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Causes of perioperative hypoproteinemia and Research progress
Causes of perioperative hypoproteinemia and Research progress. Hypoproteinemia is common in perioperative patients.
01 High incidence of perioperative hypoproteinemia
Hypoproteinemia is common in perioperative patients. After the operation, patients often have secondary traumatic capillary leakage , which is mainly manifested as capillary endothelial injury and increased vascular permeability, and hypoproteinemia will occur at this time.
In 2020, Fresenius Kabi launched a multi-center, prospective survey conducted in 115 domestic hospitals, involving 7470 non-cardiac surgery patients. The results showed that hypoproteinemia is common in perioperative patients. Among them, 2179 patients showed hypoalbuminemia after operation (marked by albumin content <30 g/L), and the incidence of hypoalbuminemia was 29.17%.
Cao Fumin and others investigated the hemodynamic data of 20 patients with cancer in thoracic surgery, and found that the serum albumin levels of the patients were 38.0 g/L and 29.0 g/L before the operation and on the 1, 3, and 5 days after the operation, respectively. , 23.0 g/L and 25.8 g/L, the incidence of hypoproteinemia was the highest on the third day after surgery, reaching 75% (15/20) . This result was also confirmed by Liu Weilin and others in a survey of 133 patients undergoing moderate or above surgery in general surgery. The plasma albumin level after surgery was significantly lower than that before surgery (t=-22.055, P<0.001), and the third after surgery Plasma albumin levels dropped to a minimum on days, and patients with preoperative plasma C-reactive protein ≥10 mg/L decreased more significantly after surgery .
02 Perioperative hypoproteinemia causes many harms
Albumin plays a key role in maintaining the balance of the body due to its wide distribution. Normal levels of plasma proteins, especially albumin, can prevent the development of edema and maintain the balance between intravascular hydrostatic pressure and colloidal osmotic pressure .
Albumin has antioxidant properties and is involved in eliminating oxygen free radicals in the pathogenesis of inflammatory diseases [5,6]. Therefore, hypoproteinemia is closely related to the occurrence of edema and inflammatory infection. The study by Boh DD et al. showed that compared with patients with normal albumin concentration, patients with hypoalbuminemia have a higher risk of surgical site infection, pneumonia, prolonged hospital stay, and readmission .
Hypoproteinemia can be associated with many diseases such as liver cirrhosis, malnutrition, nephrotic syndrome and sepsis, and its relationship with adverse surgical results is recognized. The negative impact of this indicator is in the heart, orthopedics, gastrointestinal and It has been shown in urology and other operations. A study conducted by Christian PM in the United States involving 204,819 patients with 16 common surgical procedures found that patients with preoperative hypoproteinemia (35,922 cases, accounting for 17.54%) were affected by cardiovascular disease (0.99% vs 2.09%), lung disease (3.54% vs 8.78%), neurological diseases (0.50% vs 1.02%), thromboembolism (1.48% vs 2.99%), kidney disease (0.89% vs 2.19%), urinary tract infection (2.14% vs 4.02%) and wounds The incidence of complications (11.55% vs 5.91%) is higher than that of patients with normal albumin concentration (P<0.001) .
In addition, regardless of the cause and type of surgery, hypoalbuminemia is associated with a higher mortality rate. Patients with lower albumin content on admission have a higher postoperative mortality rate, a longer hospital stay, and are more likely to be re-admitted after discharge. Gibbs J et al. found that preoperative serum albumin was the strongest predictor of postoperative mortality and morbidity in the most comprehensive study on the effect of albumin level on mortality. In major non-cardiac surgery, albumin levels decreased. The 30-day case fatality rate of the patients is about 3.9% . The study by Christian P.M and others has similar results. The postoperative mortality rate of patients with hypoalbuminemia is 3.81%, which is nearly 4 times higher than that of patients with normal albumin concentration (0.87%) (P<0.001) .
03 The main cause of perioperative hypoproteinemia
The definition of hypoalbuminemia is that the serum albumin content is less than 35 g/L, and sometimes clinically, it is lower than 25 g/L as a sign of significant hypoalbuminemia. Decreased serum albumin concentration can be caused by problems such as decreased energy or amino acid supply, impaired liver synthesis, increased loss, increased tissue catabolism or distribution .
Albumin is a negative acute phase protein, so hypoalbuminemia is often observed in acute disease states. After sepsis, infection, trauma or major surgery, the albumin content can be reduced by 10~15 g/L within 1 week of the event. The reason for the reduction is that the albumin synthesis in the liver is reduced and the leakage into the interstitial space is increased. , The catabolism of albumin is accelerated. The reduction of albumin synthesis during inflammation may be due to factors such as interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor a (TNFa), and the leakage rate of albumin through capillaries It is 10 times the amount of synthesized albumin, so the rate of leakage through capillaries plays an important role in the acute change of serum albumin concentration. In some diseases, the increase in vascular permeability accelerates the loss of transcapillary albumin and promotes the development of hypoalbuminemia. In the case of sepsis, this process becomes faster: endothelial integrity is affected. Damage leads to increased capillary permeability, which may even be 13 times higher than normal, and serum albumin is greatly reduced.
In some clinical practice, hypoalbuminemia is caused by multiple mechanisms. For example, in patients with liver cirrhosis, the synthesis of liver cells is impaired and the leakage rate through capillaries increases. Diabetes patients have reduced synthesis rate (improved by insulin infusion) and increased capillary leakage rate. During major operations, the leakage rate of albumin through capillaries increases and the rate of lymphatic flow decreases. In mucinous edema, an increase in the extravascular volume of albumin is associated with a decrease in the catabolism rate. Therefore, the etiological classification of hypoproteinemia is more complicated. Table 1 shows the experimental protocol summarized by Angelo G et al. .
04 Effective ways to deal with hypoproteinemia
Albumin plays an important role in maintaining the body’s colloidal osmotic pressure and participating in drug metabolism in the body. For hypoalbuminemia caused by various causes, perioperative drug intervention to reduce the patient’s protein extravascular leakage has important clinical significance . At present, the therapies recommended by the guidelines mainly include the infusion of artificial colloids, crystals and albumin fluids .
As a macromolecular substance, colloidal fluid can treat adult capillary leak syndrome, reduce the extravascular extravasation of albumin, and play a role in the treatment of hypoalbuminemia. Zhang Jianzhong  divided 48 orthopedic trauma patients into two groups: crystalloid fluid and colloidal fluid, and analyzed the effects of the two therapies on serum albumin. The results showed that the amount of plasma circulating endothelium in the colloidal fluid group was compared with that of crystal fluid.
It was significantly reduced after 24 h of acute hemodilution (P<0.05); serum TNF, IL-6 (inflammatory factor) and C-reactive protein in the colloidal fluid group were significantly reduced after 24 h and 48 h of acute hemodilution (P<0.05) ; Interleukin 10 (anti-inflammatory factor) in the colloidal fluid group was significantly increased after 24 h and 48 h after acute hemodilution (P<0.05). At the same time, according to the results of fluorescence spectroscopy, the colloidal fluid has a binding effect with serum albumin, which changes the spatial structure of serum albumin. The interaction between the Trp-214 structural protein in serum albumin and the colloidal fluid forms a 1:1 complex. Increased, thus conducive to mechanical plugging, which demonstrates the mechanism by which colloidal fluid reduces the occurrence of postoperative hypoproteinemia in patients.
Daisuke T et al.  conducted an 18-month single-center, prospective, observational study involving 139 patients undergoing major abdominal surgery, comparing the treatment of hemodynamics with crystalloid, colloidal fluid, and albumin solution. The results showed that the median increase rate of plasma volume of colloidal fluid (7.3%) and albumin solution (6.3%) was higher than that of crystal fluid (1.0%) after 30 minutes of infusion resuscitation; colloidal fluid (increased by 0.6 mmHg) and white The change in plasma colloidal osmotic pressure of protein solution (increased by 0.7 mmHg) was significantly better than that of crystal fluid (decreased by 0.6 mmHg); the peak stroke volume of colloidal fluid (8 ml/m2) was significantly higher than that of crystal fluid (5 ml/m2) and white Protein solution (5 ml/m2); colloidal fluid (107 ml/m2) and albumin solution (80 ml/m2) infusion and resuscitation have significantly higher stroke volume curve area than crystal fluid (26 ml/m2). This shows that the intravascular volume effect and hemodynamic effect are more significant after fluid resuscitation with colloidal fluid and albumin solution.
05 Discussion and summary
Due to the dramatic changes in the body’s perioperative volume, hypoproteinemia is extremely high, and causes an increase in the incidence of complications such as infection, pneumonia, and sepsis, which in turn leads to undesirable consequences such as prolonged hospital stay, increased risk of re-admission, and increased mortality.
For the treatment of perioperative hypoproteinemia, a goal-oriented therapy suitable for individual characteristics should be selected according to the patient’s specific etiology and various clinical indicators. In particular, colloidal fluid has the special effect of reducing intravascular inflammation and mechanical plugging, and has a certain therapeutic effect on perioperative hypoproteinemia.
(source:internet, reference only)