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Is Postoperative Albumin Level Related with Surgical Site Infection?
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ORIGINAL ARTICLE Is Postoperative Albumin Level Related with Surgical Site Infection?
Kyungtae CHO, M.D.1, Sung Woo CHO, M.D., Ph.D.1, Sangchul YUN, M.D., Ph.D.1, Suyeon Park, M.S.2
Surgical Metabolism and Nutrition 2018;9(2):59-67.
DOI: https://doi.org/10.18858/smn.2018.9.2.59
Published online: December 30, 2018

Department of Surgery, Soonchunhyang University Seoul Hospital, Seoul, Korea

Department of Biostatistics, Soonchunhyang University Seoul Hospital, Seoul, Korea

Department of Surgery, Soonchunhyang University Seoul Hospital, Seoul, Korea

Department of Biostatistics, Soonchunhyang University Seoul Hospital, Seoul, Korea

Correspondence to: Sung Woo CHO, Department of Surgery, Soonchunhyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea Tel: +82-2-709-9240, Fax: +82-2-749-0499, E-mail: orsay@schmc.ac.kr
• Received: October 5, 2018   • Accepted: October 26, 2018

Copyright: © The Korean Society of Surgical Metabolism and Nutrition

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Purpose:
    Surgical site infection (SSI) is a hospital-acquired infection (HAI) associated with increased mortality, length of hospital stay, and cost of hospitalization. The aim of this study was to identify the value of albumin as an indicator of the nutritional status, postoperative C-reactive protein (CRP), and white blood cell (WBC) levels in predicting an outbreak of SSI and SSI-related epidemiology after colorectal surgery and identifying the risk factors for SSI.
  • Materials and Methods:
    A total of 198 patients, who underwent colorectal surgery from September 1, 2015 to December 31, 2016, were included in the study. The patient identity, operation characteristics, and SSI data were analyzed retrospectively by a chart review and national SSI reporting sheet. The relationship of the SSI and clinical data was analyzed statistically, and the SSI detection time and post-operative inflammatory laboratory findings were analyzed individually using cumulative incidence analysis and cause-specific hazard model.
  • Results:
    The incidence of SSI post colorectal surgery was 15.7% (31 out of 198 cases). Chronic renal failure (CRF), open surgery, long operation time, and stoma were identified as significant risk factors for SSI using univariate analysis. The CRF, long operation time, and stoma were significant risk factors according to multivariate analysis. The decrease in albumin on post-operative day (POD)#3 and CRP elevation on POD#4 were related to the early detection of SSI.
  • Conclusion:
    The actual incidence of SSI might be higher than expected, particularly in cases where patients have several clinical and operative factors. In addition, the albumin level and multiple postoperative inflammation tests can be employed as an early predictors of SSI.
Hospital-acquired infection (HAI) is one of the biggest problems in recent medicine and surgical site infection (SSI) is the most common course of HAI. SSI occurs in 2∼5% operations in the United States.[1] SSI is associated with increase in mortality, length of hospital stay and medical cost.[2-4] It is well known that SSI incidence is high after colorectal surgery, however its frequency of occurrence may not be accurate.[5]
In Korea, SSI has been reported intermittently and indirectly during the process of investigating HAI, and accuracy of these reports was considered doubtful as the reported incidence rate ranged from 2.0 to 9.7%.[6] In 2006, the Korean Nosocomial Infections Surveillance System (KONIS) was established to survey incidences of SSI across the nation. Many hospitals voluntarily participated in this surveillance system. This system employed KONIS Web-based Report and Analysis Program.[7-9] For a more effective surveillance of SSI, Korean Surgical Site Infection Surveillance (KOSSIS) program was developed in 2014. This system focused on SSI among nosocomial infections. One prospective multicenter study employed the KOSSIS program to evaluate SSI rates and identify risk factors for SSI. A total of 197 colon surgeries were included in the study. The incidence of SSI after colon surgery was reported as 10.15%.[10]
The main purpose of this study is to confirm the effect of postoperative albumin levels which is commonly used as an indicator of the nutritional status of patient on development of SSI. Furthermore, this study aims to identify the value of postoperative c-reactive protein (CRP) and WBC levels in predicting outbreak of SSI after colorectal surgery in patients, who were rigorously examined and reported as per the standard survey process of KOSSIS. The study also aims to identify other clinical factors related to SSI after colorectal surgery.
1. Patient characteristics
A total of 198 patients who underwent colorectal surgery between Sep. 1. 2015 and Dec. 31. 2016 were included in the study. Patient characteristics are reported in Table 1. There was no difference in sex ratio. The proportion of overweight patients with body mass index (BMI) ≥25 was 29%. Approximately 14% of patients were in American society of anesthesiologists (ASA) score 3 to 4. Compared with patients with hypertension or diabetes, the number of patients with CRF and chronic respiratory disease was relatively small (10 and 5, respectively).
Table 1
Patient characteristics
 Variable Number (%)
Sex
  Male 100 (50.51)
  Female 98 (49.49)
Age (yr)
  <65 97 (48.99)
  ≥65 101 (51.01)
Body mass index (BMI; kg/m2)
  <25 135 (68.18)
  ≥25 59 (29.80)
American Society of Anesthesiologists (ASA) physical status score (1~5)
  1 or 2 170 (85.86)
  3 or 4 28 (14.14)
Hypertension
  None 111 (56.06)
  Yes 86 (43.43)
Diabetes mellitus
  None 158 (79.80)
  Yes 39 (19.70)
Chronic renal failure
  None 187 (94.44)
  Yes 10 (05.05)
Chronic respiratory disease
  None 192 (96.97)
  Yes 5 (02.53)
2. Study design
The primary end-point of the study was to identify epidemiology of clinical variables associated with SSI and the secondary end-point was to identify postoperative albumin, CRP and WBC levels as predictors of SSI after colorectal surgery.
Patient and operation characteristics were identified by review of patient charts. Patient characteristics included age, sex, BMI, ASA score, and medical conditions including hypertension, diabetes, chronic renal failure, and pulmonary respiratory disease. Operation characteristics included type and method of operation, operation time, elective or non-elective operation and formation of stoma (Table 2). Postoperative albumin, WBC and CRP levels were recorded every day starting on Postoperative day 1 (POD#1) till day 5 (POD#5). Laboratory test was not performed daily for some patients as some surgeons do not prefer daily testing.
Table 2
Operative characteristics
 Variable Numbers (%)
Laparoscopic/open surgery  
 Lapa 126 (63.6)
 Open 72 (36.4)
Elective/emergent
 Elec 136 (68.7)
 Emer 61 (30.8)
Operative time (minutes)
 <240 100 (50.5)
 ≥240 98 (49.5)
Stoma creation
 None 173 (87.4)
 Yes 25 (12.6)
Operation types
 (Extended) Right hemicolectomy 36 (18.2)
 Transverse colectomy 5 (2.5)
 Left hemicolectomy 6 (3.0)
 Anterior resection 37 (18.7)
 Low anterior resection 22 (11.1)
 Mile’s operation 5 (2.5)
 Hartmann’s operation 13 (6.6)
 Ileostomy reversal 9 (4.2)
 Hartmann’s reversal 3 (1.5)
 Ileocecectomy 27 (13.6)
 etc. 36 (18.2)
SSI was confirmed by the operating surgeons as per definition of SSI and its classification by KOSSIS. Data from each patient with SSI was recorded in a clinical reporting sheet and included in the KOSSIS reporting system. In order to diagnose SSI post patient discharge, all patients who underwent colorectal surgery were evaluated for SSI during their clinic visit by surgeons. If SSI was found during these office visit, clinicians recorded the findings in patient charts.
First, the correlation between SSI and various clinical factors was statistically analyzed.
On the other hand, patients with SSI were divided into two groups, ’early SSI (ESSI; less than 7 days)’ and ’late SSI (LSSI; 7 and more than 7 days)’ based on the time the medical staff detected the infection. Correlation between ESSI/LSSI and clinical findings was analyzed.
This study was approved by Institutional Review Board of Soonchunhyang University Seoul Hospital (IRB No.2018-06-002). Because this was a retrospective study with minimal risk to patients, the Internal Review Board, Soonchunhyang University Seoul Hospital, exempted it from obtaining informed consent from the patients whose records were included in the study.
3. Study analysis
In this study, we first tried to analyze the correlation between infection and various clinical features using the Chi-square test and then an in-depth analyzing was performed for the correlation between epidemiologic data and laboratory findings of two groups with a competing risk regression model. We employed two statistical analysis methodologies to identify the risk factors. Cut off points for continuous variables including postoperative serum albumin, CRP and WBC levels were calculated using Youden index (Table 3) and all blood lab levels were coded into binary variables based on it being higher or lower than the pre-determined reference point. First, cumulative incidence analysis was performed by using cause-specific cumulative incidence function. Cumulative incidence was estimated for different causes of failure in each groups (Albumin, WBC or CRP events) and P-value was calculated by comparison for each factor across groups. Cumulative incidences of ESSI and LSSI were calculated individually. A Second, cause specific hazard model employed was based upon an inverse probability censoring weighting (IPCW) method. In the univariate analysis, a candidate risk factor with P-value of less than 0.2 was employed, and backward variable selection was performed using a P-value of 0.05 in multiple analysis. R version 3.1.2 was employed for all statistical analysis (using ‘cmprsk’ and ‘crrstep’ packages). All statistical analyses were performed using SPSS, version 14.0.
Table 3
Cut off table of Albumin, C-reactive protein (CRP) and White blood cell count (WBC) by Youden index
   Criteria Sensitivity 95% CI* Specificity 95% CI PPV 95% CI NPV 95% CI AUC§ 95% CI
Albumin (g/dL)
 POD 1 ≤3.050 0.516 0.334~0.694 0.629 0.550~0.701 0.205 0.125~0.315 0.875 0.800~0.926 0.549 0.429~0.669
 POD 2 ≤3.35 0.678 0.485~0.827 0.467 0.390~0.546 0.190 0.125~0.280 0.886 0.797~0.941 0.496 0.387~0.606
 POD 3 ≤3.95 0.968 0.815~0.998 0.178 0.126~0.248 0.180 0.127~0.248 0.968 0.815~0.998 0.493 0.379~0.608
 POD 4 ≤2.85 0.194 0.081~0.380 0.886 0.826~0.928 0.24 0.102~0.455 0.855 0.792~0.903 0.555 0.404~0.707
 POD 5 ≤3.05 0.419 0.251~0.607 0.743 0.668~0.806 0.232 0.134~0.367 0.873 0.805~0.921 0.607 0.490~0.725
CRP (mg/L)
 POD 1 ≥3.075 0.774 0.585~0.897 0.497 0.419~0.575 0.222 0.15~0.314 0.922 0.841~0.966 0.643 0.551~0.735
 POD 2 ≥10.79 0.419 0.251~0.607 0.755 0.681~0.816 0.241 0.139~0.379 0.875 0.807~0.922 0.610 0.490~0.730
 POD 3 ≥6.87 0.645 0.454~0.802 0.653 0.575~0.724 0.256 0.167~0.37 0.908 0.838~0.951 0.659 0.551~0.767
 POD 4 ≥11.535 0.29 0.149~0.482 0.91 0.854~0.947 0.375 0.196~0.592 0.874 0.813~0.917 0.659 0.514~0.804
 POD 5 ≥4.6 0.452 0.278~0.637 0.719 0.643~0.784 0.23 0.135~0.358 0.876 0.806~0.924 0.637 0.520~0.754
WBC (/μL)
 POD 1 ≥12,750 0.419 0.251~0.607 0.623 0.544~0.696 0.171 0.977~0.278 0.853 0.774~0.908 0.544 0.425~0.663
 POD 2 ≥9,650 0.387 0.224~0.577 0.713 0.637~0.779 0.2 0.112~0.327 0.862 0.791~0.913 0.563 0.428~0.697
 POD 3 ≥9,050 0.419 0.251~0.607 0.749 0.674~0.811 0.237 0.137~0.373 0.874 0.806~0.922 0.561 0.440~0.682
 POD 4 ≥8,500 0.355 0.198~0.546 0.832 0.765~0.884 0.282 0.156~0.451 0.874 0.810~0.92 0.601 0.455~0.746
 POD 5 ≥7,350 0.484 0.306~0.666 0.713 0.637~0.779 0.238 0.144~0.365 0.881 0.812~0.929 0.595 0.485~0.706

*CI = Cumulative Index;

PPV = Positive Predictive Value;

NPV = Negative Predictive Value;

§AUC = Area under the ROC curve.

The incidence of SSI after colorectal surgery in the current study was 15.7% (31 of 198 cases).
Based on univariate analysis, CRF (OR 4.0, 95% CI, 1.046∼14.926), open surgery (OR 2.5, 95% CI, 1.136∼5.381), operation time exceeding 240 minutes (OR 3.4, 95% CI, 1.492∼8.337) and stoma formation (OR 4.8, 95% CI, 1.921∼12.122) are potential risk factors for occurrence of SSI post colorectal surgery (Table 4).
Table 4
Univariate analysis of risk factors for surgical site infection
 Variable SSI (%) OR 95% CI P-value


Yes None Upper Lower
Sex
 Male 16 (51.6) 84 (50.3) Ref.
 Female 15 (48.4) 83 (49.7) 1.054 0.489 2.269 0.893
Age (yr)
 <65 15 (48.4) 82 (49.1) Ref.
 ≥65 16 (51.6) 85 (50.9) 1.029 0.478 2.216 0.942
BMI (kg/m2)
 <25 22 (73.3) 113 (68.9) Ref.
 ≥25 8 (26.7) 51 (31.1) 0.806 0.336 1.931 0.628
ASA score (1~5)
 1 or 2 26 (83.9) 144 (86.2) Ref.
 3 or 4 5 (16.1) 23 (13.8) 1.204 0.420 3.453 0.730
Lapascopic/Open surgery
 Lapa 14 (45.2) 112 (67.1) Ref.
 Open 17 (54.8) 55 (32.9) 2.473 1.136 5.381 0.022
Elective/Emergency operation
 Elect 21 (67.7) 115 (69.3) Ref.
 Emer 10 (32.3) 51 (30.7) 1.074 0.472 2.433 0.865
Operative time (min)
 <240 8 (25.8) 92 (55.1) Ref.
 ≥240 23 (74.2) 75 (44.9) 3.527 1.492 8.337 0.004
Stoma creation
 No 21 (67.7) 152 (91) Ref.
 Yes 10 (32.3) 15 (9) 4.825 1.921 12.122 0.001
Hypertension
 No 14 (45.2) 97 (58.4) Ref.
 Yes 17 (54.8) 69 (41.6) 1.707 0.789 3.693 0.174
Diabetes mellitus
 No 26 (83.9) 132 (79.5) Ref.
 Yes 5 (16.1) 34 (20.5) 0.747 0.267 2.088 0.578
Chronic renal failure
 No 27 (87.1) 160 (96.4) Ref.
 Yes 4 (12.9) 6 (3.6) 3.951 1.046 14.926 0.043
Chronic Respiratory disease
 No 30 (96.8) 162 (97.6) Ref.
 Yes 1 (3.2) 4 (2.4) 1.350 0.146 12.501 0.792
And then multivariate analysis was performed with these significant related factors in univariate analysis. Chronic renal failure (OR 4.0, 95% CI, 1.046∼14.926), longer operation time (OR 3.8, 95% CI, 1.534∼9.167) and stoma formation (OR 5.2, 95% CI, 1.977∼13.735) were determined to be statistically significant risk factors.
In-depth analysis of statistical relationship between epidemiologic factors and inflammatory lab tests for the ESSI/LSSI, from POD #3, there is a tendency for cumulative incidence to differ between albumin declining group and non-declining groups. On POD#3, the cumulative incidences of ESSI for albumin level ([Albumin Yes and Event <7 days] and [Albumin NO and Event <7 days]) were 0.043 and 0.162, respectively. Cumulative incidence in the CRP group also tends to show a difference after POD #4. On POD #5, the cumulative incidences of ESSI for CRP level ([CRP Yes and Event <7 days] and [CRP NO and Event <7 days]) were 0 and 0.09, respectively (Fig. 1). In the cause specific hazard model for occurrence of ESSI, variables with P-values lower than 0.2 (univariate analysis) were stomy formation, open surgery, operation time longer than 240 minutes, POD#3 and #5 low albumin levels and POD#4 high CRP levels and stomy formation, long operation time, hypertension, chronic renal failure and POD #3 low albumin show lower P-values with LSSI (univariate analysis) (Table 5). These variables were considered as potentially independent and employed for multivariate analysis. The risk factors associated with ESSI and LSSI after colorectal surgery by multiple regression analysis are shown in Table 6. Statistically significant risk factors for ESSI as determined by multivariate model were operation time longer than 240 minutes (CHR=9.794 [95% CI, 1.804∼53.171], P<0.008), and decrease in albumin levels on POD#3 (Value ≤3.95 g/dL, CHR=0.096 [95% CI, 0.025∼0.369], P<0.001) and elevation in CRP level on POD#4 (Value ≥11.535 mg/L CHR=12.634 [95% CI, 4.195∼38.050], P=0.000). For LSSI, there were no statistically significant variables.
Fig. 1
Cumulative incidence curves using the stage of Albumin, CRP and WBC in the ESSI or LSSI as a competing risk.
SMN_09_059_fig_1.jpg
Table 5
Univariate analysis of relative risk for surgical site infection to early SSI (ESSI) vs late SSI (LSSI)
<7 days (ESSI) ≥7 days (LSSI)


CHR* 95% CI P-value CHR* 95% CI P-value


Lower Upper Lower Upper
Female 1.139 0.878 1.139 0.810 1.104 0.906 1.104 0.830
Year ≥65 1.132 0.884 1.132 0.820 0.711 0.711 1.407 0.460
BMI ≥25 kg/m2 0.672 0.672 1.489 0.540 1.154 0.867 1.154 0.770
Stomy formation§ 3.218 0.311 3.218 0.048 2.535 0.394 2.535 0.065
Emergency operation 0.652 1.534 0.652 0.520 1.258 0.795 1.258 0.620
Open surgery 2.939 0.340 2.939 0.055 1.299 0.770 1.299 0.570
Operaitive time ≥240 min 5.943 0.168 5.943 0.020 2.342 0.427 2.342 0.082
Hyptertension 1.542 0.649 1.542 0.430 1.851 0.540 1.851 0.180
Diabetes mellitus 0.706 0.706 1.416 0.650 1.068 0.937 1.068 0.910
Chronic renal failure 1.605 0.623 1.605 0.650 3.897 0.257 3.897 0.026
Chronic respiratory diseases 3.215 0.311 3.215 0.230 N/A
POD#1 CRP (mg/L) 1.887 0.584 6.094 0.290 1.799 0.682 4.748 0.240
WBC (/μL) 1.131 0.375 3.414 0.830 1.065 0.424 2.679 0.890
Albumin (g/dL) 1.283 0.435 3.781 0.650 1.684 0.689 4.117 0.250
POD#2 CRP 1.747 0.582 5.246 0.320 1.008 0.366 2.778 0.990
WBC 0.745 0.209 2.654 0.650 0.885 0.325 2.411 0.810
Albumin 0.766 0.261 2.253 0.630 1.609 0.638 4.060 0.310
POD#3 CRP 1.021 0.340 3.061 0.970 1.538 0.630 3.753 0.340
WBC 0.737 0.208 2.608 0.640 0.873 0.323 2.359 0.790
Albumin 0.240 0.082 0.704 0.009 4.254 0.560 32.298 0.160
POD#4 CRP 2.659 0.781 9.057 0.120 0.473 0.066 3.370 0.450
WBC 1.965 0.629 6.136 0.250 0.507 0.121 2.122 0.350
Albumin N/A 1.058 0.245 4.565 0.940
POD#5 CRP N/A 0.724 0.241 2.171 0.560
WBC 0.426 0.096 1.884 0.260 1.381 0.554 3.445 0.490
Albumin 0.231 0.031 1.732 0.150 1.317 0.510 3.403 0.570

*CHR = Cause specific hazard model;

N/A = not available;

P-value by Inverse probability censoring weighting (IPCW);

§Both Ileostomy and Colostomy are included.

Table 6
Multivariate analysis of relative risk for surgical site infection to early SSI (ESSI) vs late SSI (LSSI)
<7 days (ESSI) ≥7 days (LSSI)


CHR* 95% CI P-value CHR* 95% CI P-value


Lower Upper lower upper
Operaitive time ≥240 min 9.794 1.804 53.171 0.008
POD#3 of Albumin 0.096 0.025 0.369 0.001
POD#4 of CRP 12.634 4.195 38.050 0.000  

*CHR = Cause specific hazard model;

P-value by Inverse probability censoring weighting (IPCW).

Surgical site infection is with a significance concern in colorectal surgery. Multiple studies show that the incidence rate of SSI after colorectal surgery is higher than other surgery types.[11,12] According to the American College of Surgeons’ National Surgical Quality Improvement Program data (ACS NSQIP) widely used in United States, the SSI rates of colorectal surgery range from 9% to 14%.[13-15] According to the Japan Nosocomial Infections Surveillance (JANIS), the incidences of SSI after colon and rectal surgery from 2008 to 2010 were 15.0% and 17.8%, respectively.[16] Higher rate of SSI post colorectal surgery may be due to the inherent possibility of microbial contamination at the operation wound site.[17]
SSI rate in our study (15.7%) is minimally higher than that of previous studies. We believe this may be due to two reasons. Firstly, the reported SSI incidence may have been underestimated in previous studies. Secondly, the actual SSI rate at our hospital may be higher than that at the others. In accordance with the first reason, 9∼15% SSI rate was reported in recent US surveys,[18,19] 10.15% in Korean,[10] and 15.0∼17.8% in Japanese reports.[9] In accordance with the second reason, authors in this study focused on high rate of emergency operation. Compared to elective surgery, peritonitis due to perforation and stoma formation are relatively more frequent in emergency surgery, and the rate of SSI incidence is also expected to be higher. However, detailed analysis and risk-adjustment for these factors was not performed. For a more meaningful comparisons of SSI rates across each hospital setting, calibration is required for each hospital’s patient population as is performed by the National Healthcare Safety Network (NHSN) risk-adjusted measurement system in the United States.
In accordance with the antibiotic guideline for SSI prevention, our institute has a standard principle of administering second-generation cephalosporin IV antibiotics twice, at 30 minutes pre-operation and at post operation. However, in cases requiring emergency surgery, antibiotics are used for treatment of peritonitis or sepsis before operation, and antibiotic treatment should be continued for a longer period after surgery. Compared to previous studies, this institute conducts relatively more emergency operations, and this may have affected the outcome of this study; however, this study did not control for these differences.
In this study, we classified SSI into two groups; before POD#7 (Early SSI) and after and POD#7 (Late SSI). ‘POD#7’ was based on the average post-operative admission of a target patient population (6.2 days). This may be slightly higher than other hospitals (also when compared to our recent data), considering that the emergency operation rate is slightly higher in our hospital, however no detailed analysis focused on this factor has been performed.
We examined the possibility of employing albumin, WBC and CRP as tools to predict the occurrence of SSI by analyzing the correlation between postoperative albumin, WBC and CRP levels after surgery with occurrence of SSI using multiple statistical analysis methodologies. According to statistical results, ESSI could be reliably predicted when albumin level decreased on POD#3 (≤3.95) and CRP level was elevated on POD 4 (≥11.535 mg/L).
Malnutrition has an adverse effect on outcomes in surgical patients.[20] Albumin is most commonly used as an indicator of the nutritional status of a patient and is a negative acute-phase protein that is downregulated in response to acute illness or stress.[21] A recent study shows that hypoalbuminemia is an independent risk factor for the development of SSI following gastro-intestinal surgery. It shows that albumin <30 mg/dL was associated with an increased rate of SSI.[22]
C-reactive protein (CRP) and white blood cells (WBC) are known as biologic markers of postoperative infection. [23-25] They have limited sensitivity and are good predictors of SSI. In a recent study, postoperative CRP level at 48 hours was useful in predicting organ-space surgical site infection after colorectal surgery.[26] In a similar study, elevated CRP levels at 2nd and 4th post-operative day (POD) were considered as predictors of anastomotic leak and postoperative complication after colorectal surgery. Multivariate analysis suggested that CRP level >125 mg/L at 4th POD was a significant predictor for anastomotic leak (Odd ratio [OR] 18.15) and septic complication (OR 14.27).[27]
We carefully recommend that clinicians measure albumin level as an indicator of nutritional status and CRP level as an inflammation marker more frequently for earlier detection of SSI. Although studies should be conducted on cohorts with more homogeneous and large numbers of patient, this study is meaningful in that it raised the necessity of monitoring nutritional status including serum albumin level.
In addition to albumin and CRP levels, univariate and multivariate analysis showed that longer operation time, CRF and stoma formation were other significant risk factors of SSI.
Limitations of this study include its small sample size, which was not adequate to analyze all of the risk factors of SSI. Additionally, all of the operations were conducted in a single hospital and by a single colorectal team, thereby limiting any variation that may occur in different facilities. Most importantly, a selection bias may exist as the study data was collected retrospectively. This may limit the study to identify all of the risk factors associated with SSI.
And we did not investigate the degree of infection according to SSI classification. Although we assessed wound infection through thorough surveillance, this would be another limitation. Therefore, further research is needed in the future.
The biggest limitation is that because this study was based entirely on the national SSI survey report and chart records, we could not investigate other factors that could assess nutritional status of patients except for the albumin levels and overweight. We plan to increase the number of patients participating in the study, and to study other nutritional indicators.
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        Is Postoperative Albumin Level Related with Surgical Site Infection?
        Ann Clin Nutr Metab. 2018;9(2):59-67.   Published online December 30, 2018
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      Is Postoperative Albumin Level Related with Surgical Site Infection?
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      Fig. 1 Cumulative incidence curves using the stage of Albumin, CRP and WBC in the ESSI or LSSI as a competing risk.
      Is Postoperative Albumin Level Related with Surgical Site Infection?

      Patient characteristics

       Variable Number (%)
      Sex
        Male 100 (50.51)
        Female 98 (49.49)
      Age (yr)
        <65 97 (48.99)
        ≥65 101 (51.01)
      Body mass index (BMI; kg/m2)
        <25 135 (68.18)
        ≥25 59 (29.80)
      American Society of Anesthesiologists (ASA) physical status score (1~5)
        1 or 2 170 (85.86)
        3 or 4 28 (14.14)
      Hypertension
        None 111 (56.06)
        Yes 86 (43.43)
      Diabetes mellitus
        None 158 (79.80)
        Yes 39 (19.70)
      Chronic renal failure
        None 187 (94.44)
        Yes 10 (05.05)
      Chronic respiratory disease
        None 192 (96.97)
        Yes 5 (02.53)

      Operative characteristics

       Variable Numbers (%)
      Laparoscopic/open surgery  
       Lapa 126 (63.6)
       Open 72 (36.4)
      Elective/emergent
       Elec 136 (68.7)
       Emer 61 (30.8)
      Operative time (minutes)
       <240 100 (50.5)
       ≥240 98 (49.5)
      Stoma creation
       None 173 (87.4)
       Yes 25 (12.6)
      Operation types
       (Extended) Right hemicolectomy 36 (18.2)
       Transverse colectomy 5 (2.5)
       Left hemicolectomy 6 (3.0)
       Anterior resection 37 (18.7)
       Low anterior resection 22 (11.1)
       Mile’s operation 5 (2.5)
       Hartmann’s operation 13 (6.6)
       Ileostomy reversal 9 (4.2)
       Hartmann’s reversal 3 (1.5)
       Ileocecectomy 27 (13.6)
       etc. 36 (18.2)

      Cut off table of Albumin, C-reactive protein (CRP) and White blood cell count (WBC) by Youden index

         Criteria Sensitivity 95% CI* Specificity 95% CI PPV 95% CI NPV 95% CI AUC§ 95% CI
      Albumin (g/dL)
       POD 1 ≤3.050 0.516 0.334~0.694 0.629 0.550~0.701 0.205 0.125~0.315 0.875 0.800~0.926 0.549 0.429~0.669
       POD 2 ≤3.35 0.678 0.485~0.827 0.467 0.390~0.546 0.190 0.125~0.280 0.886 0.797~0.941 0.496 0.387~0.606
       POD 3 ≤3.95 0.968 0.815~0.998 0.178 0.126~0.248 0.180 0.127~0.248 0.968 0.815~0.998 0.493 0.379~0.608
       POD 4 ≤2.85 0.194 0.081~0.380 0.886 0.826~0.928 0.24 0.102~0.455 0.855 0.792~0.903 0.555 0.404~0.707
       POD 5 ≤3.05 0.419 0.251~0.607 0.743 0.668~0.806 0.232 0.134~0.367 0.873 0.805~0.921 0.607 0.490~0.725
      CRP (mg/L)
       POD 1 ≥3.075 0.774 0.585~0.897 0.497 0.419~0.575 0.222 0.15~0.314 0.922 0.841~0.966 0.643 0.551~0.735
       POD 2 ≥10.79 0.419 0.251~0.607 0.755 0.681~0.816 0.241 0.139~0.379 0.875 0.807~0.922 0.610 0.490~0.730
       POD 3 ≥6.87 0.645 0.454~0.802 0.653 0.575~0.724 0.256 0.167~0.37 0.908 0.838~0.951 0.659 0.551~0.767
       POD 4 ≥11.535 0.29 0.149~0.482 0.91 0.854~0.947 0.375 0.196~0.592 0.874 0.813~0.917 0.659 0.514~0.804
       POD 5 ≥4.6 0.452 0.278~0.637 0.719 0.643~0.784 0.23 0.135~0.358 0.876 0.806~0.924 0.637 0.520~0.754
      WBC (/μL)
       POD 1 ≥12,750 0.419 0.251~0.607 0.623 0.544~0.696 0.171 0.977~0.278 0.853 0.774~0.908 0.544 0.425~0.663
       POD 2 ≥9,650 0.387 0.224~0.577 0.713 0.637~0.779 0.2 0.112~0.327 0.862 0.791~0.913 0.563 0.428~0.697
       POD 3 ≥9,050 0.419 0.251~0.607 0.749 0.674~0.811 0.237 0.137~0.373 0.874 0.806~0.922 0.561 0.440~0.682
       POD 4 ≥8,500 0.355 0.198~0.546 0.832 0.765~0.884 0.282 0.156~0.451 0.874 0.810~0.92 0.601 0.455~0.746
       POD 5 ≥7,350 0.484 0.306~0.666 0.713 0.637~0.779 0.238 0.144~0.365 0.881 0.812~0.929 0.595 0.485~0.706

      *CI = Cumulative Index;

      PPV = Positive Predictive Value;

      NPV = Negative Predictive Value;

      §AUC = Area under the ROC curve.

      Univariate analysis of risk factors for surgical site infection

       Variable SSI (%) OR 95% CI P-value


      Yes None Upper Lower
      Sex
       Male 16 (51.6) 84 (50.3) Ref.
       Female 15 (48.4) 83 (49.7) 1.054 0.489 2.269 0.893
      Age (yr)
       <65 15 (48.4) 82 (49.1) Ref.
       ≥65 16 (51.6) 85 (50.9) 1.029 0.478 2.216 0.942
      BMI (kg/m2)
       <25 22 (73.3) 113 (68.9) Ref.
       ≥25 8 (26.7) 51 (31.1) 0.806 0.336 1.931 0.628
      ASA score (1~5)
       1 or 2 26 (83.9) 144 (86.2) Ref.
       3 or 4 5 (16.1) 23 (13.8) 1.204 0.420 3.453 0.730
      Lapascopic/Open surgery
       Lapa 14 (45.2) 112 (67.1) Ref.
       Open 17 (54.8) 55 (32.9) 2.473 1.136 5.381 0.022
      Elective/Emergency operation
       Elect 21 (67.7) 115 (69.3) Ref.
       Emer 10 (32.3) 51 (30.7) 1.074 0.472 2.433 0.865
      Operative time (min)
       <240 8 (25.8) 92 (55.1) Ref.
       ≥240 23 (74.2) 75 (44.9) 3.527 1.492 8.337 0.004
      Stoma creation
       No 21 (67.7) 152 (91) Ref.
       Yes 10 (32.3) 15 (9) 4.825 1.921 12.122 0.001
      Hypertension
       No 14 (45.2) 97 (58.4) Ref.
       Yes 17 (54.8) 69 (41.6) 1.707 0.789 3.693 0.174
      Diabetes mellitus
       No 26 (83.9) 132 (79.5) Ref.
       Yes 5 (16.1) 34 (20.5) 0.747 0.267 2.088 0.578
      Chronic renal failure
       No 27 (87.1) 160 (96.4) Ref.
       Yes 4 (12.9) 6 (3.6) 3.951 1.046 14.926 0.043
      Chronic Respiratory disease
       No 30 (96.8) 162 (97.6) Ref.
       Yes 1 (3.2) 4 (2.4) 1.350 0.146 12.501 0.792

      Univariate analysis of relative risk for surgical site infection to early SSI (ESSI) vs late SSI (LSSI)

      <7 days (ESSI) ≥7 days (LSSI)


      CHR* 95% CI P-value CHR* 95% CI P-value


      Lower Upper Lower Upper
      Female 1.139 0.878 1.139 0.810 1.104 0.906 1.104 0.830
      Year ≥65 1.132 0.884 1.132 0.820 0.711 0.711 1.407 0.460
      BMI ≥25 kg/m2 0.672 0.672 1.489 0.540 1.154 0.867 1.154 0.770
      Stomy formation§ 3.218 0.311 3.218 0.048 2.535 0.394 2.535 0.065
      Emergency operation 0.652 1.534 0.652 0.520 1.258 0.795 1.258 0.620
      Open surgery 2.939 0.340 2.939 0.055 1.299 0.770 1.299 0.570
      Operaitive time ≥240 min 5.943 0.168 5.943 0.020 2.342 0.427 2.342 0.082
      Hyptertension 1.542 0.649 1.542 0.430 1.851 0.540 1.851 0.180
      Diabetes mellitus 0.706 0.706 1.416 0.650 1.068 0.937 1.068 0.910
      Chronic renal failure 1.605 0.623 1.605 0.650 3.897 0.257 3.897 0.026
      Chronic respiratory diseases 3.215 0.311 3.215 0.230 N/A
      POD#1 CRP (mg/L) 1.887 0.584 6.094 0.290 1.799 0.682 4.748 0.240
      WBC (/μL) 1.131 0.375 3.414 0.830 1.065 0.424 2.679 0.890
      Albumin (g/dL) 1.283 0.435 3.781 0.650 1.684 0.689 4.117 0.250
      POD#2 CRP 1.747 0.582 5.246 0.320 1.008 0.366 2.778 0.990
      WBC 0.745 0.209 2.654 0.650 0.885 0.325 2.411 0.810
      Albumin 0.766 0.261 2.253 0.630 1.609 0.638 4.060 0.310
      POD#3 CRP 1.021 0.340 3.061 0.970 1.538 0.630 3.753 0.340
      WBC 0.737 0.208 2.608 0.640 0.873 0.323 2.359 0.790
      Albumin 0.240 0.082 0.704 0.009 4.254 0.560 32.298 0.160
      POD#4 CRP 2.659 0.781 9.057 0.120 0.473 0.066 3.370 0.450
      WBC 1.965 0.629 6.136 0.250 0.507 0.121 2.122 0.350
      Albumin N/A 1.058 0.245 4.565 0.940
      POD#5 CRP N/A 0.724 0.241 2.171 0.560
      WBC 0.426 0.096 1.884 0.260 1.381 0.554 3.445 0.490
      Albumin 0.231 0.031 1.732 0.150 1.317 0.510 3.403 0.570

      *CHR = Cause specific hazard model;

      N/A = not available;

      P-value by Inverse probability censoring weighting (IPCW);

      §Both Ileostomy and Colostomy are included.

      Multivariate analysis of relative risk for surgical site infection to early SSI (ESSI) vs late SSI (LSSI)

      <7 days (ESSI) ≥7 days (LSSI)


      CHR* 95% CI P-value CHR* 95% CI P-value


      Lower Upper lower upper
      Operaitive time ≥240 min 9.794 1.804 53.171 0.008
      POD#3 of Albumin 0.096 0.025 0.369 0.001
      POD#4 of CRP 12.634 4.195 38.050 0.000  

      *CHR = Cause specific hazard model;

      P-value by Inverse probability censoring weighting (IPCW).

      Table 1 Patient characteristics

      Table 2 Operative characteristics

      Table 3 Cut off table of Albumin, C-reactive protein (CRP) and White blood cell count (WBC) by Youden index

      CI = Cumulative Index;

      PPV = Positive Predictive Value;

      NPV = Negative Predictive Value;

      AUC = Area under the ROC curve.

      Table 4 Univariate analysis of risk factors for surgical site infection

      Table 5 Univariate analysis of relative risk for surgical site infection to early SSI (ESSI) vs late SSI (LSSI)

      CHR = Cause specific hazard model;

      N/A = not available;

      P-value by Inverse probability censoring weighting (IPCW);

      Both Ileostomy and Colostomy are included.

      Table 6 Multivariate analysis of relative risk for surgical site infection to early SSI (ESSI) vs late SSI (LSSI)

      CHR = Cause specific hazard model;

      P-value by Inverse probability censoring weighting (IPCW).


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