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Anticoagulant and Antithrombotic Drugs in Pregnancy: What Are the Anesthetic Implications for Labor and Cesarean Delivery?

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Anticoagulant and Antithrombotic Drugs in Pregnancy: What Are the Anesthetic Implications for Labor and Cesarean Delivery? Journal of Perinatology (2011) 31,73–84 r 2011 Nature America, Inc. All rights reserved. 0743-8346/11 www.nature.com/jp STATE-OF-THE-ART Anticoagulant and antithrombotic drugs in pregnancy: what are the anesthetic implications for labor and cesarean delivery? AJ Butwick and B Carvalho Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA techniques in patients receiving anticoagulation. The most feared Neuraxial anesthetic techniques are commonly used during the peripartum complication is symptomatic spinal hematoma, which can be period to provide effective pain relief for labor and anesthesia during cesarean associated with devastating neurologic outcomes (such as lower- delivery. Major neurologic complications are rare after neuraxial anesthesia; limb paralysis). Early diagnosis and the patient’s pre-operative however, spinal hematoma is associated with catastrophic neurologic neurological status are important factors that determine outcomes (including lower-limb paralysis). Anticoagulant and antithrombotic neurological outcome after surgical decompression to treat spinal drugs can increase the risk of spinal hematoma after neuraxial anesthesia, hematoma.7,8 Anticoagulant therapy is an important etiological and better understanding of the pharmacokinetics and pharmacodynamics of factor for spinal hematoma identified from case reports of patients anticoagulants has led to greater appreciation for withholding anticoagulation receiving neuraxial anesthesia.9 Spontaneous spinal hematoma before and after neuraxial anesthesia. A number of national anesthetic formation can also occur in patients who do not undergo spinal societies have produced guidelines for performing neuraxial anesthesia in instrumentation, and this has been recently reported in the patients receiving anticoagulation. However, there is limited information obstetric literature in a patient receiving therapeutic about anesthetic implications of anticoagulation during the peripartum anticoagulation with low-molecular weight heparin (LMWH).10 period. This article will review the risks of spinal hematoma after neuraxial The anesthetic management of pregnant patients receiving anesthesia in pregnant patients; current guidelines for neuraxial anesthesia anticoagulation can be particularly challenging because of for anticoagulated patients; and relevant pharmacological data of specific additional risks of spinal hematoma associated with spinal or anticoagulant and antithrombotic drugs in pregnancy. epidural anesthesia. The unpredictable timing of labor and delivery Journal of Perinatology (2011) 31, 73–84; doi:10.1038/jp.2010.64; may lead to uncertainty about using a neuraxial technique among published online 17 June 2010 anesthesiologists dealing with patients on anticoagulant or Keywords: neuraxial anesthesia; pregnancy; anticoagulants; antithrombotic drugs. In addition, new anticoagulants are being antithrombotics introduced into clinical practice (for example fondaparinux, argatroban),11 and there is limited information related to their safety in patients receiving neuraxial anesthesia. As a result, many Introduction anesthesia care providers may ‘err on the side of caution’ and Important advances in neuraxial anesthetic practice have improved choose not to offer a neuraxial technique to pregnant patients the quality of pain relief during labor1 and enhanced post-cesarean receiving anticoagulation. The implications of this empirical analgesia,2,3 and reduced maternal morbidity and mortality method of decision making are that anesthetic options for providing (because of lower rates of general anesthesia for cesarean effective pain relief during labor and anesthesia for cesarean delivery).4,5 As a result, neuraxial anesthetic techniques, which delivery become more limited. Furthermore, neuraxial anesthetic include epidural, spinal, or combined spinal–epidural, have techniques are recommended for optimizing the anesthetic become established techniques for providing analgesia in labor and management for high-risk pregnant patients during the peripartum anesthesia for cesarean delivery.6 and postpartum periods. For example, airway management in Adverse neurologic outcomes associated with neuraxial morbidly obese patients undergoing general anesthesia for cesarean anesthesia are fortunately rare; however, there is substantial delivery can often pose major problems, and epidural catheter-based concern regarding the implications of performing neuraxial techniques for providing anesthesia are recommended for these patients.12 Balancing the risks versus benefits of neuraxial Correspondence: Dr AJ Butwick, Department of Anesthesiology (MC:5640), Stanford University anesthesia in pregnant patients receiving anticoagulation during the School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA. peripartum period requires careful consideration. E-mail: [email protected] Received 16 December 2009; revised 10 March 2010; accepted 21 March 2010; published online Current guidelines for the use of anticoagulation in pregnant 13 17 June 2010 patients from the Pregnancy and Thrombosis Working Group and Neuraxial anesthesia with anticoagulant drugs AJ Butwick and B Carvalho 74 American College of Chest Physicians14 include limited discussion anesthesia in Sweden from 1990 to 1999. Two cases of spinal of the implications of anticoagulation and the use of neuraxial hematoma were reported after spinal anesthesia and epidural anesthesia during the peripartum period. Guidelines for the safe catheter removal, both in patients with HELLP syndrome. The timing and administration of central neuraxial blockade in reported rates of spinal hematoma after obstetric epidural and patients receiving anticoagulant and antithrombotic agents have spinal blocks for cesarean delivery were 1:200 000 and 1:50 000, been produced by the American Society of Regional Anesthesia15 respectively. Data from other studies of complications after epidural and several European anesthetic societies.16–21 blocks in obstetric patients (meta-analysis and national audit) This review will acquaint obstetric care providers with summary indicate that the incidence of spinal hematoma is between 0 and information on the timing and provision of neuraxial anesthesia 0.5:100 000.27,28 A review of obstetric anesthesia claims for injuries for patients receiving anticoagulant and antithrombotic agents. In between 1990 and 2003 included four cases of epidural hematoma addition, suggested algorithms for the peripartum management of related to neuraxial anesthesia (out of a total of 426 claims).29 patients on prophylactic and therapeutic unfractionated heparin Unfortunately, no supplementary background information was (UFH) and LMWH will be outlined. The physiologic changes provided for each case.29 An earlier systematic review of safety and associated with pregnancy can lead to changes in the efficacy of LMWH use in pregnancy included a subanalysis of 440 pharmacokinetic (PK) and pharmacodynamic (PD) profiles of patients who received neuraxial anesthesia. In this study, no cases anticoagulant drugs, and relevant information is also described. of spinal hematoma were reported; however, specific details of the timing and mode of neuraxial anesthesia were not included.30 Although anticoagulant drugs can increase the risk of spinal Spinal Hematoma: what is the risk of neuraxial hematoma after neuraxial anesthesia, the true incidence of spinal anesthesia in pregnant patients receiving hematoma in obstetric patients receiving anticoagulant or anticoagulation? antithrombotic drugs remains unknown. Acquired or inherited conditions (associated with coagulation or bleeding diathesis) and anticoagulant drugs are important etiological factors for the development of spinal hematoma.9,22 Antenatal multi-disciplinary assessment for Neuraxial anesthesia, which involves instrumentation of the anticoagulated pregnant patients epidural or subarachnoid space, can further increase the risk of An antenatal anesthetic assessment and consultation is spinal hematoma formation in anticoagulated patients. Spinal cord recommended for anticoagulated patients before the onset of labor injury is thought to occur by direct compression from the overlying or delivery. At our institution, all anticoagulated patients are hematoma in the epidural space, or possibly by secondary ischemic referred by our obstetricians for an anesthesia consultation in injury of the spinal cord because of compression on spinal cord advance of their estimated date of delivery. This consultation allows vessels. The early diagnosis of spinal hematoma is important in us to fully inform patients and their obstetricians about the improving neurological outcomes, as the risk of permanent indications and timing of neuraxial anesthesia for labor and neurologic deficit (ranging from mild sensory deficit to paraplegia) delivery, and to discuss alternative anesthetic options if is increased if hematoma evacuation is delayed >12 h after the anticoagulant effects persist during the peripartum and early onset of neurologic symptoms.8,9 postpartum period. Before the introduction of LMWHs, many anesthesiologists The indications for anticoagulant therapy in the antenatal considered that the risk of spinal hematoma after neuraxial period include the prophylaxis and treatment of VTE in pregnancy, anesthesia was theoretical.23 However, the introduction of LMWH in the prevention of systemic embolism in patients with mechanical the United States in 1993 for surgical thromboprophylaxis
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