Bloodless surgery began in the twentieth century with the world-renowned orthopedic surgeon Adolf Lorenz, and in the early 1960s, American cardiac surgeon Denton Cooley successfully performed bloodless endocardiocentesis on a large number of Jehovah’s Witnesses, and published an article on 500 bloodless cardiac surgeries on such patients. Bloodless cardiac surgery is a perioperative approach to cardiac surgery that involves cardiac surgery and its allied professionals to avoid allogeneic blood transfusions during cardiac surgery and to improve the patient’s prognosis. Over the years, many cardiac surgeons have used blood handling and protection techniques to perform direct endocardial surgery and avoid allogeneic blood transfusions. Findings from most centers have shown that bloodless cardiac surgery actually reduces surgical complexity, decreases patient recovery time after surgery, and improves patient prognosis. In this article, we review the techniques related to bloodless surgery and the research on its application in cardiac surgery. I. Theory of bloodless surgery and its methods 1.1 Theory of bloodless surgery Bloodless surgery is a profound and systematic perioperative approach, which aims to avoid the transfusion of allogeneic blood and improve patient prognosis. Initially, it was an approach advocated by some surgically treated patients who refused blood transfusions for religious reasons. Currently, this practice has been interpreted as a safe and effective team approach because it reduces blood loss and is the best alternative therapy to allogeneic blood transfusion, providing the best possible care for all patients. Complete bloodless surgery is an adjustable, perioperative multidisciplinary and multimodal approach. Studies in recent years have shown that the application of the principles of bloodless surgery improves patient prognosis, reduces complications and mortality, shortens the length of hospital stay, significantly reduces total hospital costs, and reduces blood stress. 1.2 Bloodless Surgery as a Complete Perioperative Approach Bloodless surgery requires the combined application of a variety of alternative strategies in the perioperative period with the goal of limiting blood loss and avoiding transfusions. Bloodless surgery has four main aims: (1) maximization of the patient’s preoperative red blood cell stores; (2) maximization of hematopoiesis; (3) minimization of blood loss; and (4) maximization of oxygen release. The above objectives are accomplished in three phases: (1) preoperative evaluation and planning; (2) surgical, anesthetic, technician, and pharmacological strategies during surgery; and (3) postoperative hemoprotection to maximize recovery of blood components and provide reasonable support. Preoperative preparation is a key factor in the success of bloodless surgery. This phase requires an individualized treatment plan based on the procedure to be performed and the patient’s condition. It should estimate the perioperative blood loss for a given procedure, calculate the patient-specific tolerance to blood loss, and identify the patient’s physiologic reserve as well as risk factors. Clarify the presence of anemia and the cause. Epo s (recombinant human erythropoietin) is effective in increasing red blood cell mass preoperatively. Surgical procedures with high blood loss are estimated to require treatment with epo s even in the absence of anemia in order to increase the patient’s tolerance. This allows the patient to obtain enough red blood cells preoperatively to tolerate intraoperative hemodilution, as well as postoperatively to return the patient’s hematocrit to normal levels more quickly. If epo s therapy is implemented, attention must be paid to iron ion supplementation. Without iron ion supplementation, epoxide therapy is ineffective even when the patient has normal iron ion stores. Oral iron may not be sufficient to synchronize with the erythropoiesis-stimulating effects of epoetin, and should be given intravenously to achieve a target hemoglobin level (or the highest stable level available) of 14-16 g/dL. red cell volume (RCV: hemoglobin x kg body weight) greater than 1,200 provides a safe reservoir for these patients, while RCV less than 800 suggests that the patient has a normal reservoir. An RCV of less than 800 suggests an increased chance of needing a transfusion. In the intraoperative phase, firstly, surgeons should dissect and separate along tissue interfaces to achieve relative hemostasis, and intraoperative bleeding can also be minimized by using relevant instruments and techniques, such as ultrasonic scalpel that can separate soft tissues without anatomical interfaces, which reduces significant bleeding compared to other methods, and vascular forceps clamps that can control bleeding from medium-sized blood vessels during soft-tissue separation. Second, intraoperative blood recovery techniques are applied, but blood cell recovery is only used to recover spilled blood. Also, anesthesiologists play a very important role in bloodless surgery such as adequate depth of anesthesia, muscle relaxation, avoidance of hypertension and hypercapnia, choice of anesthetics and technique as well as reduction of intra-abdominal and inferior vena cava pressures, all of which contribute to the reduction of bleeding. Special maneuvers include controlled hypotension, high volume and acute isovolumic hemodilution. Acute isovolumic hemodilution allows the patient to tolerate very large losses of blood volume without the need for support from allogeneic blood and related products. In the postoperative phase, there are several treatment options to reduce blood loss, maximize hematopoiesis, maximize oxygen release and reduce oxygen consumption. Reduce blood loss: e.g., avoid hypertension, maintain normovolemia, and be aware of drug interactions, some of which can increase bleeding and medical anemia. Monitor closely to differentiate between normal postoperative blood loss and active bleeding, and intervene quickly to stop active bleeding. Postoperatively, pay attention to the volume and frequency of blood specimens used for laboratory tests. Studies have shown that ICU patients use as much as 70 ml of blood specimens per day for monitoring, which can result in patient transfusions, and sophisticated planning of blood tests, implementation of microsampling techniques, and noninvasive monitoring can significantly reduce medical blood loss. Aggressive management of blood loss also includes appropriate retrieval and reinfusion of drained blood, and the application of hemostatic medications; Hematopoietic Maximization: Preoperative hemoglobin maximization means that the majority of patients will require minimal postoperative hematopoietic support. However, secondary to significant blood loss can lead to severe anemia, and although the combination of epo s and intravenous iron ion can restore hemoglobin levels more rapidly, appropriate nutritional support, applied alone with intravenous iron ion, is sometimes effective; Maximizing Oxygen Delivery: Maintain intravascular volume to avoid circulatory overload. Provide appropriate support of high concentration of oxygen ventilation, if hemodynamics can be tolerated, positive end-expiratory pressure can be increased to 7-10cm H2O. maintain ideal hemodynamics, positive inotropic drug support, etc. can achieve the purpose of maximizing oxygen delivery; Minimize oxygen consumption: the application of appropriate analgesic and sedative agents, neuromuscular blocking agents, etc. can significantly reduce the body’s oxygen consumption. Second, the application of bloodless surgery in the field of cardiac surgery In the past few decades, bloodless surgery has been widely used in the field of cardiac surgery for two main reasons: first, some cardiac surgery patients, for religious reasons and refused to transfuse allogeneic blood. Second, an increasing number of pathogenic microorganisms are being transmitted through blood transfusions. There is evidence of increased rates of postoperative infections due to downregulation of cellular immunity in stored blood. There are other effects on clinical outcomes resulting from storage-related problems, which include impaired tissue oxygenation, reduced microcirculatory blood flow, transfusion-related acute lung injury, and coagulation disorders. Recent studies have shown that blood transfusion may be associated with increased complications, mortality, length of hospital stay, and cost. Therefore, bloodless surgical techniques have been increasingly used in the field of cardiac surgery. 1, Bloodless Surgery in Adult Cardiac Surgery In the early 1960s, Denton Cooley, an American cardiac surgeon, successfully performed bloodless endocardial direct vision surgery for a large number of Jehovah’s Witnesses. The results showed that cardiac surgery could be performed safely without blood transfusion [1].From 2000-2010, bloodless cardiac surgery was performed on 40 cardiac surgical patients at Allegheny General Hospital in Pennsylvania, USA, with an average patient age of 70 ± 9.5 years, 21 males and 19 females, of which 18 were high-risk patients. The procedures included: coronary artery bypass grafting in 19, valve replacement/repair in 7, valve replacement and coronary artery bypass grafting in 7, re-valve replacement in 4, re-coronary artery bypass grafting in 2, and valve replacement and ascending aorta replacement in 1. The results of the study show that blood handling and protection strategies use a perioperative team approach with multidisciplinary participation, and that Jehovah’s Witnesses can safely tolerate both routine and complex bloodless cardiac surgery, with a smaller complication and mortality rate. The Hospital of Pennsylvania, University of Pennsylvania Medical Center, Philadelphia, USA, has developed a multidisciplinary composition of bloodless medicine procedures. Its bloodless medicine team, consisting of a patient coordinator, a nurse, and a hematologist, evaluates Jehovah’s Witnesses who come to the hospital and makes special preparations related to their treatment throughout the period of care. from May 2000-April 2010, Prof. Dr. Bridges of the Department of Cardiovascular Surgery and his team evaluated 94 Jehovah’s Witnesses at Penn Medicine. Prof. Dr. Bridges and his team performed bloodless heart surgery on 94 Jehovah’s Witnesses at the Pennsylvania Hospital. Of these, 2 patients had incomplete information to obtain receipts, 1 patient received a blood transfusion, and data on the remaining 91 patients were collected from the hospital’s cardiac surgery database. The data in this group showed that the operative mortality rate was 2.2% for coronary artery bypass grafting alone and 5.6% for aortic valve replacement alone, and that other complications included: reoperation (8.8% overall, of which 2.2% were cardiac causes), sepsis (2.2%), sternal infection (1.1%), transient ischemic attack (1.1%), renal failure requiring dialysis (1.1%). delayed ventilation (18.7%), and the incidence of major complications did not differ significantly between the elective and emergency surgery groups. The results of the study indicate that bloodless cardiac surgery in patients belonging to Jehovah’s Witnesses can be performed with favorable outcomes in both elective and emergency surgical situations. Mortality rates for both coronary artery bypass grafting alone and aortic valve replacement alone were within the 95% confidence interval of the STS (The Society of Thoracic Surgeons) predicted mortality rate. Bloodless cardiac surgery patients were evaluated preoperatively by the bloodless medicine team and cardiac surgery staff standards. All patients were treated preoperatively with oral ferrous sulfate and subcutaneous epoetin (40,000-60,000 units per week, subcutaneously). Surgery was performed when conditions permitted, with a hemoglobin concentration of at least 130 g/dL or higher. All patients taking oral clopidogrel and other antiplatelet agents are discontinued for a minimum of 5 days preoperatively, and the ideal time to discontinue the above medications is usually 7-10 days to minimize perioperative bleeding. The application of a platelet function analyzer is helpful in determining the ideal time for surgical intervention. Preoperative restoration of the internationalized standard ratio to normal levels in patients on oral warfarin can be changed to low molecular heparin or normal heparin subcutaneously, which is usually discontinued 48 hours before surgery. Special intraoperative precautions in cardiac surgery include: (1) After the patient is anesthetized, 1-3 units of blood are collected from the patient based on their RCV (RCV>900, 1 unit; RCV>1100, 2 units; RCV>1400, 3 units). The volume collected is usually replaced with 5% albumin (acute isovolumic hemodilution). (2) Heparin 100 mg/kg is applied for non-corporeal cardiac surgery to maintain an activated clotting time (ACT) of >300 seconds. Conventional extracorporeal cardiac surgery should apply heparin 300 mg/kg to maintain ACT greater than 450 seconds; (3) Extracorporeal circulation preloading should apply retrograde autogolous priming (RAP) to reduce the degree of hemodilution. A blood concentrator and 50 g mannitol were applied to maximize the hematocrit. Antifibrinolytic agents administered to the patient included aminocaproic acid at a loading dose of 150 mg/kg followed by a 1 g per hour infusion over 6 hours. Cichlidinium sulfate neutralized heparin at 1 mg per 100 units; (4) Moderate hypothermia of 34◦ C was used for all patients undergoing extracorporeal circulation surgery, and the patients were rewarmed to 36◦ C prior to withdrawal from the extracorporeal circulation; (5) Red blood cells were recovered by applying the Cell Saver technique through the extension tubing of the blood storage bag; (6) Delayed thoracotomy closure could be implemented in reoperations and in patients with coagulopathies. POSTOPERATIVE MANAGEMENT: Postoperative management should take into account the rapid recognition of potential problems. Postoperative laboratory tests should be performed in pediatric laboratory tubes to minimize blood specimen sampling. Carefully manage crystalloid administration to avoid hemodilution. Consider vasopressin (0.3 uk/kg) in patients receiving aspirin therapy or in renal failure. When there is bleeding, cold precipitation and coagulation factor VII may be applied. avoid coagulation factor VII in patients undergoing coronary artery bypass grafting. any hemodynamically unstable patient with chest tube drainage of more than 150 mL for 2 consecutive hours, vasopressors, and increased volume requirements should have the mediastinum reopened to rule out bleeding and/or pericardial tamponade. 2, Bloodless Surgery in Pediatric Cardiac Surgery Pre-autologous autologous blood donation and perioperative autologous blood transfusion methods have significantly reduced allogeneic blood transfusions in cardiac surgery, but because of the lesser blood volume in infants and small children, it is more difficult to successfully perform pediatric bloodless endocardial direct surgery. Reducing precharge is a major factor in performing pediatric bloodless cardiac surgery, and this can be achieved by narrowing the extracorporeal circulation loop. Narrowing the extracorporeal circulation loop involves not only shortening the length and reducing the internal diameter of the arterial, venous, and endocardial suction lines, but also removing any unnecessary components. Vacuum-assisted venous return also helps to reduce precharge. Vacuum-assisted venous return reduces the height of the membrane pulmonary oxygenator position, thus, significantly reducing the length of arterial, venous and suction lines [21]. Van Son et al. used a series of perioperative strategies to reduce blood loss and maintain adequate hematocrit in pediatric cardiac surgery: (1) application of synthetic erythropoietin preconditioning when the hematocrit is less than 38%; (2) avoidance of cardiac catheterization whenever possible; (3) application of low-energy electrocoagulation techniques for chest wall tissue, pericardiectomy, and macrovascular dissection; (4) minimal precavitation fluid infusion; ( (5) Reduction of extracorporeal circulation precharge by decreasing the volume of extracorporeal circulation lines; (6) Application of moderate extracorporeal circulation flow and rational intracardiac suction techniques to minimize hemocyte destruction; (7) Modified application of ultrafiltration to remove excess postoperative hydration; (8) Avoidance of deep hypothermia when possible to minimize the time to rewarming of the extracorporeal circulation; (9) Delayed heparin reversal after extracorporeal circulation until one is confident that there is not any active bleeding points. Thus continuous intracardiac suction is permitted to maximize patient blood recovery; (10) smooth return of residual perfusate from the entire extracorporeal circulatory system to the body; and (11) postoperative oral administration of ferric ions in erythrocytopenic patients to increase the erythrocyte specific volume. Miyaji et al [23] used a small precharge extracorporeal circulation system to perform bloodless intracardiac direct visualization of 68 low-birth-weight children (weighing 4-7 Kg) with congenital heart disease, and the results of the study showed that complex congenital heart disease surgery could be performed safely in children weighing more than 4 Kg by using a small precharge extracorporeal circulation. The findings suggest that the limiting factors for bloodless cardiac surgery are not the preoperative level of erythrocyte depressurization and the complexity of cardiac surgical procedures, but rather the duration of extracorporeal circulation and the weight of the child. 3, the current situation in China In 2010, the Department of Cardiac Surgery of the Children’s Hospital of Zhejiang University School of Medicine was the first in China to carry out “pediatric bloodless cardiac surgery”, which greatly reduced the incidence of postoperative renal insufficiency and pneumonia in patients, and reduced the use of postoperative ventilators and monitoring time [24]. In recent years, Beijing Fu Wai Cardiovascular Hospital, Wuhan Asian Heart Hospital and other hospitals have also successfully carried out bloodless cardiac surgery, with good surgical results, but there is still no relevant large number of cases reported in the literature. III.CONCLUSION In summary, with the continuous development of new surgical instruments and cardiac surgical techniques, as well as the successful development of therapeutic drugs to promote erythropoiesis, the methods of blood handling and protection have become quite effective. Bloodless surgery and bloodless cardiac surgery are rapidly gaining ground in major hospitals and medical centers around the world because of the many advantages of bloodless cardiac surgery over traditional cardiac surgery requiring blood transfusions: because it avoids infectious diseases such as hepatitis, AIDS, and other infectious diseases that can result from blood transfusions. Bloodless cardiac surgery reduces the risk of post-operative infections, shortens hospital stays, and lowers medical costs. In particular, recent studies have shown that blood transfusion increases the risk of postoperative complications and decreases survival rates. However, bloodless cardiac surgery is a systematic project, and a multidisciplinary bloodless medical team, as well as a systematic approach to the management of all aspects of the perioperative period, must first be available in order to successfully perform bloodless cardiac surgery.