Is replacement of albumin in major abdominal surgery useful?

Journal of Clinical Anesthesia (2011) 23, 42 46 Original contribution Is replacement of albumin in major abdominal surgery useful? Ksenija Mahkovic-Hergouth MD (Consultant in Anesthesiology), Lidija Kompan MD, PhD (Professor of Anesthesiology) Department of Anaesthesiology and Intensive Care, Institute of Oncology, Ljubljana 1000, Slovenia Received 25 August 2009; revised 5 June 2010; accepted 16 June 2010 Keywords: Abdominal cancer surgery; Albumins, postoperative; Hypoalbuminemia Abstract Study Objective: To evaluate retrospectively serum albumin concentrations as well as morbidity and mortalitiy of abdominal surgical patients who if hypoalbuminemic did not receive human albumin solutions versus those who did receive such solutions. Design: Retrospective observational study. Setting: Academic community hospital. Measurements: The records of 76 consecutive patients who had undergone elective abdominal surgery were reviewed. Preoperative and postoperative serum albumin concentrations up to the seventh day after surgery were recorded. Morbidity and mortality were followed until the time of discharge from the hospital. Results: 38 patients who received albumin replacement if they were hypoalbuminemic versus 38 patients who did not receive albumin replacement showed no significant difference in cumulative (P b 0.52) or individual postoperative complications (infections P b 0.35, cardiovascular complications P b 1.0, organ failure P b 0.67, thromboembolic incidents P b 0.26), and mortality (P b 0.47). Conclusions: Postoperative serum albumin concentration had no correlation with postoperative morbidity. There is no justification for perioperative albumin replacement in abdominal cancer surgical patients. 2011 Elsevier Inc. All rights reserved. 1. Introduction Human albumin replacement therapy for postoperative hypoalbuminemia is still a common practice [1]. Albumin replacement has become a controversial issue because the effect on morbidity and mortality has not been proven in controlled clinical trials [2]. A cochrane meta-analysis showed a harmful effect of albumin replacement to Corresponding author. E-mail address: lidija.kompan@mf.uni-lj.si (L. Kompan). critically-ill patients [3] that was not demonstrated in later meta-analyses [4,5]. There is less controversy about the pathophysiology in an acute critical event. In major injury or disease, albumin moves from the vascular bed to the interstitial space due to the increased capillary permeability. This mechanism is the most common cause of acute hypoalbuminemia; less important are dilution and direct loss of albumins [6]. Moreover, plasma oncotic pressure does not simply correlate with serum albumin concentration [7]. We retrospectively studied serum albumin concentrations as well as the morbidity and mortality of abdominal surgical 0952-8180/$ see front matter 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2010.06.007

Albumin replacement in major abdominal surgery patients who did and did not receive human albumin solutions if hypoalbuminemic. 2. Materials and methods Seventy-six successive patients aged N 18 years were retrospectively studied after elective abdominal surgery for advanced abdominal carcinoma or sarcoma. Two groups were identified. Group 1 included patients who were routinely given albumin solutions in the first postoperative week if they were hypoalbuminemic (20% albumin solutions were given up to 300 ml daily or to the serum level 30 g/l), and Group 2 included patients who received no albumin replacement if they were hypoalbuminemic. In addition to demographic data, patients' preoperative serum albumin concentration and serial postoperative serum albumin concentrations on the first, second, and fifth postoperative days, and one week after surgery, were collected. Data on ASA physical status, surgical procedure, duration of surgery, blood loss, volume of crystalloid and hetastarch colloid replacement given during surgery, volume of perioperative albumin solution substituted in the first group of patients, as well as postoperative complication rate, sepsis organ failure (SOFA) score at the end of treatment, and length of stay in the intensive care unit (ICU) were collected. All serum concentrations of albumin were quantitatively measured using the colorimetric method in the automatic Roche chemical analyzer (Roche, Rotkreuz, Switzerland). Postoperative complications, which were recorded up to hospital discharge, included surgical complications, infections, cardiovascular complications, organ insufficiencies, thromboembolic events, and bleeding gastroduodenal stress ulcers. Surgical complications were defined as postoperative bleeding, leakage of anastomosis, dehiscence of laparotomy, and postoperative enterocutaneous fistula. Infections were diagnosed if criteria from the Centers of Disease Control (CDC) definitions for nosocomial infections were fulfilled [8]. Cardiovascular complications were diagnosed by electrocardiography (ECG) and laboratory and clinical data on acute cardiac decompensation, arrhythmias (atrial flutter), and myocardial infarction. Organ insufficiencies were diagnosed as progressive and potentially reversible dysfunction of two or more organs or organ systems based on laboratory and written clinical data about acute renal insufficiency, hemodynamic instability or shock, respiratory insufficiency, and hepatic or cardiac failure [9]. Thromboembolic events were diagnosed when deep venous thrombosis and/or pulmonary embolism were confirmed by positive Doppler investigation, ventilation/ perfusion lung scan, or angiography computed tomography, or if a written clinical description was provided and treatment was performed. 2.1. Statistics Descriptive statistics were calculated for all the studied variables. Histograms and normal probability plots were examined for all numerical variables. If these variables did not deviate from normality, parametric methods were used; values are expressed as means ± standard deviation (SD). Differences between groups were tested using t-test, and correlation was assessed using Pearson correlation (r). For categorical variables, the difference between groups was tested using the Pearson chi-square test. Statistical analyses were performed using the Analyse-it Excel add-in for Windows (Microsoft, Redmond, WA, USA). 3. Results The records of 76 consecutive patients who underwent surgery for abdominal malignancy were studied. Each group included 38 patients. In Group 1, patients were treated with human albumins for postoperative hypoalbuminemia (serum albumin concentration lower than 30 g/l), as prescribed by the attending physician. Group 2 comprised consecutive patients who did not receive albumins despite their postoperative hypoalbuminemia. Demographic data, ASA physical status, SOFA scores, and data concerning surgery in both groups are shown in Table 1. There was no difference between the groups; there was also no difference in preoperative serum albumin concentration between groups. Comparison of postoperative serum albumin concentrations between the groups (Table 2) showed significantly lower albumin concentrations in Group 2. Patients in Group 1 received 458 ± 355 ml of 20% albumin solutions. The difference between the groups decreased with time; but one week after surgery, albumin concentrations were still significantly lower compared with preoperative values in both groups (Group 1: P = 1.6 10-10, Group 2: P = 2.9 10-7 ). In Group 2, negative correlation was found between postoperative albumin concentrations and duration of surgery (r = -0.44, P = 0.008 on day 2; and r = -0.51, P = 0.0017 on day 5). In Group 1, no correlation between perioperative albumin replacement and duration of surgery was found (r = -0.30, P = 0.066 on day 2, r = -0.09, P = 0.59 on days 3-5). Moreover, no correlation was found between albumin concentration and blood loss (r = -0.28, P = 0.09) or between albumin concentration and crystalloid infusion (r = -0.03, P = 0.85). Total serum proteins also decreased in both groups postoperatively, significantly more in Group 2. Preoperative concentrations in Group 1 were 75.5 ± 5.2 g/l; postoperative concentrations were 51.9 ± 5.7 g/l on day 1, 58.3 ± 5.9 g/l 43

44 K. Mahkovic-Hergouth, L. Kompan Table 1 Patient data Group 1 Group 2 P (t-test) Patients (M/F) 38 (18/20) 38 (21/17) Age (yrs) 52.4 ± 13.7 56.5 ± 15.3 0.11 ASA physical status 1.9 ± 0.7 2.0 ± 0.9 0.20 Duration of surgery (hrs) 5.9 ± 3.2 6.1 ± 2.2 0.39 Volume of blood loss (L) 3.3 ± 6.9 2.0 ± 2.6 0.14 Volume of crystalloids during surgery (L) 5.3 ± 3.0 4.5 ± 2.0 0.08 Volume of colloids during surgery (L) 0.5 ± 0.5 0.6 ± 0.5 0.11 Plasma albumin concentration before surgery (mg/l) 39.0 ± 4.5 38.1 ± 7.1 0.25 SOFA at the end of ICU treatment 4.8 ± 3.64 4.0 ± 1.63 0.67 20% albumin solution given during ICU stay (L) 0.43 ± 0.42 0 Patients with colon and stomach cancer 15 14 Patients with retroperitoneal sarcomas 16 22 Patients with gynecological tumors 7 2 Data are means ± SD. Group 1 patients received human albumins for postoperative hypoalbuminemia (serum albumin concentration lower than 30 g/l), Group 2 patients did not receive albumins despite their postoperative hypoalbuminemia. SOFA = sepsis organ failure score, ICU = intensive care unit. on day 5, and 64.6 ± 6.5 g/l a week after surgery. In Group 2, preoperative concentration was 70.4 ± 5.2 g/l, and postoperative concentrations were 44.0 ± 8.4 g/l on day 1, 49.6 ± 6.9 g/l on day 5, and 60.2 ± 9.1 g/l a week after surgery. Intensive care unit stay in Group 1 was 13.9 ± 10.2 days; in Group 2, it was 12.5 ± 6.1 days. The difference was not statistically significant (P = 0.23). In group 1, 29 postoperative complications were detected: 20 patients developed infections, 4 were hemodynamically unstable, three had one or more organ failures, one had a thromboembolic incident, and one patient died in the perioperative period of multi-organ failure due to abdominal compartment syndrome. In Group 2, 31 postoperative complications occurred: 15 patients developed infections, 5 were hemodynamically unstable, three developed one or more organ failures, three had thromboembolic events, and one patient died two months after operation due to abdominal sepsis. No significant difference in cumulative (P = 0.52) or individual postoperative complications (infections: P = 0.35, cardiovascular complications: P = 1.0, organ failure: P = 0.67, thromboembolic events: P = 0.26, or mortality: P = 1.0) was found. 4. Discussion In the present retrospective, single-center study, we looked into the data of two groups of consecutive postoperative patients after major abdominal surgery: one group with perioperative albumin replacement and the other without it. The postoperative albumin concentration values in both groups were significantly lower in comparison to the preoperative values, and albumin supplementation did not prevent a decrease in postoperative albumin concentration in the supplemented group. There were similar findings in other studies of albumin concentrations in surgical and critically ill patients [10,11]. However, in Nielsen et al's study [12] of patients after abdominal aortic surgery, albumin concentration did not decrease significantly when treated for 4 days with high volumes of albumin solutions, but their daily albumin administrations were higher than those in our study. In their group who received no perioperative albumin supplementation, serum albumin concentrations decreased to levels similar to those in our study [12]. Surgery in the abdominal cavity is followed by a larger decrease in serum albumin concentrations, as in other surgical procedures [13]. Table 2 Comparison of preoperative and postoperative serum albumin concentrations (g/l) between the groups Group 1 a Group 2 a P (t-test) Albumin concentration before surgery 39.0 ± 4.5 38.1 ± 7.2 0.25 Albumin concentration day 2 after surgery 28.8 ± 3.8 23.8 ± 4.1 1.7 10-7 b Albumin concentration day 5 after surgery 31.1 ± 3.5 25.8 ± 3.3 1.3 10-9 b Albumin concentration one week after surgery 32.1 ± 3.6 30.2 ± 5.1 0.03 c Group 1 patients received human albumins for postoperative hypoalbuminemia (serum albumin concentration lower than 30 g/l), Group 2 patients did not receive albumin despite their postoperative hypoalbuminemia. a Data are means ± SD. b P b 0.001. c P b 0.05.

Albumin replacement in major abdominal surgery Enhanced capillary permeability causing escape of fluid and albumins from the vessels, returns to normal in 12 to 24 hours after surgery; however, after extensive surgery, albumin was found extracellularly 7 to 10 days after surgery [6,10]. This finding may explain the significant hypoalbuminemia (vs. preoperative values) noted in the first days after surgery in our group who received no albumin replacement, and the slow albumin level increase in both groups in the week after surgery. Zetterström and Hedstrand reached similar conclusions [14]. The extent of hypoalbuminemia in our patients correlated with the duration of surgery. The same postoperative albumin concentration change also was detected by Nielsen et al. [12]. We noted only a trend in negative influence of blood transfusion on albumin concentration. Hypoalbuminemia after massive blood transfusion is partially also a consequence of the albumins lost with blood loss [10]. We were also unable to find any correlation among the volume of colloid or crystalloid infusion and albumin concentration, as described by Sun et al. [13]. Massive crystalloid infusion alone may cause increased permeability [15,16] and consequent organ dysfunction, especially pulmonary [17,18] dysfunction. Thus, patients after abdominal surgery should exhibit fewer postoperative complications when given a limited volume of crystalloids [19]. The definitions for restricted or liberal volume therapy regime in studies are various [20]. We never infused crystalloids alone, but always in combination with colloids. The practice may account for the inability to detect the influence of crystalloid volume on plasma albumin level. Albumin serum concentration, therefore, reflects mainly the patient's general condition due to the extent of systemic inflammatory response and capillary permeability [1,21,22]. Serum albumin concentration increases with successful recovery. The increase in serum albumin concentration in the recovery phase is more or less the same in patients who receive albumin replacement therapy as in those who do not. In our group of 76 surgical patients with advanced carcinomas, albumin infusion had no influence on postoperative morbidity or organ failure. These results are in accordance with the study of Golub and co-authors in the surgical ICU [23]. Similarly, in a recent study on the influence of albumin replacement after surgery to a target level of 30 g/l, no beneficial effect on postoperative morbidity in liver transplant surgery was observed [24]. In elderly patients after cardiac surgery, there was no difference in renal dysfunction between the group with albumin supplementation and the group given 6% hydroxyethyl starch (HES) instead of albumin; moreover, endothelial activation was even lower in the HES group [25]. In ICU patients, albumin replacement increased colloid osmotic pressure, but it did not improve fluid balance and pulmonary edema [26], nor did it reduce mortality, duration of ICU stay, mechanical ventilation, or renal replacement therapy [27]. Our results and those in the cited literature lead us to the conclusion that human albumin replacement in acute hypoalbuminemia does not influence the morbidity, but the degree of postoperative hypoalbuminemia probably does. Preoperative hypoalbuminemia is also an important risk factor for postoperative complications [28,29]. 4.1. Conclusions Postoperative albumin replacement does not diminish postoperative morbidity. There is no justification for perioperative albumin replacement in abdominal cancer surgical patients. Acknowledgments We are grateful to Assistant Professor Gaj Vidmar, PhD, Institute for Rehabilitation, Republic of Slovenia, for statistical advice. References [1] Soni N. Wonderful albumin? BMJ 1995;310(6984):887-8. [2] Boldt J. 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