Preoperative albumin as a predictor of outcome in gastrointestinal surgery

e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e248–e251

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Original Article

Preoperative albumin as a predictor of outcome in gastrointestinal surgeryq M.B. Badia-Tahull a, *, J. Llop-Talaveron a, E. Fort-Casamartina a, L. Farran-Teixidor b, J.M. Ramon-Torrel c, R. Jo´dar-Masane´s a a

Pharmacy Department, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain Surgery Department, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain c Preventive Medicine Department, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Barcelona, Spain b

a r t i c l e i n f o

s u m m a r y

Article history: Received 3 November 2006 Accepted 14 July 2009

Background & aims: The relationship between preoperative plasma albumin concentration and postoperative clinical course was determined in patients undergoing elective major gastrointestinal tract surgery, taking into account the type of surgery and values for the remaining preoperative analytical parameters.

Keywords: Preoperative hypoalbuminemia Gastrointestinal surgery Morbidity

Methods: Retrospective observational study in patients undergoing elective gastrointestinal surgery, for whom preoperative albumin values were available. Patients were classified according to the type of surgery. The independent variables studied were: age, sex, serum albumin, the parameters routinely included in the preoperative analytical work-up performed in our hospital, neoplastic disease and the type of surgery. The dependent variables included morbidity, mortality, parenteral nutrition requirements and days of hospitalization. Univariate and multivariate statistical methods were applied. Results: 158 patients were studied. On multivariate analysis, preoperative hypoalbuminemia was significantly associated with higher morbidity and lengthier hospital stay regardless of the type of surgery. Among the different procedures analyzed, gastroesophageal surgery was associated with highest morbidity, mortality, parenteral nutrition needs and hospital stay. Conclusions: Preoperative albumin determination as a predictor of morbidity in patients undergoing major gastrointestinal tract surgery is an inexpensive, simple and effective test to include in the routine preoperative analytical workup of these patients. Ó 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

1. Introduction A recent resolution laid down by the Committee of Ministers of the Council of Europe1 has recommended prevention as the initial measure against malnutrition in hospitals, and advocates routine assessment of all patients, using evidence-based methods that are simple to apply and interpret. In the clinical setting, several studies have reported that malnutrition is associated with a higher incidence of complications and, therefore, is one of the main indicators of a poor prognosis.2–4 Among the biochemical parameters used to evaluate baseline nutritional status, albumin concentration continues to be one of the

q Conference presentation: This work was partially presented as a poster in the 26th Espen Congress in Lisbon, Portugal, 11–14 september 2004. * Corresponding author. Servei de Farma`cia, Hospital Universitari de Bellvitge, C/Feixa Llarga s/n. 08917 L’Hospitalet de Llobregat, Barcelona, Spain. Tel.: þ34 932607504; fax: þ34 932607507. E-mail address: [email protected] (M.B. Badia-Tahull).

most useful,5 presenting the highest positive predictive value of all the nutritional assessment methods for predicting associated complications and mortality.6,7 Nevertheless, the utility of albumin determination has been questioned in certain clinical conditions. These include those in which alterations in the plasma redistribution mechanisms are associated with problems of hemodilution or pro-inflammatory cytokine-mediated metabolic events, as can occur in cancer patients.8–11 Since albumin determination is a simple and inexpensive method,10 a proposal was formed in the Nutrition Commission of our hospital, whereby albumin concentration would be requested in patients about to undergo scheduled gastrointestinal surgery. Various studies have related albumin level with operative morbidity and mortality. Nevertheless, only one takes into account the type of surgery performed12 and none are specific to gastrointestinal surgery, in which the risk of malnutrition may be higher, since feeding is particularly difficult in these patients.13,14 The aim of this study was, in patients undergoing elective major gastrointestinal tract surgery, to determine the relationship

1751-4991/$ - see front matter Ó 2009 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.eclnm.2009.07.001

M.B. Badia-Tahull et al. / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e248–e251

between preoperative plasma albumin concentration and postoperative clinical course (as measured by morbidity, mortality, parenteral nutrition requirements, and duration of hospitalization). As a secondary objective, this postoperative clinical course was also related with the type of surgical act and the values obtained for the remaining analytic parameters determined preoperatively. 2. Materials and methods This was a retrospective, observational study of patients undergoing elective major gastrointestinal tract surgery over a period of six months (January to June 2003), for whom preoperative albumin values were available, with the exception of individuals operated on for morbid obesity. Patients with organ dysfunction other than hepatic dysfunction were excluded, as well as those submitted to transfusion, dialysis, artificial nutrition, or immunosuppression before surgery. In an attempt to reflect the true conditions of scheduled gastrointestinal surgery in our hospital, we used the albumin value obtained together with other parameters determined preoperatively in actual clinical practice to assess the patient preoperative status. Patients were classified into four groups according to the type of procedure undertaken (Table 1). The independent variables tested were age, sex, serum albumin, the parameters usually included in the preoperative analytical work-up performed in our hospital (lymphocyte and leukocyte counts, serum creatinine and alanine aminotransferase [ALT]), the presence of neoplastic disease, and the type of surgery. Four dependent variables related with the postoperative clinical course were studied: 1) operative morbidity, considered to be the development of one or more complications diagnosed during hospitalization, including: bleeding (hemoperitoneum or upper digestive tract hemorrhage); fistula (development of suture dehiscence or spontaneous); renal failure (plasma creatinine 200 mmol/L or plasma urea 15 mmol/L, with normal preoperative plasma levels); postoperative liver dysfunction (plasma ALT and bilirubin values three-fold greater than reference values, with normal levels before surgery); infection established on at least one positive culture of samples from lung (sputum or bronchoalveolar lavage), urine, blood, abdomen (peritoneal fluid or abdominal abscess) or surgical wound; and sepsis considered to be local infection with two or more of the following conditions: leukocytes >12  109 cell/L or <4  109 cell/L; body temperature <35  C or >38  C; heart rate >90/min or Pa CO2 < 32 mm Hg (late or longterm surgical complications were not considered); 2) operative mortality, defined as death due to any cause occurring during hospitalization; 3) the need for intravenous nutritional support (TPN); and 4) total duration of hospitalization following the surgical intervention, expressed in days. The chi-square test and analysis of variance were used to determine the relationship between preoperative albumin values and type Table 1 Surgical procedures included in each of the surgery groups. Gastroesophageal Esophagectomy Coloplasty Partial gastrectomy Total gastrectomy

Colorectal and intestinal Total colectomya Hemicolectomya Sigmoidectomya Resection small intestine Rectal amputation

Pancreatic Duodenopancreatectomy Pancreatectomy of the body and tail Total pancreatectomy

Hepatic Right hepatectomy Left hepatectomy Central hepatectomy Segmentectomy o sectorectomy

a

Conventional surgical procedures or laparoscopic procedures.

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of surgery, as well as between albumin levels plus type of surgery and morbidity, mortality, TPN requirements, and days of hospitalization. Logistic regression was used to determine which factors were related with morbidity, mortality and the need for nutritional support. Cox regression was applied to study which factors were related with hospital stay. Continuous variables were entered as categorical variables using the following cut-off values: age <50, 50–70 and >70, leukocytes albumin 35 g/L; lymphocytes 1.5  109 cells/L; 9 12  10 cells/L; creatinine 200 mmol/L and plasma ALT 0.82 mkat/L (median normal range in our laboratory screening). Statistical analyses were performed with SPSS, version 13.0. 3. Results A total of 158 patients were enrolled in the 6-month study period, comprising 58.1% of all patients undergoing major gastrointestinal surgery in this period; 32% had been excluded because they did not meet the inclusion criteria and the remaining patients because albumin concentration had not been determined. The mean age of the patients studied was 61 15 years (18–87 years) and 102 (64.6%) were men. Among the total, 75.3% of patients had neoplastic disease of the gastrointestinal tract and 34.8% of the procedures were performed for colorectal tumors. The median time interval between albumin analysis and surgery was 22 days (5–62). Mean preoperative plasma albumin levels were 37.3  5.4 g/L (23–48 g/L). A total of 52 patients (32.9%) presented at least one complication following surgery, with infection being the most common (Table 2). Fourteen patients (8.9%) died and 56 (35.4%) needed parenteral nutrition for a median of 10 days (1–38 days). The median hospital stay was 12 days (1–120 days). Patients undergoing pancreatic surgery showed the lowest albumin values (34.7  5.3 g/L), followed by gastroesophageal (36.4  5.4 g/L), colorectal (37.8  5.1 g/L), and hepatic surgery (38.4  5.8 g/L) patients. The association between albumin levels and the type of surgery approached significance (P ¼ 0.072). Table 3 summarizes the results of the univariate study. Low albumin values only were statistically associated with lengthier hospital stay; whereas morbidity, mortality, TPN needs and days of hospitalization differed significantly according to the type of surgery. However, after the multivariate adjustment (Tables 4 and 5) Preoperative hypoalbuminemia was significantly associated with higher morbidity and longer hospital stay regardless of the type of surgery. Among the type of surgery, only three of them showed association with the clinical outcome: gastroesophageal surgery was significantly related with higher morbidity and mortality, more TPN requirements and longer hospital stay; pancreatic surgery required higher TPN use; and hepatic surgery was related with shorter hospitalization time. Finally, male sex was associated with lengthier hospital stay. Table 2 Incidence of postoperative complications. Morbidity

Infection Postoperative liver dysfunction Sepsis Fistula Bleeding Renal Failure a

Number of patients with morbiditya Hepatic

Gastroesophageal

Pancreatic

Colorectal and intestinal

8 14

13 7

11 5

14 18

0 1 1 3

8 7 4 1

7 4 2 0

9 9 3 4

Some patients presented two or more postoperative complications.

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M.B. Badia-Tahull et al. / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e248–e251

Table 3 Results of the univariate analysis: relationship between albumin concentration or type of surgery and the dependent variables. Patients Morbiditya Mortalitya Establishment Days of PNa hospitalizedb median (range) Total 158 Albumin <35 g/L 57 35.01–40 g/L 48 40.01–45 g/L 45 >45 g/L 8 P Surgery Gastroesophageal 32 Pancreatic 18 Hepatic 27 Colorectal and 81 intestinal P

94 (59.5)

14 (8.8)

56 (35.4)

12 (1–120)

41 23 25 5 NS

7 6 1 0 NS

25 18 13 0 NS

14 (6–120) 9.5 (1–65) 10 (5–87) 13.5 (7–26) 0.041

23 14 18 39

8 0 0 6

26 11 0 19

16 (3–68) 19.5 (8–54) 9 (1–26) 10 (5–120)

0.024

0.002

0.000

0.022

NS: not significant. a Chi-square test. b Analysis of variance.

4. Discussion In the related bibliography, apart from sporadic studies that found no relationship between albumin concentration and morbidity,15 many authors have demonstrated that hypoalbuminemia is a risk factor for postoperative recovery.2,10,12,16–19 Nevertheless, in most of these studies, heterogeneous surgical procedures are grouped together or only one type of intervention is investigated in a very specific subgroup of patients, and emergency surgery and elective surgery are assessed together. Moreover, none of the studies incorporate statistical adjusting of the results according to the remaining variables. In the present study performed in patients undergoing elective gastrointestinal tract surgery, the multivariate analysis showed a clear association between preoperative hypoalbuminemia and morbidity, despite the fact that the morbidity studied has multifactorial origins20,21 and independently of the type of surgery suffered by the patient. This relationship was further supported by the correlation between low albumin levels and lengthier hospital stay (the latter factor indicating the influence of non-quantifiable or unrecorded morbidity). As in other studies,18 infection was the most prevalent morbid condition found in our series of patients, but postoperative liver dysfunction also affected almost 28% of the total. To explain this incidence we have to take into account that since liver dysfunction was diagnosed on the basis of biochemical parameters22,23 and can have several causes (such as parenteral nutrition, drugs, transfusions, and sepsis) all of which quite common in complex surgery; in most cases, this alteration resolves without specific treatment by controlling the triggering factor. Furthermore, in some cases after liver resection increases in ALT and

bilirubin were partly mediated by the common biochemical consequences of the operation. The mortality rate in the present study is comparable to reported values12,18 and was associated with gastroesophageal surgery, but not with albumin status. Most of the studies in the related literature,24–27 which involve diverse surgical procedures, found an association between initial hypoalbuminemia and mortality, possibly attributable to the fact that the patients studied were older than those included in the present research, or were undergoing emergency hospitalization. We were interested in differentiating postoperative risk according to the type of gastrointestinal surgery. Following multivariate regression analysis, we found that gastroesophageal surgery was associated with a larger number of complications and mortality regardless of the other variables (including albumin level), probably because of the severity of the pathology and the risk inherent to the surgical act. In addition, the association we found between parenteral nutrition and certain surgical procedures may be due to the fact that intravenous nutritional treatment in the acute phase depends on the surgical technique, intestinal tract functionality and the capacity to provide access routes, rather than the status of initial albumin levels. The biochemical parameters usually included in the preoperative work-up, with known clinical value for the screening process prior to surgery, showed no predictive value for recovery in the immediate postoperative period. Although this finding is consistent with results from the majority of studies reviewed, we might have expected a certain relationship between low lymphocyte levels and morbidity, since this parameter has been used in some indexes to determine the level of malnutrition and also as a marker of immunocompetence that could be associated with a higher morbidity rate.12,18 Although patients included in the present study were candidates for elective surgery and therefore, albumin values were determined in relatively stable conditions, it is known that hypoalbuminemia can reflect not only malnutrition, but other pathologic alterations. In order to avoid this possible confounding factor, we adjusted albumin concentration according to biochemical and hematological variables that could indicate problems of hemodilution, edema, infection and/or inflammation. We found that albumin acts as a protector against postoperative complications regardless of their origin, a finding that leads us to consider preoperative hypoalbuminemia, in itself, as a factor predictive of risk after elective gastrointestinal surgery.28 The present study, which reproduces the conditions of clinical practice, includes 58% of the total population undergoing gastrointestinal tract surgery during the study period; the majority of those excluded did not meet the inclusion criteria. The fact of having or not a preoperative albumin determination depended more on the surgeon’s personal choice than on other circumstances.

Table 4 Multiple logistic regression results for the study of morbidity, mortality, and need for parenteral nutrition. Variables

Morbidity OR adjusted

Age U51–70 years U71 years Albumin U35 g/L Surgery UGastroesophageal UPancreatic

Mortality 95% CI

OR adjusted

Parenteral Nutrition 95% CI

NS NS

NS NS

2.144

1.002–4.587

NS

2.785

1.108–7.000 NS

5.111

1.472–17.074 NS

OR adjusted 5.179

95% CI 1.357–19.766 NS NS

22.694 4.622

Other adjusted variables not included in the model: sex, lymphocytes, leukocytes, creatinine, alanine aminotransferase and neoplastic disease. CI: confidence interval. NS: not significant.

6.583–78.231 1.437–14.892

M.B. Badia-Tahull et al. / e-SPEN, the European e-Journal of Clinical Nutrition and Metabolism 4 (2009) e248–e251 Table 5 Cox regression analysis for duration of hospitalization. Variables included

HR

CI (95%)

Male sex Hypoalbuminemia Gastroesophageal surgery Hepatic surgery

1.798 1.805 1.996 0.563

1.25–2.59 1.261–2.583 1.253–3.185 0.354–0.897

HR ¼ Hazard Ratio (values less than 1 are associated with shorter hospitalization). CI: confidence interval.

Our results support the concept that a part of the surgical risk for each patient can be established preoperatively, defining highrisk groups for which surgery must be considered with particular care17,29; following this concept, albumin could be used as one of the parameters to classify these patients. Many indexes and other systems30 are available to assess nutritional status, identify risk, and attempt to predict mortality or morbidity. Nonetheless, in some cases the methodology required to calculate these indexes is quite complex and may require too much time or expense to be compatible with daily clinical practice. This study was designed to determine the usefulness of a single parameter that might be helpful and is easy to obtain. 5. Conclusion From the epidemiological viewpoint, and taking into account the European Council recommendations, determination of plasma albumin concentration in the preoperative analytical workup could be an inexpensive, simple and effective method for assessing patients awaiting elective gastrointestinal surgery. Sources of funding None declared. Conflict of interest None of the authors had any conflict of interest or financial or personal relationship with companies or organizations at the time of the research was performed. Acknowledgments Statement of authorship: MB carried out the studies and data analysis, and drafted the manuscript. JL conceived the study, participated in the design and coordination of the study, and performed the statistical analysis; this author also collaborated in the critical review. EF participated in the study design and data collection, and collaborated in part of the data analysis. LF, who was one of the surgeons, provided significant advice on technical matters. JR contributed to the statistical analysis and technical review. RJ contributed to the critical review. The authors thank the physicians and nursing staff of the Departments of General Surgery, Gastroenterology and Pharmacy for their valuable collaboration and Celine Cavallo for translating the text to English. References 1. ‘‘Food and nutritional care in hospitals: how to prevent under-malnutrition’’. Ad hoc Group. Nutrition programmes in Hospitals. Committee of experts on nutrition, food safety and consumer health. 6th Meeting. Paris 6–7 February 2002. Report and Recommendations. Draft final edition (revised) P-SG (2002) 2 REV. 2. Lochs H, Deverni C. Malnutrition – the ignored risk factor. Dig Dis 2003;21(3):196–7.

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