In this trial, we proposed an individualized acute normovolemic hemodilution (ANH), and conduct a randomized controlled trial to testify the effect of individualized ANH on red cells requirement for non-cardiac surgeries with anticipating major blood loss in adults.

Allogeneic blood transfusion (ABT) is often given for patients undergoing major surgery with large amount of blood loss. However, ABT itself is associated with various complications, such as anaphylaxis, transfusion related bacterial and viral infections, and transfusion related lung injury [1-3]. Strategies for reduction of requirements for ABT during surgery continue to be of an importance in clinical practice.

The current strategies for ABT reduction during major surgery can be divided into the decrease of operative blood loss and the provision of autologous red cells. Collection of autologous red cells could be performed several weeks before admission (preoperative autologous donation, PAD), after anesthetic induction and prior to the surgical incision (acute normovolemic hemodilution, ANH), or during the operation (cell saver) [4]. ANH is a technique that remove the whole blood and infuse the colloids or crystalloids at the same time to get the hemodilution with the normal volume [5]. With the hemodilution, the amounts of red cells lost with bleeding could be reduced during surgery, and blood viscosity could be decreased beneficial for improved blood flow and increased venous return at a relative constant atrial pressure [6]. However, ANH has not been a widely accepted technique despite these advantages. One possible reason could be the mixed results about application of ANH in the literature. It was reported to decrease the risk of ABT when compared with the control group in a meta-analysis including 29 randomized controlled trials [7], but other authors reported ANH could only decrease intraoperative ABT with no differences in overall perioperative transfusion requirements [8]. Another reason could be due to the staffing shortage in clinical practice, especially in China. The implementation of AHN in the operating room requires the cooperation of a staff team including anesthesiologists, circulating nurses, and technicians from department of blood transfusion to collect the autologous blood and store it in refrigerators, and reinfuse the autologous blood under the supervision and double verification. In addition, what degree of the hemodilution should be achieved for a patient is lack of evidence and guidance, and the hemodilution can't be individualized executed.

In our previous study, we proposed the West-China-Liu's Score (Table.1) for individualized transfusion of red cells and conducted a multi-centered RCT to verify that the application of this individualized transfusion strategy can decrease the requirement of perioperative red cells transfusion when compared with the restrictive or liberal strategies without increase of complications in elective noncardiac surgeries [9]. According to the score, we can determine the tolerable lower level of hemoglobin (Hb), and it's safe for a patient to keep his Hb level above the score. With the West-China-Liu's Score, we dilute the patient's Hb level to the degree of the score plus 2, we can calculate the volume of the collected autologous blood. For example, a patient's initial Hb level is 12g/dL, the West-China-Liu's Score is 6, we dilute the Hb level to the score of 6+2=8, and the hemodilution level for him is Hb of 8g/dL. A 1g/dL Hb level is about 400ml of blood, and the decrease of Hb level from 12g/dL to 8g/dL is about 1600ml of blood. While we infuse the patient with fluids and collect blood at the same time, we will collect 800ml of the autologous blood for this patient. The collected autologous blood will be transfused to the patient when his Hb level is decreased to 6g/dL, or at the end of the operation. By this mean, ANH could be individualized.

Based on previous findings and the theory of individualized transfusion strategy, we hypothesize that individualized ANH under guidance of West-China Liu's Score can reduce the requirement of allogeneic red cells.

Inclusion Criteria:

• Patients undergoing elective non-cardiac surgery with an anticipated red blood cells transfusion >8 units (or 1600ml)
• Aged 18~75 years
• Preoperative Hb level > 120g/L for men and > 110g/L for women.

Exclusion Criteria:

• Refusal of blood transfusion
• Cardiopulmonary insufficiency
• Cerebrovascular disease
• Renal impairment
• Hemoglobinopathies or blood system diseases
• Other situations not suitable for inclusion in clinical trial.

Individual participant data (IPD) with anonymity will be uploaded to the IPD sharing platform for data sharing. Data will be available after the agreement of the correspondence author upon reasonable request.

5 years after the completion of the study.

Upon request by email to PI.

The clinical investigators, the responsible anesthesiologists and surgeons, the research assistants, and the participants will not be blinded to the treatment assignment, and the statisticians responsible for outcome analysis will be blinded.