Regional Anaesthesia in Patients Receiving Antithrombotic Drugs

This Invited Commentary accompanies the following original article: Kietaibl S, Ferrandis R, Godier A, et al. Regional anaesthesia in patients on antithrombotic drugs: Joint ESAIC/ESRA guidelines. Eur J Anaesthesiol 2022; 39:100–132 In the current issue of the European Journal of Anaesthesiology, the European Society of Anaesthesiology and Intensive Care and the European Society of Regional Anaesthesia have published practical guidelines on regional anaesthesia in patients receiving antithrombotic therapy.1 For some major surgery, regional anaesthesia may improve peri-operative outcomes compared with general anaesthesia alone, with a decreased rate of complications such as pulmonary complications, surgical site infection, blood transfusion, thromboembolic events, a reduced length of stay and reduced intensive care admissions.2 However, haemorrhagic complications are particularly feared in neuraxial blockade (epidural or spinal anaesthesia) or deep nerve blocks because of the potential for serious and catastrophic sequelae. The incidence of neurological sequelae resulting from a haematoma associated with neuraxial anaesthesia is not really known. The incidence in the literature varies widely from less than 1 in 150 000 for epidural anaesthesia and less than 1 in 220 000 for spinal anaesthesia in obstetrics, but can be as high as 1 in 3000 in elderly women undergoing knee arthroplasty.3 The risk of haemorrhagic complications increases with age, female sex, anatomical abnormalities, difficulty of puncture with bloody tap during needle placement, an indwelling catheter and impaired haemostasis due to either inherited coagulopathy or antithrombotic therapy. As regards the latter, there may errors in the time intervals of witholding or restarting antithrombotic drugs in up to 15% of cases.4 As a consequence, haemostatic function should be carefully assessed and returned to normal when performing a block with a high risk from bleeding (neuraxial blocks or deep peripheral nerve blocks). Particular attention needs to be made to the time interval between the last dose of antithrombotic drug and the performance of the procedure, and also the delay before restarting antithrombotics, especially when indwelling catheters are used. Conversely, with superficial nerve blocks, there is a low risk from bleeding, with no severe complications, therefore no interruption of antithrombotic drugs is recommended, as long as they are within the therapeutic range. Compared with other pre-existing guidelines,5,6 the current ESAIC/ESRA guidelines not only address the time from last antithrombotic drug intake to block procedure or catheter removal in both low and high risk of bleeding interventions, but also address some specific concerns affecting daily practice, for example: (1) Is there a difference in time intervals between low and high doses of antithrombotic drugs? (2) Is there a difference in time intervals when several antithrombotic drugs are combined? (3) Is there a difference in time intervals when monitoring antithrombotic effects? (4) Is there a difference in time intervals when using a specific antithrombotic drug reversal agent? (5) Is there a difference in time intervals when using ultrasound guidance for block puncture? To answer these questions, the authors followed a methodologically rigorous process: experts developed recommendations relevant to 21 PICO questions, using GRADE methodology, and the Delphi process was used for attaining consensus. The analysis of the literature was limited to adult surgical patients requiring regional anaesthesia and obstetric patients requiring neuraxial analgesia/anaesthesia. Paediatric patients were excluded because of the important overall clinical differences. As expected with most rare or unusual complications, evidence in the literature is limited in number and quality of studies: there will never be a prospective trial on how to manage antithrombotic drugs before performing regional anaesthesia. Nevertheless, the authors were able to formulate 40 recommendations with a consensus. Somewhat surprisingly, one novel recommendation is related to aspirin. Although aspirin is the most routinely prescribed antithrombotic drug, it is also the only medication with a four-fold difference in dosage recommended by expert committees, approved by regulatory agencies and prescribed by physicians.7 A comparison of the US and European guidelines brings out important differences regarding aspirin regimens: the American College of Cardiology Foundation and the American Heart Association recommend 162 to 325 mg as a loading dose followed by 81 to 325 mg in maintenance regimens, whereas the European Society of Cardiology recommend 150 to 300 mg as a loading dose followed by 75 to 100 mg daily. The rationale of an increased bleeding risk associated with high dosing of aspirin is still debated and data in the literature are inconsistent. However, it seems that low-dose aspirin (≤100 mg) is as effective as higher doses for the prevention of cardiovascular ischaemic events and is associated with a lower incidence of major bleeding. Given this doubt regarding the haemorrhagic risk associated with high doses of aspirin, the ESAIC/ESRA guidelines are the first one to recommend different time intervals between low and high doses of aspirin. Low-dose aspirin is not a contraindication for neuraxial blocks nor for deep peripheral nerve blocks and does not require witholding, while aspirin prescribed at high doses should be witheld at least three days before the procedure assuming a normal platelet count, and up to seven days before in the case of thrombocytopenia. The cut-off value of 200 mg assumed in the guidelines could be debated, but in general European practice, it should not be a problem, as the maintenance dose of aspirin for cardiovascular prevention is 75 to 100 mg in Europe. The time interval between the last antithrombotic drug intake and the block insertion is based on general pharmacologic principles, assuming that four to five half-lives are necessary for returning to normal in the case of ‘therapeutic’ doses and only two half-lives are required for ‘prophylactic’ doses. Whereas measurement of the international normalised ratio in patients on vitamin-K antagonists and measurement of anti-Xa activity or activated partial thomboplastin time for patients treated with high doses of unfractionated heparin are required to be in the normal range before performing neuraxial or deep nerve procedures, the measurement of residual drug activity is not necessary for other antithrombotic drugs. Nevertheless, the elimination of low molecular weight heparin or direct acting oral anticoagulants can be modified by several factors such as age, renal function impairment and concomitant medications, and measurement of any residual anticoagulant effect has to be considered in these situations. We perceive in this kind of situation the limit of any recommendations: guidelines are not and will never be a standard of care to apply blindly, and will never replace a physician when treating a specific patient. Guidelines should be made to help provide quality care, adapted to each situation in real life. This is one of the strengths of the ESAIC/ESRA guidelines that must be highlighted. The authors tried to provide guidance even for difficult clinical situations, which we might hope never to be faced with (urgent antiplatelet or anticoagulant therapy with a neuraxial catheter in situ, for example). In a number of situations, regional anaesthesia may be the best choice for improving patient outcomes. Although antithrombotic drugs can be an obstacle to carrying out such techniques, these guidelines will certainly help in the daily practice of regional anaesthesia both in the more usual as well as both in the more tricky situations.