Dr Sibylle A Kozek-
Department of Anesthesiology and Intensive Care, Evangelic Hospital Vienna, Austria
In 2008, the ESA Guideline Committee was formed to oversee the production of evidence-based guidelines aimed at improving the practice of anaesthesia throughout Europe.
Although many national anaesthesia societies have published their recommendations on regional anaesthesia in patients receiving anticoagulant, antiplatelet agents or both, European collaboration will hopefully help towards the harmonisation of clinical management.
The ESA is systematically developing recommendations to help the clinician in decision-making, specifically in timing regional anaesthesia in situations where there is a pharmacologically increased risk of bleeding. Recommendations may be adopted, modified, or rejected according to the clinical requirements and constraints.
The use of the ESA recommendation does not guarantee prevention of neuraxial haematoma and perioperative thrombosis, but improves risk stratification and awareness. Although intended as a scientific guideline, it might also assist in legal disputes.
In general, guidelines are subjected to revision as new evidence or experience becomes available. Specifically, the use of ultrasound-guided peripheral regional anaesthesia may, in the future, shorten the recommended withdrawal intervals of anticoagulant and antiplatelet agents and drug monitoring may individualise perioperative management. This chapter describes the ESA guideline version 2010.
Anaesthetists are confronted with patients who are being treated with highly effective anticoagulant medications or inhibitors of platelet function. Introduction of new substances into the market is expanding the drug repertoire. Patient assessment should be performed well in advance of elective surgical procedures in order to plan for the individual timing of surgery and nerve blockade, perform appropriate drug monitoring, and to optimise coagulation and pro-coagulant therapy.1 Patients have to be informed about their specific risks for bleeding or thrombosis and give their consent to potential consequences.
Incidence of neuraxial haematoma
The risk of spinal haematomas is extremely low, but it can have dramatic neurological consequences for patients. The risk in patients receiving enoxaparin for thrombosis prophylaxis (40mg once daily) was reported to be 1:18,000 after epidural anaesthesia and 1:156,000 after spinal anaesthesia, with bleeding complications occurring much more rarely in obstetrics (1:200,000) than in female orthopaedic patients (1:3,600).2
Others have found higher rates of up to 1:2,700 to 1: 19,505.3-6 Risk factors include the lack of guidelines, female sex, difficult puncture conditions and regional anaesthesia technique. The risk of haemorrhage is lowest in spinal anaesthesia and highest in catheter epidural anaesthesia.7
In order to minimise bleeding complications of regional anaesthetic techniques, care should be taken to avoid a traumatic puncture. The final decision to perform regional anaesthesia in patients receiving drugs that affect haemostasis has to be taken after assessment of the individual risk and benefit. If it is judged that the administration of the anticoagulant must not be interrupted, an alternative anaesthetic technique should be used.
Spinal haematoma can occur late after surgery.8 After performance of the block, the patient should be monitored at least until the effect of the regional anaesthesia is clearly declining, that is when there is a reduction in the extent of sensory block by two segments or a return of motor function.
Particular attention should be given to persistent sensory or motor deficits, radicular back pain, pressure sensitivity in the puncture area and bladder dysfunction. When there is a clinical suspicion of neuraxial haematoma, appropriate diagnostic (MRI) or treatment measures (decompressive laminectomy) must be started immediately.
Time intervals for drug withdrawal
It is generally perceived that adhering strictly to the appropriate time intervals between the administration of anti-haemostatic drugs and regional blockade or removal of catheters improves patient safety and reduces the risk of haematoma formation.
The ESA recommendation on time intervals are mainly based on pharmacology of the anti-haemostatic agents concerned rather than based on (scarce) prospective, randomised clinical studies (Table 1). Drug combinations or interactions as well as reduced (renal or hepatic) elimination alter pharmacokinetics significantly, increase the risk for bleeding and limit the value of recommended withdrawal times.
Aside from recommending time intervals, the ESA guideline also aggregates information on currently available anti-haemostatic agents including their pharmacology, indications and side-effects. It is important to remember that anti-haemostatic agents are prescribed because of a risk of thrombotic manifestations. Surveillance for postoperative thrombosis or ischaemia is essential during the postoperative recovery period, especially in patients receiving antiplatelet therapy. An early resumption of treatment postoperatively is essential.
Important points about antithrombotic drugs
Unfractionated heparin. In the American Society of Anesthesiologists’ (ASA) analysis of closed claims, spinal epidural haematoma occurred most frequently in vascular surgery patients, suggesting that this population is at an increased risk.9 The risk of haemorrhage after epidural anaesthesia and subsequent intraoperative heparinisation is not increased if heparinisation is delayed for one hour after spinal or epidural puncture. Removal of epidural catheters should not be carried out until at least four hours after the end of heparin administration with normalisation of coagulation parameters (using the aPTT and ACT clotting tests).
If a bloody puncture occurs in patients in whom intraoperative heparinisation is planned, it is recommended that low-dose anticoagulation (for example, 5,000 IU) should be avoided for one to two hours and full heparinisation should be avoided for six to 12 hours, with the operation being delayed to the next day if necessary.
Alternatively, to avoid delays, epidural catheter placement can be carried out the evening before surgery. This is particularly recommended in cardiac surgery using extracorporeal circulation.10 In view of the limited benefits of neuraxial blockade in cardiac surgery, with no major effect on morbidity and mortality, and considering the significant risks, it is disputable whether spinal and epidural techniques are justified at all or should be abandoned in this particular patient population.11
Low-molecular-weight heparins (LMWH). A meta-analysis of studies on the timing of thromboprophylaxis showed that LMWH given 12 hours preoperatively does not reduce the risk of thromboembolism compared with a postoperative regimen.12 Since it is known that anti-thrombotic drugs increase the risk of spinal epidural haematomas after neuraxial blockade, a postoperative start may be advantageous.
To avoid bleeding complications, there should be a time interval of at least 12 hours between subcutaneous administration of LMWH in prophylactic dosages and the placement or removal of an epidural catheter.6,13 At a therapeutic dosage, catheter placement or removal should be delayed for at least 24 hours after the last administration.
Whether a 24-hour interval is acceptable in relation to the thromboembolism risk needs to be considered on an individual basis. In cases at high risk of thromboembolism – for example, mitral or double mechanical valve replacement – one should refrain from neuraxial blockade and continue the administration of LMWH.
Following spinal or epidural puncture, or after removal of a spinal or epidural catheter, repeat administration of LMWH should be delayed for at least two to four hours.
Fondaparinux. The EXPERT study with a total of 5,387 patients14 used a time interval of 36 hours before catheter removal and 12 hours after catheter removal before the next dose of fondaparinux for thromboprophylaxis. In cases of therapeutic anticoagulation with fondaparinux (5mg–10mg per day), neuraxial anaesthesia should not be performed due to the substantial risk of accumulation.
Rivaroxaban. A time interval of 18 to 20 hours between the last dose of rivaroxaban (10mg) and puncture or catheter withdrawal is recommended. After catheter withdrawal, the next dose of rivaroxaban may be given after two to four hours.
Dabigatran. A time interval of 34 hours between the last dose of dabigatran and puncture or catheter withdrawal can be extrapolated from pharmacokinetic data. However, the manufacturer advises against the use of dabigatran in the presence of neuraxial blockade. This warning has medico-legal consequences, if a spinal epidural haematoma occurs.
Vitamin K antagonists (phenprocoumon, warfarin). Therapeutic anticoagulation with vitamin K antagonists represents an absolute contra-indication to neuraxial blockade. Vitamin K antagonists should only be administered after the catheter has been removed.
Direct thrombin inhibitor: argatroban. Patients with acute heparin-induced thrombocytopenia frequently suffer from multiple organ failure including coagulation disturbances, making neuraxial blockade inadvisable.
Important points about platelet inhibitors
Acetylsalicylic acid and thienopyridines. On the basis of the available data, it can be assumed that non-steroidal anti-inflammatory drugs – including acetylsalicylic acid – by themselves do not lead to an increased risk of spinal haematomas15-17 and thus do not represent a contraindication. A higher rate of complications has been observed in both surgical and medical patients when heparins were administered simultaneously.18
Neuraxial regional anaesthesia should only be carried out if a time interval of seven days between the last intake of clopidogrel and the neuraxial blockade is possible (10 days after the last administration of ticlopidine).
Dual antiplatelet therapy and the risk of
It is recommended that patients with acute coronary syndromes or stent implantation should continue to take acetylsalicylic acid on a lifelong basis.19 With bare metal stents (BMS), dual platelet aggregation inhibition should be administered for at least four to six weeks after implantation, and with drug-eluting stents (DES) these should be taken for 12 months.19 Elective surgery should be postponed until the mandated clopidogrel therapy will end and the surgery can be performed under acetylsalicylic acid. In an emergency, all perioperative care providers should be aware of the increased risk of intra- and postoperative bleeding. In semi-elective or urgent cases, the management should be tailored to the thrombosis/bleeding tolerance. Dual antiplatelet therapy should be restarted postoperatively as soon as possible
Peripheral nerve blocks
Peripheral nerve blocks cause less serious complications and are devoid of the risk of spinal haematoma. Peripheral nerve blocks have been divided into two groups according to their bleeding risk.20
Performance of superficial peripheral nerve blocks such as axillary plexus block, femoral nerve block or distal sciatic nerve block are not
contraindicated in the presence of anti-haemostatic agents, if there is a normal bleeding history.
However, for deep peripheral nerve blocks – close to vessels that cannot be compressed, such as infraclavicular nerve block and lumbar sympathetic blockade – time intervals established for neuraxial blockade should be followed.
- Kozek-Langenecker SA. Preoperative coagulation testing. ESA Refresher Course lectures 2008; 06RC1: 49-54.
- Moen V et al. Anesthesiology 2004;101:950-9.
- Cameron CM et al. Anesthesiology 2007;106:997-1002.
- Christie IW & McCabe S. Anaesthesia 2007;62:335-41.
- Popping DM et al. British Journal of Anaesthesia 2008;101:832-40.
- Cook TM et al. British Journal of Anaesthesia 2009;102:179-90.
- Vandermeulen EP et al. Anesthesia Analgesia 1994;79:1165-77.
- Moussallem C et al. Journal of Bone and Joint Surgery 2009;91:B1531-2.
- Lee LA et al. Anesthesiology 2004; 101:143-52.
- Chaney MA. Anesthesia Analgesia 1997;84:1211-21
- Chaney MA. Canadian Journal of Anaesthesia 2005;52:783-8.
- Strebel N et al. Archives of Internal Medicine 2002;162:1451-6.
- Bergquist D et al. Seminars in Thrombosis and Hemostasis 1993;19:147-51.
- Singelyn FJ et al. Anesthesia Analgesia 2007;105:1540-7.
- Collaborative Low-dose Aspirin Study in Pregnancy (CLASP) Collaborative Group. Lancet 1994;343:619-29.
- Horlocker TT et al. Anesthesia Analgesia 1995;80:303-9.
- Horlocker TT et al. Anesthesia Analgesia 2002;95:1691-7.
- Stafford-Smith M. Canadian Journal of Anaesthesia 1996;43:R129-35.
- Poldermans D et al. European Heart Journal 2009; doi:10.1093/eurheartj/ehp337
- Kozek-Langenecker SA et al. Anaesthesist 2005;54 476-84.