Abstract

Purpose: To determine the effect of general anesthesia on clopidogrel resistance among patients undergoing intracranial stenting procedures Background: Clopidogrel resistance is associated with increased periprocedural thromboembolic complications in neurovascular stenting procedures. Clopidogrel is metabolized by cytochrome P450 system to an active drug that irreversibly binds to the platelet ADP receptor P2Y12 and inhibits downstream platelet aggregation. General anesthetics are commonly used in intracranial stenting procedures and are known to inhibit cytochrome P450 monooxygenases. Therefore we hypothesized that the use of common general anesthetics would be associated with increased clopidogrel resistance. Methods: We conducted a retrospective chart review of 41 patients who underwent intracranial stenting and coiling procedures under general anesthesia from 2010-2013. We analyzed the 35/41 who had platelet assays performed within twenty-four hours both before and after the procedure (VerifyNow, Accumetrics, Inc., San Diego, CA, USA). P2Y12 reaction unit (PRU) was used to measure platelet resistance, with values ≤178 indicating increased bleeding risk, 179-238 therapeutic, and ≥239 thrombogenic. Pre-procedural and post-procedural mean PRU values were compared using t tests to determine the effect of general anesthesia on clopidogrel resistance. Results: We found significantly increased post-procedure PRUs compared to pre-procedure PRUs. Mean PRU twenty-four hours before procedure was 214±34 (95% CI 180-248) compared with 260±25.24 (95% CI 235-285) twenty-four hours after the procedure (p<0.05). Out of 35 patients, 27 (77%) had increased PRUs post- procedure compared to pre-procedure. Conclusion: Clopidogrel resistance is increased following endovascular stenting procedures. We propose that this occurs through competitive interaction with CYP isoforms by general anesthetics. We are not aware of any prior studies demonstrating an association between general anesthetics and clopidogrel resistance. Further prospective studies are needed to further define this observation.

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