Due to the in-depth understanding of thromboembolic diseases and the emergence of heart antithrombotic drugs, the prevention and treatment of thromboembolic diseases have developed rapidly in the past 10 years. How to deal with intraoperative anesthesia and postoperative analgesia in antithrombotic patients, how to apply antithrombotic drugs safely and reasonably intraoperatively, and how to resume antithrombotic treatment after surgery are the problems that anesthesiologists must face.
I. Current status and progress of perioperative anesthesia management in anticoagulated patients
There are three types of antithrombotic drugs commonly used in the perioperative period as follows: antithrombin III-dependent anticoagulants: heparin, low-molecular heparin, etc.; vitamin K-dependent anticoagulants: bicoumarins, such as warfarin; antiplatelet drugs, such as aspirin, COX-2, poliovir, abciximab, eptifibatide and tirofiban. tirofiban)
Currently, the antithrombotic drugs in routine clinical use are aspirin, heparin, low molecular heparin, and warfarin. Given the different pharmacokinetics and pharmacokinetics of the different anticoagulant agents, which can lead to fatal complications such as hematoma when the patient receives anticoagulants during an endovascular block, the anesthesiologist must choose the correct preanesthetic management, postoperative analgesia, and perioperative coagulation status based on the urgency of the procedure, i.e., elective or emergency, and the patient’s systemic condition, or a benefit and risk analysis. measures and perioperative coagulation status monitoring.
(i) Antiplatelet agents
Aspirin, which has been clinically used for more than 100 years, is one of the most widely studied and used drugs. It plays an important role in reducing the occurrence of cardiovascular disease (primary prevention) and improving the regression of cardiovascular disease after its occurrence or reducing recurrence (secondary prevention), and is therefore widely used in preoperative patients.
Aspirin irreversibly inhibits the synthesis and release of TXA2 from platelets by inhibiting the cyclic oxidase enzyme on platelet membranes, and inhibits platelet aggregation induced by TXA2. The plasma half-life of aspirin is only 20 min, but the inhibition of platelet cyclooxygenase is irreversible, and its function is always inhibited during the survival period of platelets (8~10 d) until new platelets are produced to maintain normal cyclooxygenase function.
Patients taking aspirin 30~50mg for 7~10d can completely inhibit the activity of platelet cyclooxygenase in the organism. in the past, it was required that patients undergoing elective surgery should stop taking aspirin at least one week before surgery to select the method of anesthesia without contraindications. in 2003, the American Society for Local Anesthesia and Pain Medicine (ASRA) issued the second guideline on the risk of hematoma in anticoagulated patients with intralesional anesthesia, clearly stating that simply Sibai et al. randomly divided 891 pregnant women who applied epidural block into a low-dose aspirin group (60 mg/d) and a placebo group, and the results showed that no complications related to epidural bleeding occurred in both groups. In 270 patients with knee or hip replacements who did not discontinue aspirin preoperatively, no complications such as epidural hemorrhage were observed by Wu et al. In an analysis of 51 patients with epidural hematoma, Wulf et al. found that two of them were associated with the non-discontinuation of aspirin preoperatively.
COX-2, like COX-1, does not increase intradural anesthesia hematoma and does not require preoperative discontinuation. Bolivar needs to be discontinued for 7 days before surgery. Abciximab needs to be discontinued 48 hours prior to surgery. Etibatide and tirofiban need to be discontinued 8 hours before surgery.
Although it is well documented that patients without preoperative aspirin discontinuation rarely cause epidural hemorrhage, emergency surgery should be performed with caution, skilled puncture technique, strict intraoperative blood pressure control, and postoperative peripheral nerve monitoring to facilitate early detection and effective management.
New platelet antagonists such as etidiotide and tirofiban are more selective and have comparable clinical effects to aspirin in the prevention and treatment of cardiovascular diseases; they hardly affect the bleeding time and do not increase the incidence of epidural hemorrhage when used preoperatively.
(ii) Heparin
Heparin, which exists naturally in the body, is a glycoprotein that binds to serine residues of core proteins in the form of covalent bonds and belongs to a family of polysaccharides with widely varying molecular weights. The anticoagulant effect of heparin lies in specific binding to antithrombin, which changes the conformation of antithrombin and exposes the active center, which interacts with relevant activated coagulation factors to inactivate serine protease classes such as coagulation factor IIa (thrombin), IXa, Xa, XIa and XIIa in plasma, and produces anticoagulant effect. Its half-life varies from dose to dose and varies greatly among individuals. If the injected heparin dose is increased from 25 to 400 U/kg, the half-life increases from 30 to 150 min, with an average of about 60 min.
In patients undergoing elective surgery with heparin anticoagulation, heparin is applied until the morning of surgery (4h before anesthesia) when it is discontinued, and general anesthesia or intrathecal block is safe. The application of intradural blocks for emergency surgery without discontinuation of heparin is controversial, mainly because of the consideration that heparin may increase the risk of trauma, subarachnoid or epidural hemorrhage. One group reported 847 cases treated with heparin and maintained their clotting time at twice normal, without any clinically detected cases of hematoma.Kassis et al. In 50 patients undergoing elective general abdominal surgery with subcutaneous injection of small doses of heparin 5000 U, venous blood was drawn before, 2h and 4h after injection to determine the activated partial clotting time (APTT) and heparin concentration, and found that heparin The concentration of heparin was found to be less than 0.2 U/ml, so it was presumed that it was safe to perform epidural block 2 h after the application of low-dose (less than or equal to 5000 U) heparin.
For safety reasons, intravertebral puncture placement is contraindicated in patients in whom subcutaneous heparin is applied within 2 h to reduce complications of medically induced intravertebral hemorrhage.Terese et al. recommended that puncture placement can be performed at least 4 h after subcutaneous heparin injection, and intravenous heparin should be used only at least 60 min after placement, and the epidural tube should be removed 4-6 h after discontinuation of heparin, and activated clotting time (ACT) or APTT reaches normal This is done after the range, and heparin application should not be resumed until at least 60 min after extubation.
A single subarachnoid block is safer than a single epidural block, and a single epidural is safer than a continuous epidural block. The risk of bleeding during puncture and tube placement, combined application of aspirin and heparinization within 1 h is increased in patients.
(iii) Low-molecular heparin (LMWH)
Low molecular heparin is the product of enzymatic or chemical degradation of common heparin, and is also an antithrombin-dependent thrombin inhibitor. It produces anticoagulant effect by binding to the lysine residue in the antithrombin molecule through the specific pentosan sequence in the molecule, which accelerates the inactivation of coagulation factors by antithrombin. It is usually injected subcutaneously, absorbed more completely, with a bioavailability of 90% (30% for heparin) and a half-life of 2-6 h. It is eliminated by the kidneys. However, compared with heparin, its anticoagulant effect is characterized by: (1) enhanced anti-Xa and weak anti-IIa effects, thus eliminating the need for monitoring in routine clinical subcutaneous application and reducing bleeding complications; (2) not easily cleared by plasma proteins in vivo, with long duration of action; (3) low impact on platelet function and number, rarely causing thrombocytopenia; (4) easy to use, high bioavailability, prolonged biological half-life. The anticoagulant effect is in a clear dose-dependent manner. Therefore, it is widely used in clinical treatment and prevention of cardiovascular and cerebrovascular diseases. The choice of anesthesia method and postoperative analgesia technique for patients receiving LMWH should be highly valued by anesthesiologists.
Since patients receive LMWH treatment before surgery, which can change the coagulation function of patients, considering that the half-life of LMWH is 2~6h and its anti-Xa activity drops to 50% of its peak at 12h after injection, intravertebral puncture should be done 10~12h after the last application of LMWH, and the application of intraoperative LMWH should preferably be done at least 2h after the anesthetic puncture placement operation, and blood staining of the epidural puncture needle is found during the puncture. The application of LMWH should be postponed after the operation.
Removal of the epidural catheter should be postponed until the day after surgery, and the application of LMWH should not be resumed until at least 2 h after removal of the catheter after surgery. Postoperative epidural analgesia generally does not affect the application of LMWH, but the epidural catheter should be removed at least 10~12 hours before the application of LMWH, and the application of LMWH should be resumed at least 2 hours after the removal of the catheter.
(iv) Warfarin
Bicoumarins anticoagulants achieve anticoagulation by inhibiting cyclo-oxidoreductase and interfering with vitamin K-dependent coagulation factors II, VII, IX and X carboxylation, so that these coagulation factors cannot be activated. It can be taken orally for a long time or even for life under the condition of monitoring the international normalized ratio (INR). The onset of action is slow and the effect is influenced by liver function, vitamin K in food, or other drugs applied concomitantly.
Patients who are receiving warfarin for elective surgery need to be discontinued 4-5 d before surgery and replaced with heparin or LMWH, and then follow the preoperative discontinuation of heparin and LMWH, while monitoring INR and APTT to keep INR within 1.6.
The choice of anesthesia for emergency surgery in patients undergoing Warfarin is controversial, although 950 patients on oral anticoagulation with up to 1000 regional blocks have been reported with no problems; Wu reported 180 patients on oral anticoagulation who received epidural cavity block or subarachnoid block, again without any complications, but most scholars have reservations because once The consequences of intradural hemorrhage are extremely serious. It is important to ask carefully about the time between the administration of the drug and the surgery, monitor the INR, and give the warfarin antagonist vitamin K1 intravenously as early as possible, but in most patients, the prothrombin time or INR decreases significantly within 6-8 h after vitamin K1 intravenous administration and is not corrected until 12-24 h. Therefore, the INR or prothrombin time needs to be monitored again before anesthesia.
Unless intradural block does have indisputable and obvious advantages over general anesthesia for a particular patient, and the benefits and risks are carefully analyzed, for safety reasons, the possibility of medically induced intradural hemorrhage should be avoided as much as possible and general anesthesia should be chosen. When resuming warfarin after surgery, low-dose intravenous or subcutaneous heparin should be added for at least 4 to 5 days, because it takes 3 to 7 days for the anticoagulant effect of warfarin to appear after oral administration, and the dose of oral anticoagulant should be adjusted by monitoring the INR.