The effect of surgical procedures on serum albumin concentration

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The effect of surgical procedures on serum albumin concentration

L.R. Alberti, A. Petroianu, Renata Indelicato Zac, J.C. Cisneiros Guedes Andrade Jr
Articole originale, no. 1, 2008
* Alfa Institute of Gastroenterology of the Hospital of Clinics of the Federal University of Minas Ger
* Alfa Institute of Gastroenterology

The identification of patients at high surgical risk is fundamental for operative indications and decisions, which are often limited by the potential morbidity and mortality of the procedure. In this respect, the clinical and laboratory parameters that may indicate situations of higher risk of postoperative complications are very important.
Starting in the 1970 decade, researchers tried to define the risk factors for different medium-sized and major operations (1). In 1975, MacLean et al first published a report emphasi-zing the delayed hypersensitivity skin test for the prediction of the postoperative course, showing the correlation between abnormal responses to the test and a higher incidence of postoperative complications and mortality (2). Along this same line of investigation, Bistran et al (3) detected malnutrition among 40% to 50% of hospitalized patients. This picture was more severe in patients operated upon, increasing their morbidity and mortality. Subsequent studies assessed the effect of therapeutic nutritional replacement, mainly total parenteral nutrition, in order to minimize the surgical risks (4, 5).
Surgical aggression, in addition to causing local changes, provokes systemic disorders mediated by the phenomena of organic adaptation to the new condition and by the response to trauma. This set of factors is denoted post-trauma acute phase reaction and is characterized by endocrine-metabolic changes and by release of adrenal and pituitary mediators, leading to increased protein and lipid catabolism, non-glucide hyperglycemia, and water and salt retention (1).
Particularly important among the systemic responses is the hepatocytic response, which involves a decrease in albumin and ferritin synthesis. In addition, there is an increase in the concentrations of serum C reactive protein, ceruloplasmin and other proteins related to immune processes (6, 7, 8). Specifically, albumin is a protein of hepatic origin with a long half-life -21 days- and therefore changes in its concentration over a short time interval cannot be explained by nutritional or hepatic function alterations (9). Some studies have shown that serum albumin concentration of less than 3 g/dl is accompanied by anergy and by more frequent and more severe surgical complications and that parenteral feeding improves the reactive status of delayed hypersensitivity skin tests and reduces the number of postoperative complications (1, 7, 10, 11, 12, 13, 14, 15). According to Puskarich et al (16), between the 5th and 10th postoperative days there is a reduction in serum albumin concentration. Several hypotheses have tried to explain this fact, such as the dilution effect and changes at the binding sites for this protein (17, 18, 19). However, we found no studies evaluating albumin concentrations during the immediate postoperative period.
In view of the need for further information about the systemic repercussions in the presence of surgical trauma, the objective of the present study was to assess albuminemia immediately after medium-sized and major surgeries.

This study was conducted according to the recommendations of the Declaration of Helsinki and Resolution no 196/96 of the Brazilian Health Ministry about research involving human beings, and was approved by the Ethics Committee of the Department of Surgery of the Medical School of the Federal University of Minas Gerais (20).
A prospective study was conducted on 200 consecutive adult patients, 100 men and 100 women, attended at the General Surgery Services of the Júlia Kubitschek Hospital, Hospital of Clinics, and of the Mário Penna Hospital, in Belo Horizonte city.
The patients were divided into two groups according to the type of surgical procedure:
- Group 1 (n = 127): major surgeries such as esophagectomy, gastrectomy, colectomy, duodenal papilosphincteroplasty, hiatal hernioplasty.
- Group 2 (n = 73): medium-sized surgeries such as inguinal or incisional hernioplasty, gastrojejunostomy, cholecystectomy, colostomy and thyroidectomy.
Blood samples (1 ml serum) were collected on the days preceding and following the surgical procedure for the determination of serum albumin concentrations and for routine exams. Albumin was determined by the biuret and bromocresol green method, using reference values for serum albumin of 3.5 to 5.5 g/ dl.
Demographic data such as age, gender and skin color (white, brown and black) were assessed comparatively in order to characterize the influence of surgery on albuminemia in different population groups.
We excluded patients who had been submitted to radiotherapy or chemotherapy for cancer, to blood transfusion during the last six weeks, to preoperative parenteral nutrition, and to emergency surgery. Patients that presented major bleedings during the surgical procedure and needed greater amount of blood transfusion were excluded from this investigation as well.
Pre- and postoperative albumin data were compared by the paired t test. The gender was compared by the Student t test. The skin color and the age were compared by the repeated measured one-way ANOVA and the Tukey-Kramer tests. The level of significance was set at P < 0.05.

Patient age ranged from 20 to 87 years, with a mean of 52.9 ± 16.6 years. There was no difference in age between men (54.1 ± 16.8 years) and women (51.6 ± 16.5 years).
Eighty-eight patients were whites (44%), 65 were browns (32.5%) and 47 were blacks (23.5%). There was no difference in this distribution between the groups submitted to major surgeries (54 whites, 45 browns and 28 blacks) and the groups submitted to medium-sized surgeries (34 whites, 20 browns and 19 blacks).
Postoperative serum albumin concentrations were reduced from 3.76 ± 0.69 to 2.87 ± 0.79 (p < 0.0001) among patients submitted to major surgeries (Group 1) and from 3.82 ± 0.70 to 3.35 ± 0.65 (p < 0.0001) among patients submitted to medium-sized surgeries (Group 2). Albumin reduction was greater in Group 1 (p=0,0398).
Table 1 shows the pre- and postoperative levels of albuminemia with respect to patient age, gender, skin color and according to surgery size.
There was no difference between gender in Group 1, whereas in Group 2 women showed a significantly lower reduction in albuminemia (p = 0.0047) compared to men (p < 0.0001).
In Group 1, there was no difference in the reduction of serum albumin concentration related to the skin colour (ANOVA p=0,7471). However, in Group 2, the black patients had the lowest reduction in albuminemia, followed by the brown and the white patients (ANOVA p < 0.001). Specifically the pre and postoperative differences to each skin color was for major operations in white (paired t test p < 0.0001), in brown (paired t test p < 0.0001) and in black patients (paired t test p < 0.0001). The differences to each skin color was for medium operations were in white (paired t test p < 0.0001), in brown (paired t test p = 0.0005) and in black patients (paired t test p < 0.0024).
The patients older than 65 years old showed the greater reduction in albuminemia, followed by patients younger than 45 years old and patients aged 45 to 65 years old (p=0,0006 in G1 and p=0,00043 in G2).

The concept of an acute fall in serum albumin concentration after major surgery or trauma has been described since the fifties of the last century (21,22). More recently the natural history of these changes in serum albumin concentration have been redescribed in the context of perioperative fluid intake (18). A decrease in the serum albumin level leading to a state of hypoalbuminemia after an operation may reflect the patient's nutritional status, which is affected by the surgical procedure.
Since reduced organic defenses and malnutrition started to be recognized as potential sources of increased postoperative morbidity and mortality, several studies have been conducted in order to obtain an early detection of immunosuppression and malnutrition in surgical patients (2, 5, 23, 24). Malnourished surgical patients are at higher risk for postopera-tive complications and death compared to well-nourished patients submitted to surgical procedures due to similar conditions. This fact is important in terms of proposing an effective treatment of nutritional control in order to reduce postoperative morbidity and mortality (5). Most investigations compared the results of clinical parameters to the results observed during the postoperative period. However, we found no studies in the literature reporting the quantification of the variation in albumin according to surgical procedure.
Major traumas, including surgical ones, are frequently followed by tissue and systemic inflammatory phenomena, with great fluid mobilization to the interstitial and intravascular space. This response to trauma is accompanied by a reduction in plasma albumin concentration (25,26).
Hypoalbuminemia can be explained in part by changes in vascular permeability and by the dilution effect secondary to infusion of saline and glucose solutions during surgery and during the immediate postoperative period. In a clinical double-blind study, Lobo et al (18) observed that infusion of two liters of 0.9% saline solution or of 5% dextrose solution reduced serum albumin. This reduction in albuminemia was proportional to the amount of fluid infused. Whereas excess water is rapidly eliminated, the sodium overload is excreted slowly, causing a more prolonged dilution of extracellular fluid and consequently of albumin. The greater change in serum albumin concentration, which is proportional to the change in hemoglobin, suggests that the distribution of protein compounds plays a fundamental role in this process (19).
Changes in bioimpedance are also reflected on water-electrolyte content and alter protein concentrations. The inflammatory phenomena that follow surgery and trauma provoke tissue edema with protein extravasation into the interstitial space (27). This exit of albumin from the capillaries can be measured by the increase in capillary hydraulic conductance and by the reduction of the reflection coefficients of macromolecules in plasma. According to Rodoman et al (28), the fluorescent albumin test shows that there is an alteration in the centers of albumin binding both during the preoperative period, due to psychic stress, and during surgery, with a less pronounced change occurring in this case.
This study determines changes in circulating albumin after surgery in a human population. A decrease in albumin after injury has been well established in the past. In fact, albumin is considered a negative acute-phase protein since its levels decrease in parallel to the increase observed in hepatic products, such as fibrinogen and protease inhibitors (28). This decrease in albumin is likely due to a post-transcription mechanism, since transcription of albumin is always low. A re-evaluation of clinical studies is always important if new paradigms are tested.
The minimum age adopted for inclusion in the study was 20 years, since before this age there is an intense process of anabolism typical of growth that may be accompanied by a fall in albumin. According to the present investigation, elder patients are more affected by major and even medium operations than the younger ones. This is an expected result considering that metabolic and immunologic responses of the organism decrease with the age. Thus this is another data, which reinforce older patients require a more intense care during the postoperative period.
We observed greater tolerance in women submitted to medium-sized surgical procedures since, even though albumin was significantly reduced both in males and females, the reduction was lower in women. We found no data in the literature that might explain this finding. A hypothesis could be the female hormonal physiology itself, which leads to variable menstrual losses every month, with the organism being adapted to smaller blood losses.
The Brazilians are a mixture of various races. Whites are from various European countries and blacks are the descendants of people from West African countries. (29) More than one third of the Brazilian population represents a mixture of various races and therefore is classified as brown. This mixed origin of our population frustrates various discussions. However, a classification based on skin color is possible and since in the present study we compared the data for the same patient at different times, i.e., we paired the data, possible controversies concerning the characterization of skin color did not affect the determination of serum albumin. In the present research, the reduction of albumin was higher in white-skin color patients, followed by the brown and black-skinned patients. These data suggest that black people may be better adapted for organic responses to trauma than white people. However, no information concerning the physiopathology of the response to trauma that might explain the differences observed with respect to skin color were found in the literature.
The exclusion criteria adopted in the present study aimed at reducing the variables that directly influence albumin synthesis (administration of corticosteroids, radiotherapy, immunosuppressors and chemotherapy) or that lead to albumin levels that do not correspond to real albumin when, for example, the patients were submitted to blood transfusion or were operated upon due to emergency conditions, especially if large volumes of colloidal solutions or of crystalloids had been administered.
In conclusion, medium-sized and major surgeries cause a reduction in albuminemia during the immediate postoperative period and this reduction is more marked among men, among white-skinned patients and among patients older than 65 years.

The authors are grateful to National Council of Science and Technology (CNPq) and Foundation for Assistance to Research of Minas Gerais (FAPEMIG) for the financial support.

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