The American Society of Regional Anesthesia and Pain Medicine (ASRA) convened a group of experts in the fields of hemostasis, biostatistics, neuraxial anesthesia, and federal drug regulation to participate in a consensus conference on anticoagulants and neuraxial anesthesia and analgesia. The impetus for the conference was developing evidence that the use of low molecular weight heparin (LMWH) thromboembolism prophylaxis in the U.S.A. is associated with a higher frequency of clinically significant neuraxial bleeding when combined with neuraxial anesthesia and analgesia regimens than LMWH thromboembolism prophylaxis regimens in European surgical patients. The original manuscripts that developed from the consensus conference held May 2-3, 1998, in Chicago, Illinois are published as a supplement to Regional Anesthesia and Pain Medicine 1998; 23 Suppl. The original manuscripts used in conjunction with these abridged consensus statements provide the necessary background to a more complete understanding of the clinical issues discussed in the Consensus Conference. The original manuscript can be viewed at the ASRA web site (WWW.ASRA.COM)

When oral anticoagulation therapy and neuraxial anesthesia are used together, physicians must be aware of the interactions of warfarin on the coagulation cascade and the role of the prothrombin time and INR in monitoring its effect. To minimize the risk of complications from this practice we believe:

1. For patients on chronic oral anticoagulation, the anticoagulant therapy must be stopped and the prothrombin time (INR) measured prior to initiation of neuraxial block. Early after discontinuation of warfarin therapy, the prothrombin time and the INR reflect predominantly factor VII levels, and in spite of acceptable factor VII levels, factors II and X levels may not be adequate for normal hemostasis.

2. The concurrent use of medications that affect other components of the clotting mechanisms may increase the risk of bleeding complications for patients receiving oral anticoagulants, and do so without influencing the prothrombin time and INR. These medications include aspirin and other NSAIDs, and heparin. One should reflect on these drug interactions when an indwelling neuraxial catheter is being considered for a patient.

3. For patients receiving an initial dose of warfarin prior to surgery, the prothrombin time and 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.

4. Patients receiving low dose warfarin therapy during epidural analgesia should have their prothrombin time and INR monitored on a daily basis, and checked before catheter removal, if initial doses of warfarin are administered more than 36 hours preoperatively. Initial studies evaluating the safety of epidural analgesia in association with oral anticoagulation utilized low dose warfarin, with the mean daily doses of approximately 5 mg of warfarin. Higher dose warfarin may require more intensive monitoring of the coagulation status.

5. Neurologic testing of sensory and motor function should be performed routinely during epidural analgesia for patients on warfarin therapy. The type of analgesic solution should be tailored to minimize the degree of sensory and motor blockade. These checks should be continued after catheter removal for at least 24 hours, and longer if the INR was greater than 1.5 at the time of catheter removal.

6. An INR > 3 should prompt the physician to withhold or reduce the warfarin dose in patients with indwelling neuraxial catheters. We can make no definitive recommendation for removal of neuraxial catheters in patients with therapeutic levels of anticoagulation during neuraxial catheter infusion. Clinical judgement must be exercised in making decisions about removing or maintaining these catheters.

7. Reduced doses of warfarin should be given to patients who are likely to have an enhanced response to the drug.

Enneking FK, Benzon HT. Oral Anticoagulants and Regional Anesthesia: A Perspective. Reg Anesth Pain Med 1998: 23 Suppl.

Antiplatelet drugs, by themselves, appear to represent no added significant risk for the development of spinal hematoma in patients having epidural or spinal anesthesia. This is an important observation since a very sizable fraction of our surgical patients receive concomitant antiplatelet therapy during their perioperative course. We believe:

1. The use of antiplatelet drugs alone does not create a level of risk that will interfere with the performance of neuraxial blocks.

2. Data on the combination of antiplatelet agents with other forms of anticoagulation are lacking. However, the concurrent use of other medications affecting clotting mechanisms, such as oral anticoagulants, standard heparin, and LMWH, may increase the risk of bleeding complications in these patients.

3. There is no wholly accepted test, including the bleeding test, which will guide antiplatelet therapy. Careful preoperative assessment of the patient to identify alterations of health that might contribute to bleeding is crucial.

4. At this time, there do not seem to be specific concerns as to the timing of single-shot or catheter techniques in relationship to the dosing of NSAIDs, postoperative monitoring, or the timing of neuraxial catheter removal.

Addendum (May, 2001)
The risk of spinal hematoma with antiplatelet medications affecting platelet GP IIb/IIIa receptors, such as ticlopidine and clopidogrel, is unknown. Clinicians should proceed cautiously until additional information is available.

Urmey WF, Rowlingson JC. Do Antiplatelet Agents Contribute to the Development of Perioperative Spinal Hematoma? Reg Anesth Pain Med 1998: 23 Suppl.

The physiologic state induced by the use of fibrinolytic and thrombolytic agents represents a unique problem in performing regional anesthesia. With the advances in fibrinolytic/thrombolytic therapy, we may see increased use of these drugs in the perioperative period which will require further increases in vigilance. We believe:

1. Patients receiving concurrent heparin with fibrinolytic and thrombolytic drugs are at high risk of adverse neuraxial bleeding during spinal or epidural anesthesia. This impression is based on limited case reports and extrapolation of data from patients receiving combined fibrinolytic or thrombolytic drugs and heparin for coronary thrombolysis.

2. Preoperative evaluation should determine whether fibrinolytic or thrombolytic drugs have been used preoperatively, or have the likelihood of being used intraoperatively or postoperatively.

3. Patients receiving fibrinolytic and thrombolytic drugs should be cautioned against receiving spinal or epidural anesthetics except in highly unusual circumstances. Guidelines detailing original contraindications for thrombolytic drugs suggest avoidance of these drugs within 10 days of puncture of noncompressible vessels. Data are not available to clearly outline the length of time neuraxial puncture should be avoided after discontinuation of these drugs.

4. In those patients who have received neuraxial blocks at or near the time of fibrinolytic and thrombolytic therapy, neurologic monitoring needs to be carried out for an appropriate interval. It may be that the interval of monitoring should not be more than 2 hours between neurologic checks. Further, if neuraxial blocks have been combined with fibrinolytic and thrombolytic therapy and ongoing epidural catheter infusion, the infusion should be limited to drugs minimizing sensory and motor blockade.

5. There is no definitive recommendation for removal of neuraxial catheters in patients who unexpectedly receive fibrinolytic and thrombolytic therapy during a neuraxial catheter infusion. Caution must be exercised in making decisions about removing or maintaining these catheters. The measurement of fibrinogen may be helpful in making a decision about catheter removal or maintenance.

Rosenquist RW, Brown DL. Neuraxial Bleeding: Fibrinolytics/Thrombolytics. Reg Anesth Pain Med 1998: 23 Suppl.

Therapeutic and full anticoagulation doses of standard (unfractionated) heparin are commonly used during the perioperative period in vascular surgery and cardiac surgery patients. Low dose heparin also is frequently used for prophylaxis against development of venous thromboembolism in general, orthopedic, and urologic surgery. Neuraxial anesthetic techniques are often attractive for these patients, as these techniques may provide reduced morbidity and improved postoperative analgesia. Combining standard heparin therapy or prophylaxis and neuraxial block demands consideration of their interactions and we believe:

1. During subcutaneous (mini-dose) prophylaxis there is no contraindication to the use of neuraxial techniques. The risk of neuraxial bleeding may be reduced by delay of the heparin injection until after the block, and may be increased in debilitated patients or after prolonged therapy.

2. Combining neuraxial techniques with intraoperative anticoagulation with heparin during vascular surgery seems acceptable with the following cautions:

• Avoid the technique in patients with other coagulopathies.
• Heparin administration should be delayed for 1 hour after needle placement.
• Remove the catheter 1 hour before any subsequent heparin administration or 2-4 hours after the last heparin dose.
• Monitor the patient postoperatively to provide early detection of motor blockade and consider use of minimal concentration of local anesthetics to enhance the early detection of a spinal hematoma.
• Although the occurrence of a bloody or difficult neuraxial needle placement may increase risk, there are no data to support mandatory cancellation of a case. Clinical judgment is needed. If a decision is made to proceed, full discussion with the surgeon and careful postoperative monitoring are warranted.

3. Currently, sufficient data and experience are not available to determine if the risk of neuraxial hematoma is increased when combining neuraxial techniques with the full anticoagulation of cardiac surgery.

4. Prolonged therapeutic anticoagulation appears to increase risk of spinal hematoma formation, especially if combined with other anticoagulants or thrombolytics. Therefore, neuraxial blocks should be avoided in this clinical setting. Whereas, if systemic anticoagulation therapy is begun with an epidural catheter in place, it is recommended to delay catheter removal for 2-4 hours following therapy discontinuation and evaluation of coagulation status.

5. The concurrent use of medications that affect other components of the clotting mechanisms may increase the risk of bleeding complications for patients receiving standard heparin. These medications include aspirin and other NSAIDs, LMWH and oral anticoagulants.

Liu SS, Mulroy MF. Neuraxial Anesthesia and Analgesia in the Presence of Standard Heparin. Reg Anesth Pain Med 1998: 23 Suppl.

The decision to perform a neuraxial block on a patient receiving perioperative LMWH must be made on an individual basis by weighing the risk of spinal hematoma with the benefits of regional anesthesia for a specific patient. Anesthesiologists in the United States can draw on the European experience to develop their own practice guidelines for the management of patients undergoing spinal and epidural blocks while receiving perioperative LMWH. Although it is impossible to devise recommendations that will completely eliminate the risk of spinal hematoma, we believe:

1. Monitoring of the anti-Xa level is not recommended. The anti-Xa level is not predictive of the risk of bleeding and is, therefore, not helpful in the management of patients undergoing neuraxial blocks.

2. Antiplatelet or oral anticoagulant medications administered in combination with LMWH may increase the risk of spinal hematoma. Concomitant administration of medications affecting hemostasis, such as antiplatelet drugs, standard heparin, or dextran represents an additional risk of hemorrhagic complications perioperatively, including spinal hematoma. Education of the entire patient care team is necessary to avoid potentiation of the anticoagulant effects.

3. The presence of blood during needle and catheter placement does not necessitate postponement of surgery. However, initiation of LMWH therapy in this setting should be delayed for 24 hours postoperatively. Traumatic needle or catheter placement may signify an increased risk of spinal hematoma, and it is recommended that this consideration be discussed with the surgeon.

4. Patients on preoperative LMWH can be assumed to have altered coagulation. A single-dose spinal anesthetic may be the safest neuraxial technique in patients receiving preoperative LMWH. In these patients needle placement should occur at least 10-12 hours after the LMWH dose, whereas patients receiving higher doses of LMWH (e.g. enoxaparin 1 mg/kg twice daily) will require longer delays (24 hours). Neuraxial techniques should be avoided in patients administered a dose of LMWH two hours preoperatively (general surgery patients), because needle placement would occur during peak anticoagulant activity.

5. Patients with postoperative initiation of LMWH thromboprophylaxis may safely undergo single-dose and continuous catheter techniques. The first dose of LMWH should be administered no earlier than 24 hours postoperatively and only in the presence of adequate hemostasis. In addition, it is recommended that indwelling catheters be removed prior to initiation of LMWH thromboprophylaxis. If a continuous technique is selected, the epidural catheter may be left indwelling overnight and removed the following day, with the first dose of LMWH administered two hours after catheter removal.

6. The decision to implement LMWH thromboprophylaxis in the presence of an indwelling catheter must be made with care. Extreme vigilance of the patient's neurological status is warranted. An opioid or dilute local anesthetic solution is recommended in these patients to allow frequent monitoring of neurological function. If epidural analgesia is anticipated to continue for more than 24 hours, LMWH administration may be delayed (in selected cases) or an alternate method of thromboprophylaxis may be selected (e.g. external pneumatic compression), based on the risk profile for the individual patient. These decisions should be made preoperatively to allow optimal management of both postoperative analgesia and thromboprophylaxis.

7. For any LMWH prophylaxis regimen, the timing of catheter removal is of paramount importance. Catheter removal should be delayed for at least 10-12 hours after a dose of LMWH. A true normalization of the patient's coagulation status could be achieved if the evening dose of LMWH was not given and the catheter was removed the following morning (24 hours after the last dose). Again, subsequent dosing should not occur for at least two hours after catheter removal.

Horlocker TT, Wedel DJ. Neuraxial Block and Low Molecular Weight Heparin: Balancing Perioperative Analgesia and Thromboprophylaxis. Reg Anesth Pain Med 1998: 23 Suppl.