Conference Lectures
Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition)
Dr.Ramgopal gupta M.D., D.A.
Consultant Anaesthetist
Maruthi hospital
Trichy
Abstract
The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with neuraxial blockade is unknown. Although the incidence cited in the literature is estimated to be less than 1 in 150,000 epidural and less than 1 in 220,000 spinal anesthetics, recent epidemiologic surveys suggest that the frequency is increasing and may be as high as 1 in 3000 in some patient populations. Overall, the risk of clinically significant bleeding increase with age, associated abnormalities of the spinal cord or vertebral column, the presence of an underlying coagulopathy, difficulty during needle placement, and an indwelling neuraxial catheter during sustained anticoagulation (particularly with standard heparin or low-molecular weight heparin). The need for prompt diagnosis and intervention to optimize is also consistently reported.
In response to these patient safety issues, the American Society of Regional Anesthesia and Pain Medicine (ASRA) convened its Third Consensus Conference on Regional Anesthesia and Anticoagulation. Practice guidelines or recommendations summarize evidence-based reviews. However, the rarity of spinal hematoma defies a prospective randomized study, and there is no current laboratory model. As a result, the ASRA consensus statements represent the collective experience of recognized experts in the field of neuraxial anesthesia and anticoagulation. These are based on case reports, clinical series, pharmacology, hematology, and risk factors for surgical bleeding. An understanding of the complexity of this issue is essential to patient management.
Improvement in patient outcomes, including mortality, major morbidity, and patient-oriented outcomes, has been demonstrated with neuraxial techniques, particularly with epidural anesthesia and continued epidural analgesia.1-5 A major component of the decreased morbidity and mortality is due to the attenuation of the hypercoagulable response and the associated reduction in the frequency of thromboembolism after neuraxial blockade. Although this beneficial effect of neuraxial techniques continues to be recognized, the effect is insufficient as the sole method of thromboprophylaxis. Consequently, anticoagulant, antiplatelet, and thrombolytic medications have been increasingly used in the prevention and treatment of thromboembolism.
The development (and evolving status) of standards for the prevention of perioperative venous thromboembolism (VTE), as well as the introduction of increasingly more potent antithrombotic medications, resulted in concerns regarding the heightened risk of neuraxial bleeding. Trends in patient management included not only in the avoidance of neuraxial techniques but also in the search for alternative therapies and likely played a prominent role in the resurgence of peripheral blockade.
In response to these patient safety issues, the American Society of Regional Anesthesia and Pain Medicine (ASRA) convened its Third Consensus Conference on Regional Anesthesia and Anticoagulation. Portions of the material presented here were published as the proceedings of the 1997 and 2002 ASRA Consensus Conferences.11-16 The information has been updated to incorporate additional data available since the time of its publication. Variances from recommendations contained in this document may be acceptable based on the judgment of the responsible anesthesiologist. The consensus statements are designed to encourage safe and quality patient care, but they cannot guarantee a specific outcome. They are also subject to timely revision as justified by evolution of information and practice.
The past 2 Consensus Conferences focused on neuraxial blocks and anticoagulants in surgical patients, with limited information on the management of thromboprophylaxis in the parturient or patients undergoing plexus or peripheral blockade. However, the hypercoagulability associated with pregnancy and the puerperium has resulted in more parturients receiving antithrombotic therapy for the treatment and prevention of thromboembolism.17 The lack of a comparable "alternative" analgesic technique has further raised concern regarding the timing of epidural catheter placement/removal and initiation of postpartum thromboprophylaxis and is addressed in this update. In addition, recent publication of large series of patients undergoing uneventful peripheral blockade in combination with antithrombotic therapy as well as case reports of hemorrhagic complications after peripheral techniques provide sufficient information to allow for evidence-based recommendations.
These recommendations focus on patients receiving neuraxial and peripheral techniques. The practice settings include inpatient (eg, operating rooms, intensive care units, postoperative surgical floors, labor and delivery settings, or hospital wards) and ambulatory facilities such as pain clinics. The recommendations are intended for use by anesthesiologists and other physicians and health care providers performing neuraxial and peripheral regional anesthetic/analgesic blockade. However, these recommendations may also serve as a resource for other health care providers involved in the management of patients who have undergone similar procedures (eg, myelography, lumbar puncture).
STRENGTH AND GRADE OF RECOMMENDATIONS
The recommendations presented are based on a thorough evaluation of the available information using a grading system based on level of evidence and class of recommendation. The level of evidence classification combines an objective description of the types of studies/expert consensus supporting the recommendation. Unfortunately, with a complication as rare as spinal hematoma, randomized clinical trials and meta-analyses, the highest (A) level of evidence, are not available. Numerous observational and epidemiologic series (typically, level of evidence B) have documented the conditions for safe performance of neuraxial anesthesia and analgesia in the anticoagulated patient. However, high-quality evidence may come from well-done observational series yielding very large risk reduction.18Hence, depending on the risk reduction, recommendations from these sources may be categorized as level of evidence A or B. Recommendations derived from case reports or expert opinion is based on a C level of evidence. Often, recommendations involving the anesthetic management of new antithrombotic agents (where data involving safety and/or risk are sparse) are based on the pharmacology of hemostasis-altering drugs, risk of surgical bleeding, and expert opinion-C level of evidence.
The grade of recommendation also indicates the strength of the guideline and the degree of consensus agreement. For example, Grade 1 represents general agreement in the efficacy, Grade 2 notes conflicting evidence or opinion on the usefulness, and Grade 3 suggests that the procedure may not be useful (but possibly harmful). In the case of regional anesthesia and anticoagulation, a Grade 1 recommendation would allow safe performance in patients who benefit from the technique, whereas Grade 3 may represent performance of the technique in a patient at unacceptably high risk for bleeding (eg, epidural analgesia in the patient receiving twice-daily LMWH) or withholding the technique from a patient who would likely benefit from its performance (eg, thoracic epidural analgesia after thoracotomy with thromboprophylaxis using twice-daily unfractionated heparin [UFH]). The phrase "we recommend" is used for strong recommendations (Grades 1A, 1B, and 1C) and "we suggest" for weaker recommendations (Grades 2A, 2B, and 2C). When appropriate, underlying preferences and values are discussed. For example, the "safe" INR for an indwelling epidural catheter remains undetermined. The authors highly valued patient safety (considering the high patient variability in response to warfarin and the associated likelihood that the INR may become excessively prolonged) with a lower value on prolonged analgesia (>48 hrs) and recommended with a more conservative timing of catheter removal.
A recent review of the evolution of practice guidelines and the strength/grade of recommendations noted that (1) there are progressively more recommendations with each update; (2) most guidelines are based on lower levels of evidence or expert opinion-level A recommendations (derived from randomized clinical trials) are rare; and (3) bias may exist owing to funding of industry trials (in restricted patient populations) as well as conflict of interest by the guideline-writing groups.19,20 This update attempts to address these concerns in that fewer recommendations are presented to allow for flexibility and individuality in patient management, and author disclosure is prominently reported; notably none of the senior authors receive industry funding in this area.
CURRENT RECOMMENDATIONS FOR THE PREVENTION AND TREATMENT OF VTE
Venous thromboembolism is an important health care problem and a significant source of morbidity and mortality. Nearly all hospitalized patients have at least one risk factor for thromboembolism; approximately 40% have 3 or more risk factors7 (Table 1). Consequently, most hospitalized patients are candidates for thromboprophylaxis.
In response to ongoing concerns regarding surgical bleeding associated with thromboprophylaxis, the American Academy of Orthopaedic Surgeons (AAOS) published guidelines in 2007 for the prevention of symptomatic PE in patients undergoing total joint replacement (www.aaos.org/guidelines.pdf). These evidence-based guidelines allowed assignment of the patient to 1 of 4 categories (based on risk of PE and bleeding) and differed from those of the ACCP. The major deviations from ACCP guidelines are as follows: (1) mechanical prophylaxis should be used in all patients, (2) warfarin is a suitable alternative in all categories, and (3) in patients in whom there is an increased risk for bleeding, regardless of the risk of PE, prophylactic options include warfarin, aspirin, or mechanical prophylaxis only (Table 3).23 These recommendations are compatible with those of the Surgical Care Improvement Project guidelines, which state that if the patient is at high risk for bleeding, the use of mechanical prophylaxis only is acceptable.
1.0 Administration of Thromboprophylaxis
1.1 In accordance with ACCP guidelines, for each of the antithrombotic agents, we recommend that clinicians follow the manufacturer-suggested dosing guidelines (Grade 1C).
RISK OF BLEEDING ASSOCIATED WITH THERAPEUTIC ANTICOAGULATION AND THROMBOLYTIC THERAPY
Bleeding is the major complication of anticoagulant and thrombolytic therapy. Bleeding is typically 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 with either warfarin or UFH include the intensity of the anticoagulant effect, increased age, female sex, history of gastrointestinal bleeding, concomitant aspirin use, and length of therapy.26,27 Large fluctuation in anticoagulant effect also increases the likelihood of a serious bleed. During warfarin therapy, an INR of 2.0 to 3.0 is associated with a low risk of bleeding: less than 3% during a 3-month treatment period. Higher-intensity regimens (INR >4) are associated with a significantly greater risk of bleeding (7%). There is no significant difference in the risk of hemorrhage between thrombolytic agents. The addition of potent anticoagulants (LMWH, hirudin) or antiplatelet (glycoprotein IIb/IIIa [GP IIb/IIIa] agents) therapy further increases the risk of major bleeding.27 Therefore, although thromboembolism remains a source of significant perioperative morbidity and mortality, its prevention and treatment are also associated with risk.
PERIOPERATIVE MANAGEMENT OF ANTITHROMBOTIC AND ANTIPLATELET THERAPY
Long-term anticoagulation with warfarin is often indicated for patients with a history of VTE, mechanical heart valves, and atrial fibrillation. In addition, patients with bare metal or drug-eluting coronary stents require antiplatelet therapy with aspirin and thienopyridine derivatives (eg, clopidogrel) for varying durations. These patients may present for elective or urgent surgical procedures. Perioperative management involves balancing the risks of surgical bleeding and thromboembolism. Minor procedures may not require interruption of antithrombotic or antiplatelet therapy. However, continuation of these medications in the setting of a major surgery increases the risk of bleeding. Thus, it is critical to determine whether the planned procedure necessitates interruption of antithrombotic/antiplatelet therapy and, if so, whether the patient will need bridging therapy to minimize the risk of thromboembolism during the time the antithrombotic effect is subtherapeutic. In many patients, antithrombotic therapy may be safely interrupted until adequate surgical hemostasis is achieved. In other patients, bridging anticoagulation with unfractionated or LMWH is required until the time of surgery (and reinitiated in the immediate postoperative period). It may also be necessary to postpone elective surgeries in patients where a suitable "bridge" has not been identified and antithrombotic therapy is critical; premature discontinuation of dual antiplatelet therapy in patients with coronary stents has been associated with stent thrombosis, myocardial infarction and death
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Evidence-based guidelines for the perioperative management of antithrombotic therapy have been recently established by the ACCP.29In general, in patients at moderate to high risk of thromboembolism, bridging therapy is recommended (and the prevention of thromboembolism is valued over the potential for increased surgical bleeding). Conversely, no bridging therapy is recommended for patients at low risk for thromboembolism. Although the recommendations for management are relatively simple, complexity arises in the determination of who is at "high risk." This evaluation is perhaps best performed within an integrated multidisciplinary clinic by thrombophilia experts.
Incidence, Risk Factors, and Neurologic Outcome of Spinal Hematoma
Spinal hematoma, defined as symptomatic bleeding within the spinal neuraxis, is a rare and potentially catastrophic complication of spinal or epidural anesthesia. The actual incidence of neurologic dysfunction resulting from hemorrhagic complications associated with central neural blockade is unknown
Hemorrhage into the spinal canal most commonly 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.
Case series suggest that the risk of clinically significant bleeding varies with age (and associated abnormalities of the spinal cord or vertebral column), the presence of an underlying coagulopathy, difficulty during needle placement, and an indwelling neuraxial catheter during sustained anticoagulation (particularly with standard heparin or LMWH), perhaps in a multifactorial manner. They also consistently demonstrate the need for prompt diagnosis and intervention.
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 dissolving fibrin clots and other plasma proteins, including several coagulation factors. Exogenous plasminogen activators such as streptokinase and urokinase not only dissolve thrombus but also affect circulating plasminogen as well. Endogenous tissue plasminogen activator formulations (Alteplase, Tenecteplase) are more fibrin-selective and have less effect on circulating plasminogen. Clot lysis leads to elevation of fibrin degradation products, which themselves have an anticoagulant effect by inhibiting platelet aggregation. In addition to the fibrinolytic agent, these patients frequently receive intravenous 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. Although the plasma half-life of thrombolytic drugs is only hours, it may take days for the thrombolytic effect to resolve; fibrinogen and plasminogen are maximally depressed at 5 hrs after thrombolytic therapy and remain significantly depressed at 27 hrs. The decrease in coagulation factor levels is greater with streptokinase compared with tissue plasminogen activator therapy. However, the frequency of hemorrhagic events is similar.27 Importantly, original contraindications to thrombolytic therapy included surgery or puncture of noncompressible vessels within 10 days.39
2.0 Anesthetic Management of the Patient Receiving Thrombolytic Therapy
Patients receiving fibrinolytic/thrombolytic medications are at risk for serious hemorrhagic events, particularly those who have undergone an invasive procedure. Recommendations are based on the profound effect on hemostasis, the use of concomitant heparin and/or antiplatelet agents (which further increase the risk of bleeding), and the potential for spontaneous neuraxial bleeding with these medications.
2.1 In patients scheduled to receive thrombolytic therapy, we recommend that the patient be queried and medical record reviewed for a recent history of lumbar puncture, spinal or epidural anesthesia, or epidural steroid injection to allow appropriate monitoring. Guidelines detailing original contraindications for thrombolytic drugs suggest avoidance of these drugs for 10 days after puncture of noncompressible vessels (Grade 1A).
2.2 In patients who have received fibrinolytic and thrombolytic drugs, we recommend against performance of spinal or epidural anesthetics except in highly unusual circumstances (Grade 1A). Data are not available to clearly outline the length of time neuraxial puncture should be avoided after discontinuation of these drugs.
2.3 In those patients who have received neuraxial blocks at or near the time of fibrinolytic and thrombolytic therapy, we recommend that neurological monitoring should be continued for an appropriate interval. It may be that the interval of monitoring should not be more than 2 hrs between neurologic checks. If neuraxial blocks have been combined with fibrinolytic and thrombolytic therapy and ongoing epidural catheter infusion, we recommend the infusion should be limited to drugs minimizing sensory and motor block to facilitate assessment of neurologic function (Grade 1C).
2.4 There is no definitive recommendation for removal of neuraxial catheters in patients who unexpectedly receive fibrinolytic and thrombolytic therapy during a neuraxial catheter infusion. We suggest the measurement of fibrinogen level (one of the last clotting factors to recover) to evaluate the presence of residual thrombolytic effect and appropriate timing of catheter removal (Grade 2C).
UNFRACTIONATED INTRAVENOUS AND SUBCUTANEOUS HEPARIN
Pharmacology of UFH
The major anticoagulant effect of heparin is due to a unique pentasaccharide that binds to antithrombin (AT) with high affinity and is present in approximately one-third of heparin molecules. Binding of this heparin pentasaccharide to AT accelerates its ability to inactivate thrombin (factor IIa), factor Xa, and factor IXa. Anticoagulant activities of UFH depend on both the number of heparin molecules with the pentasaccharide chain and the size of the molecules containing the pentasaccharide sequence. Larger-molecular weight heparins will catalyze inhibition of both factor IIa and Xa. Smaller-molecular weight heparins will catalyze inhibition of only factor Xa.62,63 Intravenous injection results in immediate anticoagulant activity, whereas subcutaneous injection results in a 1 to 2 hrs' delay. The anticoagulant effect of heparin is both dose- and molecular size-dependent and is not linear but increases disproportionately with increasing doses.
When given in therapeutic doses, the anticoagulant effect of heparin is typically monitored with the aPTT. The activated clotting time is typically used to monitor higher doses given during cardiopulmonary bypass. Adequate therapeutic effect (in patients with VTE or unstable angina) is achieved with a prolongation of the aPTT to between 1.5 and 2.5 times the baseline value,62 heparin level between 0.2 and 0.4 U/mL, or anti-Xa level between 0.3 and 0.7 U/mL.64Administration of small-dose (5000 U) subcutaneous heparin for prophylaxis of DVT generally does not prolong the aPTT and is typically not monitored. However, it can result in unpredictable (10-fold variability) and therapeutic blood concentrations of heparin in some patients within 2 hrs after administration.65
One of the advantages of heparin anticoagulation is that its effect may be rapidly reversed with protamine. Each mg of protamine can neutralize 100 U of heparin. Neutralization of subcutaneously administered heparin may require a prolonged infusion of protamine owing to the continued absorption.
Risk Factors for Spinal Hematoma in the Heparinized Patient Undergoing Neuraxial Blockade
Three factors associated with increased risk were identified: less than 60-min time interval between the administration of heparin and lumbar puncture, traumatic needle placement, and concomitant use of other anticoagulants (aspirin). These risk factors have been verified in subsequent large reviews of case reports of hematomas associated with neuraxial procedures in the presence of UFH
Intravenous UFH
Intraoperative heparinization typically involves injection of 5 to 10,000 U of heparin intravenously during the operative period, particularly in the setting of vascular surgery to prevent coagulation during cross clamping of arterial vessels.63 Neuraxial anesthetic techniques are often attractive for these patients because these techniques may provide reduced morbidity and improved postoperative analgesia.2,4However, the use of neuraxial procedures in the presence of UFH may be associated with an increased risk of epidural hematoma, as demonstrated by case series, epidemiologic surveys, and the continued claims in the ASA Closed Claims database.33,34,38,69
Most published case series used similar guidelines for patient management, including exclusion of high-risk patients (preexisting coagulopathy) and performance of neuraxial procedure at least 1 hr before administration of heparin.14 The question of how to manage the situation of a bloody or traumatic neuraxial procedure has been raised. Previous case reports suggest that presence of a bloody tap or a traumatic regional block is an associated factor in approximately 50% of spinal hematomas.34 Although some investigators have recommended cancellation of the surgical procedures should these events occur,67 there are no clinical data to support this recommendation.56,70 Direct communication with the surgeon and a specific risk-benefit decision about proceeding in each case is warranted.
Overall, large published series and extensive clinical experience suggest that the use of regional techniques in the setting of intraoperative systemic heparinization does not seem to represent systemic heparinization and does not seem to represent a significant risk. Vigilance is necessary to diagnose and intervene as early as possible should spinal hematoma be suspected.
The risk of hematoma resulting from catheter removal has lead to the recommendation that in patients who have undergone systemic heparinization, the heparin should be discontinued for 2 to 4 hrs before neuraxial catheter removal, coagulation status assessed before manipulation of the catheter, and careful assessment of the presence of sensory and motor function in the lower extremities for at least 12 hrs after the catheter removal.
Heparinization During Cardiopulmonary Bypass
Since the publication of the initial ASRA guidelines in 1998,14 there have been continued discussions regarding the relative risk (and benefit) of neuraxial anesthesia and analgesia in the patient undergoing heparinization for cardiopulmonary bypass. Further reports of small series have appeared, again with no reported complications. Two of these series are retrospective reviews of pediatric cardiac surgery including a total of 250 patients that report no spinal hematomas.71,72 In these pediatric patients, the blocks were performed after induction of general anesthesia before surgery 1 hr before full systemic heparinization. In contrast, the adult experience with coronary bypass surgery has continued to follow the practice of placement of the epidural catheters on the evening before surgery. Sanchez and Nygard73 report a large prospective series of 558 patients without complications. Despite the absence of serious sequelae, the debate continues as to the risk-benefit advantages of this technique.74,75 Recently, the efficacy has been examined in the newer "off-pump" approach to cardiac surgery.76,77 In a series of 50 patients, Priestley et al78 reported improved postoperative analgesia and earlier extubation. However, there was no difference in time to hospital discharge. Although there were no spinal hematomas, the authors observe that "the use of thoracic epidural analgesia during coronary artery bypass grafting is controversial because the anticoagulation required during surgery raises the concern of increasing the rare but serious risk of permanent spinal cord damage from an epidural hematoma. Such a risk must be balanced by important clinical advantages if the technique is to be justified." Despite improved analgesia, they note that "convincing respiratory, cardiac, or other organ outcome data are lacking."
To date, there is a single case of spinal hematoma after the full heparinization associated with cardiopulmonary bypass.79
A review has recommended certain precautions to be taken to minimize the risk69:
1. Neuraxial blocks should be avoided in a patient with known coagulopathy from any cause,
2. Surgery should be delayed 24 hrs in the event of a traumatic tap,
3. Time from instrumentation to systemic heparinization should exceed 60 mins,
4. Heparin effect and reversal should be tightly controlled (smallest amount of heparin for the shortest duration compatible with therapeutic objectives),
5. Epidural catheters should be removed when normal coagulation is restored, and patients should be closely monitored postoperatively for signs and symptoms of hematoma formation.
These recommendations, as well as the practice of inserting epidural catheters 24 hrs in advance of surgery, have been used by most of the published case series. Validity of these and future recommendations will need to be determined.
Subcutaneous UFH
Low-dose heparin is commonly used for prophylaxis against development of VTE in general and urologic surgery.81 Administration of 5000 U of heparin subcutaneously every 12 hrs has been used extensively and effectively for prophylaxis against DVT. There is often no detectable change in the clotting parameters, as measured by the aPTT. There is a minority of patients, perhaps up to 15%, who may develop measurable changes in coagulation, although the aPTT rarely exceeds 1.5 times the normal level.65 There is a smaller subset (2%-4%) of patients who may become therapeutically anticoagulated during subcutaneous heparin therapy. With therapy longer than 5 days, there is a subset of patients who will develop a decrease in the platelet count.62
Subcutaneous Heparin With Thrice-Daily Dosing
It has become conventional treatment for patients to receive subcutaneous UFH 3 times per day rather than 2 times per day based on the 2008 ACCP conference guidelines.7
As to a decrease in the incidence of VTE, 3 times a day of therapy proved to be more beneficial; however, there was an increased risk of major bleeding. Thus, the authors concluded that the clinician must pick the anticoagulant regimen in correlation to the patient's risk (in this case for prevention of the VTE).
3.0 Anesthetic Management of the Patient Receiving UFH
Recent thromboprophylaxis guidelines identifying more patients as candidates for thrice-daily subcutaneous heparin and the potential for increased bleeding with this therapy have prompted a modification of the previous ASRA guidelines.
3.1 We recommend daily review of the patient's medical record to determine the concurrent use of medications that affect other components of the clotting mechanisms. These medications include antiplatelet medications, LMWH, and oral anticoagulants (Grade 1B).
3.2 In patients receiving prophylaxis with subcutaneous UFH with dosing regimens of 5000 U twice daily, there is no contraindication to the use of neuraxial techniques. The risk of neuraxial bleeding may be reduced by delay of the heparin injection until after the block and may be increased in debilitated patients after prolonged therapy (Grade 1C).
3.3 The safety of neuraxial blockade in patients receiving doses greater than 10,000 U of UFH daily or more than twice-daily dosing of UFH has not been established. Although the use of thrice-daily UFH may lead to an increased risk of surgical-related bleeding, it is unclear whether there is an increased risk of spinal hematoma. We suggest that the risk and benefits of thrice-daily UFH be assessed on an individual basis and that techniques to facilitate detection of new/progressive neurodeficits (eg, enhanced neurologic monitoring occur and neuraxial solutions to minimize sensory and motor block) be applied (Grade 2C).
3.4 Because heparin-induced thrombocytopenia may occur during heparin administration, we recommend that patients receiving heparin for more than 4 days have a platelet count assessed before neuraxial block and catheter removal (Grade 1C).
3.5 Combining neuraxial techniques with intraoperative anticoagulation with heparin during vascular surgery is acceptable with the following recommendations (Grade 1A):
3.5.1. Avoid the technique in patients with other coagulopathies.
3.5.2. Delay heparin administration for 1 hr after needle placement.
3.5.3. Remove indwelling neuraxial catheters 2 to 4 hrs after the last heparin dose and assess the patient's coagulation status; re-heparin 1 hr after catheter removal.
3.5.4. Monitor the patient postoperatively to provide early detection of motor blockade and consider use of minimal concentration of local anesthetics to enhance the early detection of a spinal hematoma.
3.5.5. Although the occurrence of a bloody or difficult neuraxial needle placement may increase risk, there are no data to support mandatory cancellation of a case. Direct communication with the surgeon and a specific risk-benefit decision about proceeding in each case is warranted.
3.6 Currently, insufficient data and experience are available to determine if the risk of neuraxial hematoma is increased when combining neuraxial techniques with the full anticoagulation of cardiac surgery. We suggest postoperative monitoring of neurologic function and selection of neuraxial solutions that minimize sensory and motor block to facilitate detection of new/progressive neurodeficits (Grade 2C).
LOW-MOLECULAR WEIGHT HEPARIN
Pharmacology, Monitoring, and Reversal of the Anticoagulant Effect of LMWH
The biochemical and pharmacologic properties of LMWH differ from those of UFH.62,93-96 Most relevant are the lack of monitoring of the anticoagulant response (anti-Xa level), prolonged half-life, and irreversibility with protamine. For example, the elimination half-life of LMWH, which is 3-6 hrs after subcutaneous injection, is dose-independent. Anti-Xa levels peak 3 to 5 hrs after administration. However, because the half-life is 3 to 4 times that of UFH, significant anti-Xa activity is still present 12 hrs after injection. A recent clinical investigation has reported a significant anticoagulant effect present at the time of epidural catheter removal in patients receiving twice-daily LMWH compared with once-daily LMWH administration.97
Prolonged LMWH therapy may be associated with an accumulation of anti-Xa activity and fibrinolysis.98 The plasma half-life of LMWH also increases in patients with renal failure.93 The anticoagulant effects of standard heparin are neutralized by an equimolar dose of protamine. Because of reduced protamine binding to LMWH fractions, only the anti-IIa activity of LMWH is completely reversed, whereas anti-Xa activity is not fully neutralized. Both anti-IIa and anti-Xa activity may return up to 3 hrs after protamine reversal, possibly due to release of additional LMWH from the subcutaneous depot. The clinical significance of the residual anti-Xa effect is unknown.93
L-molecular weight heparins vary both biochemically and pharmacologically, including molecular weight, anti-IIa and anti-Xa activities, and plasma half-life. However, because there are no adequate trials comparing the efficacy and safety of one LMWH to another, it is impossible to recommend one specific LMWH over another.62 Experience in Europe suggests that the rate of spinal hematoma is similar among LMWH preparations.99
Spinal and Epidural Anesthesia in the Patient Receiving LMWH
Risk Factors for Spinal Hematomas With LMWH Thromboprophylaxis
In summary, age and sex seem to be significant patient factors, perhaps through vertebral canal compromise (smaller volume need to produce critical ischemic pressure) and/or drug effect (exaggerated response to LMWH, renal insufficiency). Finally, the additive, if not synergistic effect of multiple hemostasis-altering medications cannot be overstated and may elevate the risk of once-daily LMWH to that of twice-daily dosing.
4.0 Anesthetic Management of the Patient Receiving LMWH
Anesthesiologists in North America can draw on the extensive European experience to develop practice guidelines for the management of patients undergoing spinal and epidural blocks while receiving perioperative LMWH. All consensus statements contained herein respect the labeled dosing regimens of LMWH as established by the FDA. Although it is impossible to devise recommendations that will completely eliminate the risk of spinal hematoma, previous consensus recommendations have seemed to improve outcome. Concern remains for higher dose applications, where sustained therapeutic levels of anticoagulation are present.
4.1 The anti-Xa level is not predictive of the risk of bleeding. We recommend against the routine use of monitoring of the anti-Xa level (Grade 1A).
4.2 Antiplatelet or oral anticoagulant medications administered in combination with LMWH increase the risk of spinal hematoma. Education of the entire patient care team is necessary to avoid potentiation of the anticoagulant effects. We recommend against concomitant administration of medications affecting hemostasis, such as antiplatelet drugs, standard heparin, or dextran, regardless of LMWH dosing regimen (Grade 1A).
4.3 The presence of blood during needle and catheter placement does not necessitate postponement of surgery. We suggest that initiation of LMWH therapy in this setting should be delayed for 24 hrs postoperatively and that this consideration be discussed with the surgeon (Grade 2C).
4.4 Preoperative LMWH
4.4.1 Patients on preoperative LMWH thromboprophylaxis can be assumed to have altered coagulation. In these patients, we recommend that needle placement should occur at least 10 to 12 hrs after the LMWH dose (Grade 1C).
4.4.2 In patients receiving higher (treatment) doses of LMWH, such as enoxaparin 1 mg/kg every 12 hrs, enoxaparin 1.5 mg/kg daily, dalteparin 120 U/kg every 12 hrs, dalteparin 200 U/kg daily, or tinzaparin 175 U/kg daily, we recommend delay of at least 24 hrs to ensure normal hemostasis at the time of needle insertion (Grade 1C).
4.4.3 In patients administered a dose of LMWH 2 hrs preoperatively (general surgery patients), we recommend against a neuraxial techniques because needle placement would occur during peak anticoagulant activity (Grade 1A).
4.5 Postoperative LMWHPatients with postoperative LMWH thromboprophylaxis may safely undergo single-injection and continuous catheter techniques. Management is based on total daily dose, timing of the first postoperative dose and dosing schedule (Grade 1C).
4.5.1 Twice-daily dosing. This dosage regimen is associated with an increased risk of spinal hematoma. The first dose of LMWH should be administered no earlier than 24 hrs postoperatively, regardless of anesthetic technique, and only in the presence of adequate (surgical) hemostasis. Indwelling catheters should be removed before initiation of LMWH thromboprophylaxis. If a continuous technique is selected, the epidural catheter may be left indwelling overnight, but must be removed before the first dose of LMWH. Administration of LMWH should be delayed for 2 hrs after catheter removal.
4.5.2 Single-daily dosing. The first postoperative LMWH dose should be administered 6 to 8 hrs postoperatively. The second postoperative dose should occur no sooner than 24 hrs after the first dose. Indwelling neuraxial catheters may be safely maintained. However, the catheter should be removed a minimum of 10 to 12 hrs after the last dose of LMWH. Subsequent LMWH dosing should occur a minimum of 2 hrs after catheter removal. No additional hemostasis-altering medications should be administered due to the additive effects.
Oral Anticoagulants (Warfarin)
Warfarin Pharmacology
Oral anticoagulants, including warfarin, exert their anticoagulant effect indirectly by interfering with the synthesis of the vitamin K-dependent clotting factors, factor II (thrombin), VII, IX, and X. The effects of warfarin are not apparent until a significant amount of biologically inactive factors are synthesized and are dependent on factor half-life115:
An understanding of the correlation between the various vitamin K-dependent factor levels and the PT is critical to regional anesthetic management. Calculation of the INR allows for standardization/comparison of PT values between laboratories. Importantly, the INR is based on values from patients who were on stable anticoagulant doses for at least 6 weeks. Therefore, the INR is less reliable early in the course of warfarin therapy.115
TABLE. No caption av...
Clinical experience with patients who, congenitally, are deficient in factors II, IX, or X suggests that a factor activity level of 40% for eachfactor is adequate for normal or near-normal hemostasis.116 Bleeding may occur if the level of any clotting factor is decreased to 20% to 40% of baseline. The PT is most sensitive to the activities of factors VII and X and is relatively insensitive to factor II. During the first few days of therapy, the PT reflects primarily a reduction of factor VII, the half-life of which is approximately 6 hrs. After a single dose, marked prolongation of the INR may occur, although adequate factor levels are still present. However, with additional doses, an INR greater than 1.4 is typically associated with factor VII activity less that 40% (and the potential for inadequate clotting).117 The reduction of factors X and II also contributes to the PT prolongation as therapy continues.115
Factor VII activity will rapidly increase, as demonstrated by a decrease in the INR. However, factors II and X activities recover much more slowly. Theoretically, there may be a time when the INR approaches a normal value because factor VII has been restored. However, factors II and X have not been restored to a hemostatic range of 40% activity.11 In urgent/emergent situations, the effects of warfarin may be reversed by oral or intravenous of vitamin K and/or transfusion of fresh-frozen plasma
Factors Affecting Warfarin Response
The measured response to anticoagulant therapy at the initiation of treatment varies significantly. Some of the variability may be attributed to drug interactions, but in addition, there are patient variables such as age, female sex, and preexisting medical conditions (lower patient weight, liver, cardiac, and renal disease) that are associated with an enhanced response to warfarin and/or a lower dose requirement for maintenance anticoagulation.82,115,118 Asian patients require lower doses than white patients during long-term therapy.115,118 In addition, there are many drug interactions described with warfarin therapy that potentiate the anticoagulant effect, including concomitant administration of antiplatelet medications, heparin, and LMWH.115,119,120
The ACCP recommends against the use of pharmacogenetic-based initial dosing owing to the lack of randomized trials.115
5.0 Regional Anesthetic Management of the Patient on Oral Anticoagulants
The management of patients receiving warfarin perioperatively remains controversial. Recommendations are based on warfarin pharmacology, the clinical relevance of vitamin K coagulation factor levels/deficiencies, case series, and the case reports of spinal hematoma among these patients. Web sites are available to assist clinicians with warfarin dosing
5.1 Caution should be used when performing neuraxial techniques in patients recently discontinued from long-term warfarin therapy. In the first 1 to 3 days after discontinuation of warfarin therapy, the coagulation status (reflected primarily by factor II and X levels) may not be adequate for hemostasis despite a decrease in the INR (indicating a return of factor VII activity). Adequate levels of II, VII, IX, and X may not be present until the INR is within reference limits. We recommend that the anticoagulant therapy must be stopped (ideally 4-5 days before the planned procedure) and the INR must be normalized before initiation of neuraxial block (Grade 1B).
5.2 We recommend against the concurrent use of medications that affect other components of the clotting mechanisms and may increase the risk of bleeding complications for patients receiving oral anticoagulants and do so without influencing the INR. These medications include aspirin and other NSAIDs, ticlopidine and clopidogrel, UFH, and LMWH (Grade 1A).
5.3 In patients who are likely to have an enhanced response to the drug, we recommend that a reduced dose be administered. Algorithms have been developed to guide physicians in the appropriate dosing of warfarin based on desired indication, patient factors, and surgical factors. These algorithms may be extremely useful in patients at risk for an enhanced response to warfarin (Grade 1B).
5.4 In patients receiving an initial dose of warfarin before surgery, we suggest that the INR should be checked before neuraxial block if the first dose was given more than 24 hrs earlier or if a second dose of oral anticoagulant has been administered (Grade 2C).
5.5 In patients receiving low-dose warfarin therapy during epidural analgesia, we suggest that their INR be monitored on a daily basis (Grade 2C).
5.6 Neurologic testing of sensory and motor function should be performed routinely during epidural analgesia for patients on warfarin therapy. To facilitate neurologic evaluation, we recommend that the type of analgesic solution be tailored to minimize the degree of sensory and motor blockade (Grade 1C).
5.7 As thromboprophylaxis with warfarin is initiated, we suggest that neuraxial catheters should be removed when the INR is less than 1.5. This value was derived from studies correlating hemostasis with clotting factor activity levels greater than 40%. We suggest that neurologic assessment be continued for at least 24 hrs after catheter removal for these patients (Grade 2C).
5.8 In patients with INR greater than 1.5 but less than 3, we recommend that removal of indwelling catheters should be done with caution and the medication record reviewed for other medications that may influence hemostasis that may not effect the INR (eg, NSAIDs, ASA, clopidogrel, ticlopidine, UFH, LMWH) (Grade 2C). We also recommend that neurologic status be assessed before catheter removal and continued until the INR has stabilized at the desired prophylaxis level (Grade 1C).
5.9 In patients with an INR greater than 3, we recommend that the warfarin dose be held or reduced in patients with indwelling neuraxial catheters (Grade 1A). We can make no definitive recommendation regarding the management to facilitate removal of neuraxial catheters in patients with therapeutic levels of anticoagulation during neuraxial catheter infusion (Grade 2C).
Antiplatelet Medications
Pharmacology of Antiplatelet Medications
Antiplatelet agents include NSAIDs, thienopyridine derivatives (ticlopidine and clopidogrel), and platelet GP IIb/IIIa receptor antagonists (abciximab, eptifibatide, and tirofiban). It is important to note the pharmacologic differences among the drugs with antiplatelet effects.
Cyclooxygenase (COX) exists in 2 forms. Cyclooxygenase-1 regulates constitutive mechanisms, whereas COX-2 mediates pain and inflammation. Nonsteroidal anti-inflammatory drugs inhibit platelet cyclooxygenase and prevent the synthesis of thromboxane A2. Platelets from patients who have been taking these medications have normal platelet adherence to subendothelium and normal primary hemostatic plug formation. Depending on the dose administered, aspirin (and other NSAIDs) may produce opposing effects on the hemostatic mechanism. For example, platelet cyclooxygenase is inhibited by low-dose aspirin (60-325 mg/d), whereas larger doses (1.5-2 g/d) will also inhibit the production of prostacyclin (a potent vasodilator and platelet aggregation inhibitor) by vascular endothelial cells and thus result in a paradoxical thrombogenic effect.130,131 As a result, low-dose aspirin (81-325 mg/d) is theoretically a greater risk factor for bleeding than higher doses. Spontaneous132 and postoperative (unrelated to neuraxial technique)133 spinal hematomas have been reported with low-dose aspirin therapy.
Celecoxib (Celebrex) is an anti-inflammatory agent that primarily inhibits COX-2, an inducible enzyme that is not expressed in platelets and thus does not cause platelet dysfunction.136 After single and multidosing, there have not been findings of significant disruption of platelet aggregation, and there is no history of undesirable bleeding events. The concomitant use of COX-2 inhibitors and warfarin may increase the risk of hemorrhagic complications by increasing the PT.
The antiplatelet effect of the thienopyridine derivatives, ticlopidine, and clopidogrel results from the inhibition of adenosine diphosphate-induced platelet aggregation. These antiplatelet agents, used in the prevention of cerebrovascular thromboembolic events, affect both primary and secondary platelet aggregation. Ticlopidine (Ticlid) and clopidogrel (Plavix) also interfere with platelet-fibrinogen binding and subsequent platelet-platelet interactions.137 Thienopyridine derivatives demonstrate both time- and dose-dependent effects; steady state is achieved within 7 days for clopidogrel and 14 to 21 days for ticlopidine, although this may be accomplished with higher loading doses (eg, clopidogrel 300 mg). " The ACCP recommends discontinuation of clopidogrel for 7 to 10 days,29 whereas in patients at high risk for recurrent angina, 5 days have been suggested.139 Although it is possible to assess residual clopidogrel effect using assays of platelet function (eg, PFA II, P2Y12 assay), only a normal result would be reassuring, and the clinical applicability of these tests remains undetermined at this time.140,141 The potency of these medications is demonstrated by recent reports of spontaneous spinal hematomas during clopidogrel therapy.
Platelet GP IIb/IIIa receptor antagonists, including abciximab (Reopro), eptifibatide (Integrilin) and tirofiban (Aggrastat), inhibit platelet aggregation by interfering with platelet-fibrinogen and platelet-von Willebrand factor binding. Because fibrinogen and von Willebrand factor have multiple binding sites, they can bind to multiple platelets, causing cross-linking and platelet aggregation. Conversely, inhibition of GP IIb/IIIa receptors blocks the final common pathway to platelet aggregation.137 Most clinical trials involving the GP IIb/IIIa antagonists have evaluated their use in the treatment of acute coronary syndrome (with or without percutaneous coronary intervention). Importantly, the GP IIb/IIIa antagonists are typically administered in combination with aspirin and heparin. Contraindications include a history of surgery within 4 to 6 weeks. Time to normal platelet aggregation after discontinuation of therapy ranges from 8 hrs (eptifibatide, tirofiban) to 24 to 48 hrs (abciximab). During therapy with GP IIb/IIIa antagonists, labeling precautions recommend that puncture of noncompressible sites and "epidural" procedures be avoided.
6.0 Anesthetic Management of the Patient Receiving Antiplatelet Medications
Antiplatelet medications, including NSAIDs, thienopyridine derivatives (ticlopidine and clopidogrel) and platelet GP IIb/IIIa antagonists (abciximab, eptifibatide, tirofiban) exert diverse effects on platelet function. The pharmacologic differences make it impossible to extrapolate between the groups of drugs regarding the practice of neuraxial techniques. There is no wholly accepted test, including the bleeding time, which will guide antiplatelet therapy. Careful preoperative assessment of the patient to identify alterations of health that might contribute to bleeding is crucial. These conditions include a history of easy bruisability/excessive bleeding, female sex, and increased age.
6.1 Nonsteroidal anti-inflammatory drugs seem to represent no added significant risk for the development of spinal hematoma in patients having epidural or spinal anesthesia. Nonsteroidal anti-inflammatory drugs (including aspirin) do not create a level of risk that will interfere with the performance of neuraxial blocks. In patients receiving these medications, we do not identify specific concerns as to the timing of single-shot or catheter techniques in relationship to the dosing of NSAIDs, postoperative monitoring, or the timing of neuraxial catheter removal (Grade 1A).
6.2 In patients receiving NSAIDS, we recommend against the performance of neuraxial techniques if the concurrent use of other medications affecting clotting mechanisms, such as oral anticoagulants, UFH, and LMWH, is anticipated in the early postoperative period because of the increased risk of bleeding complications. Cyclooxygenase-2 inhibitors have minimal effect on platelet function and should be considered in patients who require anti-inflammatory therapy in the presence of anticoagulation (Grade 2C).
6.3 The actual risk of spinal hematoma with ticlopidine and clopidogrel and the GP IIb/IIIa antagonists is unknown. Management is based on labeling precautions and the surgical, interventional cardiology/radiology experience (Grade 1C).
6.3.1 On the basis of labeling and surgical reviews, the suggested time interval between discontinuation of thienopyridine therapy and neuraxial blockade is 14 days for ticlopidine and 7 days for clopidogrel. If a neuraxial block is indicated between 5 and 7 days of discontinuation of clopidogrel, normalization of platelet function should be documented.
6.3.2 Platelet GP IIb/IIIa inhibitors exert a profound effect on platelet aggregation. After administration, the time to normal platelet aggregation is 24 to 48 hrs for abciximab and 4 to 8 hrs for eptifibatide and tirofiban. Neuraxial techniques should be avoided until platelet function has recovered. Although GP IIb/IIIa antagonists are contraindicated within 4 weeks of surgery, should one be administered in the postoperative period (after a neuraxial technique), we recommend that the patient be carefully monitored neurologically.
Herbal Medications
7.0 Anesthetic Management of the Patient Receiving Herbal Therapy
Herbal drugs, by themselves, seem to represent no added significant risk for the development of spinal hematoma in patients having epidural or spinal anesthesia. This is an important observation because it is likely that a significant number of our surgical patients use alternative medications preoperatively and perhaps during their postoperative course.
7.1 The use of herbal medications does not create a level of risk that will interfere with the performance of neuraxial block. We recommend against mandatory discontinuation of these medications or avoidance of regional anesthetic techniques in patients in whom these medications have been administered (Grade 1C).
New Anticoagulants
New antithrombotic drugs that target various steps in the hemostatic system, such as inhibiting platelet aggregation, blocking coagulation factors, or enhancing fibrinolysis, are continually under development.
Thrombin Inhibitors (Desirudin, Lepirudin, Bivalirudin, and Argatroban)
8.0 Anesthetic Management of Patients Receiving Thrombin Inhibitors (Desirudin, Lepirudin, Bivalirudin, and Argatroban)
8.1 In patients receiving thrombin inhibitors, we recommend against the performance of neuraxial techniques (Grade 2C).
Fondaparinux
Fondaparinux, an injectable synthetic pentasaccharide, was approved in December 2001. The FDA released fondaparinux (Arixtra) with a black box warning similar to that of the LMWHs and heparinoids. Fondaparinux produces its antithrombotic effect through factor Xa inhibition. The plasma half-life of fondaparinux is 21 hrs, allowing for single-daily dosing, with the first dose administered 6 hrs postoperatively.179
9.0 Anesthetic Management of the Patient Receiving Fondaparinux
The actual risk of spinal hematoma with fondaparinux is unknown. Consensus statements are based on the sustained and irreversible antithrombotic effect, early postoperative dosing, and the spinal hematoma reported during initial clinical trials. Close monitoring of the surgical literature for risk factors associated with surgical bleeding may be helpful in risk assessment and patient management.
9.1 Until further clinical experience is available, performance of neuraxial techniques should occur under conditions used in clinical trials (single-needle pass, atraumatic needle placement, avoidance of indwelling neuraxial catheters). If this is not feasible, an alternate method of prophylaxis should be considered.
Oral Direct Thrombin and Activated Factor Xa Inhibitors in Development
Dabigatran Etexilate
Dabigatran etexilate is a prodrug that specifically and reversibly inhibits both free and clot-bound thrombin. The drug is absorbed from the gastrointestinal tract with a bioavailability of 5%.182 Once absorbed, it is converted by esterases into its active metabolite, dabigatran. Plasma levels peak at 2 hrs. The half-life is 8 hrs after a single dose and up to 17 hrs after multiple doses.
Although there have been no reported spinal hematomas, the lack of information regarding the specifics of block performance and the prolonged half-life warrants a cautious approach.
Rivaroxaban
Rivaroxaban is a potent selective and reversible oral activated factor Xa inhibitor, with an oral bioavailability of 80%. After administration, the maximum inhibitory effect occurs 1 to 4 hrs; however, inhibition is maintained for 12 hrs.
Clinical trials comparing rivaroxaban (5-40 mg daily, with the first dose 6 to 8 hrs after surgery) with enoxaparin (40 mg, beginning 12 hrs before surgery) demonstrate similar rates of bleeding and a comparable efficacy. Although a "regional anesthetic" was performed in more than half of the patients included in the clinical trials, no information regarding needle placement or catheter management was included. Although there have been no reported spinal hematomas, the lack of information regarding the specifics of block performance and the prolonged half-life warrants a cautious approach.
Antithrombotic Therapy and Pregnancy
Despite decreased maternal mortality over the past 70 years, pulmonary embolism continues to be one of the most common causes of maternal death in both the United States and the United Kingdom.191 The age-adjusted incidence of VTE ranges from 5 to 50 times higher in pregnant versus nonpregnant women.192 Common risk factors that increase the incidence of thrombosis in pregnant women include increasing age, prolonged immobilization, obesity, thrombophilia, previous thromboembolism, and cesarean delivery193-196 (Table 10). The puerperium, defined as the 6-week period after delivery, is associated with a higher rate of thrombosis and pulmonary embolism than that associated with pregnancy itself.191,192
The ACCP guidelines on the use of antithrombotic agents during pregnancy have not recommended anticoagulation in pregnant women without thrombophilia or women with thrombophilia in the absence of a history of thromboembolism or poor pregnancy outcome. Owing to the high risk of thrombosis, the exceptions to this recommendation are as follows: women with (1) AT deficiency, (2) homozygosity for the factor V Leiden mutation, (3) homozygosity for the prothrombin gene G20210A mutation, or (4) heterozygosity for both mutations.17 The degree and duration of Prophylaxis are dependent on risk of thromboembolism in the antepartum and postpartum periods.
Obstetrical Management
A major component of management is for delivery (and needle/catheter placement) to occur during normal hemostasis. Consequently, the delivery should be scheduled whenever possible. In general, it is recommended that (1) no later than 36 weeks, oral anticoagulants should be switched to LMWH or UFH with similar dosing and monitoring as when used for anticoagulation throughout pregnancy; (2) at least 36 hrs before induction of labor or cesarean delivery, LMWH should be discontinued and the patient converted to intravenous or subcutaneous UFH if needed; (3) intravenous UFH should be discontinued 4 to 6 hrs before anticipated delivery.210 The pregnant patient on LMWH should be advised to withhold her heparin injection if she believes she may be in labor until evaluated by her obstetrician. If it is determined that she is in labor, further doses are usually held until after delivery. When possible, an induction or elective cesarean delivery should be scheduled. Adherence to these guidelines also facilitates the performance of neuraxial techniques for labor and delivery.
The plan for reinitiating anticoagulation postpartum must also be considered when planning the anesthetic management, and is often the limiting factor when determining the safety of a neuraxial technique. Typically, resumption of prophylaxis (eg, 5000 U of UFH every 12 hrs, 40 mg of enoxaparin once daily) should be held until at least 12 hrs after abdominal delivery, or epidural removal, whichever is later. After cesarean delivery, thromboprophylaxis should be held for at least 24 hrs.210,211 If higher levels (eg, enoxaparin 1 mg/kg every 12 hrs or adjusted-dose UFH for therapeutic aPTT) are required, prophylaxis should be delayed for 24 hrs, regardless of mode of delivery. These are consistent with recommendations for the nonpregnant patient.
10.0 Anesthetic Management of the Anticoagulated Patient
10.1 In the absence of a large series of neuraxial techniques in the pregnant population receiving prophylaxis or treatment of VTE, we suggest that the ASRA guidelines (derived from mainly from surgical patients) be applied to parturients (Grade 2C).
Plexus and Peripheral Blockade in the Anticoagulated Patient
11.0 Anesthetic Management of the Patient Undergoing Plexus or Peripheral Block
11.1 For patients undergoing deep plexus or peripheral block, we recommend that recommendations regarding neuraxial techniques be similarly applied (Grade 1C).
SUMMARY
Practice guidelines or recommendations summarize evidence-based reviews. However, the rarity of spinal hematoma defies a prospective-randomized study, and there is no current laboratory model. As a result, these consensus statements represent the collective experience of recognized experts in neuraxial anesthesia and anticoagulation. They are based on case reports, clinical series, pharmacology, hematology, and risk factors for surgical bleeding. An understanding of the complexity of this issue is essential to patient management; a "cookbook" approach is not appropriate. Rather, the decision to perform spinal or epidural anesthesia/analgesia and the timing of catheter removal in a patient receiving antithrombotic therapy should be made on an individual basis, weighing the small, although definite risk of spinal hematoma with the benefits of regional anesthesia for a specific patient. Alternative anesthetic and analgesic techniques exist for patients considered an unacceptable risk. The patient's coagulation status should be optimized at the time of spinal or epidural needle/catheter placement, and the level of anticoagulation must be carefully monitored during the period of epidural catheterization. Indwelling catheters should not be removed in the presence of therapeutic anticoagulation because this seems to significantly increase the risk of spinal hematoma. It must also be remembered that identification of risk factors and establishment of guidelines will not completely eliminate the complication of spinal hematoma. In the series of Vandermeulen et al,34 although 87% of patients had a hemostatic abnormality or difficulty with needle puncture, 13% had no identifiable risk factor. Vigilance in monitoring is critical to allow early evaluation of neurologic dysfunction and prompt intervention. Protocols must be in place for urgent magnetic resonance imaging and hematoma evacuation if there is a change in neurologic status. We must focus not only on the prevention of spinal hematoma but also on rapid diagnosis and treatment optimize neurologic outcome.