The new antiplatelet agents, ticlopidine (Ticlid®) and clopidogrel (Plavix®) affect the use and timing of central neuraxial regional techniques. Anesthesiologists are often faced with questions regarding the timing and risk/benefit ratio of discontinuing these agents prior to regional (and sometimes general) anesthesia. The 1998 American Society of Regional Anesthesia and Pain Medicine (ASRA) Consensus Conference on Anticoagulation and Neuraxial Blockade noted that antiplatelet agents such as anti-inflammatory drugs (NSAIDs) and aspirin do not present an increased risk for intraspinal bleeding when used as single agents concurrently with central neuraxial regional anesthesia.1 Since that time, the use of ticlopidine and clopidogrel has become increasingly common in patients with atherosclerotic disorders. Therefore, in response to these and other advances in clinical anticoagulation, ASRA reconvened the Consensus Conference in April 2002 for the purpose of updating previous recommendations.
Ticlopidine and clopidogrel are prescribed for the prevention of myocardial infarction, stroke, and vaso-occlusive disorders. These drugs are commonly initiated and continued for 30-60 days following coronary artery stent placement. Their mechanism of action involves selective platelet receptor binding of adenylate cyclase-coupled ADP, with consequent inhibition of platelet-fibrinogen binding, reduced platelet aggregation, and subsequent inhibition of clot formation. This is different from, and possibly additive to, aspirin’s mechanism of action. But similar to aspirin, the antiplatelet effects are long-lasting. For instance, the half-life of ticlopidine is 12 hours after a single dose, but 4 to 5 days once steady-state is reached. Clopidogrel’s half-life is 5 to 7 days at steady-state. Ticlopidine is associated with more serious bleeding, especially in patients with renal or hepatic impairment. Conversely, clopidogrel (which is 40-100 times more potent than ticlopidine) does not require dosage adjustment for renal insufficiency. Although both drugs prolong bleeding time, the clinical utility of this test to determine safety and timing of central neuraxial trespass is unknown. When an emergency dictates operating on an individual patient taking ticlopidine, its effects may be reversed with platelet transfusion or methylprednisolone, yet the efficacy of these interventions for facilitating safe block placement has not been established, nor are specific recommendations available for patients taking clopidogrel.
There are no studies available that establish the safety of regional anesthesia performed in the setting of recent ticlopidine or clopidogrel use, nor are there data regarding their interaction with other anticoagulants such as NSAIDs, aspirin, coumadin, or heparinoids. Thus, recommendations concerning concomitant central regional techniques are ultimately speculative. Based on the known increased risk for intraspinal hematoma caused by concurrent usage of several antiplatelet or anticoagulant drugs, one may reasonably opine that their combination with ticlopidine or clopidogrel may increase the risk of intraspinal bleeding. The safe time interval between administration of these drugs and subsequent central neuraxial block is less clear. Because ticlopidine and clopidogrel have relatively short initial half-lives, it again seems reasonable to suggest that their use can be initiated 12 to 24 hours after placement of an uncomplicated spinal or epidural anesthetic. The discontinuation of drug therapy before central instrumentation is not well understood. Recall that aspirin is generally held 10 to 14 days prior to surgery, but is safe to use up until the time of central blockade. However, clinical studies have established the superiority of ticlopidine and clopidogrel over aspirin for the prevention of some thromboembolic events, which suggests that their antiplatelet effects are stronger than those of aspirin. Indeed, the surgical literature now reports incidents of unexpected postoperative bleeding in patients who had received clopidogrel. Until such time as more data are available, ASRA guidelines for the provision of concomitant central neuraxial regional techniques are conservative and parallel those for surgical intervention–stopping ticlopidine for 10-14 days and clopidogrel for 7 days prior to performing a spinal or epidural anesthetic. While these recommendations may ultimately prove to be too conservative, it must be appreciated that patients receiving this class of long-lasting antiplatelet drugs are also likely to have other anticoagulants administered in the immediate postoperative period, thus raising the issue of concurrent multidrug administration.
Dr. Neal is a staff anesthesiologist at the Virginia Mason Medical Center, Seattle, WA, and Dr. Rowlingson is Professor of Anesthesiology and Director of the Acute Pain Clinic at the University of Virginia Medical School, Charlottesville, VA.