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Regional Anaesthesia
And Antithrombotic
Drugs
BY
DR. CHAMIKA HURUGGAMUWA
(REGISTRAR IN ANESTHESIA)
Key points
#Vertebral canal haematoma is a rare but potentially
devastating complication of central neuraxial blockade. Significant risk
factors include clotting abnormalities and drug-induced coagulation
disturbance.
#Careful timing of administration of antithrombotic drugs in relation to
regional anaesthesia is important to minimize potential bleeding
complications.
#Several new classes of antithrombotic drugs have been introduced into
clinical practice over recent years. These are often used in combination
making risk assessment difficult.
The benefits of regional anaesthesia are well documented.
Increasing number of patients receiving antithrombotic medication, concerns exist about the
risk of perineural bleeding complications or neurological damage from compressive vertebral
canal haematoma (VCH).
Patients taking antithrombotic agents often stand to gain the most benefit from regional
anaesthesia.
VCH
Very rare but potentially devastating complication of central neuraxial blockade (CNB).
Without rapid diagnosis and surgical decompression, permanent neurological damage is likely.
Risk factors associated with VCH occurring after CNB,
Taking anticoagulant drugs
Coagulopathy
Bleeding occurred immediately after catheter removal, demonstrating that this procedure is as
important as catheter insertion
Technical difficulty with the block.
Increasing age, female sex, and significant co-morbidities also appeared to be risk factors.
several new classes of antithrombotic agents have been introduced into clinical practice.
Often used in combination, making risk assessment difficult.
A balance between the benefits ( prevention of thrombosis) and risks (major bleeding and VCH)
should be determined for each patient and depends on the type and dose of antithrombotic,
the choice of a regional technique, and patient characteristics.
Antiplatelet agents
Aspirin and non-steroidal anti-inflammatory drugs
These drugs impair platelet function by inhibiting platelet cyclo-oxygenase (COX).
Aspirin irreversible blockade and other NSAIDS reversible blockade.
The antiplatelet effect of aspirin persists until a new platelet population is manufactured (7 days),
whereas platelet function generally returns to normal within 2–3 days after stopping an NSAID.
NSAIDs including aspirin do not increase the risk of VCH and are not a contraindication to CNB.
When NSAIDs, including aspirin, are used in combination with other drugs that affect coagulation,
an increased risk of bleeding complications exists
The current guidance from the American Society of Regional Anesthesia and Pain Medicine
(ASRA) recommends against using CNB in patients receiving NSAIDs when the concurrent use of
other medication affecting coagulation, for example, LMWH, is planned in the early
postoperative period.
The European Society of Anaesthesiology suggests commencing thromboprophylaxis after
operation rather than before operation in the presence of aspirin.
Thienopyridines
Clopidogrel (half life of 6–8 h) and prasugrel (half life around 7 h) are potent antiplatelet agents.
They reduce platelet aggregation by the irreversible inhibition of the platelet ADP receptor and
the subsequent ADP-mediated activation of the glycoprotein IIb/IIIa (GPIIb/IIIa) complex.
prasugrel exerts its antiplatelet effect more consistently and to a greater extent than
clopidogrel but is associated with an increased risk of major bleeding.
A recent study of clopidogrel use in patients undergoing non-elective orthopaedic surgery
demonstrated no increase in blood loss or transfusion requirements compared with patients
not taking clopidogrel.
The product data sheets for both clopidogrel and prasugrel currently recommend discontinuing
at least 7 days before surgery.
period of 7–10 days has been recommended for prasugrel due to the higher incidence of
bleeding when compared with clopidogrel.
A minimum of 6 weeks DAPT after bare-metal stentinsertion recommended to avoid thrombotic
complications. If surgery cannot be delayed beyond these high-risk periods, consultation with a
cardiologist is strongly recommended before any planned interruption of treatment and an
individual management plan.
Heparin therapy alone has no antiplatelet properties and is unlikely to protect against stent
thrombosis.
Dipyridamole
Inhibit plt adhesion to damaged vessel walls.
Dipyridamole has antiplatelet and vasodilating actions and is oftenused in combination with
aspirin in the management of cerebrovascular disease. The half life is 10 h. There are a lack of
data in the literature with regard to regional anaesthesia and dipyridamole.
The current guidelines suggest that when used alone, there is no need to discontinue before
CNB.
GPIIb/IIIa receptor antagonists
Block the final common pathway of plt aggregation.
Abciximab, eptifibatide, and tirofiban
Abciximab is a monoclonal antibody and although low levels of GPIIb/IIIa receptor blockade are
present for more than 10 days after cessation of abciximab infusion, platelet function typically
returned to normal over a period of 24–48 h.
Platelet function returns to baseline 6–8 h after discontinuing eptifibatide and tirofiban.
Epidural catheters should be removed before starting these drugs.
Parenteral anticoagulants
Unfractionated heparin
I.V. heparin provides an immediate anticoagulant effect which lasts for 4–6 h. It can be
monitored with the activated partial thromboplastin time (APTT) and one of its advantages is
the availability of protamine for rapid reversal.
Administration of subcutaneous UFH for thromboprophylaxis does not usually prolong the
APTT; however, with prolonged administration (.>4 days), the platelet count should be checked
before a regional technique or catheter removal due to the incidence of heparin-induced
thrombocytopenia (HIT)
I.V. heparin infusion should be discontinued for 2–4 h and the APTT normal before regional
block or catheter removal.
Low-molecular-weight heparin
LMWHs potentiate factor Xa inhibition and are used for thromboprophylaxis, treatment of
venous thromboembolism (VTE), and in unstable coronary artery disease.
Compared with UFH, LMWHs have a longer half-life (prolonged in renal impairment), more
predictable pharmacokinetics, and less effect on platelet function.
They are not reliably reversed by protamine sulphate.
The current guidelines recommend waiting 12 h after the last prophylactic dose of LMWH
before CNB or epidural catheter removal.
After CNB or catheter removal, a period of 2–4 h should elapse before LMWH administration
When LMWHs are administered in therapeutic doses for anticoagulation (typical doses; enoxaparin 40–
100 mg twice daily ) an interval of at least 24 h should elapse before regional anaesthesia.
Fondaparinux
Fondaparinux is a synthetic pentasaccharide that has potent anticoagulant activity. It selectively
inhibits factor Xa, does not inactivate thrombin, and has no effect on platelets.
The half-life is 17–21 h in healthy patients, but this may be significantly prolonged in renal
impairment.
The EXPERT study demonstrated that neuraxial or deep peripheral nerve catheters can be used
safely in patients receiving once-daily prophylactic dose fondaparinux, provided a drug-free
period of 48 h is observed; 36 h before catheter removal and re-starting treatment 12 h after
catheter removal.
CNB is not recommended when fondaparinux is used for therapeutic anticoagulation.
Oral anticoagulants
Warfarin
Warfarin inhibits the synthesis of the vitamin K-dependent clotting factors (II, VII, IX, and X)
Therapeutic anticoagulation with warfarin is an absolute contraindication to CNB.
For all but the most minor procedures, warfarin should be discontinued 4–5 days before surgery
allowing the international normalized ratio (INR) to decrease to 1.5
Warfarin should only be recommenced once an epidural/nerve catheter has been removed.
In emergency situations, warfarin can be reversed with vitamin K, prothrombin complex
concentrates, or fresh frozen plasma.
Oral thrombin blockers
Dabigatran and rivaroxaban
The manufacturer recommends a minimum time period of 2 h after epidural catheter removal
before starting dabigatran after operation; however, the current guidelines suggest 6 h based
on the initial studies in which all epidural catheters were removed at least
4–6 h before the first dose.
Peripheral nerve block
The complications of peripheral nerve blocks are generally less serious than those of CNB,
although significant and even fatal retroperitoneal haematomas have been reported after
lumbar sympathetic blockade in patients on thienopyridines (clopidogrel and ticlopidine)
Heparin bridging therapy: when is it
necessary?
Approximately 1% of the UK population are on lifelong warfarin, the most common indication being
atrial fibrillation. The risks of thrombosis vs bleeding need to be quantified before a decision can be
made about perioperative drug management.
Even temporary interruption of these drugs may increase the risk of thrombosis with potential for
morbidity and mortality.
Heparin-bridging therapy is a substitution of therapeutic doses of UFH or LMWH for patients on
long-term warfarin, to provide antithrombotic cover when it is required to be stopped for surgical
procedures.
In patients with a high risk of thromboembolism bridging therapy is recommended.
Minor surgical procedures, for example, extracapsular cataract removal and cystoscopy, may
not require interruption of anticoagulation.
Thank you

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Regional anaesthesia and antithrombotic

  • 1. Regional Anaesthesia And Antithrombotic Drugs BY DR. CHAMIKA HURUGGAMUWA (REGISTRAR IN ANESTHESIA)
  • 2. Key points #Vertebral canal haematoma is a rare but potentially devastating complication of central neuraxial blockade. Significant risk factors include clotting abnormalities and drug-induced coagulation disturbance. #Careful timing of administration of antithrombotic drugs in relation to regional anaesthesia is important to minimize potential bleeding complications. #Several new classes of antithrombotic drugs have been introduced into clinical practice over recent years. These are often used in combination making risk assessment difficult.
  • 3. The benefits of regional anaesthesia are well documented. Increasing number of patients receiving antithrombotic medication, concerns exist about the risk of perineural bleeding complications or neurological damage from compressive vertebral canal haematoma (VCH). Patients taking antithrombotic agents often stand to gain the most benefit from regional anaesthesia.
  • 4. VCH Very rare but potentially devastating complication of central neuraxial blockade (CNB). Without rapid diagnosis and surgical decompression, permanent neurological damage is likely. Risk factors associated with VCH occurring after CNB, Taking anticoagulant drugs Coagulopathy Bleeding occurred immediately after catheter removal, demonstrating that this procedure is as important as catheter insertion Technical difficulty with the block.
  • 5. Increasing age, female sex, and significant co-morbidities also appeared to be risk factors.
  • 6. several new classes of antithrombotic agents have been introduced into clinical practice. Often used in combination, making risk assessment difficult. A balance between the benefits ( prevention of thrombosis) and risks (major bleeding and VCH) should be determined for each patient and depends on the type and dose of antithrombotic, the choice of a regional technique, and patient characteristics.
  • 7. Antiplatelet agents Aspirin and non-steroidal anti-inflammatory drugs These drugs impair platelet function by inhibiting platelet cyclo-oxygenase (COX). Aspirin irreversible blockade and other NSAIDS reversible blockade. The antiplatelet effect of aspirin persists until a new platelet population is manufactured (7 days), whereas platelet function generally returns to normal within 2–3 days after stopping an NSAID. NSAIDs including aspirin do not increase the risk of VCH and are not a contraindication to CNB. When NSAIDs, including aspirin, are used in combination with other drugs that affect coagulation, an increased risk of bleeding complications exists
  • 8. The current guidance from the American Society of Regional Anesthesia and Pain Medicine (ASRA) recommends against using CNB in patients receiving NSAIDs when the concurrent use of other medication affecting coagulation, for example, LMWH, is planned in the early postoperative period. The European Society of Anaesthesiology suggests commencing thromboprophylaxis after operation rather than before operation in the presence of aspirin.
  • 9. Thienopyridines Clopidogrel (half life of 6–8 h) and prasugrel (half life around 7 h) are potent antiplatelet agents. They reduce platelet aggregation by the irreversible inhibition of the platelet ADP receptor and the subsequent ADP-mediated activation of the glycoprotein IIb/IIIa (GPIIb/IIIa) complex. prasugrel exerts its antiplatelet effect more consistently and to a greater extent than clopidogrel but is associated with an increased risk of major bleeding.
  • 10. A recent study of clopidogrel use in patients undergoing non-elective orthopaedic surgery demonstrated no increase in blood loss or transfusion requirements compared with patients not taking clopidogrel. The product data sheets for both clopidogrel and prasugrel currently recommend discontinuing at least 7 days before surgery. period of 7–10 days has been recommended for prasugrel due to the higher incidence of bleeding when compared with clopidogrel.
  • 11. A minimum of 6 weeks DAPT after bare-metal stentinsertion recommended to avoid thrombotic complications. If surgery cannot be delayed beyond these high-risk periods, consultation with a cardiologist is strongly recommended before any planned interruption of treatment and an individual management plan. Heparin therapy alone has no antiplatelet properties and is unlikely to protect against stent thrombosis.
  • 12. Dipyridamole Inhibit plt adhesion to damaged vessel walls. Dipyridamole has antiplatelet and vasodilating actions and is oftenused in combination with aspirin in the management of cerebrovascular disease. The half life is 10 h. There are a lack of data in the literature with regard to regional anaesthesia and dipyridamole. The current guidelines suggest that when used alone, there is no need to discontinue before CNB.
  • 13. GPIIb/IIIa receptor antagonists Block the final common pathway of plt aggregation. Abciximab, eptifibatide, and tirofiban Abciximab is a monoclonal antibody and although low levels of GPIIb/IIIa receptor blockade are present for more than 10 days after cessation of abciximab infusion, platelet function typically returned to normal over a period of 24–48 h. Platelet function returns to baseline 6–8 h after discontinuing eptifibatide and tirofiban. Epidural catheters should be removed before starting these drugs.
  • 14. Parenteral anticoagulants Unfractionated heparin I.V. heparin provides an immediate anticoagulant effect which lasts for 4–6 h. It can be monitored with the activated partial thromboplastin time (APTT) and one of its advantages is the availability of protamine for rapid reversal. Administration of subcutaneous UFH for thromboprophylaxis does not usually prolong the APTT; however, with prolonged administration (.>4 days), the platelet count should be checked before a regional technique or catheter removal due to the incidence of heparin-induced thrombocytopenia (HIT) I.V. heparin infusion should be discontinued for 2–4 h and the APTT normal before regional block or catheter removal.
  • 15. Low-molecular-weight heparin LMWHs potentiate factor Xa inhibition and are used for thromboprophylaxis, treatment of venous thromboembolism (VTE), and in unstable coronary artery disease. Compared with UFH, LMWHs have a longer half-life (prolonged in renal impairment), more predictable pharmacokinetics, and less effect on platelet function. They are not reliably reversed by protamine sulphate. The current guidelines recommend waiting 12 h after the last prophylactic dose of LMWH before CNB or epidural catheter removal.
  • 16. After CNB or catheter removal, a period of 2–4 h should elapse before LMWH administration When LMWHs are administered in therapeutic doses for anticoagulation (typical doses; enoxaparin 40– 100 mg twice daily ) an interval of at least 24 h should elapse before regional anaesthesia.
  • 17. Fondaparinux Fondaparinux is a synthetic pentasaccharide that has potent anticoagulant activity. It selectively inhibits factor Xa, does not inactivate thrombin, and has no effect on platelets. The half-life is 17–21 h in healthy patients, but this may be significantly prolonged in renal impairment. The EXPERT study demonstrated that neuraxial or deep peripheral nerve catheters can be used safely in patients receiving once-daily prophylactic dose fondaparinux, provided a drug-free period of 48 h is observed; 36 h before catheter removal and re-starting treatment 12 h after catheter removal.
  • 18. CNB is not recommended when fondaparinux is used for therapeutic anticoagulation.
  • 19. Oral anticoagulants Warfarin Warfarin inhibits the synthesis of the vitamin K-dependent clotting factors (II, VII, IX, and X) Therapeutic anticoagulation with warfarin is an absolute contraindication to CNB. For all but the most minor procedures, warfarin should be discontinued 4–5 days before surgery allowing the international normalized ratio (INR) to decrease to 1.5 Warfarin should only be recommenced once an epidural/nerve catheter has been removed. In emergency situations, warfarin can be reversed with vitamin K, prothrombin complex concentrates, or fresh frozen plasma.
  • 20. Oral thrombin blockers Dabigatran and rivaroxaban The manufacturer recommends a minimum time period of 2 h after epidural catheter removal before starting dabigatran after operation; however, the current guidelines suggest 6 h based on the initial studies in which all epidural catheters were removed at least 4–6 h before the first dose.
  • 21. Peripheral nerve block The complications of peripheral nerve blocks are generally less serious than those of CNB, although significant and even fatal retroperitoneal haematomas have been reported after lumbar sympathetic blockade in patients on thienopyridines (clopidogrel and ticlopidine)
  • 22. Heparin bridging therapy: when is it necessary? Approximately 1% of the UK population are on lifelong warfarin, the most common indication being atrial fibrillation. The risks of thrombosis vs bleeding need to be quantified before a decision can be made about perioperative drug management. Even temporary interruption of these drugs may increase the risk of thrombosis with potential for morbidity and mortality. Heparin-bridging therapy is a substitution of therapeutic doses of UFH or LMWH for patients on long-term warfarin, to provide antithrombotic cover when it is required to be stopped for surgical procedures.
  • 23. In patients with a high risk of thromboembolism bridging therapy is recommended. Minor surgical procedures, for example, extracapsular cataract removal and cystoscopy, may not require interruption of anticoagulation.
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