European Journal of Cardiovascular Medicine

A Surgical Site Infection is an infection that occurs after surgery in the part of the body where the surgery took place, SSI can sometimes be superficial infections involving skin only or can include structures below skin, organs or implanted material.

 SSI are the 2^nd most common type of adverse events occurring in a hospitalized patient following surgery and are one of the most common surgical complication. SSI are responsible for an increased economic burden to health care systems including additional postoperative hospital duration and costs. Identifying predictive factors such as hypocholesterolemia can help in risk stratification and improving patient outcomes.

According to the US Centers for Disease Control (CDC) National Nosocomial Infections Surveillance system, SSI is the third most frequent nosocomial infection, accounting for 14%-16% of infections among hospitalized patients and 38% of infections in surgical patients. The surgical site infection rates for laparotomy procedures are still higher i.e., up to 20% (range from 3.4% - 36.1% in different studies).

In India, among tertiary care hospitals, incidence of SSI is 2.06% and 16.16% in MIS (minimal invasive surgery) and OS (open surgery) respectively.

Although malnutrition can cause major problems, as many as 50% of cases of pre-existing malnutrition go undetectable in the hospital population; a probable explanation is that visible symptoms of malnutrition only show in severe cases.

Of brain, nerve cells, cell membranes, bile, which aids the body in absorbing fats and fat-soluble vitamins, cholesterol is a basic component. Levels of cholesterol, its fractions (high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) also represent nutritional status.

Malnutrition is an important secondary cause and is present in majority of patients presenting in a government setup in India. In this study we find the association of the incidence of SSI in relation to Total cholesterol levels in 165 patients undergoing emergency and elective laparotomies in Department Of General Surgery, KMCRI, Hubballi.

Southampton Wound Assessment Scale

• Purpose

To classify the severity of wound complications, particularly in surgical site infections (SSIs).

• Grading

The Southampton scale grades the severity of wound infection based on the presence and severity of signs

 like erythema, bruising, discharge, and pus.

• Grades

1. Grade 0: Normal healing.
2. Grade 1: Normal healing with mild erythema/bruising.
3. Grade 2: Erythema plus other signs of inflammation.
4. Grade 3: Haemoserous discharge.
5. Grade 4: Pus or purulent discharge.

 Grade 1                           Grade 2

Grade 3                       Grade 4                   Grade 5 

Application

Used to assess the severity of wound complications and to monitor the progress of wound healing. 

Cholesterol in Wound Healing

Almost all nucleated cells (including arterial walls) can synthesise cholesterol. It is widely distributed in the body. It is the most important animal steroid from which other steroid compounds are formed. Cholesterol is widely distributed in animal tissues. It is absent in prokaryotes. Implants, cholesterol is absent ^[4]

Clinical Significance of Cholesterol: The level of cholesterol in blood is related to the development of atherosclerosis and myocardial infarction. Abnormality of cholesterol metabolism may lead to cardiovascular accidents and heart attacks. ^[21]

Cholesterol and Wound Healing

Modulating Inflammation 

Cholesterol influences the inflammatory response, which is a crucial part of the wound healing process. 

Angiogenesis 

Cholesterol is involved in angiogenesis, the formation of new blood vessels, which is essential for delivering oxygen and nutrients to the wound site. 

Tissue Repair

Cholesterol plays a role in the organization of lipid rafts, which are involved in cell signaling during wound closure. ²⁴

Impact of High Cholesterol

Reduced Blood Flow

High cholesterol levels can lead to plaque buildup in arteries, restricting blood flow and oxygen delivery to the wound site.

Delayed Wound Closure

Impaired blood flow and oxygen delivery can lead to delayed wound closure and increased risk of complications.

Increased Inflammation

• High cholesterol can contribute to systemic inflammation, which can impair the immune response and prolong the inflammatory phase of wound healing. 
• HDL Cholesterol and Wound Healing
• Higher HDL (good) cholesterol levels have been associated with better wound healing. 
• LDL Cholesterol and Wound Healing
• High levels of LDL (bad) cholesterol can impair angiogenesis and delay wound healing. ^[21]

Cholesterol Deficiency

Cholesterol deficiency can lead to dryness and other skin problems Hypolipidemia (hypocholesterolemia - total cholesterol <150 mg/dl) is an independent predictor of clinical outcome in critically ill patients.

There is strong evidence that patients who exhibit signs of malnutrition are more likely to suffer complications and mortality than those who have enough nutritional reserves.

Cholesterol in different phases of wound healing:

Cholesterol

Cholesterol plays a crucial role in wound healing, influencing inflammation, angiogenesis (new blood vessel formation), and tissue repair, with high levels potentially hindering the process by restricting blood flow and oxygen delivery. 

Angiogenesis

Cholesterol is involved in angiogenesis, the formation of new blood vessels, which is essential for delivering oxygen and nutrients to the wound site. 

Tissue Repair

Cholesterol plays a role in the organization of lipid rafts, which are involved in cell signaling during wound closure. 

Objectives of the study

To determine the relationship of serum cholesterol and serum albumin with surgical site infections.

Source of data: The study includes operated cases of exploratory laparotomies (elective and emergencies) done for patients in all units of Department of General Surgery KIMS Hubballi. Study design A prospective observational study Ethical clearance This study was approved by Ethical Committee of the institution on 30-3-2023 registration number - ECR/486/Inst/KA/2013/RR-16 Sample size calculation A final sample size of 130 patients who undergo elective or emergency laparotomy in KIMS, Hubballi will be included in the study. Inclusion criteria Emergency and exploratory laparotomies in all units of Department of General Surgery, KMCRI, Hubballi. Exclusion criteria • Patients with immunocompromised states like HIV positive, on corticosteroids, Diabetes mellitus. • Pregnant females • Patients who lost follow up • Patients more than 70 years and less than 12 years Statistical techniques: A simple descriptive statistics was applied. Method of Collection of Data Informed consent was obtained from all patients participating in the study. Preoperative shaving was done in all cases. Antibiotic prophylaxis of Inj.Ceftriaxone1g i.v. was given half an hour before the skin incision and repeated 6 and 12 hours. Strict aseptic precautions were taken to minimize the chances of SSI including standard preparation of a patient before incision like spirit povidone iodine spirit sequence, irrigation with normal saline and povidone iodine solution before closing the wound, changing of gloves when handling a mesh(if indicated in the procedure).Patients are monitored till the date of discharge.

Data contains measurement on 165 patients

Statistical Analysis

Data were entered into Microsoft Excel and statistical analysis was carried out in SPSS software version 17.0. Qualitative variables like age categories, total cholesterol, and HDL levels on Day 0, 3 and 5and presence of surgical site infection were presented as frequency and percentages. Quantitative variables like serum total cholesterol, and HDL levels on Day 0, 3 and 5 across participants with and without SSI were compared with independent t test and were presented as mean and standard deviation. Association of categories of serum total cholesterol, and HDL levels on Day 0, 3 and 5 across participants with and without SSI were done with chi squared test. Pie charts and bar diagrams were used for graphical representation of data. A ‘p’ value of less than 0.05 was considered as statistically significant.

The data collected were analyzed and the details are given under appropriate heads.

Analysis and Interpretation of data:

Distribution of sample according to age: The details of distribution of sample according to age is given in Table 1

Table 1: Distribution of sample according to age

The study sample includes participants from a wide range of ages, from 13 to over 69 years. The distribution is fairly balanced, with the largest proportion of participants being in the >50 years age group, followed closely by the 13-30 years age group, and then the 31-50 years age group.

Fig 1: Distribution of sample according to age

Table 4: Distribution of sample based on Serum total cholesterol and HDL

The table 2 presents the distribution of patients based on their serum total cholesterol, and HDL levels at Day 0, Day 3, and Day 5. It shows the number and percentage of subjects falling into different categories for each parameter and time point. For total cholesterol, the prevalence of hypocholesterolemia decreased over time, from 50.3% at Day 0 to 37.0% at Day 5. The percentage of patients with normal total cholesterol levels increased from 43.6% at Day 0 to 61.2% at Day 5. It is also found that hypercholesterolemia was present in a small percentage of patients, decreasing from 6.1% at Day 0 to 1.8% at Day 5.

A large majority of the patients had hypocholesterolemia for HDL across all time points: Day 0 (85.5%), Day 3 (84.9%), and Day 5 (82.4%). The percentage of patients with normal HDL levels remained low and increased slightly from Day 0 (14.5%) to Day 5 (17.6%).

The graphical representations of distribution of patients based on Serum total cholesterol and HDL are given below-

Fig 2: Distribution of patients based on Total Cholesterol

Fig 3: Distribution of patients based on HDL

Presence of Surgical Site Infection (SSI)    

The data collected were analyzed and the details are given in Table 3.

Table 3: Presence of Surgical Site Infection (SSI)

The table presents the distribution of patients based on the presence or absence of Surgical Site Infection (SSI). It is seen that 28.5% of the patients developed SSI and 71.5% did not develop SSI.

The graphical representation of Presence of Surgical Site Infection is shown below

Fig 4: Presence of Surgical Site Infection

Association of Total cholesterol on day 0 with SSI

The data collected were analyzed and the details are given in table 5

Table 5: Association of Total cholesterol on day 0 with SSI

This table examines the relationship between total cholesterol levels on Day 0 and the subsequent development of surgical site infection (SSI). It compares the number and percentage of patients with hypocholesterolemia, normal cholesterol, and hypercholesterolemia levels in those who developed SSI and those who did not.

Higher Hypocholesterolemia in SSI Group: Out of 83 patients who had hypocholesterolemia on day 0, 40 of them have developed SSI. Alao, a higher proportion of patients who developed SSI had hypocholesterolemia on Day 0 (40 out of 47, 85.2%) compared to those who did not develop SSI (43 out of 118, 36.4%).

Lower Normal Cholesterol in SSI Group: Only 6 patients who developed SSI had normal cholesterol levels on Day 0 (12.7%), compared to 66 patients (56%) in the group that did not develop SSI.

Low Hypercholesterolemia in SSI Group: Only 1 patient who developed SSI had hypercholesterolemia on Day 0 (2.1%), compared to 9 patients (7.6%) in the group that did not develop SSI.

Statistical Significance: The P-value is <0.001, indicating that this association between Day 0 total cholesterol levels and SSI is highly statistically significant.

The table shows a strong association between hypocholesterolemia on Day 0 and the development of SSI. Patients with low total cholesterol levels at the start of the study had a significantly higher risk of developing a surgical site infection. Normal and high cholesterol levels were more protective against SSI.

Fig 5: Association of Total cholesterol on day 3 with SSI

Table 6: A significantly higher proportion of patients with hypocholesterolemia on postoperative day 3 developed surgical site infections compared to those with normal or high cholesterol levels (P < 0.001).

This table examines the relationship between total cholesterol levels on Day 3 and the subsequent development of surgical site infection (SSI). It compares the number and percentage of patients with hypocholesterolemia, normal cholesterol, and hypercholesterolemia levels in those who developed SSI and those who did not.

Higher Hypocholesterolemia in SSI Group: Among 69 patients with hypocholesterolemia, 40 of them developed SSI on day 3. Also, a higher proportion of patients who developed SSI had hypocholesterolemia on Day 3 (40 out of 47, 85.1%) compared to those who did not develop SSI (29 out of 118, 24.6%).

Lower Normal Cholesterol in SSI Group: Only 7 patients who developed SSI had normal cholesterol levels on Day 3 (14.9%), compared to 84 patients (71.2%) in the group that did not develop SSI.

No Hypercholesterolemia in SSI Group: No patients who developed SSI had hypercholesterolemia on Day 3 (0 out of 47, 0%), compared to 5 patients (4.2%) in the group that did not develop SSI.

Statistical Significance: The P-value is <0.001, indicating that this association between Day 3 total cholesterol levels and SSI is highly statistically significant.

The table shows a strong association between hypocholesterolemia on Day 3 and the development of SSI. Patients with low total cholesterol levels on Day 3 had a significantly higher risk of developing a surgical site infection. Normal and high cholesterol levels on Day 3 were protective against SSI.

Fig 6: Total Cholesterol on Day 3 and SSI

Table 7: Association of Total cholesterol on day 5 with SSI

This table examines the relationship between total cholesterol levels on Day 5 and the subsequent development of surgical site infection (SSI). It compares the number and percentage of patients with hypocholesterolemia, normal cholesterol, and hypercholesterolemia levels in those who developed SSI and those who did not.

Higher Hypocholesterolemia in SSI Group: Out of 61 patients with hypocholesterolemia, 46 of them developed SSI. Higher proportion of patients who developed SSI had hypocholesterolemia on Day 5 (40 out of 47, 85.2%) compared to patients who did not develop SSI (43out of 118, 36.4%).

Lower Normal Cholesterol in SSI Group: Only 6 patients who developed SSI had normal cholesterol levels on Day 5 (12.7%), compared to 66 patients (56%) in the group that did not develop SSI.

Hypercholesterolemia in SSI Group: One patient who developed SSI had hypercholesterolemia on Day 5 (1 out of 47, 2.1%), compared to 9 patients (7.6%) in the group that did not develop SSI.

Statistical Significance: The P-value is <0.001, indicating that this association between Day 5 total cholesterol levels and SSI is highly statistically significant.

The table shows a strong association between hypocholesterolemia on Day 5 and the development of SSI. Patients with low total cholesterol levels on Day 5 had a significantly higher risk of developing a surgical site infection. Normal and high cholesterol levels on Day 5 were protective against SSI.

Fig 6: Total Cholestrol on Day 5 and SSI

Table 8: Comparison of Serum total cholesterol on day 0, 3, 5 and SSI

Fig 7: Total Cholestrol and SSI

Table 9: Association of HDL cholesterol on day 0 with SSI

Among 141 patients with low serum HDL, 47 developed SSI. A higher proportion of patients who developed SSI had low serum HDL on Day 0 (47 out of 47, 100%) compared to those who did not develop SSI (94 out of 118, 79.7%). No patients who developed SSI had normal HDL cholesterol levels on Day 0 (0 out of 47, 0%), compared to 24 patients (20.3%) in the group that did not develop SSI. The P-value is 0.001, indicating that this association between Day 0 HDL cholesterol levels and SSI is statistically significant. The table shows a strong association between hypocholesterolemia on Day 0 and the development of SSI. Patients with low HDL cholesterol levels at the start of the study had a significantly higher risk of developing a surgical site infection.

.

Fig 8: HDL on Day 0 and SSI

Table 10: HDL Cholesterol on Day 3 and SSI

Among 140 patients with low serum HDL on day 3, 46 of them had developed SSI. A higher proportion of patients who developed SSI had hypocholesterolemia on Day 3 (46/47, 97.9%) compared to those who did not develop SSI (94/118, 79.7%). Only 1 patient who developed SSI had normal HDL cholesterol levels on Day 3 (2.1%), compared to 24 patients (20.3%) in the group that did not develop SSI. The P-value is 0.003, indicating that this association between Day 3 HDL cholesterol levels and SSI is statistically significant. The table shows a strong association between hypocholesterolemia on Day 3 and the development of SSI. Patients with low HDL cholesterol levels at this time point had a significantly higher risk of developing surgical site infection.

Fig 9: HDL on day 3 and SSI

Table 11: HDL cholesterol on day 5 and SSI

Out of 136 patients who had low serum HDL on day 5, 45 of them developed SSI. A higher proportion of patients who developed SSI had hypocholesterolemia on Day 5 (45/ 47, 95.7%) compared to those who did not develop SSI (91/118, 77.1%). Only 2 patients who developed SSI had normal HDL cholesterol levels on Day 5 (4.3%), compared to 27 patients (22.9%) in the group that did not develop SSI. The P-value is 0.005, indicating that this association between Day 5 HDL cholesterol levels and SSI is statistically significant. The table shows a strong association between low serum HDL levels on Day 5 and the development of SSI. Patients with low HDL cholesterol levels at this time point had a significantly higher risk of developing a surgical site infection.

Fig 10: HDL on Day 5 and SSI

 Table 12: Comparison of Serum HDL on day 0, 3, 5 and SSI

Fig 11: HDL and SSI

Association of serum Total cholesterol with SSI

It is found that among 83 patients with hypocholesterolemia 40 has developed SSI on day 0. Also a higher proportion of patients who developed SSI had hypocholesterolemia on Day 0 (40 out of 47, 85.2%) compared to those who did not develop SSI (43 out of 118, 36.4%). Only 6 patients who developed SSI had normal cholesterol levels on Day 0 (12.7%), compared to 66 patients (56%) in the group that did not develop SSI. Only 1 patient who developed SSI had hypercholesterolemia on Day 0 (2.1%), compared to 9 patients (7.6%) in the group that did not develop SSI. The P-value is <0.001, indicating that this association between Day 0 total cholesterol levels and SSI is highly statistically significant. Patients with low total cholesterol levels at the start of the study had a significantly higher risk of developing a surgical site infection. Normal and high cholesterol levels were more protective against SSI. Out of 69 patients with hypocholesterolemia on day 3, 40 of them developed SSI (40/47, 85.1%). Also, it is evident that a higher proportion of patients who developed SSI had hypocholesterolemia on Day 3 compared to those who did not develop SSI (29 out of 118, 24.6%). Only 7 patients who developed SSI had normal cholesterol levels on Day 3 (14.9%), compared to 84 patients (71.2%) in the group that did not develop SSI. No patients who developed SSI had hypercholesterolemia on Day 3 (0 out of 47, 0%), compared to 5 patients (4.2%) in the group that did not develop SSI. The P-value is <0.001, indicating that this association between Day 3 total cholesterol levels and SSI is highly statistically significant. Among 61 patients with hypocholesterolemia on day 5, 40 of them developed SSI (40/ 47, 85.2%). Also, a higher proportion of patients who developed SSI had hypocholesterolemia on Day 5 compared to patients who did not develop SSI (43out of 118, 36.4%). Only 6 patients who developed SSI had normal cholesterol levels on Day 5 (12.7%), compared to 66 patients (56%) in the group that did not develop SSI. One patient who developed SSI had hypercholesterolemia on Day 5 (1 out of 47, 2.1%), compared to 9 patients (7.6%) in the group that did not develop SSI. The P-value is <0.001, indicating that this association between Day 5 total cholesterol levels and SSI is highly statistically significant.

HDL cholesterol and SSI-

It is found that out of 141 patients with low HDL on day 0, 47 developed SSI (47/47, 100%). Among 24 patients with normal levels of HDL 0 (0 out of 47, 0%) develop SSI. The P-value is 0.001, indicating that this association between Day 0 HDL cholesterol levels and SSI is statistically significant. This shows a strong association between hypocholesterolemia on Day 0 and the development of SSI. Patients with low HDL cholesterol levels at the start of the study had a significantly higher risk of developing a surgical site infection. Among 140 patients with low serum HDL on day 3, 46 of them developed SSI (46/47,97.9). Only 1 patient who developed SSI had normal HDL cholesterol levels on Day 3 (2.1%), compared to 24 patients (20.3%) in the group that did not develop SSI. The P-value is 0.003, indicating that this association between Day 3 HDL cholesterol levels and SSI is statistically significant.

Out of 136 patients with low serum HDL on day 5, 45 of them developed SSI (45/ 47, 95.7%). Only 2 patients who developed SSI had normal HDL cholesterol levels on Day 5 (4.3%), compared to 27 patients (22.9%) in the group that did not develop SSI. The P-value is 0.005, indicating that this association between Day 5 HDL cholesterol levels and SSI is statistically significant. It shows a strong association between hypocholesterolemia on Day 5 and the development of SSI.

Limitation of our study

• Single-Center Study: The research was conducted at a single tertiary healthcare center. Multi-center studies would help determine if the results are consistent across different healthcare settings and patient populations.
• Specific Patient Population: The study focused on patients undergoing laparotomy procedures.
• Other cormobidities like hypertension and diabetes as risk factors were not considered.
• Other factors that could contribute to SSI risk, such as surgical technique, intraoperative contamination, and postoperative care, were not extensively evaluated.
• Observational Design: As an observational study, it can show correlations but cannot establish a cause-and-effect relationship between low cholesterol, low albumin, and SSI.

Present study is aimed to determine the role of serum cholesterol levels as a risk factor for developing surgical site infection following laparotomies. Study was conducted on 165 cases undergoing laparotomies. Observations made in the present study showed that pre-operative cholesterol levels are good prognostic indicators for predicting the development of surgical site infections after surgery.

Hypocholesterolemia (total cholesterol less than 100 mg/dl) has been found to statistical significant (P<0.001) in development of SSI and can be considered as a risk factor.

Post op day 3, and day 5 levels of serum cholesterol shows that patients with better nutrition to begin with has less chance of developing SSI, compared to undernourished and over nourished. Patients with normal levels of serum total cholesterol (100 mg% to 200 mg%) and higher values of serum HDL (>40 mg%) are found to be at low risk for developing SSI.

Increase in HDL cholesterol is associated with decrease in the surgical site infections.

We thus conclude that serum cholesterol levels are significant predictors for development of surgical site infections and should be done in all cases prior to surgery. By estimating there levels before surgery and adequately correcting lower levels, post-operative morbidity could be reduced in these patients.

Nutritional optimization and correction of cholesterol levels may help reduce SSI incidences. Patients undergoing emergency laparotomies had a higher risk of developing SSIs compared to elective surgery.

Summary

The study was conducted in the General Surgery department of Karnataka Institute of Medical Sciences, Hubballi.

Our study findings indicate that majority of patients presenting to government hospital are undernourished with poor socioeconomic conditions. Majority of them had hypocholesterolemia with low values of HDL. These patients are hence more prone for surgical site infections and other hospital acquired infections.

However other parameters which can interfere with wound healing like anemia, DM, etc, has not been considered in our study.

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