Deep Vein Thrombosis Prophylaxis With Heparin and Heparin-Like Drugs Used in Combination With Neuraxial Anesthesia and Deep Plexus Blocks

INTRODUCTION

Early recovery after surgery (ERAS) and the current opioid pandemic have made health care providers and patients consider regional anesthesia (RA) options, including neuraxial anesthesia and nerve/nerve plexus blocks, as alternatives to traditional opioids. RA has been shown to be associated with additional benefits of lower volume of blood loss and transfusion rate, decreased perioperative infections such as pneumonia, and decreased length of stay. In the meantime, continuously evolving standards for the prevention of perioperative venous thromboembolism (VTE) in conjunction with the introduction of new antithrombotic medications (e.g., fondaparinux, rivaroxaban) and an increase in the dosage or frequency of existing medications (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH]) have resulted in concerns regarding the potentially heightened risk for neuraxial bleeding.

Neuraxial hematoma is a rare and catastrophic complication associated with both epidural and spinal anesthesia. The incidence of symptomatic hematoma has been estimated to be less than 1 per 220,000 for spinal anesthesia and less than 1 per 150,000 for epidural anesthesia in the population, with a much lower rate in labor epidural (1: 200,000) and a much higher rate in elderly females undergoing total knee arthroplasty (TKA; 1: 3600). Risk factors for bleeding associated with spinal epidural anesthesia have been identified in retrospective studies and include thrombocytopenia, hepatic dysfunction, renal insufficiency, the use of anticoagulants or antiplatelet agents, difficult needle placement, multiple punctures, anatomic abnormalities such as spina bifida occulta and vascularized tumor, the use of epidural anesthesia rather than spinal anesthesia, and catheter removal.

Spontaneous spinal epidural hematoma is a rare condition with an estimated incidence of 0.1 per 100,000 patients per year. A meta-analysis of 613 cases of all neuraxial hematomas indicated that about one-third of the cases belonged to this idiopathic spontaneous hemorrhage group, forming the largest group of patients who developed spinal/epidural hematomas. The second-largest group included patients on anticoagulation therapy (17%) without neuraxial blocks. Neuraxial anesthesia placed in patients with anticoagulation therapy was actually the fifth most common cause, and spinal and epidural procedures alone without anticoagulation were the tenth most common etiologic factor. This result is confirmed by a recent study of 83,71l lumbar puncture patients; the rate of 30-day spinal hematoma was 0.2% in patients without coagulopathy and 0.23% with coagulopathy. When making clinical decisions, bear in mind that the published estimations are from retrospective studies and/or self-reported with inherent limitations.

Symptoms of spinal hematoma are often occult, making diagnosis challenging; presenting symptoms could include lower extremity weakness (46%), radicular back pain (38%), paresthesia (14%), and occasionally stroke-like hemiparesis, myocardial infarction, and atypical abdominal pain. The diagnosis may be complicated or even delayed because of residual paresthesia or anesthesia produced by the neuraxial anesthesia or deep plexus block. There is likely a temporal relationship between the onset of paraplegia, surgical evacuation of hematoma, and recovery, even though the exact treatment for a neuraxial hematoma remains controversial. Short-acting and motor block–sparing local anesthetic agents are therefore recommended to be used in neuraxial and deep plexus blocks, especially in high-risk patients, to facilitate frequent neurologic monitoring and early detection of bleeding should it occur.

Increased emphasis has been placed on perioperative VTE prophylaxis because of the catastrophic outcome of VTE in moderate- to high-risk surgeries. Although for certain procedures, such as major neurosurgery, transurethral resection of the prostate, or radical prostatectomy, it is recommended against pharmacologic prophylaxis, for major trauma surgery or major gynecologic surgery, the American Society of Hematology (ASH) 2019 guideline suggests pharmacologic prophylaxis over no prophylaxis. For major general surgery, ASH suggests pharmacologic prophylaxis over no prophylaxis, using LMWH or UFH. For patients undergoing major orthopedic procedures such as total hip arthroplasty (THA) or TKA, even though there are variations on preferred pharmacologic agents, it is universally accepted that mechanical prophylaxis alone is not sufficient unless chemoprophylaxis is contraindicated according to the American Academy of Orthopedic Surgeons (AAOS) guideline ( www.aaos.org/research/guidelines/VTE/VTE_full_guideline.pdf ).

ASH has conditionally recommended using either aspirin or anticoagulants for VTE perioperative prophylaxis, and it recommends a direct oral anticoagulant over LMWH, whereas the American College of Chest Physicians (ACCP) has chosen LMWH over other oral agents such as fondaparinux, dabigatran, apixaban, or rivaroxaban. For nonorthopedic and noncancer procedures with moderate to high VTE risk, the ACCP recommends UFH or LMWH, whereas for patients undergoing abdominal or pelvic surgery because of cancer with a high risk for VTE, the ACCP recommends LMWH for the extended duration of 4 weeks.

Societies and organizations historically have issued conflicting recommendations regarding RA bleeding in the context of perioperative VTE prophylaxis or treatment, but the fourth edition of American Society of Regional Anesthesia and Pain Medicine (ASRA) anticoagulation guideline changed that by working in conjunction with the European Society of Anaesthesiology (ESA), incorporating information from the National Partnership for Maternal Safety (NPMS) and Society for Obstetric Anesthesia and Perinatology (SOAP), and using US Food and Drug Administration (FDA)-approved labeling. This offered practitioners a more unified set of recommendations across governing agencies and across broader geographic locations. As the ASRA 2018 guideline states well, these guidelines have the intention to foster safety and quality care but cannot guarantee outcomes because spinal epidural hematoma can still occur even if the guidelines are followed and there are no additional identifiable risk factors. The ASRA guideline further highlights the importance of daily chart review of medications changes and routine and repeated monitoring of anticoagulation status because concurrent use of other hemostasis-altering medications such as antiplatelets have been associated with a higher risk for bleeding. In addition, in the cases of new anticoagulants where insufficient clinical data are available, some recommendations are often pharmacologically based. Recommended time intervals between discontinuation of an anticoagulant at therapeutic dosage and subsequent neuraxial block are often 5 half-lives (adjust with renal function), with about 3% residual anticoagulation effect. With lower levels of anticoagulation effects associated with prophylactic dosage, only a 2-half-life interval may be sufficient. The time to start or restart the next dose of VTE is calculated as 8 hours, which is the time that it takes for a stable platelet plug to form, minus the time it takes for the anticoagulant to reach peak effect.

In this chapter we present a synopsis of the use of neuraxial anesthesia and deep plexus block techniques in patients receiving heparin and heparin-like drugs (UFH, LMWH, fondaparinux, and rivaroxaban) in the perioperative setting under VTE prophylaxis or treatment. The use of direct thrombin inhibitors, vitamin K antagonists, platelet inhibitors, and other hemostasis-altering medications is discussed elsewhere either in this or earlier editions of this text.