ASA抗凝病人区域麻醉指南

Regional Anesthesia in the Anticoagulated Patient: Defining the Risks (The Second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation) Terese T. Horlocker, M.D., Denise J. Wedel, M.D., Honorio Benzon, M.D., David L. Brown, M.D., F. Kayser Enneking, M.D., John A. Heit, M.D., Michael F. Mulroy, M.D., Richard W. Rosenquist, M.D., John Rowlingson, M.D., Michael Tryba, M.D., and Chun-Su Yuan, M.D., Ph.D. Neuraxial anesthesia and analgesia provide sev-eral advantages over systemic opioids, includ- ing superior analgesia, reduced blood loss and need for transfusion, decreased incidence of graft occlu- sion, and improved joint mobility following major knee surgery.1-4 New challenges in the manage- ment of patients undergoing neuraxial block have arisen over the last 2 decades, as medical standards for the prevention of perioperative venous throm- boembolism were established.5,6 Concern for pa- tient safety in the presence of potent antithrombotic drugs has resulted in avoidance of regional anesthe- sia. Indeed, perioperative anesthesia and analgesia are often determined by the antithrombotic agent.7 Conversely, although the anesthesia community is well aware of the potential for spinal bleeding, other specialties have only recently become cogni- zant of the risk, as documented by case reports published in the cardiology and neurology litera- ture.8,9 In response to these patient safety issues, the Amer- ican Society of Regional Anesthesia and Pain Medi- cine (ASRA) convened its Second Consensus Confer- ence on Neuraxial Anesthesia and Anticoagulation. Portions of the material presented here were pub- lished as the proceedings of the 1998 ASRA Consen- sus Conference.10-14 The information has been up- dated to incorporate additional data available since the time of its publication. It is important to note that although the consensus statements are based on a thorough evaluation of the available information, in some cases data are sparse. Numerous studies have documented the safety of neuraxial anesthesia and analgesia in the anticoagulated patient. Unfortu- nately, with a complication as rare as spinal hema- toma, no clinical study to date has sufficient power to definitively determine patient management. Conse- quently, the pharmacology of hemostasis-altering drugs and case reports of spinal hematoma are also essential to regional anesthetic management. Vari- ances from recommendations contained in this docu- ment may be acceptable based on the judgment of the responsible anesthesiologist. The consensus state- ments are designed to encourage safe and quality patient care, but cannot guarantee a specific outcome. They are also subject to timely revision as justified by evolution of information and practice. Finally, the current information focuses on neuraxial blocks and anticoagulants; the risk following plexus and periph- eral techniques remains undefined. Although sev- eral case reports of vascular injury with (or without) resultant nerve dysfunction have been described,15,16 additional experience is needed to allow statements for non-neuraxial blocks. The current literature in- volving hemorrhagic complications of plexus and pe- ripheral block is included for completeness. See Editorial page 163 From the Department of Anesthesiology, Mayo Clinic (T.T.H., D.J.W., J.A.H.), Rochester, Minnesota; Northwestern University (H.B.), Chicago, Illinois; University of Iowa (D.L.B., R.W.R.), Iowa City, Iowa; University of Florida (F.K.E.), Gainesville, Florida; Vir- ginia Mason Medical Center (M.F.M.), Seattle, Washington; Uni- versity of Virginia Health Science Center (J.R.), Charlottesville, Virginia; Department of Anesthesiology, Intensive Care and Pain Medicine (M.T.), Kassel, Germany; and Tang Center for Herbal Medicine Research, Department of Anesthesia and Critical Care, University of Chicago (C-S.Y.), Chicago, Illinois. Accepted for publication January 29, 2003. Reprint requests: Terese T. Horlocker, M.D., Department of Anesthesiology, Mayo Clinic, Rochester, MN, 55905. E-mail: horlocker.terese@mayo.edu © 2003 by the American Society of Regional Anesthesia and Pain Medicine. 1098-7339/03/2803-0004$30.00/0 doi:10.1053/rapm.2003.50046 172 Regional Anesthesia and Pain Medicine, Vol 28, No 3 (May–June), 2003: pp 172–197 Current Recommendations for the Prevention and Treatment of Venous Thromboembolism Thromboprophylaxis is based upon identification of risk factors. Guidelines for antithrombotic ther- apy including appropriate pharmacologic agent, de- gree of anticoagulation desired, and duration of therapy continue to evolve.5,6 Recommendations from the Sixth American College of Chest Physi- cians (ACCP) Consensus Conference in 2001 are based upon prospective randomized studies that as- sess the efficacy of therapy using contrast venogra- phy or fibrinogen leg scanning to diagnose asymp- tomatic thrombi (Table 1). Clinical outcomes, such as fatal pulmonary embolism (PE) and symptomatic deep venous thrombosis (DVT) are not primary endpoints.17 Despite the successful reduction of asymptomatic thromboembolic events with routine use of antithrombotic therapy, an actual reduction of clinically relevant events has been more difficult to demonstrate.18,19 This is in contrast to the docu- mented improvement in perioperative outcomes in selected patient populations that undergo neuraxial anesthesia and analgesia.1-4 Thus, estab- lishment of overall risks and benefits of antithrom- botic therapy in the patient undergoing neuraxial block is difficult. Compared with thromboprophylaxis, the pres- ence of acute thromboembolism or unstable angina necessitates more aggressive antithrombotic (and potentially thrombolytic) therapy. For example, acute DVT/PE is treated with therapeutic anticoag- ulation with unfractionated or low molecular weight heparin (LMWH); thrombolytic therapy may also be utilized alone or concomitantly (Table 1). Likewise, the American College of Cardiology and American Heart Association Task Force on Practice Guidelines for the Management of Patients with Acute Myocardial Infarction recommends a combination therapy of (1) aspirin or (2) ticlopi- dine/clopidogrel for patients with aspirin intoler- ance, (3) therapeutic anticoagulation with unfrac- tionated heparin or LMWH, and (4) administration of a platelet glycoprotein (GP) IIb/IIIa receptor an- tagonist. Intravenous (IV) thrombolytic therapy is recommended in patients with acute (less than 6 hours) symptoms.20 These treatment modalities have a dramatic impact on the patient’s ability to maintain hemostasis. Major bleeding complications may occur spontaneously or at the site of previous trauma, such as vascular access, surgery, or regional block. Risk of Bleeding Associated With Antithrombotic and Thrombolytic Therapy Bleeding is the major complication of anticoagu- lant and thrombolytic therapy. Bleeding is typically Table 1. Pharmacological Venous Thromboembolism Prophylaxis and Treatment Regimens and Treatment Regimens for Acute Coronary Syndromes Total Hip or Knee Replacement Thromboprophylaxis Adjusted-dose unfractionated heparin 3,500 U SC q 8 hours, started 2 hours before surgery; after surgery, the dose is adjusted to maintain the aPTT within the upper normal range Low molecular weight heparin Ardeparin sodium (Normiflow®) 50 U/kg SC q 12 h, started 12-24 hours after surgery Dalteparin sodium (Fragmin®) 5,000 U SC qd, started 12 hours before surgery, or 2,500 U SC given 7 hours after surgery, then 5,000 U SC daily Danaparoid sodium (Orgaran®) 750 U SC q 12 h, started 2 hours before surgery Enoxaparin sodium (Lovenox®) 30 mg SC q 12 h, started 12-24 hours after surgery, or 40 mg SC qd, started 10-12 hours before surgery Tinzaparin (Innohep®) 75 U/kg SC qd, started 10-12 hours before surgery Warfarin sodium 5 mg orally, started the night before or immediately after surgery and adjusted to prolong the INR � 2.0-3.0 General Surgery Thromboprophylaxis Unfractionated heparin 5,000 U SC q 8-12 hours, started 2 hours before surgery Low molecular weight heparin Dalteparin sodium 2,500 U SC qd, started 1-2 hours before surgery Enoxaparin sodium 40 mg SC qd, started 2 hours before surgery Acute Coronary Syndrome and Venous Thromboembolism Therapy Enoxaparin sodium 1 mg/kg SC q12 hours (outpatient DVT or non q-wave MI) 1 mg/kg SC q12 hours, or 1.5 mg/kg SC qd (inpatient treatment of DVT or PE) Dalteparin 120 U/kg q 12 hours or 200 U/kg qd (non q-wave MI) Tinzaparin 175 U/kg qd NOTE. Dosing recommendations from Beerts et al.6 Abbreviations: SC, subcutaneous; MI, myocardial infarction; aPTT, activated partial thromboplastin time; INR, international normalized ratio. Neuraxial Anesthesia and Anticoagulation • Horlocker et al. 173 classified as major if it is intracranial, intraspinal, intraocular, mediastinal or retroperitoneal, leads directly to death, or results in hospitalization or transfusion. Risk factors for major bleeding during anticoagulation include the intensity of the anti- coagulant effect, increased age, female gender, his- tory of gastrointestinal bleeding, concomitant aspi- rin use, and length of therapy.21 During warfarin therapy, an international normalized ratio (INR) of 2.0 to 3.0 is associated with a low risk of bleeding: � 3% during a 3-month treatment period. Higher intensity regimens (INR � 4) are associated with a significantly greater risk of bleeding (7%). The in- cidence of hemorrhagic complications during ther- apeutic anticoagulation with IV or subcutaneous (SC) heparin, as well as LMWH is � 3%.21 Throm- bolytic therapy represents the greatest risk of bleed- ing; between 6% and 30% of patients were treated with thrombolytic therapy for DVT.22 Therefore, although thromboembolism remains a source of significant perioperative morbidity and mortality, its prevention and treatment are also associated with risk. Incidence, Risk Factors, and Neurologic Outcome of Spinal Hematoma Spinal hematoma, defined as symptomatic bleed- ing within the spinal neuraxis, is a rare and poten- tially catastrophic complication of spinal or epidural anesthesia. The actual incidence of neurologic dys- function resulting from hemorrhagic complications associated with central neural block is unknown. In an extensive review of the literature, Tryba23 iden- tified 13 cases of spinal hematoma following 850,000 epidural anesthetics and 7 cases among 650,000 spinal techniques. Based on these observa- tions, the calculated incidence is approximated to be less than 1 in 150,000 epidurals and less than 1 in 220,000 spinal anesthetics.23 Because these esti- mates represent the upper limit of the 95% confi- dence interval, the actual frequency may be much less. Hemorrhage into the spinal canal most com- monly occurs in the epidural space, most likely because of the prominent epidural venous plexus, although anesthetic variables, such as needle size and catheter placement, may also affect the site of clinically significant bleeding.24,25 In a review of the literature between 1906 and 1994, Vandermeulen et al.26 reported 61 cases of spinal hematoma associated with epidural or spinal anesthesia. In 42 of the 61 patients (68%), the spinal hematomas associated with central neural block occurred in patients with evidence of hemo- static abnormality. Twenty-five of the patients had received IV or SC (unfractionated or LMWH), while an additional 5 patients were presumably adminis- tered heparin as they were undergoing a vascular surgical procedure. In addition, 12 patients had ev- idence of coagulopathy or thrombocytopenia or were treated with antiplatelet medications (aspirin, indomethacin, ticlopidine), oral anticoagulants (phenprocoumone), thrombolytics (urokinase), or dextran 70 immediately before or after the spinal or epidural anesthetic. Needle and catheter placement was reported to be difficult in 15 (25%), or bloody in 15 (25%) patients. Overall, in 53 of the 61 cases (87%), either a clotting abnormality or needle placement difficulty was present. A spinal anes- thetic was performed in 15 patients. The remaining 46 patients received an epidural anesthetic, includ- ing 32 patients with an indwelling catheter. In 15 of these 32 patients, the spinal hematoma occurred immediately after the removal of the epidural cath- eter. Nine of these catheters were removed during therapeutic levels of heparinization. Neurologic compromise presented as progression of sensory or motor block (68% of patients) or bowel/bladder dysfunction (8% of patients), not severe radicular back pain. Importantly, although only 38% of pa- tients had partial or good neurologic recovery, spi- nal cord ischemia tended to be reversible in patients who underwent laminectomy within 8 hours of onset of neurologic dysfunction26 (Table 2). The need for prompt diagnosis and intervention in the event of a spinal hematoma was also dem- onstrated in a recent review of the American Soci- ety of Anesthesiologists (ASA) Closed Claims data- base, which noted that spinal cord injuries were the Table 2. Neurologic Outcome in Patients With Spinal Hematoma Following Neuraxial Block Interval Between Onset of Paraplegia and Surgery Good N � 15 Partial N � 11 Poor N � 29 Less than 8 hours (N � 13) 6 4 3 Between 8 and 24 hours (N � 7) 1 2 4 Greater than 24 hours (N � 12) 2 0 10 No surgical intervention (N � 13) 4 1 8 Unknown (N � 10) 2 4 4 NOTE. Neurologic outcome was reported for 55 of 61 cases of spinal hematoma following neuraxial block. Adapted and reprinted with permission.26 174 Regional Anesthesia and Pain Medicine Vol. 28 No. 3 May–June 2003 leading cause of claims in the 1990s.27 Spinal he- matomas accounted for nearly half of the spinal cord injuries. Risk factors for spinal hematoma in- cluded epidural anesthesia in the presence of IV heparin during a vascular surgical or diagnostic pro- cedure. Importantly, the presence of postoperative numbness or weakness was typically attributed to local anesthetic effect rather than spinal cord ische- mia, which delayed the diagnosis. Patient care was rarely judged to have met standards (1 of 13 cases) and the median payment was very high. Fibrinolytic and Thrombolytic Therapy Pharmacology of Fibrinolytics/Thrombolytics The fibrinolytic system dissolves intravascular clots as a result of the action of plasmin. Plasmin is produced by the cleavage of a single peptide bond of the inactive precursor, plasminogen. The resulting compound is a nonspecific protease capable of dis- solving fibrin clots and other plasma proteins, in- cluding several coagulation factors. Exogenous plasminogen activators, such as streptokinase and urokinase, not only dissolve thrombus, but also affect circulating plasminogen as well. Endogenous t-PA formulations (alteplase and tenecteplase) are more fibrin-selective and have less effect on circu- lating plasminogen. Clot lysis leads to elevation of fibrin degradation products, which themselves have an anticoagulant effect by inhibiting platelet aggre- gation. In addition to the fibrinolytic agent, these patients frequently receive IV heparin to maintain an activated partial thromboplastin time (aPTT) of 1.5 to 2 times normal, and often an antiplatelet agent, such as aspirin or clopidogrel. While the plasma half-life of thrombolytic drugs is only hours, it may take days for the thrombolytic effect to re- solve; fibrinogen and plasminogen are maximally depressed at 5 hours after thrombolytic therapy and remain significantly depressed at 27 hours. The de- crease in coagulation factor levels is greater with streptokinase compared with t-PA therapy. How- ever, the frequency of hemorrhagic events is simi- lar.28 Importantly, original contraindications to thrombolytic therapy included surgery or puncture of noncompressible vessels within 10 days.28 Case Reports of Spontaneous and Regional Anesthesia-Related Spinal Hematomas Related to Thrombolytic Therapy There are no published studies addressing spinal, epidural, or regional anesthesia in the patient re- ceiving fibrinolytic/thrombolytic therapy. However, there is limited information about these settings available in the form of case reports of spinal he- matoma. The majority of published reports involve spontaneous spinal or epidural hematomas after thrombolytic therapy.29-35 To date, there are 5 cases of spinal hematoma involving the concomitant use of neuraxial anesthesia and fibrinolytic/thrombo- lytic therapy. Four cases appeared in the litera- ture8,36-38; 1 additional case was reported through the MedWatch1 system. An epidural technique had been performed in 3 patients, a continuous spinal anesthetic in 1 patient, and an epidural steroid in- jection in the remaining patient. In 3 of the cases, the patients presented with lower extremity ische- mia, and a neuraxial anesthetic was performed to allow surgical revascularization. However, 2 of the recent spinal hematomas (including the MedWatch case) occurred in patients who underwent a neuraxial technique (epidural anesthesia for litho- tripsy, epidural steroid injection2) and subsequently complained of myocardial ischemia and were treated with a thrombolytic.8 The potential for sig- nificant spinal bleeding was not appreciated despite recent neuraxial needle placement in these 2 pa- tients. Anesthetic Management of the Patient Receiving Thrombolytic Therapy Patients receiving fibrinolytic/thrombolytic med- ications are at risk of serious hemorrhagic events, particularly those who have undergone an invasive procedure. Consensus statements are based on the profound effect on hemostasis, the use of concom- itant heparin and/or antiplatelet agents (which fur- ther increase the risk of bleeding), and the potential for spontaneous neuraxial bleeding with these medications. Advances in fibrinolytic/thrombolytic therapy have been associated with an increased use of these drugs, which will require further increases in vigi- lance. Ideally, the patient should be queried prior to the thrombolytic therapy for a recent history of lumbar puncture, spinal or epidural anesthesia, or epidural steroid injection to allow appropriate mon- itoring. Guidelines detailing original contraindica- 1 The MedWatch program was initiated in 1993. Reporting of serious adverse events by health care professionals and hospitals is voluntary. Confidentiality is maintained. However, manufac- turers and distributors of FDA-approved pharmaceuticals have mandatory reporting requirements. The FDA estimates that less than 1% of serious adverse drug reactions are reported (Gold- man, 1996). 2 An 84-year-old male received an uncomplicated epidural steroid injection in the morning. He developed chest pain later that day, was admitted to the hospital, diagnosed with an acute myocardial infarction (MI), and treated with t-PA and heparin. He subsequently developed back pain and paraplegia. MRI dem- onstrated an epidural hematoma extending from T10 to the sacrum. Treatment and outcome were not reported. Neuraxial Anesthesia and Anticoagulation • Horlocker et al. 175 tions for thrombolytic drugs suggest avoidance of these drugs for 10 days following puncture of non- compressible vessels. Preoperative evaluation should determine whether fibrinolytic or thrombolytic drugs have been used preoperatively or have the likelihood of being used intraoperatively or postoperatively. Pa- tients receiving fibrinolytic and thrombolytic drugs should be cautioned against receiving spinal or epi- dural anesthetics except in highly unusual circum- stances. Data are not available to clearly outline the length of time neuraxial puncture should be avoided after discontinuation of these drugs. In those patients who have received neuraxial blocks at or near the time of fibrinolytic and throm- bolytic therapy, neurologic monitoring should be continued for an appropriate interval. It may be that the interval of monitoring should not be more than 2 hours bet