Indian Journal of Anaesthesia 2008;52:Suppl (5):699-704

Neuraxial Blocks and Anticoagulation

CVR Mohan

Summary
Haemorrhagic complications can follow most regional anaesthetic techniques. However bleeding inside the spinal canal may be unrecognised at the time of the placement of the block (intrathecal or epidural) and may continue unrecognised, and, as the spinal canal is a confined space, an expanding space-occupying lesion may develop which may compress the contents of the spinal canal and can lead to catastrophic permanent neurologic damage. These lesions can remain masked by, or interpreted as, the effects of the central neural blockade, delaying prompt diagnosis and treatment. Spinal haematoma may be spontaneous, with no prior instrumentation in the region, or in association with therapeutic anticoagulant treatment, or with the pathology of the clotting mechanisms. Existing guidelines on the subject are revised and alternatives are discussed. Key words Neuraxial blocks, Anticoagulants, Anti platelet agents, Spinal anaesthesia, Epidural anaesthesia, Epidural haematoma

Introduction
Man exists in a naturally prothrombotic state. This has been a survival advantage during his early evolution, protecting him against blood loss when wounded. The downside of this tendency to coagulate is that we are prone to develop myocardial infarctions and ischemic cerebrovascular accidents, and that the stents and valves we place in our patients vasculature are prone to thrombose, rendering them non functional and blocking off circulation to vital organs, anticoagulants have been widely prescribed in patients to prevent these catastrophes. However, the widespread prescription of antithrombotics may have serious adverse consequences when such a patient undergoes surgery. It is the balancing of the risk between stopping anticoagulation which may lead to thrombosis and continuing anticoagulation which may lead to fatal intraoperative bleeding which makes the management such patients challenging. An additional concern is the risk that administering a central neuraxis block in such a patient might lead to the formation of an expanding hematoma, with cata-

strophic permanent neurologic damage. These lesions can remain masked by, or interpreted as, the effects of the central neural blockade, delaying prompt diagnosis and treatment. Spinal hematoma may be spontaneous, with no prior instrumentation in the region, or in association with therapeutic anticoagulant treatment, or with the pathology of the clotting mechanisms. The debate between continuing and interrupting anticoagulation has been sharpened by two factors: Firstly numerous reports of spinal hematoma following central neuraxis blockade when low molecular weight heparin was given to patients for thromboprophylaxis1 and secondly numerous reports of stent thrombosis, frequently with fatal results in patients who had recently implanted stents presenting for surgery.2 Amongst patients undergoing surgery there are definable groups of patients undergoing definable surgeries who have a higher risk for thrombo-embolism (Table 1). It has been shown that, without prophylaxis, the incidence of deep vein thrombosis (DVT) is about 14% in gynaecological surgery, 22% in neurosurgery, 26% in abdominal surgery and 4560% in orthopaedic surgery. In patients with malignancy these rates are

Professor and HOD, Correspondence to: CVR Mohan, Department of Anaesthesiology, Critical Care, Resuscitation and Pain Management, Armed Forces Medical College, Pune. Email: severemohan@rediffmail.com 699

Indian Journal of Anaesthesia, October 2008(P.G.Issue)

markedly higher.3 A number of risk assessment models (RAMs) have been created to assist physicians in making decisions about whether prophylaxis is needed and which type is required.3-6 An example of an RAM, published by the American College of Chest Physicians,8 is given in Table 2. Neuraxial anaesthesia and analgesia provide excellent postoperative analgesia and allow early mobility after major surgery.9-12. Epidural anaesthesia and analgesia are therefore used frequently in many centres, although a true outcome benefit in terms of mortality or major organ dysfunction could not be confirmed

in two recent large-scale prospective randomized studies, with the exception of reduced pulmonary complications.11,12.

Spinal Hematoma
The most feared complication of neuraxial anaesthesia is epidural haematoma, which can have potentially crippling neurological complications. As more and more patients are treated with drugs interfering with blood coagulation or platelet function, the anaesthesiologist is frequently faced with the problem of whether neuraxial anaesthesia is still an option or whether such co-medication means it is contraindicated.

Table 1 Patient-specific risk factors influencing the perioperative risk of thrombosis

Clinical risk factors History of thromboembolism Malignancy Age>40 yr Obesity Varicose veins Prolonged immobilization Dehydration Heart failure Nephrotic syndrome Stroke Myeloproliferative syndrome BehVets disease Pregnancy, puerperium Drugs Oral contraceptives Hormone replacement therapy Inherited thrombophilia Acquired thrombophilia (FV Leiden mutation) Antiphospholipid antibody Activated protein C resistance Sustained elevated FVIII levels Prothrombin gene mutation G20210A Antithrombin deficiency Protein C deficiency Protein S deficiency Hyperhomocysteinaemia

Table 2 Risk assessment model (RAM) from the American College of Chest Physicians. Adapted from Samama8.
Low risk Moderate risk High risk Major surgery in patients >40 yr who have additional risk factors Very high risk Major surgery in patients >40 yr plus previous venous thromboembolic or malignant disease or hypercoagulable state Elective major orthopaedic surgery or hip fracture or stroke or spinal cord injury Uncomplicated minor Major and minor surgery in surgery in patients <40 yr patients 4060 yr with no with no clinical risk factors clinical risk factors Major surgery in patients <40 yr with no additional risk factors Minor surgery in patients with risk factors or multiple trauma 700

CVR Mohan. Neuraxial blocks and anticoagulation

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 block is unknown. In an extensive review of the literature, Tryba13 identified 13 cases of spinal hematoma following 850,000 epidural anaesthetics and 7 cases among 650,000 spinal techniques. Based on these observations, the calculated incidence is approximated to be less than 1 in 150,000 epidurals and less than 1 in 220,000 spinal anaesthetics. Hemorrhage into the spinal canal most commonly occurs in the epidural space, most likely because of the prominent epidural venous plexus although anaesthetic variables, such as needle size and catheter placement, may also affect the site of clinically significant bleeding.14-16 In a review of the literature between 1906 and 1994, Vandermeulen et al16 reported 61 cases of spinal hematoma associated with epidural or spinal anaesthesia. In 42 of the 61 patients (68%), the spinal hematomas associated with central neural block occurred in patients with evidence of hemostatic abnormality. Twenty-five of the patients had received IV or SC (unfractionated or LMWH), while an additional 5 patients were presumably administered heparin as they were undergoing a vascular surgical procedure. In addition, 12 patients had evidence 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 anaesthetic. 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 anaesthetic was performed in 15 patients. The remaining 46 patients received an epidural anaesthetic, including 32 patients with an indwelling catheter. In 15 of these 32 patients, the spinal hematoma occurred immediately after the removal of the epidural catheter. Nine of these catheters were removed during therapeutic levels of hep701

arinization. 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 patients had partial or good neurologic recovery, spinal cord ischemia tended to be reversible in patients who underwent laminectomy within 8 hours of onset of neurologic dysfunction. The need for prompt diagnosis and intervention in the event of a spinal hematoma was also demonstrated in a recent review of the American Society of Anesthesiologists (ASA) Closed Claims database, which noted that spinal cord injuries were the leading cause of claims in the 1990s.15 Spinal hematomas accounted for nearly half of the spinal cord injuries. Risk factors for spinal hematoma included epidural anaesthesia in the presence of IV heparin during a vascular surgical or diagnostic procedure. Importantly, the presence of postoperative numbness or weakness was typically attributed to local anaesthetic effect rather than spinal cord ischemia, which delayed the diagnosis. Patient care was rarely judged to have met standards (1 of 13 cases) and the median payment was very high. Several US and European societies have issued guidelines on locoregional anaesthesia in patients treated with heparin, oral anticoagulation, drugs interfering with platelet function, and other drugs used for thromboprophylaxis.10,18,19 These guidelines are similar in the following respects:

Admitting that data are incomplete and, in the case of the newer antiplatelet and antithrombotic drugs, virtually non-existent. This applies equally to drug combinations.

Regarding the risk of epidural haematoma during placement and removal of an epidural catheter to be similar and therefore applying the same rules.

Considering the risk of peripheral nerve and plexus blocks to be smaller than the risk of epidural analgesia.

Indian Journal of Anaesthesia, October 2008(P.G.Issue)

Suggesting the use of low concentrations of local anaesthetics in combination with opioids (and epinephrine).

Monitoring the patient after surgery to detect paralysis suggestive of an early epidural haematoma. 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 anaesthesia and analgesia in the anticoagulated patient. Unfortunately, with a complication as rare as spinal hematoma, no clinical study to date has sufficient power to definitively determine patient management. Consequently, the pharmacology of hemostasisaltering drugs and case reports of spinal hematoma are also essential to regional anaesthetic management. Moreover, variations from available guidelines may be acceptable based on the experience of the anaesthesiologist. The following seems a reasonable summary of the numerous guidelines , although the reader is urged to consult the original references to get a better idea of the grounds on which such guidelines have been made. 1. Patients should not receive intravenous unfractionated heparin within one hour of administering a central neuraxis block. The last dose of fractionated heparin should be given at least four hours before the block. A bloody tap should lead to greater vigilance, though the decision regarding whether to postpone the surgery should be indiviualised. 2. Subcutaneous Unfractionated heparin has attracted less strictures, although the German Society of Anaesthesiologists has placed identical restrictions to Intravenous heparin on its use18 3. Low molecular weight heparin should be given at least 12 to 24 hours before the neuraxial block. The first dose should be given at least four hours after the block, and removal of catheters should be 12 hours after the last dose and at least 4 hours before the next
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dose. These guidelines may not apply to the newer longer acting LMWHs ,which are becoming available, and the reader is urged to consult the package inserts for guidance in these drugs. 4. With regards to warfarin, the INR should be less than 1.5 prior to performing the block. If the risk of thrombosis due to stoppage of warfarin is unacceptably high, bridging therapy with heparin should be considered, although short term stoppage of warfarin seems fairly benign with respect to complications.24 5. Certain herbal remedies, especially garlic, may increase the tendency to bleeding. It is advisable to stop garlic seven days in advance and other such medications (ginkgo and ginseng) 36 hours in advance. The use of antiplatelet drugs is fraught with controversy. NSAIDS seem fairly safe with respect to neuraxial block, and need not be stopped for this reason25Clopidogrel should ideally be stopped seven days before surgery. This may however lead to an unacceptably high risk of stent thrombosis 2. Choices include the following, in patients in whom central neuraxis block would be advantageous or in whom continuation of antiplatelet drugs would pose an unacceptable risk of bleeding a) If dilatation has been done without stenting, postpone all elective surgery by 2-4 weeks. b) If a bare metal stent has been placed, postpone elective surgery for six weeks and chose a window between 6 and 12 weeks of stent placement after which restenosis can occur. c) If a drug eluting stent is inserted, postpone elective surgery by 12 months If surgery is unavoidable, a risk benefit balance should be made between continuation and stopping of clopidogrel and aspirin. Choices include a) continuing the surgery while continuing to give clopidogrel, and discussing the risks of surgery and

CVR Mohan. Neuraxial blocks and anticoagulation

neuraxis blockade with the patient and surgeon b) Stopping clopidogrel 5 days in advance, bridging the perioperative period with Gp IIb/IIIa inhibitors (eptifibatide or tirofiban) which can be stopped on the morning of surgery26 c) Stopping clopidogrel 7 days in advance and accepting the risk of stent thrombosis d) Avoiding neuraxial techniques in such patients e) One possible option, which the author has found invaluable in such situations, is to use paravertebral blocks as an alternative to neuraxis blocks. It would be prudent both from a patient care standpoint and from a medicolegal standpoint to discuss the risks and benefits of the alternative approaches fully with the patient, surgeon and the patients cardiologist before choosing an option. It should be remembered that placing the patient on heparin as a substitute for clopidogrel is not an adequate approach, since heparin is not an antiplatelet agent. Preoperative platelet transfusion prior to performing a neuraxial block adds the risk of transfusion, without guaranteeing safety. The effect of neuraxis block on thrombosis: One fact which is frequently forgotten is that epidural and spinal anaesthesia also have a beneficial effect on coagulation, in that they reduce the incidence of deep venous thrombosis in high risk individuals. In one study conducted between 1970 and 1974, on patients receiving toal hip replacements, operative and postoperative blood loss, transfusion requirements, thromboembolism, and overall rate of complications were reduced in the group that received spinal anaesthesia.27 In another retrospective study, it was observed that inhospital deaths resulting from PE declined six fold from 0.12% with general anaesthesia28 Spinal anesthesia reduces blood loss and the prevalence of VTE by 40% to 50% in comparison to general anaesthesia29 Conclusion: Since the incidence of spinal hematoma is simultaneously so rare, and when it occurs,
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so devastating, it is impossible to make recommendations based on Level I evidence. While a measure of concordance has been reached on guidelines regarding anticoagulants used for thromboprophylaxis, agreement is still scant with regards to antiplatelet drugs, with cardiology journals stressing the risks of stent thrombosis and anaesthesia journals stressing the risks of spinal hematoma. In such an atmosphere of disagreement, full and frank discussion of the risks and benefits of all approaches with all interested parties is perhaps the most intelligent approach.

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