Intravenously and subcutaneously administered standard heparin

Several large studies have documented the safety of short-term intravenously administered heparinization in patients undergoing neuraxial anesthesia, provided that the heparin activity is closely monitored, indwelling catheters are removed at a time when circulating heparin levels are relatively low, and patients with a preexisting coagulation disorder are not included in the study. Conversely, traumatic needle placement, initiation of anticoagulation within 1 h of needle insertion, or concomitant aspirin therapy have been identified as risk factors in the development of spinal hematoma in patients receiving anticoagulant therapy.

Intravenous heparin administration should be delayed for 1 h after needle placement. Indwelling catheters should be removed 1 h before a subsequent heparin administration or 2 to 4 h after the last heparin dose. Evaluation of the patient’s coagulation status may be appropriate before catheter removal if the patient has demonstrated enhanced response to heparin or is receiving high doses of heparin. Although a bloody or difficult needle placement may increase risk, no data support mandatory cancellation of a case should this occur. Prolonged therapeutic anticoagulation appears to increase the risk of spinal hematoma formation, especially if combined with other anticoagulants or thrombolytic agents. Therefore, neuraxial blocks should be avoided in this clinical setting. If systematic anticoagulation therapy is begun with an epidural catheter in place, catheter removal should be delayed for 2 to 4 h after discontinuation of heparin and after evaluation of coagulation status (Table 125-1).

Low-dose standard (unfractionated) heparin is subcutaneously administered for thromboprophylaxis in patients undergoing major thoracoabdominal operations. Despite the widespread use of thromboprophylaxis with subcutaneously administered heparin, only a few cases of spinal hematoma have been associated with neuraxial blockade in the presence of low-dose heparin. It is important to note that, although the American College of Chest Physicians’ guidelines for prevention of thromboembolism more often recommend thrice daily administration of subcutaneous heparin (due to patient comorbid conditions and increased risk of thromboembolism), the safety of neuraxial block in these patients is unknown.

There is no contradiction to the use of neuraxial techniques along with standard heparin therapy administered subcutaneously in a twice-daily (5000 units) regimen. However, more frequent administration or higher doses may be associated with an increased risk of neuraxial bleeding. Regardless of dosing regimen, the risk of neuraxial bleeding may be reduced by delaying the heparin injection until after the block is performed and may be increased in debilitated patients or after prolonged therapy.

The concurrent use of medications that affect other components of the clotting mechanisms may increase the risk of bleeding complications for patients receiving intravenously or subcutaneously administered standard heparin. These medications include antiplatelet medications, LMWH, and oral anticoagulants.

Low-molecular-weight heparin

LMWH was introduced for thromboprophylaxis following knee or hip arthroplasty. Extensive clinical testing and use of LMWH in Europe over the last 10 years has suggested that no increased risk of spinal hematoma exists in patients undergoing neuraxial anesthesia while perioperatively receiving LMWH thromboprophylaxis. However, in the first 5 years after LMWH was released for general use in the United States in May 1993, more than 60 cases of spinal hematoma associated with neuraxial anesthesia administered in the presence of perioperative LMWH prophylaxis were reported. Many of these events occurred when LMWH was administered intraoperatively or early postoperatively to patients undergoing continuous epidural anesthesia and analgesia. Concomitant antiplatelet therapy was present in several cases (Box 125-1). Timing of catheter removal may also have an impact. Although the actual frequency of spinal hematoma in patients receiving LMWH while undergoing spinal or epidural anesthesia is difficult to determine, the incidence has been estimated to be 1 in 3100 continuous epidural anesthetics and 1 in 41,000 spinal anesthetics. This frequency of spinal hematoma is similar to that reported for women undergoing total knee replacement with epidural analgesia.

The indications and labeled uses for LMWH continue to evolve. Indications for thromboprophylaxis as well as treatment of thromboembolism or myocardial infarction have been introduced. Several off-label applications of LMWH are of special interest to the anesthesia provider. LMWH has been demonstrated to be efficacious as a “bridge therapy” for patients chronically anticoagulated with warfarin, including parturients and patients with prosthetic cardiac valves, a history of atrial fibrillation, or a preexisting hypercoagulable condition. The doses of LMWH are those associated with thromboembolism treatment, not prophylaxis, and are much higher. An interval of at least 24 h is required for the anticoagulant activity to resolve.

Using an antifactor Xa assay to measure patients’ levels of heparin, low molecular weight heparin, danaparoid, etc., is not predictive of the risk of bleeding and, thus, is not helpful in the management of patients undergoing neuraxial blocks. Antiplatelet or orally administered anticoagulant medications in combination with LMWH may increase the risk of spinal hematoma.

A single-dose spinal anesthetic may be the safest neuraxial technique in patients preoperatively receiving LMWH. In these patients, needle placement should be done at least 10 to 12 h after the last dose of LMWH. Patients receiving higher “treatment” doses of LMWH (e.g., enoxaparin 1 mg/kg twice daily) will require longer delays (24 h). Neuraxial techniques should be avoided in patients receiving a dose of LMWH within 2 h preoperatively (i.e., patients undergoing general surgery) because needle placement occurs during peak anticoagulant activity; ideally, at least 12 h should elapse after the last dose of LMWH is administered before proceeding with a neuraxial technique (see Table 125-1).

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 h postoperatively. In addition, it is recommended that indwelling catheters be removed before initiation of LMWH thromboprophylaxis. The decision to implement LMWH therapy in the presence of an indwelling catheter must be made with care, and this therapy should occur only (1) with once-daily dosing of LMWH and (2) all other medications that affect hemostasis should be avoided. Extreme vigilance of the patient’s neurologic status is warranted.

For any LMWH prophylaxis regimen, timing of catheter removal is of paramount importance. Catheter removal should be delayed for at least 10 to 12 h after a dose of LMWH is administered. Subsequent dosing should be withheld for at least 2 h after catheter removal.

Oral anticoagulants

Little data exist regarding the risk of spinal hematoma in patients with indwelling epidural catheters receiving anticoagulation with warfarin. Importantly, most clinicians recommend that, except in extraordinary circumstances, spinal or epidural needle/catheter placement and removal should not be performed in fully anticoagulated patients. Although neuraxial anesthesia, including postoperative epidural analgesia, may be safely performed in patients who are anticoagulated perioperatively with warfarin, the optimal duration of indwelling catheter use and the timing of its removal remain controversial. Variable patient response to warfarin anticoagulation is also well documented; a prothrombin time (PT) and corresponding international normalized ratio (INR) must be assessed daily to guide therapy.

Anesthetic management of patients who are anticoagulated perioperatively with warfarin depends on the dose and timing of initiation of therapy. PT and INR values in patients on chronic oral anticoagulation therapy will take 3 to 5 days to normalize after discontinuation of anticoagulant therapy. It is recommended that the patient’s normal coagulation status be documented before implementation of the neuraxial block.

Often, the first dose of warfarin is administered the night before surgery. For these patients, the PT and INR should be checked before the neuraxial block is placed if the first dose of warfarin was given more than 24 h earlier, or if a second dose of oral anticoagulant was administered. Patients receiving low-dose warfarin therapy during epidural analgesia should have their PT and INR monitored on a daily basis, and these values should be checked before catheter removal if the initial dose of warfarin was administered more than 36 h beforehand. Initial studies evaluating the safety of epidural analgesia in association with oral anticoagulation used low-dose warfarin, with mean daily doses of approximately 5 mg. Higher-dose warfarin therapy may require more intensive monitoring of coagulation status. Reduced doses of warfarin should be given to patients who are likely to have an enhanced response to the drug. There is no definitive recommendation for removal of neuraxial catheters in patients with an INR greater than 1.5 and less than 3. Caution must be exercised in making decisions about removing or maintaining these catheters (see Table 125-1).

Antiplatelet medications

Antiplatelet medications are seldom used as primary agents of thromboprophylaxis. Several large studies have demonstrated the relative safety of neuraxial blockade in both obstetric and surgical patients receiving nonsteroidal anti-inflammatory drugs (NSAIDs). The use of NSAIDs does not appear to represent a significant risk for the development of spinal hematoma in patients having epidural or spinal anesthesia. However, the concurrent use of medications that affect other components of clotting mechanisms—such as oral anticoagulants, standard heparin, and LMWH—may increase the risk of bleeding complications for patients receiving antiplatelet agents (see Box 125-1).

Ticlopidine (Ticlid) and clopidogrel (Plavix) are also platelet-aggregation inhibitors. These agents interfere with platelet-fibrinogen binding and subsequent platelet-platelet interactions. The effect is irreversible for the life of the platelet. Ticlopidine and clopidogrel have no effect on platelet cyclooxygenase, acting independently of aspirin. Platelet dysfunction is present for 5 to 7 days after discontinuation of clopidogrel and 10 to 14 days with ticlopidine. Platelet glycoprotein IIb/IIIa receptor antagonists—including abciximab (ReoPro), eptifibatide (Integrilin), and tirofiban (Aggrastat)—inhibit platelet aggregation by interfering with platelet-fibrinogen binding and subsequent platelet-platelet interactions. Time to normal platelet aggregation following discontinuation of therapy ranges from 8 h (eptifibatide, tirofiban) to 48 h (abciximab). Increased perioperative bleeding in patients undergoing cardiac and vascular operations after receiving ticlopidine, clopidogrel, or glycoprotein IIb/IIIa antagonists warrants concern regarding the risk of anesthesia-related hemorrhagic complications. It is recommended that platelet function be allowed to recover prior to neuraxial block in patients receiving ticlopidine, clopidogrel, or platelet glycoprotein IIb/IIIa inhibitors.

Conclusion

The decision to perform spinal or epidural anesthesia or analgesia and the timing of catheter removal in a patient receiving anticoagulants perioperatively should be made on an individual basis, weighing the definite (albeit small) risk of spinal hematoma with the benefits of regional anesthesia for a specific patient. The patient’s coagulation status should be optimized at the time of spinal or epidural needle or catheter placement, and the level of anticoagulation must be carefully monitored during the period of epidural catheterization (see Table 125-1). Patients should be closely monitored in the perioperative period for early signs of cord compression, such as severe back pain, progression of numbness or weakness, and bowel and bladder dysfunction. A delay in diagnosis may lead to irreversible cord ischemia. Significant neurologic recovery is unlikely if surgery is postponed more than 8 h.