Patients most likely to benefit from regional anesthesia are often treated with anticoagulants, which increases the risk of hemorrhagic complications. Importantly, anticoagulated patients are at an increased risk of developing vertebral canal hematoma (VCH), a complication of neuraxial anesthesia which may result in permanent neurological complications if not rapidly recognized and treated. Therefore, the decision-making strategy of patients at risk of bleeding is important when considering neuraxial or regional anesthesia techniques.

INTRODUCTION

Most organized societies of anesthesiologists, such as the American Society of Regional Anesthesia (ASRA), have published a set of recommendations or guidelines for the management of patients being treated with antiplatelet or anticoagulant medications who are planned to receive central neuraxial blocks (CNB). Recommendations by different organized societies may vary somewhat because no firm evidence exists for most recommendations. Regardless, the available guidelines recommend time intervals after stopping the treatment at which performing regional anesthesia technique may be safer. The recommendations also suggest time intervals at which the treatment with anticoagulants and/or antiplatelet agents can be restarted after the procedure or removal of an epidural catheter. Factors that may increase the patient’s risk of bleeding should also be considered, such as female gender, age (>65 years), history of early bruising or excessive (surgical) bleeding, spinal column abnormalities, and renal insufficiency. Furthermore, the risk of VCH in an anticoagulated patient should be weighed against the benefits of regional anesthesia. 

ANTIPLATELET AGENTS

Table 1 summarizes the current ASRA guidelines on time intervals before and after neuraxial blocks for antiplatelet agents. 

Table 1. Guidelines on time intervals before and after neuraxial blocks for antiplatelet agents (2021)*

Aspirin and NSAIDS

Aspirin and NSAIDS inhibit cyclo-oxygenase (COX), which prevents the formation of the potent platelet aggregation of thromboxane-A2. They are indicated at low doses for primary and secondary prevention of stroke and myocardial infarction. Aspirin affects platelet function for the duration of platelet life; NSAID’s affect function only temporarily. ASRA guidelines recommend no additional precautions in patients treated with these medications before CNB performance.

P2Y12 receptor antagonists

Blocking the P2Y12 receptor inhibits adenosine-diphosphate-mediated platelet aggregation. P2Y12 receptor antagonists include the thienopyridines (clopidogrel, prasugrel, ticlopidine) and the non-thienopyridines (ticagrelor, cangrelor). ASRA guidelines recommend discontinuing all these drugs (excluding cangrelor) for 5-7 days before receiving a CNB (10 days for ticlopidine). Cangrelor should be stopped 3 h before the administration of a neuraxial block. A non-loading dose of clopidogrel, prasugrel, ticlopidine, or ticagrelor can be given immediately after catheter removal or block performance. With an indwelling neuraxial catheter, clopidogrel or ticlopidine can be given from 24 h postoperatively. If a loading dose is not given, the catheter should only be used for 1-2 days. 

Platelet glycoprotein IIb/IIIa receptor antagonists (abciximab, tirofiban, eptifibatide)

Platelet glycoprotein IIb/IIIa receptor antagonists inhibit platelet aggregation via interference with platelet fibrinogen and platelet von Willebrand factor binding. The time intervals are based on the time to return to normal platelet aggregation. The intervals are longer for abciximab (24-48 h) than for eptifibatide and tirofiban (4-8 h). 

Dipyridamole

Dipyridamole is used to prevent ischemic stroke. ASRA guidelines recommend discontinuing the extended-release formulation 24 h before CNB performance. Moreover, the agent should not be given with a neuraxial catheter in situ. 

Cilostazol

Cilostazol inhibits phosphodiesterase IIIa and thus platelet aggregation. ASRA guidelines recommend discontinuation for 48 h before CNB performance. 

ANTICOAGULANT AGENTS

Table 2 summarizes the current ASRA guidelines on time intervals before and after neuraxial blocks for anticoagulant agents.

Table 2. Guidelines on time intervals before and after neuraxial blocks for anticoagulant agents (2021)*

Heparin and low-molecular-weight heparins (LMWH)

Unfractionated heparin (UFH)

UFH binds to antithrombin, leading to the inactivation of thrombin (factor IIa), factor Xa, and factor IXa. Intravenous (i.v.) UFH acts immediately while subcutaneously (s.c.) administered 5,000 I.U. exerts its effects after 1 h. The ASRA guidelines recommended time intervals are dependent on the route of administration and for s.c. UFH on the dose. Time intervals before CNB for s.c. UFH can be up to 24 h after the last dose. Furthermore, patients receiving UFH >4 days should have a platelet count before CNB or catheter removal to exclude heparin-induced thrombocytopenia. 

LMWH

LMWHs inhibit factor Xa and are indicated for venous thromboembolism prophylaxis and treatment. Guidelines by ASRA recommend against routine testing of anti-factor Xa levels since there is no known safe level for performing CNBs. A 12 h time interval should be considered after neuraxial puncture until the first prophylactic dose and a 24 h time interval for therapeutic LMWH. Maintain catheters if the patient receives a prophylactic dose daily. The catheter should be removed 12 h after the last daily prophylactic dose.

Parenteral heparin alternatives

Factor Xa inhibitors (fondaparinux)

A CNB is only appropriate in the following circumstances for a patient treated with fondaparinux: single-needle pass, atraumatic procedure, and no neuraxial catheter.

Direct thrombin inhibitors (argatroban, bivalirudin)

Direct thrombin inhibitors’ effects are monitored via activated partial thromboplastin time (APTT) and last for 3 h after i.v. administration. Neuraxial techniques are not recommended in patients taking argatroban or bivalirudin.

Direct oral anticoagulants

Oral factor Xa inhibitors (rivaroxaban, edoxaban, apixaban)

For rivaroxaban, the time intervals depend on the dose and the patient’s renal function. Edoxaban and apixaban have similar time intervals as rivaroxaban (i.e., 72 h). 

Oral thrombin inhibitors (dabigatran)

Dabigatran is indicated for the prevention and treatment of venous thromboembolism and to lower the risk of a stroke. The time intervals largely depend on the patient’s renal function as >80% is excreted by the kidneys. ASRA guidelines recommend a time interval of 120 h after the last dose before neuraxial puncture in the absence of renal function measurement. A graduated approach based on creatinine clearance should be followed if there are no additional risk factors and a renal function measurement is available. ASRA guidelines advise against administering dabigatran when a neuraxial catheter is in situ. Moreover, the catheter must be removed 6 h before administering the agent again.

Warfarin

Warfarin inhibits the vitamin-K-dependent clotting factors II, VII, IX, and X synthesis. ASRA guidelines recommend a normal international normalized ratio (INR; i.e., ≤1.1). Administration of the drug with a neuraxial catheter in place is acceptable with caution (e.g., neurological observations of sensory and motor function) when the INR is 1.5-3.0. Catheters can be removed with an INR <1.5 and continued neurological observations for 24 h. 

Warfarin can be reversed with vitamin K in the absence of major bleeding, an i.v. infusion acts within 6-8 h. Prothrombin complex concentrate (Octaplex and Beriplex) can also be used. 

Thrombolytic/fibrinolytic agents (alteplase, streptokinase)

Thrombolytic/fibrinolytic agents interact with plasminogen to produce plasmin that lyses links between fibrin molecules to dissolve clots. These drugs are used in acute myocardial infarction, pulmonary embolism, and cerebrovascular accidents. A neuraxial puncture should only be considered 48 h after administration of these agents in patients where clotting studies (including fibrinogen count) are normal. In addition, patients should be neurologically monitored, ideally every 2 h.

HOW TO USE THE GUIDELINES IN PERIPHERAL NERVE BLOCKS?

Even less objective information is available regarding the frequency and outcome of hemorrhagic complications after peripheral nerve blocks (PNBs). 

The ASRA guidelines of 2021 include a summary of 32 case reports of patients having severe hemorrhagic complications after PNBs and observed the following trends:

• Patients suffering from neurological deficits all completely recovered within 12 months.
• Patients requiring hospitalization after developing complications had a prolonged stay.
• Complications in anticoagulated patients resulted more from blood loss than from neurological damage.
• Deep plexus (e.g., lumbar plexus block) and deep peripheral blocks (e.g., proximal sciatic nerve block) carried a higher risk.
• There was often no evidence of vessel trauma.

In conclusion, anticoagulated patients receiving perineuraxial, deep plexus, or deep peripheral nerve blocks should be managed as if they are undergoing neuraxial anesthesia. Clinical discretion should be used for decision-making regarding the safety of other regional anesthesia techniques, such as superficial plexus blocks and nerve blocks. As an example, the vascularity and compressibility of the anatomical site where the blocks are being performed and the potential consequences of bleeding at those sites should be kept in mind. The risks of discontinuing anticoagulation therapy in these patients should be weighed versus the benefits of neuraxial and nerve block anesthesia and analgesia. 

READ MORE about Anticoagulants at this link on NYSORA: Neuraxial Anesthesia and Peripheral Nerve Blocks in Patients on Anticoagulants

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