Regional anaesthesia in patients on antithrombotic drugs: Joint ESAIC/ESRA guidelines.

BACKGROUND: Bleeding is a potential complication after neuraxial and peripheral nerve blocks. The risk is increased in patients on antiplatelet and anticoagulant drugs. This joint guideline from the European Society of Anaesthesiology and Intensive Care and the European Society of Regional Anaesthesia aims to provide an evidence-based set of recommendations and suggestions on how to reduce the risk of antithrombotic drug-induced haematoma formation related to the practice of regional anaesthesia and analgesia. DESIGN: A systematic literature search was performed, examining seven drug comparators and 10 types of clinical intervention with the outcome being peripheral and neuraxial haematoma. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used for assessing the methodological quality of the included studies and for formulating recommendations. A Delphi process was used to prepare a clinical practice guideline. RESULTS: Clinical studies were limited in number and quality and the certainty of evidence was assessed to be GRADE C throughout. Forty clinical practice statements were formulated. Using the Delphi-process, strong consensus (>90% agreement) was achieved in 57.5% of recommendations and consensus (75 to 90% agreement) in 42.5%. DISCUSSION: Specific time intervals should be observed concerning the adminstration of antithrombotic drugs both prior to, and after, neuraxial procedures or those peripheral nerve blocks with higher bleeding risk (deep, noncompressible). These time intervals vary according to the type and dose of anticoagulant drugs, renal function and whether a traumatic puncture has occured. Drug measurements may be used to guide certain time intervals, whilst specific reversal for vitamin K antagonists and dabigatran may also influence these. Ultrasound guidance, drug combinations and bleeding risk scores do not modify the time intervals. In peripheral nerve blocks with low bleeding risk (superficial, compressible), these time intervals do not apply. CONCLUSION: In patients taking antiplatelet or anticoagulant medications, practitioners must consider the bleeding risk both before and after nerve blockade and during insertion or removal of a catheter. Healthcare teams managing such patients must be aware of the risk and be competent in detecting and managing any possible haematomas.

Monitoring and reversal strategies for new oral anticoagulants.

Thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban, apixaban and edoxaban form a new class of non-vitamin K antagonist oral anticoagulants and have been extensively studied in patients with venous thromboembolism and atrial fibrillation. They offer anticoagulation that is as effective and at least as safe compared to warfarin without the need for routine laboratory monitoring; however, no reversal strategies are currently validated in case of a non-vitamin K antagonist oral anticoagulant-associated bleed. In emergency situations, laboratory drug measurement and well-defined management for non-vitamin K antagonist oral anticoagulant-induced hemorrhage may improve clinical outcome. In this review, the merits and limitations of the routine coagulation tests and some of the more specific laboratory assays are compared. Furthermore, prohemostatic measures are reviewed and the recommended strategies in case of bleeding are summarized. Specific reversal agents are currently under development (idarucizumab for dabigatran, andexanet alfa for Xa inhibitors, and PER977 for both Xa- and thrombin inhibitors), which will facilitate clinical management of severe bleeding and emergency surgery.

Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology.

BACKGROUND AND OBJECTIVES: performing neuraxial anaesthesia in patients receiving antithrombotic drugs is controversial due to the increased risk of spinal epidural haematoma. Strict adherence to the recommended time intervals between the administration of anticoagulants, neuraxial blockade and the removal of catheters is thought to improve patient safety and reduce the risk of haematoma. Appropriate guidelines have been prepared by a number of national societies of anaesthesiologists, but they do not have universal acceptance. The introduction of new anticoagulants together with recent reports of stent thrombosis in patients with perioperative cessation of antiplatelet drugs have considerably broadened the issue and made revision necessary. To overcome deficiencies in content and applicability, the European Society of Anaesthesiology has taken the initiative to provide current and comprehensive guidelines for the continent as a whole. METHODS: extensive review of the literature. RESULTS AND CONCLUSIONS: in order to minimise bleeding complications during regional anaesthetic techniques, care should be taken to avoid traumatic puncture. If a bloody tap occurs when intraoperative anticoagulation is planned, postponing surgery should be considered. Alternatively, catheters can be placed the night before surgery. Regional anaesthesia in patients receiving full anticoagulation treatment continues to be contraindicated. Catheter manipulation and removal carry similar risks to insertion and the same criteria should apply. Appropriate neurological monitoring is essential during the postoperative recovery period and following catheter removal. The final decision to perform regional anaesthesia in patients receiving drugs that affect haemostasis has to be taken after careful assessment of individual risks and benefits.

Regional anaesthesia and anticoagulation.

As the life expectancy of our Western population progressively increases, so does the prevalence of cardiovascular disease and thus the use of antithrombotic drugs. The use of central neuraxial anaesthesia techniques in patients treated with these drugs is a major clinical problem as the presence of an impaired coagulation has been found to be the most important risk factor contributing to the formation of a spinal haematoma. The growing number of case reports of spinal haematoma has led many national societies of anaesthetists to come up with guidelines. This article presents an overview of current guidelines on the use of regional anaesthetic techniques in patients treated with various anticoagulants and also describes a possible strategy to deal with new antithrombotic drugs that have recently been introduced in some countries or will be shortly in others.

Risk assessment in patients with heart valve disease facing non-cardiac surgery.

Cardiac-related perioperative complications are well-known in general practice. The role of echocardiography in preoperative risk assessment before non-cardiac surgery remains unclear though. In this article we discuss recently published guidelines, articles and opinions in the domain of preoperative risk assessment of patients with valvular heart disease undergoing non-cardiac surgery. We created a risk stratification model that can be used in daily practice. This model may increase our awareness of the risks associated with heart valve disease in the perioperative period.

Anaesthesia and new antithrombotic drugs.

PURPOSE OF REVIEW: New anticoagulant drugs are introduced by the pharmaceutical industry on a regular basis. Anaesthesiologists are not always very familiar with these drugs although their use may augment perioperative bleeding and increase the likelihood of a compressing spinal haematoma when combined with epidural or spinal anaesthetic techniques. This review discusses the latest of these new anticoagulants and their consequences for anaesthesiological practice. RECENT FINDINGS: Durning the last few years, selective factor Xa inhibitors, glycoprotein IIb/IIIa receptor antagonists and direct thrombin inhibitors have been introduced into clinical practice. These drugs are typically more reliable and efficacious, have a lower incidence of side effects, are easier to use and will not need routine monitoring of their anticoagulant effects. In addition, their superior efficacy often implies a more profound anticoagulant action while reversing agents are mostly lacking and clinical experience is limited. SUMMARY: There is currently not enough information available to make any firm statements about the safety of combining regional anaesthesia and the new anticoagulant agents. Until such information becomes available, knowledge of the pharmacological profile of these drugs in terms of elimination half-life, the potential for thrombocytopenia and the availability of antagonizing drugs will help us to decide whether or not a major regional anaesthetic technique will be feasible in the individual patient treated with these new compounds.

Effect of plantar local anesthetic injection on dorsal horn neuron activity and pain behaviors caused by incision.

Hypersensitivity after tissue injury is an expression of neuronal plasticity in the central nervous system. This has been explored most extensively using in vitro preparations and animal models of inflammatory pain and chemical irritation. For pain after surgery, a similar process has been proposed. In the present study, we examined dorsal horn neuron (DHN) sensitization using the plantar incision model for post-operative pain. In behavioral experiments, the effect of a local anesthetic injection (or saline vehicle) 15 min before plantar incision on pain behaviors several days after incision was studied. Bupivacaine injection before incision prevented pain behaviors until 4 h afterwards; injection after incision produced the same effect. One day after incision, pain behaviors were not different between rats injected with saline or bupivacaine. In neurophysiologic experiments, however, bupivacaine injection blocked activation of DHNs during incision. One hour after incision, expansion of receptive fields (RFs) to pinch and increased background activity occurred in 14 of 16 neurons in the saline group but only in two of 22 neurons in the bupivacaine group. The difference was not due to a systemic effect of bupivacaine. Ten sensitized neurons were studied using the injection of bupivacaine 90 min after incision. Increased background activity (n=7) and expanded RFs (n=7) were reversed by bupivacaine. Sensitization was re-established in seven of eight neurons 2 h after injection as the local anesthetic dissipated. These results indicate that activation of DHNs during plantar incision and sensitization 1 h later are not necessary for subsequent pain behaviors. Because sensitization was reversed 90 min after plantar incision and then re-established as the local anesthetic effect diminished, enhanced responsiveness of DHN requires ongoing afferent input during the first day after incision.

Characterization of a rat model of incisional pain.

In this study, we developed a rat model of incisional pain. A 1-cm longitudinal incision was made through skin, fascia and muscle of the plantar aspect of the hindpaw in halothane-anesthetized rats. Withdrawal responses were measured using von Frey filaments at different areas around the wound before surgery and for the next 6 days. A cumulative pain score based on the weight bearing behavior of the animals was also utilized. The results of tests for withdrawal responses and scores based on weight bearing suggest that a surgical incision of the rat foot causes a reliable and quantifiable mechanical hyperalgesia lasting for several days after surgery. An incision that only included skin and fascia but not muscle in the foot caused less severe hyperalgesia during the initial postoperative period. Distinct areas around the wound had different withdrawal thresholds during the study period. Even remote sites as much as 10 mm from the wound showed persistent mechanical hyperalgesia. Selective denervations of the rat hindpaw prior to foot incision revealed both the sural and tibial nerves were responsible for transmitting input from the incision that produces hyperalgesia. This model should allow us to understand mechanisms of sensitization caused by surgery and investigate new therapies for postoperative pain in humans.