Evaluating the efficacy of dilute povidone-iodine versus normal saline for preventing surgical site infections following appendectomy: a prospective observational study in Ghanaian tertiary hospital

Abstract

Background

and Aims: Surgical site infection (SSI) remains a common postoperative complication for patients with acute appendicitis. This study aimed to compare the effectiveness of dilute povidone-iodine and normal saline in preventing post-appendectomy surgical site infections.

Methods

The study included 224 consecutive patients who underwent open appendectomy for acute appendicitis between October 2020 and December 2021 at Komfo Anokye Teaching Hospital in Ghana. Patients were randomly assigned to have irrigation with either povidone iodine or normal saline after appendectomy. The surgical wounds were assessed for infection using the Southampton wound grading system at 5 days post-surgery till 30 days.

Result

The mean age of the patients was 30.8 ± 14.4 years. The overall incidence of SSI was 8.04% (10.7% in the N/S group and 5.4% in the PI group). Both groups had a higher percentage of male patients (58% in the N/S group and 58.9% in the PI group). The mean length of hospital stays for patients with and without SSI was 10.11 ± 5.06 days and 4.69 ± 2.07 days respectively. The mean length of stay for the N/S group and PI group patients was 5.25 ± 2.95 days and 5.02 ± 2.81 days respectively. The mean cost for patients with and without SSI was GHC3,813.64(US$238.3) and GHC2,364.45 (US$147.7) respectively.

Conclusion

We conclude that there was no difference in SSI rates when comparing normal saline and povidone-iodine as irrigant fluids in patients undergoing an open appendectomy.

Introduction

Appendicitis is one of the most common surgical emergencies worldwide with an incidence of 230 cases per 100,000 population [1, 2]. Appendectomy is the standard management for most cases of acute appendicitis [3] although antibiotic therapy for some cases of uncomplicated appendicitis is becoming increasingly acceptable [4]. Appendectomy can be performed by the traditional open approach or minimally invasive (laparoscopic and robotic) approach. Complications of appendectomy include surgical site infection (SSI), wound dehiscence, bowel obstruction, abdominal/pelvic abscess, and stump appendicitis [5].

Surgical site infection describes an infectious complication of surgical wounds. This single complication is thought to occur in close to 20% of surgical cases. This complication has been described in several surgical procedures including minimally invasive procedures [6]. The causes of SSI are multifactorial, deriving from the interplay among surgical, environmental, and patient-related factors [7]. A recent study revealed that open appendectomy had a higher incidence of overall and incisional SSI than laparoscopic appendectomy (6.7% vs. 4.5%). However, the incidence of organ/space SSI in both groups was similar (3%). Another observational study found higher rates of superficial SSI after open appendectomy (9%) as compared to laparoscopic appendectomy (5%) [3, 8]. As a result of a high SSI rate, several authors have proved that the use of pre-operative antibiotics is effective in preventing infective complications after surgery [9]. Therefore, as a standard practice, patients undergoing appendectomy receive antibiotic prophylaxis 30 min to 1 h before the procedure.

Another strategy to reduce SSI rates is wound irrigation. Several studies have compared wound irrigation with an antiseptic solution, with an antimicrobial agent, and with normal saline in patients undergoing open appendectomy and concluded that antibiotic wound irrigation was more effective at reducing SSI relative to normal saline and antiseptic solution [4, 8, 11]. Povidone-iodine (PI) is a commonly employed antiseptic solution comprising iodide, polyvinylpyrrolidone with water, and 1% available iodine. A broad spectrum of microorganisms is susceptible to its bactericidal activity. It starts functioning within 30 s and remains effective up to 14 h after application. The efficacy of PI on non-incised skin is well documented [10]. However, its application as an intraoperative irrigation solution in open surgical wounds is not as common due to some concerns regarding its safety in open wounds. Normal saline (N/S) is a frequently employed irrigation solution, due to its isotonicity and the fact that it does not interfere with wound healing [11]. Hence, irrigation with normal saline is regarded as an easy and economical method to reduce SSI [12].

Despite multiple types of solutions being explored for incision irrigation, studies specifically designed to assess the efficacy of intraperitoneal and post-fascial closure irrigation with N/S and PI in reducing SSI occurrence are scarce, with a lack of solid evidence to support routine wound irrigation. The present study aims to compare the 30-day SSI rate of 1% dilute PI to that of N/S as irrigant solutions during an open appendectomy.

Patients and methods

Study sesign and setting

This Prospective observational study involved patients recruited at the General Surgery Department of Komfo Anokye Teaching Hospital, Kumasi - Ghana from October 2020 to December 2021. Based on a study by [13], the rate of SSI among PI-irrigated wounds was 4.6% and 10.9% for N/S-irrigated wounds. Using the formula by [14]utilized in clinical trials where treatment arms involve experimental and control arms, the sample size was calculated as 224 after considering a power of 80% and a 10% attrition rate. Study participants comprised patients with acute appendicitis who underwent open appendectomy.

Subject selections

Subjects were recruited at the Accident and Emergency Unit after consent had been obtained for an emergency open appendectomy. Patients were randomly allocated to one of two equal groups:

• Group I patients had their wounds irrigated (i.e., both intra-peritoneal and post-fascial closure) with 2 L of N/S after appendectomy.

• Group II patients had their wounds irrigated with 2 L of 1% dilute PI solution after appendectomy.

The study was single-blinded. Participants were unaware of their group allocation, which was performed using a computer-generated randomization sequence with a block size of 10 and a 1:1 allocation. The generated schedule was sealed in serially numbered opaque envelopes placed in a container at the operating theatre. The next serially numbered envelope was opened for each new participant. An independent statistician not privy to the enrolment, management/treatment, or assignment of participants generated the sequence. The Principal Investigator enrolled patients, while theatre staff was chosen to pick the envelopes and assign participants to either group. study participants were not informed of their assignment. However, the operating surgeon was notified of the group the patient had been enrolled in by the theatre staff who opened the assigned envelope.

Inclusion criteria

All patients above 16 years admitted through the Accident and Emergency Unit at KATH with a diagnosis of acute appendicitis and scheduled for open surgery were assessed for eligibility. Acute appendicitis was diagnosed by clinical examination. Confirmation was by intraoperative findings and histopathologic examination of the removed appendix.

Exclusion criteria

We excluded patients with appendicular masses, immunocompromised patients, pregnant or lactating patients, and patients who declined to consent.

Pre-operative assessment

The Principal Investigator did a pre-operative assessment of patients with help from three trained junior doctors. Abdominal examinations were carried out to confirm clinical signs of acute appendicitis and exclude any palpable masses. CT scanning was requested in selected patients to exclude the presence of appendicular masses or other abdominal pathologies.

Surgical procedure

After obtaining written informed consent from study participants, surgical procedures were conducted under either general or spinal anaesthesia with patients lying in the supine position. To control bias, a uniform protocol was established. After a 10-minute skin prep with 1% PI, the surgeon selected an appropriate skin incision, either Lanz incisions or lower midline, and ensured meticulous tissue manipulation and suture ligation of the mesoappendix and appendiceal stump with polyglactin suture. Intraperitoneal irrigation was then carried out with the randomised irrigant fluid. 2 L of lavage fluid were administered in two parts: 1 L was used for intraperitoneal lavage before fascial closure, and the second litre was used after fascial closure for wound irrigation. The lavage was performed in multiple smaller aliquots, with suctioning of fluid before the next aliquot was introduced. This cycle was repeated until the full volume was utilized. The lavage fluid included 200 mL of povidone iodine diluted in 2 L of normal saline. Gloves were changed after fascial closure to carry out irrigation of the incision and skin closure was done with non-absorbable 2/0 polypropylene monofilament suture in an interrupted fashion. To avoid the risk of bias, all patients in the two groups had layer-by-layer wound closure in a standardised manner. All procedures were performed by three surgical residents with similar levels of experience under the supervision of General Surgery Consultants.

Post-operative care and follow-up

Patients in both groups were given antibiotic treatment using ciprofloxacin (400 mg bid) and metronidazole (500 mg tid) postoperatively. Antibiotic therapy was administered for up to 7 days. Patients were admitted to the general ward with regular monitoring of vital signs. Patients were discharged if the following were present.

• they had sustained hemodynamic stability,

• they were able to tolerate diet enterally and.

• the surgical wound was clean after the first inspection on postoperative day 3.

The patients were scheduled for 3 reviews (postoperative days 7, 14, and 30) on admission or in the outpatient clinic if discharged before these scheduled days. Symptoms and signs of SSI were assessed at each visit. At every visit, we evaluated and documented any local signs of infection such as redness, pain, swelling, discharge, or wound opening. Patients diagnosed with SSI were investigated with a wound swab for culture and sensitivity and antibiotic therapy was tailored based on the sensitivity pattern. Abdominal ultrasound or Abdominal CT scan was requested in patients with evidence of intra-abdominal abscesses. The severity of SSI was graded by the Southampton wound scoring system [15] and grouped as follows.

• Grade 0 -: normal healing.

• Grade I -: normal healing with mild bruising or erythema.

• Grade II -: erythema with other signs of inflammation.

• Grade III -: clear or serosanguinous discharge.

• Grade IV -: pus or purulent discharge.

• Grade V -: deep or severe wound infection with or without tissue breakdown.

During scheduled reviews, independent surgical residents, and general surgery consultants, who were not involved in the study and thus blinded to the group allocation, assessed the wound.

No adverse events were reported in the care of the study participants during the study period.

Outcome of study

The study’s primary outcome was to determine the incidence of surgical site infection (SSI) among both groups. SSI was defined according to the standard criteria established by the Centers for Disease Control and Prevention (CDC) [12]. The secondary outcomes included the length of hospital stay (in days) and the cost of treatment. The cost of treatment was determined by assessing the total hospital bill at the time of discharge.

Ethics and consent to participate

Ethical approval was obtained from the Committee on Human Research Publication and Ethics, Kwame Nkrumah University of Science and Technology, Kumasi (SMS/DS.KATH/165). The study was registered with the Food and Drugs Authority (FDA)(FDAHT/VVC/CTD/CTM/23/0147), Ghana.

Informed consent

Written informed consent was obtained from all patients before the procedure or information was collected. Strict confidentiality of participants’ information was maintained throughout the study. All methods were performed in accordance with the declaration of Helsinki.

Data management and analysis

The data was gathered by filling out a structured data entry form, which can be found in the Appendix. Then, it was entered into Microsoft Access software version 216 to create an electronic database. To ensure consistency, data comparison and cleaning were carried out every week. Statistical Package for the Social Sciences (SPSS) version 20 (SPSS Inc., Chicago, USA) was used to analyze the data. The Chi-square test was used to compare categorical data, test were 2 sided with P-values less than 0.05 considered statistically significant.

Results

A total of 224 patients were enrolled in the study. The mean overall participant age was 30 years and 58.5% were male. (Table 1).

Table 1.

Socio-demographic characteristics of participants

Variable	N/S Group (n = 112) n (%)	PI Group (n = 112) n (%)	Total (N = 224) N (%)
Age (Years)
Mean (SD)	31.52 ± 13.33	30.23 ± 15.48	30.88 ± 14.40
Less than 20	24 (21.4%)	39 (34.8%)	63 (28.1%)
20–29	38 (33.9%)	28 (25.0%)	66 (29.5%)
30–39	25 (22.4%)	21 (18.8%)	46 (20.5%)
40–49	11 (9.8%)	10 (8.9%)	21 (9.4%)
Above 49	14 (12.5%)	14 (12.5%)	28 (12.5%)
Sex
Male	65 (58.0%)	66 (58.9%)	131 (58.5%)
Female	47 (42.0%)	46 (41.9%)	93 (41.5%)

Out of 224 participants, 8.03% had SSI diagnosed after the 30-day follow-up (Table 2). The SSI rate among the N/S group participants was 10.7% while that of the PI group participants was 5.4% with a p-value of 0.28. The overall mortality among the study participants was 1.3%. The mean length of stay between the two groups was similar (N/S group - 5.25±2.95 days; PI group - 5.02±2.81 days; p-value – 0.61). Grade IV wounds accounted for over 60% (11/18) of the overall patients with SSI with N/S group participants making up 81.8% (9/11) of them (p-value – 0.09).

Table 2.

Representation of intraoperative findings, SSI rate, mortality, and severity of SSI per various groups

		N/S Group (n = 112) n(%)	PI Group (n = 112) n(%)	Total (N = 224)	Chi-square		P-value
Intraoperative Findings					4.83		0.44
Phlegmonous appendix without abscess	16(14.3%)		7(0.9%)	23(20.5%)
Phlegmonous appendix with localized abscess	29(25.9%)		31(27.7%)	60(53.6%)
Perforated appendix without abscess	21(18.8%)		19(17.0%)	40(35.8%)
Perforated appendix with pelvic abscess	20(17.9%)		26(23.2%)	46(41.1%)
Perforated appendix with intraperitoneal abscess (generalized)	15(13.4%)		15(13.4%)	30(26.7%)
Gangrenous appendix	11(9.8%)		14(12.5%)	25(22.3%)
Comparison of SSI rate and mortality						2.57	0.28
SSI present		12(10.7%)	6(5.4%)	18(8.1%)
SSI absent		98(87.5%)	105(93.7%)	203(90.6%)
Deaths		2(1.8%)	1(0.9%)	3(1.3%)
Mean Length of Hospital Stay of Patients (days)							0.61
		5.25±2.95	5.02±2.81
Mean cost of Treatment (GHC)							0.316
		2,520.98 ± 742.00	2,417.05 ± 804.95
Severity of SSI (according to Southampton wound scoring system)					2.92		0.09
Grade II wounds		3(42.9%)	4(57.1%)	7(38.9%)
Grade IV wounds		9(81.8%)	2(18.2%)	11(61.1%)

The study also showed that SSI was associated with an average length of stay of about 10 days while patients without SSI stayed for about 5 days. This was found to reach statistical significance (p-= 0.02). Also, the cost of treatment between patients with and without SSI (Table 3) was GH₵ 3,813.64 and GH₵ 2,364.45 respectively (P=0.00). Table 3: Mean length of stay and cost of treatment against occurrence of SSI

Table 3.

Mean length of stay and cost of treatment against occurrence of SSI

SSI present (n = 18)	SSI absent (n = 203)	Mean difference	p-value
10.11 ± 5.06	4.69 ± 2.07	5.42	0.02
3,813.64 ± 1,633.10 238.3 ± 102.0	2,364.45 ± 684.64 147.7 ± 42,7	1,373.83 90.6	0.00

Discussion

Open appendectomies are the predominant surgical approach in low-middle-income countries, including Ghana. It accounts for over 90% of total appendectomies performed [6, 17] in Ghana. In this study, we sought to compare the efficacy of dilute povidone-iodine and normal saline intraoperative irrigation in preventing post-appendectomy SSI. The average age of participants in our study was 30.8 years, which aligns with findings from a retrospective survey of Fleming [18]. In contrast, a study by Izmalov et. al., in Russia reported a mean age of 34.8 years [19], while Ahmadet. al., in Peshawar reported a lower mean age of 26.7 years [20]. The variation in age may be attributed to differences in study design, geographical distribution, and early access to health care.

Our study found no statistically significant difference in SSI rates between povidone-iodine, and normal saline during an open appendectomy. The reported rate of post-appendectomy SSI in the literature ranges from 2.1 to 20% [19,20,21]. Although there was no difference in overall SSI rates between povidone-iodine and normal saline, povidone-iodine was associated with a lower incidence of severe forms of SSI. This finding corroborates with reports from a systematic review by Chundamala and Bright, which documented the efficacy of variable concentrations of povidone-iodine irrigation compared with sterile water, normal saline, or no irrigation. Though the scope of surgical procedures was broad (spine fusion, sternotomy, and general surgical procedures including appendectomy), the majority of the studies found PI to be effective in preventing SSI with no associated risks [13, 21]. A similar study conducted by Owais et. al., in 2019 which compared 1% PI and N/S as irrigant solutions for post-appendectomy surgical incisions after fascial closure also reported PI as being effective in reducing the severity of SSI [22]. These studies have shown that PI is similar to N/S in reducing SSI.

There is a consensus that SSI incurs significant costs, but the magnitude of that cost varies widely among various studies. The variations can be attributed to differences in the comprehensives of cost considerations, including factors beyond prolonged hospital stays and pharmaceutical costs [23].

In our study, the average cost for patients with SSI was GHC 3,813.64 (US$238.3), compared to GHC 2,364.45 (US$ 147.7) for patients without SSI. Fenny et al., [24] also demonstrated that on average patients with SSI spent US$ 298 more than those without SSI for patients that were similar in age, sex, wound class, and type of surgery. Our result is also in agreement with several studies that have shown that SSIs are costly and constitute a heavy and potentially preventable burden on both patients and the healthcare system [25-27]. This can be attributed to the duration of anti-microbial therapy, laboratory and imaging investigations, length of hospital admission, wound care management costs, and procedures performed. SSI prolongs the hospital's length of stay and increases the readmission rate and healthcare costs [28]. Ban et al. documented an extension of hospital stay by 9.7 days [29]. Though it is higher than the 5.4 days in the present study, it still demonstrates the added burden of SSI on patient care. Literature on both normal saline and povidone-iodine irrigation had varied results in terms of their effectiveness in preventing surgical site infections. Findings from our study found no difference in effectiveness of povidone-iodine and normal saline in preventing SSI after appendectomy. SSI is common in appendectomy for complicated appendicitis than uncomplicated appendicitis. In this study, there were few cases of uncomplicated appendicitis 23(20.5%) compared to complicated cases 201(79.5%). This difference did not affect the findings of this study. The rate of SSI in the normal saline group were high compared to the PI despite the fact that there were more uncomplicated appendicitis in NS group. The difference however, was not significant(p=0.28).This study had few limitations, first, most of the available data on the subjects used in similar studies were from Caucasian populations, with very limited data from Sub-Saharan Africa, where SSI is most predominant[30]. The adoption, particularly in terms of the choice of using povidone iodine irrigation fluid was because the number of uncomplicated appendicitis cases was low and also to determine its efficacy, cost and easy-to-deploy measure in preventing SSI. Secondly, although this single centre approach reduced participant bias and easier implementation of study, we suggest further studies with a large number of patients in a multi-centre study to explore further the effect of povidone iodine versus normal saline wound irrigation on SSI following appendectomy.

Conclusion

There was no difference in the overall SSI rates when comparing irrigation with N/S and 1% PI. However, PI was associated with a lower incidence of severe forms of SSI following an appendectomy. Findings of this study will be shared with other surgical units. We anticipate that this will contribute to reducing the incidence of severe surgical site infections, improving patient outcomes, shortening hospital stays, and reducing treatment costs.

Limitation

Limitations of our study include its single-centre design and small sample size. Additionally, the accurate determination of health care costs was hindered by subsidies from the National Health Insurance Scheme, which limited our ability to assess the true cost-effectiveness of the study interventions.

Recommendation

Further, multiple-centre studies with long-term follow-up are needed.

Author contributions

Sulemana Abdul-Latif, Joseph Yorke, Joseph Kwaku Oppong, Samuel Gyasi Brenu, Francis Somiah-Kwao Aitpillah, Michael Ofoe Adinku, Kwabena Agbedinu, Charles Kofi Dally and Ishmael Kyei wrote and reviewed the literature review and methodology. Tonnies Abeku Buckman, Frank Enoch Gyamfi, Kwabena Agbedinu, Francis Akwaw Yamoah, Samuel Mensah, Anita Eseenam Agbeko, Dominic Akuoku Darkwa Kingsley Bosompem, and Samuel Gyasi Brenu were involved in designing the study, administered the project, and collected resources. Dennis Afful Yorke, Akwasi Opoku Agyapong, Nana Akosua Oppong-Nkrumah, Martin Kofi Adjei, Theodora-Ann Fremponma Ellis, Wilfred Sam-Awortwi Jnr, Yaa Takyi Baffowa administered the project and collected data. Sulemana Abdul-Latif cleaned and analyzed the data. Joseph Yorke, Sulemana Abdul-Latif, Samuel Gyasi Brenu, Tonnies Abeku Buckman, Jonathan Laryea, and Gifty Kwakye wrote the original draft of the article. All authors have read and approved the final version of the manuscript. Corresponding had full access to all of the data in this study and takes complete responsibility for the integrity of the data and the accuracy of the data analysis.

Funding

The authors received no funding for the conduct of the study or publication of this article.

Data availability

The datasets during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethical approval

was obtained from the Committee on Human Research Publication and Ethics, Kwame Nkrumah University of Science and Technology, Kumasi (SMS/DS.KATH/165). The study was registered with the Food and Drugs Authority (FDA)(FDAHT/VVC/CTD/CTM/23/0147), Ghana.

Declaration of Transparency

This manuscript is an honest, accurate and transparent account of the study being reported. No important aspect has been omitted; and any discrepancies from a study as planned (and, if relevant, registered) have been explained.