroendocrine responses and overall parenteral morphine use.

11. SAFETY OF REGIONAL ANESTHESIA Not safe for all patients ever-growing elderly population and patients with comorbidities leading to the use of anticoagulants To determine the best course of action to provide the safest and most beneficial care to the patient. Incidence: less than 1 in 150,000 epidural less than 1 in 220,000 spinal anesthetics

12. ANTIPLATELET AGENTS In 3 of the 61 cases of spinal hematoma , the patient was on either aspirin, indomethacin, or ticlopidine . ASRA fourth edition consensus conference: NSAIDs represent “ no added risk ” for the development of spinal hematomas in patients receiving epidural or spinal anesthesia

13. N o studies to determine the appropriate timing and safety of P2Y12 or GP IIb / IIIa receptor antagonist administration and needle/catheter placement for regional Anesthesia ASRA recommendations: abciximab be discontinued for 24 to 48 hours at minimum, and 4 to 8 hours at minimum for eptifibatide and tirofiban . Case report: patient who became quadriplegic 30 minutes after receiving a steroid epidural while on diclofenac, clopidogrel , and aspirin CONCLUSION: Before any neuraxial technique is used in the context of chronic pain or in regional anesthesia with patients on these medications, the patient should be engaged in a careful and deliberate discussion of the benefits and potentially catastrophic hemorrhagic risks.

14. Mechanism of action

15. The effect of P2Y12 inhibition is apparent in platelet inhibition for 5 to 7 days after discontinuation of clopidogrel , and 10 to 14 days with ticlopidine . Normal platelet aggregation requires 8 hours from discontinuation for eptifibatide and tirofiban and approximately 48 hours for abciximab .

16. Monitoring Bleeding time : high interindividual and intraindividual variability There is no adequate method available for routine laboratory testing of the antiplatelet effect of ASA.

17. Antiplatelet effects of P2Y12 inhibitors: based on platelet reactivity tests . Thromboelastography : has not been studied to reflect antiplatelet activity of P2Y12 inhibitors.

18. Light transmission aggregometry measures platelet responsiveness under GP IIb / IIIa inhibitors There is no universally recognized assay to measure bleeding risk after the administration of GP IIB/ IIIa inhibitors

19. Reversal Platelet transfusion Desmopression @ 0.4mcg/kg

20. Nonsteroidal anti-inflammatory drugs: no added significant risk In patients receiving NSAIDS : caution in the performance of neuraxial techniques if the concurrent use of other medications: other (non-NSAID) antiplatelet agents, oral anticoagulants, UFH , and LMWH is anticipated in the early postoperative period. ASRA recommendations

21. Thenopyridines ( ticlopidine , clopidogrel , prasugrel ) ASRA recommendations… Neuraxial anesthesia 10 days 24 hrs Ticlopidine 5-7 days 24 hrs Clopidogrel 7-10 days 24 hrs Prasugrel 5-7 days 24 hrs Ticagrelor Neuraxial catheters should not be maintained with prasugrel or ticagrelor because of the rapid onset. With ticlopidine and clopidogrel , neuraxial catheters may be maintained for 1 to 2 days, provided a loading dose of the antiplatelet agent is not administered. 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, time interval between catheter removal and administration should be 6 hours.

22. GP IIb / IIIa inhibitors Neuraxial techniques should be avoided until platelet has recovered . Although GP IIb / IIIa antagonists are contraindicated within 4 weeks of surgery, should one be emergently administered in the postoperative period ( following a neuraxial technique), infusion should be limited to drugs minimizing sensory and motor block to facilitate assessment of neurologic function and that the patient be carefully monitored neurologically. ASRA recommendations… abciximab : 24 to 48 hours minimum eptifibatide and tirofiban : 4-8 hours minimum .

23. ASRA recommendations Neuraxial anesthesia- catheter removal 2 days 6 hrs Cilostazol 24 hrs 6 hrs Dipyrimadole

24. HEPARIN

25. Pharmacokinetics Bad absorption : only paraenteral use Distribution : binds to plasma proteins, endothelial cells, and macrophages Plasma clearance : 2 phases. Saturable phase: initial binding of heparin Slower first-order mechanism: renal excretion.

26. Plasma half-life : varies on whether or not the dose reaches a steady-state concentration and bypasses the saturable phase of clearance The apparent biologic half-life of heparin increases from approximately 30 minutes after an IV bolus of 25 U/kg, to 60 minutes with an IV bolus of 100 U/kg, to 150 minutes with a bolus of 400 U/kg. Pharmacokinetics…

27. activated partial thromboplastin time ( aPTT ): 1.5 to 2.5 times the upper limit of normal activated clotting time The aPTT should be measured 6 hours after a bolus administration, and continuous IV administration rates should be adjusted accordingly to target therapeutic heparin levels of 0.3 to 0.7 IU/mL Monitoring

28. Adverse effects heparin-induced thrombocytopenia heparin-induced osteoporosis

29. Reversal Protamine (1 mg of protamine neutralizes approximately 100 U UFH).

30. Low molecular weight heparin ↓ molecular weight → ↑ potentiation of the inhibition of factor Xa bypass the initial saturable phase of plasma clearance: more predictable dose-response

31. Low molecular weight heparin

32. 4-6 hrs 1 hr 4-6 hrs 1 hr IV HEPARIN Platelets count if patient is receiving heparin for > 4 days

33. 4-6 hrs / Normal aPTT 1 hr 4-6 hrs SC UNFRACTIONATEDHEPARIN Platelets count if patient is receiving heparin for > 4 days 12 hrs 1 hr UFH upto 15000U/day 5000U BD or TDS No C/I to maintain neuraxial catheter 24 hrs UFH < 20000U/day 7500-10000U BD UFH > 10000U/dose, >20000U/day Safety of placement of catheter not established

34. 12 hrs 12 hrs SC ENOXAPARIN Platelets count if patient is receiving heparin for > 4 days 12 hrs 4 hrs LMWX Prophylactic OD No C/I to maintain neuraxial catheter 24 hrs LMWX Prophylactic BD LMWX Therapeutic 24 hrs for low risk 48 hrs for high risk

35. Neuraxial anesthesia Catheter removal 24 12 1 4-6 4-6 1 4 LMWX Therapeutic, SC UFH Therapeutic LMWX Prophylactic, UFH higher dose IV heparin, UFH low dose IV heparin LMWX IV heparin IV heparin, UFH low dose 12 24 48 LMWX Prophylactic LMWX Therapeutic-Low risk LMWX Therapeutic-High risk LMWX Prophylactic 12

36. VITAMIN K ANTAGONISTS

37. Pharmacokinetics 2 enantiomers: R and S isoforms. [S-more potent] Absorption: oral Time to peak concentration: 90 minutes. T 1/2 =36- 42 hours Hepatic metabolism: CYP-450 system

38. Adverse effects Hemorrhage : GI, hematuria , intracranial haemorrhage Warfarin-induced skin necrosis Teratogenicity: bone agenesis and stillbirth

39. Reversal 4-tiered approach: withholding the VKA vitamin K FFP PCCs Non bleeding patients Bleeding patients

40. Reversal Nonbleeding patients with supratherapeutic INR: withholding the VKA ± administering vitamin K Patients with INR 6.0 to 10.0, withholding alone decreasesINR 4.0 in on average of 2.6 days. M ore rapid correction: vitamin K: corrects INR to below 3.0 within 24 hours .

41. ASRA recommendations Warfarin therapy must be stopped (ideally 5 days prior to the planned procedure), and the INR should be normalized prior to initiation of neuraxial block In patients receiving an initial dose of warfarin prior to surgery, INR should be checked prior to neuraxial block if the first dose was given more than 24 hours earlier or a second dose of oral anticoagulant has been administered.

42. ASRA recommendations… INR should be monitored daily if low dose warfarin is being given in a patient with an indwelling epidural catheter. Patient should receive routine neurologic evaluation of sensory and motor function. As thromboprophylaxis with warfarin is initiated, neuraxial catheters should be removed when the INR is less than 1.5.

43. ASRA recommendations… INR 1.5-3: indwelling catheters may be maintained with caution, based on INR and duration of warfarin therapy. INR > 3 , hold or reduce warfarin dose in patients with indwelling neuraxial catheters No definitive recommendation regarding the management to facilitate removal of neuraxial catheters in patients with therapeutic levels of anticoagulation during neuraxial catheter infusion

44. ASRA recommendations… Continue neurologic assessment for at least 24 hours following catheter removal.

45. Need of clinical viligance and engagement of the patient in a discussion of hemorrhagic risks

46. NOVEL ANTICOAGULANTS ( Direct Thrombin Inhibitors and Factor Xa Inhibitors) NAGs use has grown to 4.21 million treatment visits in 2014 since their introduction in 2010

47. Direct thrombin inhibitors Paraenteral Lepirudin : treatment of HIT-associated thrombosis Desirudin : VTE prophylaxis after hip replacement Bivalirudin : alternative to heparin in patients undergoing percutaneous coronary interventions, specifically for those with HIT Argatroban : anticoagulation of patients with proved HIT Oral: dabigatran: nonvalvular atrial fibrillation, acute treatment and secondary prevention of VTE

48. Factor Xa inhibitors Rivaroxaban : 20 mg daily for VTE and stroke prophylaxis, 15 mg twice daily for treatment of VTE Apixaban : 2.5 mg to 5 mg twice daily for VTE and stroke prophylaxis, 10 mg twice daily for treatment of VTE Edoxaban : 30 mg to 60 mg daily

49. Mechanism of action

50. Difference from heparin

51. 15% to 25% of patients on NAGs for atrial fibrillation will require an invasive procedure in 2 years!!!!! Importance of the need for newer national and international recommendations for the management of regional techniques for patients on these medications

52. Monitoring of novel anticoagulants Most sensitive for detecting the presence and serum concentrations of apixaban and rivaroxaban : Anti Xa assays Most sensitive for detecting the effects of dabigatran: Thrombin time

53. Reversal of NAGs Antifibrinolytics : transexamic acid aminocaproic acid Prothrombin concentrate complexes Yet to be validated by literature

54. Direct thrombin inhibitors-reversal Idarucizumab humanized mouse monoclonal antibody fragment binds dabigatran and neutralizes its anticoagulant effects Its affinity for dabigatran is 350 times stronger than dabigatran’s affinity for thrombin Can reverse the anticoagulation effects in a 1:1 ratio . T ime to effect: 11.4 hours

55. Factor Xa inhibitors- reversal Andexanet alfa recombinant factor Xa decoy protein Binds factor Xa inhibitors Effects seen almost immediately (2–5 minutes after administration ), persists for 2 hours Ciraparantag cationic molecule binds factor Xa inhibitors, DTIs, UFH and LMWH reverses anticoagulation activity within 10 to 30 minutes, effects sustained for 24 hours

56. Neuraxial anesthesia – catheter removal Rivaraxoban Apixaban Edoxaban Betrixaban 72 hrs 6 hrs Unanticipated administration Unanticipated administration 22-26 hrs 26-30 hrs 20-28 hrs 72 hrs

57. Neuraxial anesthesia – catheter removal 120 hrs 6 hrs Dabigatran If renal function has been reliably determined, and there are no additional risk factors for bleeding ( eg , age >65 years, hypertension, concomitant antiplatelet medications ), a more graded approach may be considered CrCl ≥ 80 mL/min: 72 hrs CrCl 50-79 mL/min: 96 hrs CrCl 30-49 mL/min: 120 hrs CrCl <30 mL/min: No neuraxial anesthesis 34-36 hrs Unanticipated administration No neuraxial anesthesia in patients receiving paraenteral thrombin inhibitors

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