Thrombocytosis Is a Risk Factor for Surgical Site Infections after Colon Resection: A Prospective Observational Study

Abstract

Background:

Colon operations have the highest rate of surgical site infections (SSI) among all general surgical procedures. The aim of this study was to identify the risk factors associated with the development of SSI after colon resection.

Patients and Methods:

A prospective study was conducted including patients over 18 years of age who underwent colon resection at a tertiary center. Data concerning peri-operative parameters were collected. Uni-variable and multi-variable statistics were employed. For identifying the potential risk factors, we used odds ratio (OR) with 95% confidence interval (CI).

Results:

A total of 44 SSI were recorded from a total patient cohort of 300, yielding a rate of 14.7%. The SSIs were categorized into incisional (n = 37, 77.1%), deep (n = 4, 8.3%), and organ/space SSI (n = 11, 22.9%). Escherichia coli was the most common culprit micro-organism. Seventeen (35.4%) infections were poly-microbial. The following factors were found to be associated with the development of SSI after colon resection: male gender (OR: 2.01, 95% CI: 1.03–3.90, p = 0.03), age ≥60 years (OR: 3.18, 95% CI: 1.46–6.89, p = 0.003), pre-operative anemia (hemoglobin <12.5 g/dL) (OR: 4.61, 95% CI: 2.37–8.98, p = < 0.0001), leukocytosis (white blood cell count ≥10,100/mm³) (OR: 0.04, 95% CI: 0.02–0.11, p < 0.0001), thrombocytosis (thrombocytes ≥450,000/mm³) (OR: 39.35, 95% CI: 10.69–144.86, p < 0.0001), peritoneal contamination (OR: 4.11, 95% CI: 2.12–7.97, p < 0.0001).

Conclusion:

In addition to other known risk factors (male gender, age over 60 years, pre-operative anemia, leukocytosis, gross peritoneal contamination), this study identified thrombocytosis as a new risk factor for SSI after colon resection.

Colon surgery is associated with one of the highest rates of surgical site infections (SSI). The occurrence of SSI is in 15%–30% of patients undergoing colon operations, accounting for one-fifth of all hospital-acquired infections, generating up to $10 billion in direct medical costs in the United States alone [1 –3]. The SSIs are associated with re-admission and a 3% mortality rate adding to the healthcare costs [4 –6].

Various risk factors are associated with the development of SSI. These are dichotomized into patient-related and operation-related. Patient-related factors may be further subdivided into modifiable and non-modifiable. Modifiable factors include high body mass index, type 2 diabetes mellitus, alcohol abuse, and smoking. Non-modifiable factors comprise male gender, advanced age, hypoalbuminemia, immunosuppression, recent radiotherapy, and a history of SSI. Operation-related factors refer to laparotomy, emergency operations, major complex surgical procedures, longer operative time, intra-operative blood transfusion [6,7 –12,17 –19].

This aim of this study was to identify the risk factors with the development of SSI after colon operations in a tertiary center.

Patients and Methods

Study design

This is an Institutional Review Board-approved prospective observational study (Registration Number 27.621/05.11.2015). The reporting was performed according to the STROBE statement [17].

Settings

This study was performed over a 13-month period between May 17, 2015 and May 31, 2016 in the department of general surgery of a tertiary referral hospital. The study ran for a year, and there was a minimum 30-day follow-up.

Inclusion criteria

All consecutive adult patients presenting at Bucharest Emergency Hospital with the following criteria were candidates for inclusion in the study: Colon resection for either a benign or malignant indication, age 18 years or above, and informed consent.

Exclusion criteria

Patients who underwent abdominal perineal resection were excluded from the study.

Data collection

Data concerning demographics, pre-operative blood test results, intra-operative parameters, and post-operative follow-up were collected. The SSIs were documented and recorded.

Variables

A total of 24 variables were studied as potential risk factors, categorized into demographics, pre-operative, intra-operative, and post-operative factors. Demographic factors referred to gender and age. Pre-operative factors encompassed patient characteristics such as co-morbidities objectified by the American Society of Anesthesiologists score, smoking status, type of admission, surgical indication, tumor features, vital signs, and pre-operative blood test results. Tumor features refer to location (left/right) and the presence or absence of distant metastases. Pre-operative blood test results comprised hemoglobin levels, leukocyte and thrombocyte counts, and glycemia. Vital signs included blood pressure, heart rate, and oxygen saturation. Intra-operative factors spanned operation type (major/major complex), operation character (elective/urgent/emergency), type of anastomosis, operative time, peritoneal contamination, and intra-operative blood transfusion. Tumor grade was the only post-operative factor evaluated.

Definitions

The SSIs were defined according with the Centers for Disease Control and Prevention guidelines [18]. Because of local constraints, Enhanced Recovery after Surgery (ERAS) protocols were not used. Antibiotic prophylaxis was employed for elective cases (first generation intravenous cephalosporin and metronidazole). In cases with gross contamination, antibiotherapy was used first empirically and then guided accordingly to the antibiogram.

Emergency operation was defined as a surgical procedure that commenced within two hours of admission, while an urgent surgical procedure took place within four hours of admission. Major complex operation was defined as multi-visceral resection. Gross fecal contamination was defined as the presence of fecal material noticed on entrance into the peritoneal cavity that was not the result of spillage during the operation. Third quartile operation time was defined as operative time exceeding 180 minutes.

Outcomes

The primary outcome of this study was the development of SSI. Secondary outcomes included re-operation, in-hospital death, length of stay, and re-admission. We have analyzed the development of post-operative SSI prospectively and the follow-up of outpatient SSI on the basis of re-admission.

Statistical analysis

A univariable statistical analysis was performed. The categoric data were expressed as counts and percentages, while continuous data were presented as means and standard deviation. Chi-square and subsequent p value were calculated for parametric variables. To evaluate potential risk factors, odds ratio (OR) with 95% confidence interval (CI) was calculated. Statistical significance was set at p < 0.05.

Results

Between May 17, 2015 and May 31, 2016, a total of 35,933 patients were admitted to one of the three general surgical departments of a tertiary center. Of these 35,933 admissions, 300 (0.8%) patients underwent colon resection: 147 (49%) males and 153 (51%) females. The mean age of participants was 66.8 ± 13.4 years (range: 19–92 years—Table 1).

Table 1.

Pre-operative Parameters

Parameter	SSI group (n = 44)	No SSI group (n = 256)	Odds ratio	95% CI	p
Gender
Males	28 (63.6%)	119 (46.5%)	2.01	1.03–3.90	0.03
Females	16 (36.4%)	137 (53.5%)	2.01	1.03–3.90	0.03
Age
<60 y	12 (27.3%)	27 (10.5%)	3.18	1.46–6.89	0.003
>60 y	32 (72.7%)	229 (89.5%)	3.18	1.46–6.89	0.003
Smoking
Yes	10 (22.7%)	43 (16.8%)	1.45	0.66–3.17	0.34
No	34 (77.3%)	213 (83.2%)	1.45	0.66–3.17	0.34
Type of admission
Elective	38 (86.3%)	237 (89.5%)	0.50	0.19–1.35	0.17
Emergency	6 (13.7%)	19 (10.5%)	0.50	0.19–1.35	0.17
Surgical indication
Malignant	32 (72.7%)	229 (89.5%)	0.37	0.16–0.85	0.01
Benign	12 (27.3%)	27 (10.5%)	0.37	0.16–0.85	0.01
Tumor location
Right	14 (40.9%)	136 (53.1%)	0.40	0.18–0.85	0.01
Left	18 (59.1%)	120 (47.9%)	0.40	0.18–0.85	0.01
Tumor grade
G1–G2	22 (68.8%)	207 (80.9%)	0.52	0.23–1.17	0.11
G3–G4	10 (31.2%)	49 (19.1%)	0.52	0.23–1.17	0.11
Hb level
<12.5 g/dL	26 (58.1%)	61 (23.8%)	4.61	2.37–8.98	<0.0001
>12.5 g/dL	18 (40.9%)	195 (76.2%)	4.61	2.37–8.98	<0.0001
WBC count
<4,000/mm³	22 (50%)	244 (95.3%)	0.04	0.02–0.11	<0.0001
>10,000/mm³	22 (50%)	12 (4.7%)	0.04	0.02–0.11	<0.0001
Thrombocyte count
Thrombocytosis (>450,000)	14 (31.8%)	3 (98.8%)	39.35	10.69–144.86	<0.0001
Normal (150,000–449,000)	30 (68.2%)	253 (1.2%)	39.35	10.69–144.86	<0.0001
Thrombocyte count
Thrombocytopenia (<150,000)	0 (0%)	5 (2%)	0.51	0.02–9.45	0.65
Normal (150,000–449,000)	44 (100%)	251 (98%)	0.51	0.02–9.45	0.65
Glycemia
Hyperglycemia (>127)	12 (27.3%)	53 (20.7%)	1.43	0.69–2.97	0.33
Normoglycemia (70–126)	32 (72.7%)	203 (79.2%)	1.43	0.69–2.97	0.33
SBP
<90 mm Hg	1 (2.3%)	5 (2%)	1.16	0.07–6.18	0.72
90–139 mm Hg	43 (97.7%)	251 (98%)	1.16	0.07–6.18	0.72
SBP
<140 90 mm Hg	17 (38.6%)	102 (39.8%)	0.95	0.49–1.83	0.87
90–139 mm Hg	27 (61.4%)	154 (60.2%)	0.95	0.49–1.83	0.87
HR
60–99 bpm	40 (90.1%)	222 (86.7%)	1.53	0.51–4.55	0.44
>100 bpm	4 (9.9%)	34 (13.3%)	1.53	0.51–4.55	0.44
SpO₂
≤94%	1 (2.3%)	4 (98.4%)	1.46	0.15–13.42	0.73
95–100%	43 (97.7%)	252 (1.6%)	1.46	0.15–13.42	0.73
BMI
18.5–24.9 kg/m²	2 (4.5%)	40 (84.3%)	0.25	0.05–1.10	0.06
>30 kg/m²	42 (95.5%)	216 (15.6%)	0.25	0.05–1.10	0.06
Temperature
>38°C	10 (22.7%)	18 (18%)	3.88	1.65–9.12	0.0018
37.6–37.9°C	34 (77.3%)	238 (93%)	3.88	1.65–9.12	0.0018
Distant metastases
Present	8 (18.2%)	62 (75.7%)	0.69	0.30–1.57	0.38
Absent	36 (81.2%)	194 (24.3%)	0.69	0.30–1.57	0.38

SSO = surgical site infection; CI = confidence interval; Hb = hemoglobin; WBC = white blood cell; SBP = systolic blood pressure; HR = heart rate; SpO₂ = peripheral capillary oxygen saturation; BMI = body mass index.

A total of 44 SSI were recorded in 44 patients during their hospital stay, yielding a rate of 14.7%. The SSIs were categorized into superficial SSI (n = 33, 75%), deep SSI (n = 4, 9.1%), and organ/space SSI (n = 7, 15.9%). Incisional SSI was the predominant type of SSI, accounting for 75% of all SSI. Deep SSI developed in proximity of the drainage tubes, while organ/space SSIs consisted of intra-abdominal abscesses located in various locations such as parietocolic (n = 4), peri-hepatic (n = 2), and peri-splenic (n = 1).

Of the 44 SSI, 17 (38.6%) were documented as poly-microbial. The following pathogens were isolated from cultures harvested from the 44 SSIs, in descending order: Escherichia coli (n = 17, 38.6%), Klebsiella spp. (n = 10, 22.7%), Enterococcus spp. (n = 5, 11.4%), Pseudomonas spp. (n = 4, 9.1%), Staphylococcus epidermidis (n = 4, 9.1%), Proteus spp. (n = 2, 4.5%), and Aeromonas sobria (n = 2, 4.5%) (Fig. 1).

FIG. 1.

Bacterial isolates from 44 surgical site infections. E. coli = Escherichia coli; S. epidermidis = Staphylococcus epidermidis; A. sobria = Aeromonas sobria.

The average length of stay was significantly prolonged for patients in whom an SSI developed compared with patients without a SSI: 24 ± 9.32 days versus 15.7 ± 9.32 days. The length of stay is higher even for patients without SSI, this being the local practice. Re-operation (n = 24, 8%) was also more frequent for patients who incurred a SSI: 14 versus 10 re-operations for patients without a SSI (OR: 11.48, 95% CI: 4.68–28.11, p < 0.0001). A total of 26 deaths were reported throughout this study, yielding a mortality rate of 8.7%. Seven (26.9%) deaths were recorded in patients in whom a SSI developed, while 19 patients died without development of a SSI (73.1%) (OR: 2.35, 95% CI: 0.92–6.00, p = 0.07). Four of the 44 (9.1%) patients in whom a SSI developed were re-admitted, in comparison with 16 patients (6.25%) in whom a SSI did not develop SSI (OR: 1.50, 95% CI: 0.47–4.71 p = 0.48).

Seven risk factors associated with SSI occurrence were identified—six pre-operative and one intra-operative (Table 2). Male gender was more prone to development of a SSI (OR: 2.01, 95% CI: 1.03–3.90, p = 0.03), age ≥60 years (OR: 3.18, 95% CI: 1.46–6.89, p = 0.003). Anemia (Hb <12.5 g/dL) (OR: 4.61, 95% CI: 2.37–8.98, p = < 0.0001), leukocytosis (WBC ≥10,100/mm³) (OR: 0.04, 95% CI: 0.02–0.11, p < 0.0001), and thrombocytosis (thrombocytes ≥450,000/mm³) (OR: 39.35, 95% CI: 10.69–144.86, p < 0.0001) were correlated with the development of SSI. Also, patients operated for malignancy were more prone to have a SSI compared with those with benign pathology (p < 0.01, 95% CI: 0.16–0.85—Table 1 and Table 3). Peritoneal contamination was another important risk factor for development of SSI (OR: 4.11, 95%CI: 2.12–7.97, p < 0.0001). Interestingly, emergency operation was not found to be a risk factor for SSI.

Table 2.

Intra-Operative Parameters

Parameter	SSI group (n = 44)	No SSI group (n = 256)	Odds ratio	95% CI	p
Operation character
Elective	37 (84.1%)	206 (80.4%)	1.46	0.61–3.45	0.38
Urgent/emergency	7 (15.9%)	50 (19.6%)	1.46	0.61–3.45	0.38
Operation type
Major	26 (59.1%)	181 (70.3%)	0.59	0.00–1.15	0.12
Major complex	18 (40.9%)	75 (29.7%)	0.59	0.00–1.15	0.12
Anastomosis
Manual	34 (77.3%)	199 (77.7%)	0.97	0.45–2.09	0.94
Mechanical	10 (22.7%)	57 (22.3%)	0.97	0.45–2.09	0.94
Operative time
<3rd quartile (>180 min)	23 (52.3%)	148 (56.6%)	0.80	0.42–1.52	0.50
>3rd quartile (<180 min)	21 (47.7%)	108 (43.4%)	0.80	0.42–1.52	0.50
ASA class
<3	8 (18.2%)	55 (21.5%)	0.81	0.35–1.84	0.61
≥3	36 (81.8%)	201 (78.5%)	0.81	0.35–1.84	0.61
Peritoneal contamination
Present	25 (56.8%)	62 (75.8%)	4.11	2.12–7.97	<0.0001
Absent	19 (43.2%)	194 (24.2%)	4.11	2.12–7.97	<0.0001
Blood transfusion
Required	20 (45.5%)	104 (40.6%)	1.21	0.63–2.31	0.54
Not required	24 (54.5%)	152 (59.4%)	1.21	0.63–2.31	0.54

SSI = surgical site infection; CI = confidence interval; ASA = American Society of Anesthesiologists.

Table 3.

Post-Operative Parameters

Parameter	SSI group (n = 44)	No SSI group (n = 256)	Odds ratio	95% CI	p
Tumor grade
G1–G2	22 (68.8%)	207 (80.9%)	0.52	0.23–1.17	0.11
G3–G4	10 (31.2%)	49 (19.1%)	0.52	0.23–1.17	0.11
Length of stay	24 ± 9.32 days	15.7 ± 9.32 days	−	−	−

SSI = surgical site infection; CI = confidence interval.

Discussion

The SSIs are the most significant source of morbidity after colon operations. The present study examined both the incidence as well as the potential risk factors of SSI after colon resection. This study, based on prospective data collection, determined that the incidence of SSI after colon resection was 14.7%, being comparable with the data from the literature [1,7,8].

The majority of SSI that occur after colon surgical procedures are poly-microbial in nature. This was not the case in our study (n = 17, 38.6%), however. In terms of pathogens, E. coli is the most common culprit microorganism in SSI after colon operation, followed by Bacteroides fragilis [9,19,20]. Indeed, E. coli was the most frequently isolated bacterium from wounds in our study (n = 17, 38.6%); however, interestingly enough, B. fragilis was not isolated from any of the SSI. The explanation of the latter succumbs to the delayed transportation of isolates to the laboratory, during which the aerobe micro-organisms died. Four deep SSI developed throughout this study. It is possible that prolonged use of drainage tubes in these patients had an important role in the occurrence of deep SSI.

Superficial SSI was the most common type of SSI (75% of all registered SSI). In 2011, Ho et al. [10] conducted a study comparing the risk factors for incisional and organ/space SSI in a cohort of 1082 patients who underwent colon surgery. A SSI developed in 146 (22.5%) patients. Of the 146 SSI, 82 (56.2%) were incisional, while 64 (43.8%) were organ/space. Ho et al. [10] demonstrated that the morbidity attributed by organ/space infections surpasses that of incisional infections in terms of length of stay and re-admission.

Of the seven risk factors identified in this study, six are consistent with published surgical literature (male gender, advanced age, pre-operative anemia, leukocytosis, fever on admission, and peritoneal contamination) [11 –16,21]. Pre-operative thrombocytosis negatively impacts the disease free-survival interval of colorectal cancer patients [22,23]. Our data, however, show that thrombocytosis is also a risk factor for SSI after colon resection. We hypothesize that pre-existing thrombocytosis can play a role in the development of SSI through the inflammatory pathways, where thrombocytosis may present earlier than leukocytosis.

With regard to the secondary outcomes of this study, re-operation was more common in patients in whom SSI developed (14/24 patients, 58.3%) (OR: 11.48, 95% CI: 4.68–28.11, p < 0.0001). In a study of 10,882 patients who underwent colon resection over a seven-year period, Wick et al. [12] had a re-operation rate of 43.6% in patients with SSI, while only 24.1% of patients in whom SSI did not develop underwent re-operation. Nine percent of patients in whom SSI developed were re-admitted, in comparison with 6.3% of patients in whom SSI did not develop. Although re-admission was more frequent in the SSI group, the authors failed to demonstrate a statistically significant correlation (OR: 1.50, 95% CI: 0.47–4.71 p = 0.48).

In a retrospective study of 67,595 open colectomies, open left hemicolectomy emerged as the procedure with the highest risk of development of a SSI [24]. These results were obtained after a logistic regression model was developed and adjusted for age, gender, and co-morbidities [22].

Nakamura et al. [25] recently published a study evaluating risk factors associated with SSI after laparoscopic colectomy for malignancy. From a total of 670 patients, SSI developed in 27 (4%). In addition to obtaining an incidence of SSI at least four times lower than that of open colectomy, notably the study recorded no surgery-related deaths. In our study, laparoscopy was seldom employed because of economic constraints.

In this study, we have identified thrombocytosis as a novel risk factor associated with the development of SSI after colon resection. Further, the study population was diverse, including colectomies for both malignant and benign indications in addition to both elective and emergency surgical procedures.

A limitation of this study was the insufficient number of laparoscopic colectomies, making the comparison irrelevant. Also, unfortunately, because of local constraints, ERAS protocols are still not implemented.

Conclusion

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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