Published guidelines advise on the timing for the discontinuation of antiplatelet agents before neuraxial instrumentation, however, no reports or recommendations are available for managing patients requiring epidural or intrathecal procedures in the setting of continual dual-antiplatelet therapy.1 The effects of clopidogrel and the risks and consequences of epidural hematoma are well documented.2 In the case of neurointerventional procedures, however, extreme circumstances may warrant intrathecal access in the setting of current antiplatelet therapy. We report our management of this situation and the actions intended to mitigate the inherent risks.
Written consent was obtained before publication, and this case report is in compliance with IRB requirements.
A 63-year-old woman presented with a Hunt-and-Hess grade II (moderate to severe headache, stiff neck, and no neurological deficit except cranial nerve palsy) subarachnoid hematoma found to be secondary to a blister aneurysm of the right internal carotid artery. The patient underwent emergent pipeline (Covidien, Irvine, CA) embolization and deployment of 3.5 mm × 16 mm and 3.5 mm × 20 mm bare metal braided flow diversion stents. Because of the thrombogenicity of the stents, dual-antiplatelet therapy consisting of daily clopidogrel 75 mg and aspirin 325 mg were started on postoperative day 0. Immediately after the procedure, the patient was oriented and had symmetric strength throughout. On postoperative day 5, the patient developed progressive neurological changes with lethargy, left upper extremity paraplegia, and facial drop. The clinical changes were associated with radiographic ventriculomegaly and consistent with symptomatic hydrocephalus. Fortunately, temporary or permanent cerebrospinal fluid (CSF) diversion can minimize the devastating effects of hydrocephalus after subarachnoid hemorrhage.3
The attending neurosurgeon consulted the anesthesiology service for placement of a percutaneous lumbar CSF catheter for temporary drainage. After an interdisciplinary discussion with the intensive care team, neurosurgeon, and health care power of attorney (POA), the decision was made to proceed with the procedure despite published guidelines to the contrary.4 In addition, the patient’s daily dual-antiplatelet therapy would not be interrupted.
The procedure took place in the intensive care unit and was performed by the most experienced member of the anesthesiology team (C.W.C.). Immediately after transfusing 1 unit of platelets, the patient was placed in the left lateral decubitus position and the L2-3 intrathecal space was easily accessed by utilizing the 14g introducer available from the spinal drain kit (Integra LifeSciences, Plainsboro, NJ). The catheter was threaded 5 cm into the intrathecal space with return of clear CSF. Postprocedure lumbar computed tomography (CT) scanning revealed “no suspicion of an epidural hemorrhage associated with this procedure.” The patient remained in the intensive care unit and underwent hourly neurological checks to allow for early detection of a developing epidural hematoma. By the next morning, the attending intensivist noted “substantial improvement since placement of the lumbar drain,” and the patient was “alert, interactive, and following commands with moderate (4/5) weakness on the left side.” The patient exhibited no sequelae from the lumbar drain insertion.
After completing a prolonged clinical course, the lumbar drain was removed after 14 days following the transfusion of 1 unit of platelets. A postremoval CT revealed “no obvious epidural hematoma or other unexpected findings” and every 2-hour neurological checks were unremarkable. The patient was ultimately discharged to rehabilitation without any untoward effects related to the lumbar drain.
Current guidelines clearly recommend avoiding neuraxial instrumentation in the setting of ongoing clopidogrel administration.4 However, antiplatelet agents are ubiquitous in clinical practice and continue to present challenges to the anesthesiologist when either deliberately or inadvertently administered.2,5 Unfortunately, there are no reports and only a paucity of guidance exists when presented with a patient who requires or has received epidural or spinal instrumentation in the setting of concomitant continuous anticoagulation. This case highlights the decision making in an otherwise undocumented scenario wherein an intrathecal drain was inserted and removed in the setting of continuous aspirin and clopidogrel dual-antiplatelet therapy.
Both aspirin and clopidogrel irreversibly inhibit platelet activity, albeit through different mechanisms. By inhibiting cyclooxygenase-1, aspirin inhibits platelet activation, aggregation, and thrombosis. With daily aspirin dosing, 92% to 95% of cyclooxygenase activity is inhibited over 6 to 12 days.4 Clopidogrel, on the other hand, blocks the adenosine diphosphate receptor, thereby limiting platelet aggregation and has a time to peak effect of 4 to 24 hours depending on loading dose.4 Knowledge of the lifespan of a platelet, platelet pool turnover, and the pharmacokinetics of each drug allows for informed decision making. Laboratory investigations may provide further aid in intermittent antiplatelet agent dosing. Platelet count, prothrombin time, activated partial thromboplastin time, and standard thromboelastogram are unaffected by clopidogrel.2 If available, the VerifyNow System (Accumetrics, San Diego, CA), standard thromboelastogram platelet mapping test, or light transmittance aggregometry may be utilized to evaluate platelet inhibition.2 Because this patient had received 5 doses of clopidogrel and aspirin, she was presumed to be have been fully inhibited. Thus, further delay for laboratory investigation and platelet aggregation testing was deferred. Platelet count was available at the time of insertion and removal and were 163,000/μL and 223,000/μL, respectively.
With the close cooperation of the neurosurgical and intensive care team, the patient’s medical decision maker was counseled in regard to the potential risks, benefits, and unusual nature of this high-risk procedure.4 In consultation with the treatment team and family, alternative therapies, such as an external ventricular drain and its risks (uncontrollable intraparenchymal hemorrhage), delayed intervention, or avoidance of any invasive procedure (intracranial hypertension and anticipated clinical decompensation) were evaluated. The discussions surrounding this difficult situation were clearly documented in the chart in addition to the health care POA’s wishes to proceed with lumbar drain insertion in the setting of elevated risk and published contraindications.
The treatment team and POA favored accessing the intrathecal space via the least invasive mechanism available, namely a percutaneous approach, and, at our institution, anesthesiologists are the specialists most experienced with this procedure. The health care POA was clearly counseled and accepted the elevated risk of epidural hematoma and potential for necessary surgical decompression or paralysis. In the event of a traumatic or failed insertion attempt, a neurosurgical operative team and anesthesiology team were readily available to gain open access to the dural space or to perform a lumbar exploration or a lumbar decompression.
In the setting of clopidogrel therapy and neurosurgical bleeding, Beshay et al6 recommend transfusing 2 doses of platelets for reversal of platelet dysfunction. Each platelet dose is expected to provide approximately 50,000 functioning platelets.6 Furthermore, transfused platelets will generate thromboxane and recruit aspirin-inhibited platelets.7 One unit of platelets substantially reverses an aspirin inhibitory effect.8 Because platelet transfusion is not without risk (transfusion-related acute lung injury, infection, hemolytic transfusion reactions, stent thrombosis) and available recommendations are for active bleeding, the clinical team chose to administer 1 prophylactic unit versus 2 at the time of both insertion and removal. Platelet transfusion was timed to occur just before the lumbar drain insertion and removal because active clopidogrel metabolites would be expected to provide rapid inhibition.
Ex vivo rFVIIa reverses the effects of aspirin plus clopidogrel on platelet thrombin generation, but risks well-documented thrombotic complications.9 Through direct stimulation of GIIb-IIIa receptors, desmopressin promotes platelet aggregation in the setting of adenosine diphosphate-dependent receptor blockade.10 Furthermore, desmopressin reverses aspirin effect, but may cause hyponatremia and increased risk of arterial thombosis.6,10 Last, Qureshi and Suri11 report a case where methyl prednisolone was utilized to reduce platelet inhibition in a patient with an intracranial hemorrhage who had received aspirin and clopidogrel dual-antiplatelet therapy. Without apparent active bleeding and in the presence of a recently deployed intracerebral stent, the prophylactic administration of reversal agents beyond platelets was not entertained because of concerns of promoting potentially devastating in-stent thrombosis.
The spinal drain was inserted in the intensive care unit to facilitate close postprocedure monitoring and hourly neurological checks. The anesthesiology, neurosurgical, and intensive care team maintained a low threshold for neurosurgical intervention in the event of lower extremity neurological change. Furthermore, the most experienced member of the available anesthesiology team performed the procedure with the patient in the left lateral position. Although the patient’s mental status at the time would have made insertion in the sitting position challenging, the lateral position has the added benefit of theoretically decreasing the risk of vascular puncture due to diminished epidural venous plexus distension.12
After insertion and removal, the patient received a lumbar (CT) scan. Although magnetic resonance imaging remains the imaging modality of choice to evaluate suspected spinal epidural hematoma, magnetic resonance imaging is susceptible to motion artifact and requires a cooperative or anesthetized patient.13 Plain high-resolution CT, however, can diagnose acute spinal epidural hematoma with the added benefit of increased availability, efficiency in performance, and reduced motion artifact.14 Fortuitously, postprocedural CT scan evaluation did not reveal a hematoma. Had radiographic or clinical evidence been consistent with a significant or expanding hematoma, it would have precipitated emergent neurosurgical decompression. A subjectively small, noncompressive hematoma may have been followed clinically and with serial CT scanning to evaluate for further expansion or evidence of cord compression.
Over 20 years ago, Vandermeulen et al wrote “knowledge of the pharmacologic properties of the different anticoagulants and their combination with strict patient selection, individual risk-benefit analysis, appropriate regional anesthetic techniques, respecting proper time intervals separating anticoagulant and epidural or spinal anesthesia, and continuous awareness of the possibility that a compressing spinal hematoma may develop should enable us to make anesthetic practice safer without withholding anesthetic techniques from patients who would most certainly benefit from them.”15 Our case demonstrates the interdisciplinary cooperation, options, and informed decision making necessary when presented with a scenario in which neuraxial instrumentation is warranted in the setting of dual-antiplatelet therapy.
Name: Christopher W. Connors, MD.
Contribution: This author helped conceive the idea, collect, analyze, and interpret the data, and write and revise the manuscript.
Name: Janie D. Nguyen, DO.
Contribution: This author helped conceive the idea, collect, analyze and interpret the data, and write and edit the manuscript.
This manuscript was handled by: Raymond C. Roy, MD.
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