Application of acute isovolatic hemodilution techniques in cardiac surgery

Authors: Cai Chenghui, Zhao Liyun, Department of Anesthesiology, Beijing Anzhen Hospital-Beijing Institute of Cardiopulmonary and Vascular Diseases, Capital Medical University

Postoperative bleeding is an extremely important surgical complication in cardiac surgery, according to foreign studies, blood for cardiovascular surgery accounts for 15% to 20% of the total transfusion, and allosomal blood transfusion is related to
postoperative adverse outcomes 。 At present, cardiac surgery is still one of the largest departments of allogeneic blood transfusion, how to carry out blood protection, how to reduce blood transfusion in the perioperative period and other issues, has obvious clinical significance in cardiac surgery, for which we have conducted a series of clinical studies, including acute normovolemic hemodilution (ANH) related research
.
This review will review ANH-related physiological changes, specific implementation procedures, safety and effectiveness in different cardiac surgeries
.

1.
Introduction to acute isovolatic hemodilution

In 1964, ANH was first used in surgery as a perioperative autologous blood transfusion, which has been widely used
today.
ANH is usually isolated from the central vein or radial artery before the start of an important surgical step or before systemic heparinization, isolated from the central vein or radial artery and stored at room temperature in a blood collection bag containing glucose citrate phosphoglucose anticoagulant, while returning an equal volume of crystallofluid> and colloidal fluid to maintain the patient's hemodynamic stability and autologous blood re-transfusion
after reaching the indication for blood transfusion or after surgery 。 ANH can effectively reduce the loss of red blood cells during surgery, and is widely used in cancer, orthopedic surgery, cardiac surgery and other surgeries
with high bleeding risk and often requiring postoperative blood transfusion.

2.
Pathophysiological changes of acute isovolatic hemodilution

In the clinic, by the determination of hematocrit (hematocri, Hct), ANH is divided into three categories according to the degree of hemodity: mild (Hct>30%), moderate (Hct20% to 30%), and severe (Hct<20%)
.
Hemodilution reduces blood viscosity by reducing hematocrit, thereby reducing peripheral resistance, reduced ventricular ejection resistance, complete ventricular emptying, and increased cardiac stroke volume, resulting in increased
total blood flow and peripheral tissue perfusion blood flow.
In addition, in the first 1 to 2 h after hemodilution, cardiac sympathetic activity is enhanced, and the total effect causes a significant increase in
cardiac output.
Hematodilation reduces the concentration of HGB in the blood, and the body's ability to carry oxygen decreases, while some compensatory mechanisms are activated to maintain the body's normal oxygen supply
.

MURRAY et al.
found that the body has the maximum oxygen carrying capacity at about 30% of the time in Hct, and then decreases, so 30% is considered to be the best for hematocrit, and the blood viscosity at this time is low and the oxygen carrying capacity is the largest
.
The distribution of blood flow to the vital organs also changes significantly during acute hemodilution
.
Heart: myocardial oxygen supply and consumption are balanced
when cardiac output increases, coronary artery dilation increases blood flow, and Hct is in the range of 20% to 60%.

Brain: in the blood dilution of cerebrovascular resistance decreases, cerebral blood flow increases to ensure normal oxygen supply to brain tissue, in the cerebral blood flow automatic regulation system when this increase in blood flow is not too obvious, will not cause intracranial pressure and postoperative cerebral edema occurrence, but for patients with abnormal regulation mechanism should be cautious blood dilution
.

Renal: mild hemodilution can increase renal blood flow, renal filtration rate increases, the oxygen supply of the kidney begins to decline when Hct is 30%, mild and moderate hemodality will not have too much impact on the oxygen supply and demand and blood flow of the kidney, and further blood dilution shows a significant decrease in
renal blood flow.

3.
Key points for the implementation of acute isovolatric hemodilution

Studies have shown that HGB > 110g/L, Hct>33%, PLT >100×109/L, prothrombin time is normal, and patients with normal cardiac function can implement ANH
.
Blood collection via radial artery or central vein is recommended, but the amount of blood collected is not uniformly labeled
.
Gross et al.
's recommended blood collection formula V = EBV× (Hi-Hf)÷ Hav, where V refers to the amount of blood that can be collected; EBV is an estimate of blood volume (adult female patients: kg body mass ×65, adult male: kg body mass ×70); Hi refers to Hct before hemothination and Hf refers to the target Hct level at the end of hemothination; Hav refers to the average level of Hct during bloodlution, and the target Hct is usually set at 30%.

In 2019, the expert consensus on the clinical path management of autologous blood transfusion proposed that the general blood collection volume is 10% to 15% of the total blood volume, and patients with good physical condition can reach 20% to 30% of the total blood volume (generally not more than 1200~1500mL).

Excessive blood collection will cause excessive blood dilution, hemodynamic instability, and imbalance of oxygen supply and consumption of the body, but insufficient blood collection will also make the blood dilution effect is not good, and the purpose of
blood protection cannot be achieved.
A relationship between low-dose ANH and perioperative outcomes has been reported, and mild ANH (defined as blood collection volume of 5 to 8 mL/kg) can only reduce the amount of allopathic transfusion during surgery, but there is no difference between
the amount of infusion of red blood cells after surgery and the total transfusion volume of perioperative period compared with the control group.

Another study, which included 13,534 patients undergoing heart surgery from 26 hospitals, divided patients into four groups (no ANH, < 400 mL, 400 to 799 mL, >800 mL) based on the amount of blood collected by ANH, found that patients with blood collection volume of >800 mL had the most significant reduction in infusion red blood cell rate (RR=0.
74, P<0.
001).

。 This study concluded that ANH correlates with a decrease in postoperative transfusion in cardiac surgery, and that the reduction in ANH transfusion after a large blood collection volume is more pronounced, and the amount of ANH may be an important factor
affecting the effectiveness of blood protection strategies in heart surgery.

Conventional blood replacement is an equal-volume hemodilution
of colloidal 1:1 or crystalline 1:(2 to 3) or crystalline glue combinations.
Due to the large amount of crystal requirements, reducing plasma osmolality is not conducive to hemodynamic stability, and the crystalloid is easy to enter the peripheral tissue and the third gap, causing postoperative tissue edema is not conducive to wound recovery, clinically for this acute controllable blood loss, colloid-based fluid is often used instead
.
Due to the variety of colloids, each with its own characteristics, potential allergic reactions, and the impact on coagulation function and liver and kidney function, the type and extreme amount of colloidal use have also become a key point
affecting the blood protection effect and safety of ANH.

Stephanie et al.
divided patients undergoing ANH into ringer'slactate (RL), 5% albumin (ALB), 6% hydroxyethyl starch (HES) and 6% dextran (DEX) according to the different alternative fluids, and the results showed that the four alternative fluids had less effect on hemodynamics, However, the RL group had a greater
probability of developing hypotension.
In addition, the use of DEX and HES compared to RL and ALB can reduce hypercoagulant states caused by surgical stimulation, but whether it is beneficial to patients needs further research
.

4.
Current status of acute isovolatic hemodilution in cardiac surgery

(1) Acute isovolatic hemothination should be applied to off-pump coronary artery bypass grafting (OPCABG)

1) Safety: patients with coronary heart disease repeated ischemia and hypoxia caused by myocardial degeneration and fibrosis, myocardial tolerance to hypoxia weakened, although appropriate blood thinning, blood viscosity reduction can reduce vascular resistance, reduce cardiac afterload, reduce myocardial oxygen consumption, but there are basic studies found that in severe blood thinning of the left ventricular myocardial layer ischemia, can lead to blood dilution after the cardiac discharge can not increase and the body's oxygen supply is insufficient
。 Therefore, in patients with coronary artery stenosis or in the elderly, preoperative cardiac function should be assessed, appropriate, monitored hemodilization should be carried out with caution, and once signs of myocardial ischemia are found, hemothination should be stopped immediately and corresponding measures
should be taken.

Zhang Liang et al.
selected 60 patients with good cardiac function and OPCABG to use 6% hydroxyethyl starch under the monitoring of floating catheters, and ANH
was performed with a target Hct value of 30%.
Studies have shown that the application of ANH to OPCABG has no significant change in the body's oxygen metabolism, myocardial oxygen supply and energy consumption has reached a balance, and there is no obvious impact on the internal environment, and it is considered that ANH is safe
for patients with OPCABG under the premise of strictly mastering the indications of ANH.

2) Effectiveness: In heart surgery, allogeneic blood transfusions caused by postoperative bleeding account for 15% to 20% of the total transfusion, although there are currently guidelines proposing a variety of methods to reduce bleeding and reduce the transfusion threshold, but according to statistics, in patients receiving coronary artery bypass grafting (CABG), more than 50% still have received allogeneic blood transfusion
.
OPCABG has less platelet consumption during surgery than CABG under cardiopulmonary bypass, but the consumption of intraoperative bleeding and antithrombin fibrinogen is similar and there is a higher risk
of bleeding.
Therefore, CABG is a good indication for ANH, however there is still controversy
about whether ANH can reduce the need for allogeneic blood in such patients and have a positive impact on postoperative complications and mortality.

A recent meta-analysis pooled 22 RCT studies involving 1688 patients, 19 of which were CABG under cardiopulmonary bypass and three of which were OPCABG, showed a significant reduction in allogeneic transfusion rates in the ANH group compared with the control group, with a relative risk RR=0.
65, and less
total postoperative blood loss in the ANH group.
However, the methods in which ANH were implemented in the articles included in the analysis varied and most of them used colloids as alternatives, and the authors suggest that the use of colloids increases the risk of postoperative bleeding and that inadequate hematurisation may lead to a decrease
in the efficacy of ANH.
The heterogeneity of the findings suggests that ANH needs more normalization to make the technology more generally acceptable and rationally applied
.

(2) Acute isovolatic hemothination is applied to cardiopulmonary bypass (CPB) cardiopulmonary bypass cardiac surgery

1) Safety: Because the deep and low temperature of CPB reduces the body's demand for oxygen during this period, in the study of Wang Zhong et al.
, the Hct of patients after ANH is often lower than 24%, but there is no tissue hypoxia or related complications, so the acceptable range of Hct value in CPB surgery is wider, but considering the amount and nature of pre-filling fluid and cardiac arrest fluid used by different operators for different patients, we need to clarify the target Hct value after ANH according to the actual situation.
Further hemodilization during CPB should be taken into account, adequate communication with a perfusion doctor to determine the appropriate blood collection volume, application of filtration devices during CPB, postoperative application of mannitol diuretics, etc.
, with a view to avoiding excessive dilution
of blood while achieving an effective ANH blood collection.

2) Effectiveness: CPB as the starting factor to stimulate coagulation, fibrinolysis, inflammatory response, these three pathophysiological processes intersect with each other, multiple factors involved in this process, such as blood dilution, blood and oxygen and the blood interface in the device, contact with non-biological pipes, low temperature, the role of heparin and protamine, the loss of coagulation factors, the destruction of platelets and a series of surgical operations, resulting in coagulation dysfunction, serious non-surgical bleeding, organ failure, and many other adverse prognosis
。

ANH has many benefits in patients requiring CPB, including reduced damage to red blood cells and platelets, improved blood perfusion during CPB to increase tissue oxygen supply, avoidance of heparin-induced changes in coagulation or cell activation, reduced activation of inflammatory pathways, and reduced risk of
transfusion adverse effects and infection.
Regarding the effect of hemodilution on the body's coagulation function, Yuan Conghu et al.
performed ANH in patients with cardiopulmonary bypass cardiac surgery compared with the control group, and the reduction of fibrinogen and platelets in the ANH group one day after surgery was small, and there was no significant difference
in blood loss between the two.
Tan Guanxian et al.
used acute high-volume hemodilization in liver resection surgery to make the blood show a moderate dilution state, and there was no significant change in the relevant indicators of the body's coagulation function, which proved that there was no significant effect
on coagulation function in mild to moderate hemodilution.

Many studies and guidelines have recognized the application of ANH technology to cardiac surgery under CPB, especially in deep and low temperature circulatory surgery, which has a good blood saving effect, but many studies have questioned this, a recent prospective experiment on patients who need to undergo a single CPB heart surgery ANH, in the protamine protein and 5 min after and autologous blood retransfusion end two time points to detect the patient's coagulation function, the results found that ANH to improve part of the thrombin time The difference in the values of fibrinogen and HGB was statistically significant, but in the absence of sustained surgical bleeding in the control group, coagulation indicators (except fibrinogen) after extracorporeal circulation tended to be normal, and the authors still have doubts about
the true clinical value of ANH.

There are many influencing factors in cardiac surgery under CPB, and more rigorous randomized controlled studies are needed to prove the safety, efficacy and establishment of clearer guidelines
for ANH.

5.
Outlook

At present, there are some specific problems in the application of ANH that have not been solved, such as the optimal amount of blood collection for different surgeries, the upper and lower limits of the amount of blood that can be collected, the minimum safe hemoglobin level to avoid extreme blood dilution, the relationship between the maximum allowable blood loss of patients and the patient's body mass or body surface area, whether it has promotional value in patients with mild anemia or chronic renal dysfunction with high risk of blood transfusion, Does it make sense
to perform ANH for surgery with a low risk of blood loss.

In addition, for the ideal alternative solution, whether it is crystals or colloids, and the ideal substitution ratio, it is still necessary to make more scientific suggestions
.
Although these practical problems still need to be solved and optimized, ANH as an effective blood protection measure is beyond reproach, especially in combination with other effective blood saving methods in surgery, and is expected to achieve significant clinical results
in reducing blood transfusions.

Source: Cai Chenghui,Zhao Liyun.
Application of acute isovolatic hemodilution technique in cardiac surgery[J].
Journal of Cardiopulmonary Vascular Diseases,2022,41(04):444-447.