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Effect of wound irrigation on the prevention of surgical site infections: A meta‐analysis

Abstract We performed a meta‐analysis to evaluate the effect of wound irrigation on the prevention of surgical site infections. A systematic literature search up to January 2022 was done and 24 studies included 4967 subjects under surgery at the start of the study; antibiotic irrigation was used with 1372 of them, 1261 were aqueous povidone‐iodine irrigation, and 2334 were saline irrigation or no irrigation for surgical site infections prevention in all surgical populations. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to evaluate the effect of different wound irrigation on the prevention of surgical site infections by the dichotomous method with a random or fixed‐influence model. Antibiotic irrigation had significantly lower surgical site infections in all surgical populations (OR, 0.48; 95% CI, 0.36‐0.62, P < .001) compared with saline irrigation or no irrigation for the subject under surgery. Aqueous povidone‐iodine irrigation had significantly lower surgical site infections in all surgical populations (OR, 0.40; 95% CI, 0.20‐0.81, P = .01) compared with saline irrigation or no irrigation for the subject under surgery. Antibiotic irrigation and aqueous povidone‐iodine irrigation significantly lowered surgical site infections in all surgical populations compared with saline irrigation or no irrigation for the subject under surgery. Further studies are required.


| BACKGROUND
Surgical site infections are an opposing result of surgery and are accounting for the majority of health care-related infections worldwide. 1 More than 10% of all surgical operations are accompanied by surgical site infections in developing countries. 1 Though the overall surgical site infections risk is far lower in developed countries, they pay serious attention to patient safety. 1 Such infection rise morbidity and mortality rates and extend hospital stays. 1,2 The average surgical site infection is related to nearly one extra week of hospital stay and raises the risk of death to 11 fold. 2 Furthermore, surgical site infections were found to increase health care costs, very much. 2 Many reasons have been related to the risk of surgical site infection, and therefore, a variety of preventive methods has been suggested. One of these is prophylactic intraoperative wound irrigation, a simple intervention that is the movement of a solution through the surface of an open wound to accomplish tissue hydration. It eliminates and dilutes body fluids, bacteria, and cellular debris and also might have a bactericidal effect when antibiotics or antiseptic agents are used. Many surgeons usually practice intraoperative wound irrigation. 3 However, it is not part of general practice in every country or hospital. Furthermore, methods vary based on the population, application surface, method, and solutions used. Similar differences in techniques and outcomes could be seen in studies examining the influence of intraoperative wound irrigation. 4 Between the existing guidelines on surgical site infection prevention, a limited number of them have addressed the topic of intraoperative wound irrigation and provided opposing suggestions. The National Institute for Health and Care Excellence guidelines in 2008 and updated in 2013, recommended intraoperative wound irrigation and intra-peritoneal lavage. 5 However, in 2014 the Society for Healthcare Epidemiology of America guideline and the Infectious Diseases Society of America guideline suggested the use of antiseptic incision lavage. 6 Many of the solutions frequently used for irrigation are not approved for open incisions by the Food and Drug Administration. 7 In 2015, a meta-analysis showed the present state of the art on prophylactic intraoperative wound irrigation. 4 However, they did not take into account that other infection prevention methods included studies have improved over time. So, the presented indication might not be generalisable to the present standard of care. The previous meta-analysis has comprised studies where prophylactic intraoperative wound irrigation is a therapeutic intervention for infection rather than a prophylactic measure. The present meta-analysis aimed to evaluate the effect of wound irrigation on the prevention of surgical site infections.

| METHODS
This meta-analysis is organised according to the epidemiology statement, 8 after the established methodology.

| Study selection
The main objective of this study was to compare the effect of different wound irrigation on the prevention of surgical site infections using the following tools, for example, odds ratio (OR), mean difference (MD), frequency rate, or relative risk, and confidence interval (CI) of 95%.
The search was not narrowed to English, and inclusion criteria were not restricted by study type or size. Studies with no correlation were exempted from the study, for example, editorials, review article letters, and commentary. Figure 1 exhibits the mode of analysis.
The article inclusion criteria were classified and integrated into the meta-analysis when 1. The study was a randomised control trial, prospective study, or retrospective study. 2. The target population was subject to surgery. 3. The intervention programme was antibiotic irrigation, or aqueous povidone-iodine irrigation compared to saline irrigation or no irrigation. 4. The study comprised comparisons between antibiotic irrigation, aqueous povidone-iodine irrigation, and saline irrigation or no irrigation for surgical site infections prevention in all surgical populations.
The next exclusion criteria were adopted among the intervention groups 1. Studies that did not determine the effect of wound irrigation on the prevention of surgical site infections. 2. Studies with management other than antibiotic irrigation, aqueous povidone-iodine, and irrigation and saline irrigation. 3. Studies that did not concentrate on the influence of comparative outcomes.

| Identification
PICOS principle was the protocol for the search strategy 9 and asserted the critical elements of PICOS as P (population): subject under surgery; I (intervention/exposure): antibiotic irrigation, or aqueous povidone-iodine irrigation compared with saline irrigation or no irrigation; C (comparison): antibiotic irrigation, or aqueous povidoneiodine irrigation compared with saline irrigation or no irrigation for surgical site infections prevention in all surgical populations; O (outcome): surgical site infections; and S (study design): had no limitation. 10 We conducted a systematic and brief search on MEDLINE/PubMed, Google Scholar, Embase, OVID, and Cochrane Library until January 2022, by a combination of keywords and correlated words for wound irrigation, surgical site infections, antibiotic irrigation, aqueous povidone-iodine irrigation, and saline irrigation as shown in Table 1. The selected studies were pooled in EndNote software to exclude the duplicates. In addition, a thorough screening on the title and abstracts were done to erase any data that did not show any influence of antibiotic irrigation, or aqueous povidone-iodine irrigation compared with saline irrigation or no irrigation for the subject under surgery on the outcomes studied. Related pieces of information were collected from the remaining studies.

| Screening
Subject-related and study-related data characteristics were considered for the collection and classification of data, and it was pooled into a standardised form. The categorisation was made into the standard form like the surname of the first author, duration of the trial, place of practice, design of the study, subject type, sample size, categories, demography, treatment methodology, information source, method of evaluation (both qualitative and quantitative), statistical analysis, and primary outcome evaluation. 9 Methodological quality was assessed by the 'risk of bias tool' adopted from Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. This metaanalysis recommended that if a trial with inclusion criteria is based on the standards mentioned earlier, any conflicts that arose during the data collection by two reviewers must be resolved through discussion and when necessary by the 'corresponding author' to ensure the quality of the methodology. 11 When there were different data from one study based on the evaluation of the relationship, we extracted them separately.

| The level of risk of bias is counted in the assessment criteria
The level of risk was considered low if all quality parameters were met; it was considered moderate if one of the quality parameters was not met/or partially met and was considered high if one of the quality parameters was not met/or not included. A re-examination of the original article was addressed for any inconsistencies.

| Eligibility criteria
The main eligibility criteria concentrated on the effect of wound irrigation on the prevention of surgical site infections. An evaluation of the influence of antibiotic irrigation, or aqueous povidone-iodine irrigation compared with saline irrigation or no irrigation for surgical site infections prevention in all surgical populations was conducted and the data were extracted forming a summary.

| Inclusion
Studies reporting the effect of wound irrigation on the prevention of surgical site infections were only included in the sensitivity analysis. In comparison, the impact of antibiotic irrigation, or aqueous povidoneiodine irrigation compared with saline irrigation or no irrigation for surgical site infections prevention in all surgical populations was considered a subcategory of sensitivity analysis.

| Statistical analysis
The dichotomous methods were used to compute the OR at a 95% CI on a fixed-influence or random-influence model. First, the I 2 index range was established between 0% and 100%, when the I 2 index scale for heterogeneity was indicated as no, low, moderate, and high as 0%, 25%, 50%, and 75%, respectively. 12 Random-influence was considered if I 2 was >50%, and if <50%, as fixed-influence. The initial evaluation of the result was stratified, and in subgroup analysis, a P-value <.05 was reported statistically significant. Egger regression test was used quantitatively and qualitatively to assess the publication bias (if P ≥ .05) by inspecting funnel plots of the logarithm of odds ratios compared with their standard errors. 9 The entire P-values were two-tailed. The statistical analysis and graphs were done by 'Reviewer manager version 5.3' (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark).

| RESULTS
A total of 1867 distinctive studies were found, of which 24 studies (between 1979 and 2021) satisfied the inclusion criteria and were comprised in the study.  This metaanalysis study based on 24 studies included 4967 subjects under surgery at the start of the study; antibiotic irrigation was used with 1372 of them, 1261 were aqueous povidoneiodine irrigation, and 2334 were saline irrigation or no irrigation for surgical site infections prevention in all surgical populations. All studies evaluated the effect of wound irrigation on the prevention of surgical site infections. Fourteen studies reported data stratified to the surgical site infections prevention in all surgical populations using antibiotic irrigation compared with saline irrigation or no irrigation, and 11 studies reported data stratified to the surgical site infections prevention in all surgical populations using aqueous povidone-iodine irrigation compared with saline irrigation or no irrigation. The study size ranged from 40 to 822 subjects under surgery at the beginning of the study. The information of the 24 studies is shown in Table 2. One study used the two studied techniques of wound irrigation compared with saline irrigation or no irrigation on the prevention of surgical site infections and was extracted separately. 32 Antibiotic irrigation had significantly lower surgical site infections in all surgical populations (OR, 0.48; 95% CI, 0.36-0.62, P < .001) with low heterogeneity (I 2 = 47%) compared with saline irrigation or no irrigation for the subject under surgery as shown in Figure 2.
Aqueous povidone-iodine irrigation had significantly lower surgical site infections in all surgical populations (OR, 0.40; 95% CI, 0.20-0.81, P = .01) with moderate heterogeneity (I 2 = 66%) compared with saline irrigation or no irrigation for the subject under surgery as shown in Figure 3.
The stratified data did not examine the factors like age, gender, and ethnicity between the two groups because no studies adjusted or outlined these factors. No publication bias (P = .87) was detected when the quantitative measurement was conducted using the Egger regression test and examination of the funnel plot. However, low methodological quality was observed in selected randomised control trials. No articles had selective reporting or incomplete data, which proved that selected articles devoid of selective reporting bias.

| DISCUSSION
This meta-analysis study based on 24 studies included 4967 subjects under surgery at the start of the study; antibiotic irrigation was used with 1372 of them, 1261 were aqueous povidone-iodine irrigation, and 2334 were saline irrigation or no irrigation for surgical site infections prevention in all surgical populations.  Antibiotic irrigation and aqueous povidone-iodine irrigation had significantly lower surgical site infections in all surgical populations compared with saline irrigation or no irrigation for the subject under surgery. However, the analysis of outcomes should be performed with consideration because of the low sample size of many of the selected studies found for the meta-analysis, 5 out of 24 studies with ≤100 subjects as sample size; recommending the need for other studies to confirm these findings or perhaps to significantly impact confidence in the influence evaluation.
Many studies have shown that prophylactic incisional irrigation with different antibiotics or aqueous povidoneiodine solution has a significant value on the surgical site infection, mainly in clean and clean-contaminated wounds, however, no dose-response effect was detected.  In addition, some other studies have shown a significant effect on surgical site infection was observed when used with force or using pulse pressure, nevertheless not with regular irrigation. Some studies showed that there is no significant advantage to the use of antibiotic solutions for prophylactic incisional wound irrigation or the use of prophylactic intraoperative wound irrigation in the abdomen or mediastinum. When categorising those studies we could say that the positive effect of antibiotic irrigation was observed more in the developing countries rather than the developed countries. That could be due to the overall surgical site infections risk being far lower in developed countries since they pay serious attention to patient safety. 1 Though suggestions from existing guidelines are contradictory 5,6 and well-designed randomised control trials are missing, as many as 97% of surgeons irrigate wounds in a struggle to decrease the risk of surgical site infection. 3 The most usually used irrigation solution is saline followed by aqueous povidone-iodine or antibiotic solutions. 37 The effectiveness and clinical safety of irrigation with these solutions have been the subject of discussion. 7 Different concentrations of povidone-iodine are effective against a broad spectrum of pathogens, including methicillin-resistant Staphylococcus aureus. 38 Though some in-vitro studies 39,40 have shown a negative outcome of povidone-iodine on tissue regeneration, some old studies label serum iodine toxicity as an outcome of irrigation. 41,42 Though, these adverse effects cannot be validated in clinical trials.  When considering antibiotics, however, our results favour its use, the bactericidal influence of most agents needs a contact time. It is improbable that prophylactic intraoperative wound irrigation with antibiotic solutions is done with adequate time to accomplish clinical effectiveness, and anaphylactic reactions might occur. 43 In addition, the abuse of antibiotics is considered to be a major reason for the appearance of antimicrobial resistance. 44 In contrast, the resistance of organisms to antiseptics is recommended to be low, perhaps due to their numerous pharmacological targets. 45 Wound irrigation using aqueous chlorhexidine might be a substitute when extrapolating the favourable outcomes from alcohol-based chlorhexidine used for preoperative skin formulations, but F I G U R E 3 A forest plot of the surgical site infections in all surgical populations of the aqueous povidone-iodine irrigation compared with the saline irrigation or no irrigation for the subject under surgery clinical data are missing. The outcomes of aqueous 0.05% chlorhexidine gluconate as a wound irrigation fluid in the laboratory and animal studies are promising. 46 Earlier meta-analyses have measured the effect of prophylactic intraoperative wound irrigation but with thoughtful limitations in their study selection, obstructing extrapolation to current clinical practice. Fournel et al 47 48 Though, the first two metaanalyses comprised studies examining intraoperative wound irrigation as a healing measure for current infections rather than as a preventive measure, and studies examining intraoperative wound irrigation did not meet present standards of systemic antibiotic prophylaxis, which were included by the third one. 48 Fournel et al 47 conducted a subgroup analysis of studies comprising standard systemic antibiotic prophylaxis but left some important studies out. 29,30,35 Mueller et al comprised povidone-iodine powder (spray) application between intraoperative wound irrigation studies with an irrigation solution, but the mechanical influence of removal and dilution of the bacterial load was not done by powder application. The current meta-analysis examined the prophylactic influence of intraoperative wound irrigation on the occurrence of surgical site infection against the background of the current standard of care.
This meta-analysis showed the relationship between the influences of different wound irrigations on the prevention of surgical site infections. However, further studies are needed to validate these potential associations. In addition, further studies are needed to deliver a clinically meaningful difference in the results. This was suggested in other meta-analyses, which showed similar effects. 4,[48][49][50][51][52] This needs additional examination and clarification because no clear reasoning was found to clarify these outcomes. Well-designed clinical trials are also required to evaluate these factors with the blend of diverse ages, gender, and ethnicity; as our meta-analysis study could not answer whether these factors are related to the outcomes. In summary, antibiotic irrigation and aqueous povidone-iodine irrigation had significantly lower surgical site infections in all surgical populations compared with saline irrigation or no irrigation for the subject under surgery.

| LIMITATIONS
There may be a collection bias in this meta-analysis since several studies found were excluded from the meta-analysis. Though, the studies excluded did not satisfy the inclusion criteria of the meta-analysis. Furthermore, we could not decide if the results were linked to age, gender, and ethnicity or not. The study was designed to assess the relationship between the influences of antibiotic irrigation, or aqueous povidoneiodine irrigation compared with saline irrigation or no irrigation for surgical site infections prevention in all surgical populations was depending on data from former studies, which may result in bias brought by incomplete details. The meta-analysis was depending on 24 studies; 5 studies of them were small, ≤100. Features comprising the age, gender, obedience, nutritional status, and ethnicity of subjects were also likely biasencouraging features. Several unpublished studies and lost data may result in a pooled influence bias. Subjects were using diverse chief pharmacological medicines, treatment schedules, doses, and health care schemes. The types of antibiotic irrigation, or aqueous povidoneiodine irrigation concentration, used for surgical site infections prevention in all surgical populations' treatment of the included studies were varying. The comprised studies did not sufficiently assess the hospital costs of the subjects studied, which is a vital result.
Published studies on prophylactic intraoperative wound irrigation were conducted in the 1980seconds, which may represent a limitation, as infection prevention and control measures have changed substantially since that time. Similarly, standards for the conduct and reporting of clinical trials have changed, resulting in a stringent assessment of the quality of evidence.

| CONCLUSIONS
Antibiotic irrigation and aqueous povidone-iodine irrigation had significantly lower surgical site infections in all surgical populations compared with saline irrigation or no irrigation for the subject under surgery. However, the analysis of outcomes should be done with consideration because of the low sample size of many of the selected studies found for the meta-analysis; recommending the need for added studies to confirm these results or perhaps to significantly influence confidence in the effect evaluation. More studies are essential to confirm these outcomes.

CONFLICT OF INTEREST
The authors declare no potential conflict of interest.

DATA AVAILABILITY STATEMENT
The datasets analyzed during the current study are available from the corresponding author on reasonable request.