Warning on LMW Heparin Use with Regionals is Valid

Joseph M. Neal, MD

[Editor’s Note: In the Spring issue, there were two discussions of use of low molecular weight heparin concurrent with neuraxial conduction anesthesia. Additional thoughts are presented here.]

The December 1997 FDA Public Health Advisory1 warning against central neuraxis regional anesthesia concurrent with the perioperative administration of low molecular weight heparin (LMWH) is appropriate. Many anesthesiologists may hastily conclude from this warning that regional anesthesia is no longer an option in patients such as those having total joint arthroplasty, but this need not be the case. The Department of Anesthesiology at the Virginia Mason Medical Center has taken a very conservative approach to this issue, yet still employs regional anesthesia as the technique of choice in these patients.

The FDA advisory reports 30 cases of epidural hematoma in patients who concurrently received LMWH (Lovenox™; enoxaparin). Most of these patients were elderly females undergoing total joint arthroplasty. While not establishing cause-and-effect, the FDA’s warning is highly suggestive that the risk of central neuraxis complications is increased when a regional anesthetic is followed or preceded by LMWH administration. Concurrent use of antiplatelet drugs, other anticoagulants, non-steroidal anti-inflammatory drugs, or indwelling epidural catheters may further increase this risk.2 The unique pharmacology of LMWH impacts decisions anesthesiologists must now make regarding regional anesthesia in patients who are anticoagulated during the perioperative period. The anesthetic implications of LMWH pharmacology are summarized as follows:

• Enoxaparin inhibits Xa four times more than antifactor IIa; that is, the antithrombotic properties of LMWH exceed its anticoagulation activity. This characteristic provides a conceptual basis for the belief that LMWH is potentially a safer alternative to unfractionated heparin for thromboprophylaxis during the perioperative period. Unfortunately, antifactor Xa levels are not routinely measured in most hospitals and thus the extent to which a patient has a safe or acceptable level of antithrombotic or anticoagulant activity cannot be assessed under routine circumstances. Furthermore, LMWH does not cause major alterations in PT or PTT measurements, so these widely available tests offer no useful information. The implication for anesthesiologists is that they cannot rely on objective laboratory data to guide the timing of regional anesthetic interventions.

• The half-life of LMWH is 3-4 hours, but anti-Xa activity is still approximately 50% of peak levels at 12 hours, and requires 24 hours to return to baseline. This implies that placement of central neuraxis blocks, or removal of indwelling catheters, should not occur within at least 12 hours before or after the last administration of LMWH, or conservatively, not within the last 24 hours. After catheter removal, LMWH should not be given until sufficient time has elapsed to determine that a hematoma is not in evolution. Some clinicians suggest that at least 2 hours is needed to make this assessment, but there are obviously many patient-specific variables that require consideration.

• The risk of epidural hematoma following regional anesthesia in patients treated with LMWH can be estimated to be between 1:1,000 and 1:10,000. The implication is that the benefits of regional anesthesia can rarely, if ever, outweigh the risk of potentially permanent paralysis.

Recognizing the need for a strategy to minimize the potential risk of a patient on LMWH receiving a regional anesthetic, the Virginia Mason Department of Anesthesiology recently developed internal guidelines addressing this issue. Simply stated, we are unwilling to perform central neuraxis regional anesthesia on any patient who has received LMWH within 24 hours. If the patient has already received a central neuraxis regional anesthetic, we will institute LMWH only after 24 hours, documentation of full neurologic recovery from the prior anesthetic, and removal of any indwelling catheter at least two hours beforehand. Furthermore, under the leadership of Robert A. Caplan, MD, we are implementing a medical center-wide mechanism to clearly identify any patient being treated with LMWH, such as oncology patients or others with thromboembolic disease. The concern is that these patients may undergo procedures such as diagnostic lumbar puncture or retrobulbar block by practitioners who lack appreciation of the risks involved.

LMWH Not Used

Total joint arthroplasty patients at Virginia Mason continue to receive regional anesthesia for their intraoperative care. The rationale for this decision is two-fold: one, a fortuitous policy by our orthopedic surgeons, and two, our hopefully educated choice of regional anesthetic and analgesic techniques. Our surgeons have decided against the use of LMWH; citing the high incidence of clinically irrelevant lower leg DVT versus the truly rare occurrence of significant thigh DVT and pulmonary embolism. Internal data suggests that our thromboembolic complications are well within national norms. Our orthopedists are also concerned that LMWH-induced hemarthrosis following total knee replacement is a catastrophic complication. Total joint arthroplasty patients at the Mason Clinic are treated with low-dose coumadin which is started the night before surgery, and intermittent compression stockings. The significance of this surgical regimen should not be lost, for it implies that not all orthopedic surgeons have “bought into” the necessity of using LMWH in their patients.

The decision of our surgeons not to use LMWH has doubtlessly made our lives easier. While grateful for this advantage, we nevertheless believe that our anesthetic management of total joint arthroplasty patients presents a viable alternative to LMWH use-one that retains all of the purported benefits of regional anesthesia. Summarized here are the central points to our approach:

1. Postoperative epidural analgesia has not added value to our care of these patients. Total hip arthroplasty patients usually walk and take oral analgesics the morning following surgery; seldom requiring more than IV-PCA the day of surgery. As for total knee replacement, a recent study performed here by Hugh Allen, MD,3 documented that postoperative femoral nerve block provides superior analgesia to that attained with IV-PCA.

2. We use spinal anesthesia for all of our total joint arthroplasty patients. Since spinal techniques are associated with fewer central neuraxis bleeding complications than epidural techniques,4 our patients enjoy an extra margin of safety regardless of anticoagulant use. Furthermore, we believe regional anesthesia per se significantly decreases the risk of thromboembolic complications in this cohort of patients,5 and adds an extra margin of safety as they become fully anticoagulated with coumadin.

3. We believe that the risk of central neuraxis bleeding following regional anesthesia and concurrent LMWH is real. This explains our conservative approach of separating any regional technique from LMWH administration by a minimum of 24 hours. Nevertheless, should our surgeons change their minds and start to use LMWH, the above protocol potentially allows for the concurrent use of regional anesthesia. Specifically, a single-dose spinal anesthetic and the avoidance of an indwelling catheter would not necessarily obviate the utilization of LMWH, providing that the first dose is not given until at least 24 hours after subarachnoid block placement, and the patient has no associated risk factors such as additional antiplatelet therapy. We speculate that the risk of thromboembolic complications occurring within the 24 hour period between the subarachnoid block and the first LMWH administration is acceptably low, and takes advantage of the known anticoagulant effects of spinal or epidural anesthesia.

Additional Approaches

In summary, the FDA has acted responsibly in calling attention to the danger of combining regional anesthesia with LMWH administration. This should not, however, mandate a moratorium on regional anesthesia in the total joint arthroplasty patient. The combination of regional anesthesia and analgesia with perioperative coumadin and intermittent compression stockings appears to result in an acceptably low risk of thromboembolic complications. For those practitioners who wish to use LMWH, regional anesthesia may still be an alternative, provided that its use is separated from LMWH administration by at least 12, and preferably 24, hours.

Dr. Neal is from the Department of Anesthesiology, The Virginia Mason Clinic, Seattle, WA.

References

1. FDA Public Health Advisory. Reports of epidural or spinal hematomas with the concurrent use of low molecular weight heparin and spinal/epidural anesthesia or spinal puncture. US Department of Health and Human Services. December 15, 1997.

2. Horlocker TT, Heit JA. Low molecular weight heparin: biochemistry, pharmacology, perioperative prophylaxis regimens, and guidelines for regional anesthetic management. Anesth Analg 1997;85:874-885.

3. Allen HW, Liu SS, Ware PD, Nairn CS, Owens BD. Peripheral nerve blocks improve analgesia after total knee replacement surgery. 1997;85:874-885.

4. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg 1994;79:1165-1177.

5. Liu SS, Carpenter RL, Neal JM. Epidural anesthesia and analgesia. Their role in perioperative outcome. Anesthesiology 1995;82:1474-1506.