Systematic Review and Meta-Analysis of Randomized Controlled Trials Evaluating Prophylactic Intra-Operative Wound Irrigation for the Prevention of Surgical Site Infections

Abstract

Background:

Surgical site infections (SSIs) are one of the most common hospital-acquired infections. To reduce SSIs, prophylactic intra-operative wound irrigation (pIOWI) has been advocated, although the results to date are equivocal. To develop recommendations for the new World Health Organization (WHO) SSI prevention guidelines, a systematic literature review and a meta-analysis were conducted on the effectiveness of pIOWI using different agents as a means of reducing SSI.

Methods:

The PUBMED, Embase, CENTRAL, CINAHL, and WHO databases were searched. Randomized controlled trials (RCTs) comparing either pIOWI with no pIOWI or with pIOWI using different solutions and techniques were retrieved with SSI as the primary outcome. Meta-analyses were performed, and odds ratios (OR) and the mean difference with 95% confidence intervals (CI) were extracted and pooled with a random effects model.

Results:

Twenty-one studies were suitable for analysis, and a distinction was made between intra-peritoneal, mediastinal, and incisional wound irrigation. A low quality of evidence demonstrated a statistically significant benefit for incisional wound irrigation with an aqueous povidone–iodine (PVP-I) solution in clean and clean contaminated wounds (OR 0.31; 95% CI 0.13–0.73; p = 0.007); 50 fewer SSIs per 1,000 procedures (from 19 fewer to 64 fewer)). Antibiotic irrigation had no significant effect in reducing SSIs (OR 1.16; 95% CI 0.64–2.12; p = 0.63).

Conclusion:

Low-quality evidence suggests considering the use of prophylactic incisional wound irrigation to prevent SSI with an aqueous povidone–iodine solution. Antibiotic irrigation does not show a benefit and therefore is discouraged.

Surgical site infections (SSIs) are an adverse outcome of surgery accounting for the majority of healthcare-associated infections around the world [1 -3]. In developing countries, more than one in ten of all surgical procedures is complicated by an SSI [2]. Although the overall risk of SSIs is much lower in developed countries, they remain a serious threat to patient safety [1,3]. Such infections increase morbidity and mortality rates and prolong hospital stays [1,4,5]. The average SSI is associated with approximately one additional week of hospitalization and increases the risk of death two to 11 fold [5]. Moreover, SSIs increase healthcare costs, in the U.S. by as much as $1.6 billion per year [4].

Many factors have been associated with the risk of SSI, and consequently, a range of preventive measures has been proposed. One of these is prophylactic intra-operative wound irrigation (pIOWI), a seemingly simple intervention defined by the flow of a solution across the surface of an open wound to achieve tissue hydration. It removes and dilutes body fluids, bacteria, and cellular debris and additionally may have a bactericidal effect when additives such as antibiotics or antiseptic agents are used (see Table 1 for an overview of the definitions used). As many as 97% of surgeons commonly practice IOWI [6,7]. Nonetheless, it is not part of general practice in every country or hospital. Moreover, methods differ depending on the patient population, surface of application, technique, and solutions used. Similar variations in methods and results can be observed in studies investigating the effect of IOWI [8].

Table 1.

Definitions Used

Prophylactic intra-operative wound irrigation (pIOWI)	The flow of a solution across the surface of an open wound to achieve wound hydration. It physically removes and dilutes body fluids, bacteria, and cellular debris and has a bactericidal effect when additives such as antibiotics or antiseptic agents are used
Intra-operative wound irrigation as therapeutic intervention	CDC wound class IV was considered a pre-existent infection; irrigation field was considered to be therapeutic, not prophylactic
Intra-operative wound irrigation as prophylactic intervention	CDC wound class I–III was considered potentially contaminated; irrigation was considered to be prophylactic
	Irrigation of the newly made incision was always considered prophylactic, regardless of the wound classification, as the incision did not exist prior to the procedure and established infection was impossible.
Syringe pressure irrigation	Solution delivered with a syringe with an intravenous catheter applying force by hand.
Pulse pressure irrigation	Irrigation with a mechanical device that delivers pulsatile saline irrigation.
US Centers for Disease Control and Prevention (CDC) surgical wound classification	Class I/Clean: An uninfected operative wound in which no inflammation is encountered and the respiratory, alimentary, genital, or uninfected urinary tract is not entered. In addition, clean sites are closed primarily and, if necessary, drained with closed drainage. Operative incisions that follow non-penetrating (blunt) trauma should be included in this category if they meet the criteria.
	Class II/Clean–Contaminated: An operative wound in which the respiratory, alimentary, genital, or urinary tracts are entered under controlled conditions and without unusual contamination. Specifically, operations involving the biliary tract, appendix, vagina, and oropharynx are included in this category, provided no evidence of infection or major break in technique is encountered.
	Class III/Contaminated: Open, fresh, accidental wounds. In addition, operations with major breaks in sterile technique (e.g., open cardiac massage) or gross spillage from the gastrointestinal tract, and incisions in which acute, nonpurulent inflammation is encountered, are included in this category.
	Class IV/Dirty–Infected: Old traumatic wounds with retained devitalized tissue and those that involve existing clinical infection or perforated viscera. This definition suggests that the organisms causing postoperative infection were present in the operative field before the operation.

Among the available guidelines on SSI prevention, few have addressed the topic of IOWI and give contradictory recommendations. The guidelines from the United Kingdom National Institute for Health and Care Excellence (NICE), issued in 2008 and updated in 2013, advised against IOWI and intra-peritoneal lavage [9]. In contrast, the 2014 guidelines of the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) recommend using antiseptic incision lavage [10]. Many of the solutions commonly used for irrigation are not licensed for open incisions by the U.S. Food and Drug Administration [11].

In 2015, a meta-analysis has been published to determine the current state of knowledge on pIOWI [8]. However, that review does not take into account that (other) infection prevention measures among included studies have improved over decades. Therefore, the presented evidence may not be generalizable to current standard of care (i.e., no appropriate standard systemic antibiotic prophylaxis). Importantly, the previous review has included studies where pIOWI represents a therapeutic intervention for infection rather than a prophylactic measure. Also, a substantial heterogeneity between studies has not been accounted for as the previous review does not account for differences in irrigation solutions and in application methods. For the purpose of developing recommendations for the new World Health Organization (WHO) SSI prevention guidelines [12,13], a systematic literature review and meta-analysis were conducted. In present systematic review we aim to assess all available data reasonably applicable to current standard of care and clarify the effect of pIOWI on the incidence of surgical site infection in all surgical populations, while accounting for inter-study differences in application method and solution.

Patients and Methods

The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed [14].

Search strategy and selection criteria

The following databases were searched: Medline (PubMed); Excerpta Medica Database (EMBASE); Cumulative Index to Nursing and Allied Health Literature (CINAHL); Cochrane Central Register of Controlled Trials (CENTRAL); and WHO regional medical databases. No time limit was used because most studies were published before 1990. Language was restricted to English, French, German and Spanish. A comprehensive list of search terms was used, including Medical Subject Headings (MESH), the complete search is included in Appendix A (Appendices maybe found at www.liebertpub.com/sur).

Two independent reviewers screened titles and abstracts of retrieved references for potentially relevant studies. The full text of these articles was obtained and independently reviewed for eligibility based on inclusion criteria. Duplicate studies were excluded. Only randomized studies investigating pIOWI as described in Table 1 were included. Studies investigating the topical application of antibiotics and antiseptics (e.g., powder, gels, sponges) without the mechanical effect of irrigation, physically rinsing and diluting the bacterial load, were not included. To ensure that only evidence reasonably relevant to the current standard of care was included in our analyses, description of appropriate administration of preoperative antibiotic prophylaxis (i.e., before incision and intravenous) was a minimum requirement for inclusion. In addition, studies where the irrigated field was infected prior to the start of surgery and wound irrigation, represented a therapeutic intervention rather than a prophylactic measure and were also excluded. Wound contamination was ranked according to the US Centers for Disease Control and Prevention (CDC) wound classification [15]. As described in table 1, wound class I-III were considered not infected and therefore irrigation of the contaminated field a prophylactic measure, whereas CDC Wound class IV was considered a pre-existent infection and therefore irrigation of the contaminated field represented a therapeutic intervention. Irrigation of the newly made incisional wound was always considered prophylactic, regardless of the wound classification, as the incisional wound did not exist prior to the procedure and pre-existent infection would be impossible. For example, peritoneal cavity irrigation of a dirty, infected abdomen (CDC Wound class IV) represents a therapeutic intervention. In contrast, in the same procedure incisional wound irrigation was considered a prophylactic measure.

Data extraction and assessment of study quality

Data were extracted from the text, according to a pre specified data abstraction form including design, publication date, scope, number of patients, contamination according to the US CDC wound classification [15], irrigation surface, type of intervention (solution, application, volume), type of control, Follow-up, primary outcome, results and adverse events (AE) (Appendix B). The Cochrane Collaboration's tool [16] for assessing risk of bias was assessed for the quality of the studies. Any disagreements were resolved through discussion or after consultation with the senior author, when necessary. Publication bias was assessed using a funnel plot [17]. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology (GRADE Pro software, http://gradepro.org/) [18] was used to assess the quality of the body of retrieved evidence.

Synthesis of results

Trials were grouped in comparisons according to irrigation location and their intervention and control arm. Of each comparison meta-analysis were performed using Review Manager (RevMan, Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) as appropriate. If there was only one study no data could be pooled, but data were plotted as forest plot for illustrative purposes. Odds ratios (OR) and the mean difference with 95% confidence intervals (CI) were extracted and pooled for each comparison with a random effects model (Mantel-Haenszel method) to account for potential heterogeneity [19]. Forest plots were constructed and P < 0.05 was considered to be statistically significant. Heterogeneity was assessed using the I² statistic. I² of >60% was assessed as serious inconsistency. When inconsistency was detected stratified subgroup analysis where made for wound contamination and for irrigation solution.

Results

Study selection

We identified 955 studies, of which 113 were assessed for full review. Twenty-one randomized controlled trials (RCTs) were found eligible for full critical appraisal. The process of selection is summarized in Figure 1. The reasons for exclusion after full text assessment are described in Appendix C.

FIG. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart of the systematic review.

Study characteristics

In total we identified 21 RCTs [20 -40] (6,224 patients) comparing pIOWI to no pIOWI or to pIOWI using different solutions and techniques, in patients undergoing various surgical procedures with SSI as an outcome. All but two [27,28] were single center RCTs. There was substantial heterogeneity in the study protocols. A distinction was made between peritoneal cavity, mediastinal cavity and incisional wound irrigation. Other main differences were the composition of the irrigation fluid, and the type of surgery with associated contamination. Due to this heterogeneity of the evidence, nine separate comparisons were composed. Five studies describing intraoperative peritoneal cavity irrigation [20 –24] comparing saline vs. no irrigation [20], taurolidine vs. saline [21], and antibiotic irrigation vs. saline or no irrigation [22 -24]; fifteen describing incisional wound irrigation [25 -39] comparing saline solution vs. no irrigation [25], syringe pressure irrigation with saline solution vs. no irrigation [26], pulse pressure irrigation with saline solution vs. normal saline solution [27,28], aqueous povidone iodine (PVP-I) vs. saline [29 -35] and antibiotic vs. saline solution or no irrigation [22,36-39]; and one study describing intra-operative mediastinal cavity irrigation [40] comparing aqueous PVP-I vs. saline solution. Most studies were conducted in patients undergoing abdominal surgery [20 -24,26,28,31,32,36,37] but spine [33,34], orthopedic [27,35,39], gynecologic [25], vascular [38], thoracic [40], and general surgery [29,30] also were included. Of the included studies, three RCTs [20, 23, 31] described sterility of the irrigation fluid. The other studies did not report whether the irrigation fluid was sterile. The data on study characteristics are summarized in Table 2 and entirely presented in Appendix B.

Table 2.

Summary of Evidence

Study	Type of surgery	Irrigation surface	Intervention	Control	Follow-up	Primary outcome	Results
Tanaka et al. (2015) [20]	Elective liver resection	PC	1000–3000mL warm sterile saline solution directed at the dissected area	No irrigation	28 d	Incisional:Clinically apparent cellulitis, induration, or purulent discharge from closure site	TotalI: 21/96C: 13/97Incisional I:7/96C: 6/97
						Organ/space:radiologic evidence of fluid collection necessitating drainage or antibiotic therapy	AbscessI: 16/96C: 7/97
Baker et al. (1994) [21]	Elective colorectal surgery	PC	250 mL taurolidine 2% in PVP-I 5%.Diluted in 250 mL of salinefollowed by suction	500 mL salinefollowed by suction	6 wks	Spontaneous or incisional discharge with an infective organism identified on culture	Total:I: 17/150C: 17/150
							IncisionalI: 17/150C: 17/150
							AbscessI: 2/150C: 1/150
Freischlag et al. (1984) [22]	Elective biliary operations	IW & PC	Cefamandole nafate 0.4% solution (4 g in 1,000 mL normal saline)	No irrigation	30 d	Incision and intra-abdominal infections were defined by spontaneous or surgical drainage of pus	TotalI: 1/26C: 0/36
							SSII: 1/26C: 0/36
							AbscessI: 0/26C: 0/36
Silverman et al. (1986) [23]	Elective or emergency trans-peritoneal intestinal surgery	PC	2 L 0.9% Sterile saline solution containing2 g tetracycline	Sterile saline solution irrigation	6 weeks	Incision infection:Pus discharge from the site	TotalI: 15/85C: 25/74
						Intra-abdominal abscess: a mass palpable/identified radiologically plus spontaneous discharge requiring surgical drainage	SSII :10/85C: 24/74
							AbscessI: 11/85C: 10/74
Ruiz Tovar et al. (2012) [24]	Colorectal surgery	PC	Saline solution followed by a second lavage withgentamicin (240 mg) and clindamycin (600 mg) solution	Saline solution irrigation	30 days	Purulent discharge from the surgical site confirmed by microbiological culture	SSII: 2/51C: 10/51
							IncisionalI: 2/51C: 7/51
							AbscessI: 0/51C: 3/51
Al Ramahi et al. (2006) [25]	Caesarean sections	IW	50 mL 0.9% saline	No irrigation	4 weeks	Discontinuation associated with purulent discharge and local tenderness, hotness and/or redness	SSII: 11/104C: 10/102
Cervantes-Sanchez et al. (2000) [26]	Appendectomy	IW	300 mL saline delivered with a 20-mL syringe with a 1- gauge intravenous catheter applying the force of one hand at a distance of 2 cm from the site	No irrigation	4 weeks	Clear collection of pus, which empties spontaneously or after incision	SSII: 11/127C: 39/156
Hargrove et al. (2006) [27]	Orthopaedics	IW	2 L pulse lavage with saline	2 L saline via syringe	Discharge/ 30 days	CDC	SSII: 9/164C: 30/192
Nikfarjam et al. (2014) [28]	Laparotomy extending 2 h	IW	Pressurized pulse lavage (15 psi)Surgical irrigation device (Medline Industries, Mundelein, IL, USA)	Normal	30 days	CDC	SSII:4/68C: 12/62
Rogers et al. (1983) [29]	General surgery	IW	60-second irrigation with a PVP-I 10% solution	Saline	1 month	Purulent discharge	SSII: 04/86C: 11/101
Sindelar et al. (1979) [30]	General surgery	IW	60-second irrigation with a PVP-I 10% solution	Saline	12 weeks	If any amount of pus was discharged/serous drainage with bacterial growth	SSII: 7/242C: 39/258
Sindelar et al. (1985) [31]^a	Intra-abdominal surgery	IW	IW: PVP-I 10%	Saline in PCSaline in IW	NR mean hospitalization >3 wks	NR	SSII: 1/37C: 3/38
Lau et al. (1986) [32]	Appendectomy	IW	10-minute irrigation with a PVP-I 1% solution	No irrigation	6 weeks	Clear collection of pus, which empties spontaneously or after incision	SSII: 9/159C: 3/156
Chang et al. (2006) [33]	Spine surgery	IW	180-sec irrigation with PVP-I 0.35%, followed by copious irrigation with 0.9% saline	Irrigation with a copious saline	19.4 mos	All deep infections were confirmed by laboratory parameters, including erythrocyte sedimentation rate and level of C-reactive protein and a positive culture of biopsy	SSII: 0/120C: 6/124
Cheng et al. (2005) [34]	Spine surgery	IW	180-second irrigation with PVP-I 0.35%, followed by copious irrigation with a normal saline solution	Irrigation with a copious saline	15.5 month	Infection suspected when unusual pain, tenderness, erythema, induration, fever or incisional drainage was observed. Confirmed by erythrocyte sedimentation rate, C-reactive protein, and cultures from operative site or blood	SSII: 0/ 208C: 7/ 206
Kokavec et al. (2008) [35]	Orthopaedic	IW	PVP-I 0.35%	Saline	7.8 month	Pain, redness, swelling, and increased temperature of the incision	SSII: 0/89C: 2/73
Juul et al. (1985) [36]	Elective colorectal surgery	IW	Ampicillin 1 g in 10 mL of saline	No further prophylactic treatment	Until sutures removed	Accumulation of pus requiring surgical drainage	SSII: 5/105C: 5/98
Moesgaard et al. (1989) [37]	Intra-abdominal surgery	IW	Cefotaxime 2 g applied topically to the subcutaneous layer at time of incision closure	No irrigation	1 mo	Incision infection: accumulation of pus, draining spontaneously/after opening the site	TotalI: 19/87C: 19/90
						IA: proved by surgical drainage or ultrasound-guided aspiration.	SSII: 15/87C: 14/90
							AbscessI: 4/87C: 5/90
Pitt et al. (1980) [38]	Vascular surgery	IW	Cephradine (1.0 g) dissolved in 25 ml of saline solution	Saline irrigation	4 wks	Purulent materialdrained from the incision without evidence of priorischemia of the skin edges	SSII: 3/51C: 0/55
Ruiz Tovar et al. (2013) [39]	Lymph node dissection	IW	Saline plus gentamicin 240 mg in 500 mL	Saline irrigation	NR	Incision infection	SSII: 0/20C: 0/20
Ko et al. (1992) [40]	Cardiac bypass surgery	MC	Irrigation with a PVP-I 0.5% solution	Irrigation with saline	30 d	Mediastinitis. Pain, fever, erythema, drainage, sternal instability, tenderness on palpation, and leukocytosis. Occasionally, mediastinal aspiration or CT was needed. Subcutaneous wound problems were not included	MediastinalSSII: 11/990C: 6/990

This study described peritoneal as well as incisional irrigation. However, intra-abdominal infections were not included in the analyses because infection of this field was established.

C = control; CDC = Centers for Disease Control and Prevention; I = intervention; IW = incisional wound; LMW = low molecular weight; NA = not applicable; NR = not reported; PC = peritoneal cavity; PVP-I = aqueous povidone–iodine; SSI = surgical site infection; MC = mediastinal cavity.

Risk of bias

The results of the risk of bias evaluation are presented in Table 3. Overall, there was a serious risk of bias, predominantly attributable to unclear or high risk of selection and performance bias. Publication bias could not be detected or excluded. There was an insufficient number of studies included in the separate meta-analyses for appropriate interpretation of the funnel plots.

Table 3.

Risk of Bias

Series	Year	Sequence generation	Allocation concealment	Blinding of patients and staff	Blinding of outcome assessors	Incomplete outcome data	Selective reporting	Other bias
Tanaka et al. [20]	2015	Low	Low	High	High	Low	Low	Low
Baker et al. [21]	1994	Low	Low	Low	Low	Low	Low	Low
Freischlag et al. [22]	1984	Low	High	Unclear	Unclear	Low	Low	Low
Silverman et al. [23]	1986	Low	Low	Unclear	Low	Low	High	Low
Ruiz Tovar et al. [24]	2012	Low	Low	Unclear	Low	High	Low	Low
Al-Ramahi et al. [25]	2006	High	High	High	High	Low	Low	Low
Cervantes-Sánchez et al. [26]	2000	Low	Low	High	Low	Low	Low	Low
Hargrove et al. [27]	2006	Unclear	Unclear	Unclear	Unclear	High	Low	Low
Nikfarjam et al. [28]	2014	Low	Unclear	High	High	Low	Low	Low
Rogers et al. [29]	1983	High	High	High	Unclear	Low	Low	Low
Sindelar et al. [30]	1979	Unclear	Unclear	High	Unclear	Low	Low	Low
Sindelar et al. [31]	1985	Unclear	Unclear	High	Unclear	Low	Low	Low
Lau et al. [32]	1986	Unclear	Unclear	High	Low	Low	Low	Low
Chang et al. [33]	2006	Low	Unclear	High	Low	Low	Low	Low
Cheng et al. [34]	2005	Low	Unclear	High	Low	Low	Low	Low
Kokavec et al. [35]	2008	Unclear	Unclear	Unclear	Unclear	Low	Low	Low
Juul et al. [36]	1985	Low	High	Unclear	Unclear	Low	Low	Low
Moesgaard et al. [37]	1989	Unclear	High	High	Low	Low	Low	Low
Pitt et al. [38]	1980	Unclear	Unclear	Unclear	Low	Low	Low	Low
Ruiz Tovar et al. [39]	2013	Low	Low	Unclear	Unclear	Low	High	Low
Ko et al. [40]	1992	High	High	Unclear	Unlcear	Low	Low	Low

Data and analyses

A summary of the meta-analyses is presented in Table 4. For an extensive overview of all nine comparisons, corresponding data, and meta-analyses, we refer you to Appendix D.

Table 4.

Odds Ratios and 95% Confidence Intervals (CI) of Comparisons of Intraperitoneal Cavity, Incisional, and Mediastinal Cavity Irrigation

Intervention group	Control group	No. studies	Odds ratio (95% CI)	P
Intraperitoneal irrigation
Saline	No irrigation	1 [20]	1.81 (0.85–3.86)	0.13
Taurolidine 2%	Saline	1 [21]	1.00 (0.49–2.04)	1.00
Antibiotic solution	Saline/no irrigation	3 [22 –24]	0.42 (0.14–1.29)	0.19
Incisional wound
Saline	No irrigation	1 [25]	1.09 (0.44–2.69)	0.85
Syringe pressure saline	No irrigation	1 [26]	0.35 (0.19–0.65)	0.0009
Pulse pressure irrigation saline	Saline irrigation	2 [27,28]	0.30 (0.15–0.57)	0.0003
Aqueous povidone–iodine	Saline irrigation	7 [29 –35]	0.31 (0.13–0.73)	0.007
Antibiotic solution	Saline irrigation/no irrigation	5 [22,36 –39]	1.16 (0.64–2.12)	0.63
Mediastinal cavity
Aqueous povidone–iodine	Saline irrigation	1 [40]	1.84 (0.68–5.00)	0.23

No effective strategy for the reduction of SSIs with prophylactic peritoneal cavity irrigation was identified. Regarding incisional wound irrigation, mere saline was not effective in reducing SSIs [25]. However, when the saline was applied with a syringe to generate some pressure [26], a reduction in the risk of SSI compared with no irrigation was shown in one study (OR 0.35; 95% CI 0.19–0.65; P = 0.0009). This benefit also was demonstrated when pulse pressure irrigation with saline was compared with normal saline irrigation in a meta-analysis of two RCTs [27,28] (OR 0.30; 95% CI 0.08–0.86; p = 0.0003).

Irrigation with aqueous povidone–iodine demonstrated a significant benefit compared with saline irrigation in a meta-analysis of seven RCTs [29 -35] (OR 0.31; 95% CI 0.13–0.73; p = 0.007; Fig. 2A–C). This effect equals 50 fewer SSIs per 1,000 procedures (from 19 fewer to 64 fewer) (Appendices D and E comparison 7). The results where stratified according to subgroups based on the extent of wound contamination (Fig. 2B) and povidone–iodine concentration (Fig. 2C) to account for heterogeneity in the pooled analysis (I² = 63%). With this measure, heterogeneity decreased to an I² of 43%. The effect of irrigation with aqueous povidone–iodine on SSIs was attributable to incisional wound irrigation in clean and clean-contaminated procedures with PVP-I 10% and PVP-I 0.35%, respectively. No dose–response effect was seen.

FIG. 2.

Forest plot of incisional irrigation with various solutions. (A) Aqueous povidone–iodine vs. saline irrigation. (B) Aqueous povidone–iodine vs. saline stratified by wound contamination. (C) Aqueous povidone–iodine vs. saline stratified by concentration of povidone–iodine.

Antibiotic irrigation of the incisional wound showed no effect on SSI rate compared with no irrigation or saline irrigation in a meta-analysis of five RCTs [22,36-39] (OR 1.16; 95% CI 0.64–2.12; p = 0.63) (Fig. 3). This lack of effect equals 12 more SSIs per 1,000 (from 27 fewer to 76 more) (Appendices D and E comparison 8). Only one study reported on mediastinal irrigation with aqueous povidone–iodine compared with saline and showed no benefit of the former [40].

FIG. 3.

Forest plot of incisional wound irrigation with antibiotic vs. saline irrigation or no irrigation.

Adverse events

Among the included studies, six [29,31,33,34,36,41] reported no adverse events attributable to the intervention. Among these, two studies [33,34] investigating PVP-I incision irrigation in spinal surgery specifically reported no difference in fusion time or bone quality. One study [31] investigating PVP-I incision irrigation in abdominal surgery specifically reports a transient nine-fold serum iodine elevation (median 162 mcg/dL; range 27–1170 mcg/dL) but no signs of toxicity. After seven days, serum iodine concentrations had returned to the pre-operative range.

GRADE

GRADE tables with full assessment of the individual comparisons are presented in Appendix E. Overall, the quality of evidence was assessed as moderate to very low because of the serious risk of bias and serious imprecision.

Discussion

Evidence of low quality shows that prophylactic incisional irrigation with aqueous PVP-I solution has a significant benefit on the SSI rate, particularly in clean and clean-contaminated wounds. No dose–response effect was detected. With respect to incisional irrigation with saline, evidence of moderate to very low quality shows a significant effect on SSI rate when applied with force or using pulse pressure, but not with regular irrigation. There is no significant benefit to the use of antibiotic solutions for prophylactic incisional wound irrigation or for the use of pIOWI in the abdomen or mediastinum.

Although recommendations from existing guidelines are conflicting [9,10] and recent well-designed RCTs are lacking, as many as 97% of surgeons irrigate wounds in an effort to reduce the risk of SSI [6,7]. The most commonly used irrigation solution is saline followed by aqueous PVP-I or antibiotic solutions [6,42,43]. The efficacy and clinical safety of irrigation with these solutions has been the subject of debate [11, 44]. Various concentrations of PVP-I are effective rapidly against a broad spectrum of pathogens, methicillin-resistant Staphylococcus aureus (MRSA) included [45,46]. However, some in vitro studies [47 -49] have reported a negative effect of PVP-I on tissue regeneration, and older case studies describe serum iodine toxicity as a result of irrigation [50 -52]. However, these adverse effects could not be substantiated in clinical trials [29 -35;41]. When considering antibiotics, the bactericidal effect of most agents requires a substantial duration of contact time. It is unlikely that pIOWI with antibiotic solutions is performed with sufficient time to achieve clinical efficacy, and anaphylactic reactions have been reported [53]. In addition, the misuse of antibiotics is considered to be a major driving force in the emergence of antimicrobial resistance [54 -56]. In contrast, resistance of organisms to antiseptics is suggested to be low, possibly because of their multiple pharmacological targets [57,58]. Wound irrigation using aqueous chlorhexidine (CHX) may be an alternative when extrapolating the favourable results from alcohol-based CHX used for pre-operative skin preparation, but clinical data are lacking. The results of aqueous 0.05% chlorhexidine gluconate as a wound irrigation fluid in the laboratory and animal studies are promising [59,60].

Previous meta-analyses have assessed the effect of pIOWI but with serious limitations in their study selection, impeding extrapolation to current clinical practice. Fournel et al. [61] performed a systematic review of PVP-I in various applications and found a reduction of the incidence of SSI after aqueous PVP-I irrigation. Mueller et al. [8] assessed pIOWI systematically with saline, PVP-I, and antibiotic solutions and concluded that both PVP-I and antibiotic irrigation are effective in the reduction of SSI. However, both these reviews included studies investigating IOWI as a therapeutic measure for existing infections rather than as a preventive measure, and studies investigating IOWI did not meet current standards of systemic antibiotic prophylaxis. Fournel et al. [61] conducted a subgroup analysis of studies involving standard systemic antibiotic prophylaxis but left relevant studies out [29,30,35]. Mueller et al. included PVP-I powder (spray) application among IOWI studies using an irrigation solution, but the mechanical effect of removal and dilution of the bacterial load is not achieved by powder application. Present systematic review specifically investigates the prophylactic effect of IOWI on the incidence of SSI against the background of current standard of care.

The limitations of the present study are generally the result of deficiencies of the individual studies. The samples are small, resulting in little power per study and a high risk of failing to detect a true effect (β or Type two error). By conducting a meta-analysis, the power is increased and the risk of failing to detect a true effect reduced. Published studies on pIOWI were conducted mostly in the 1980s, 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. Strict inclusion criteria have limited the total number of appropriate studies to 21 RCTs. Variation is seen in the definition of SSI and followup duration (Appendix B), as the widely accepted definition of the CDC was first published in 1999 [15]. Therefore, SSIs may be overdiagnosed or underreported. And finally, the exposure times and application methods were heterogeneous.

In the absence of a proved effect of antibiotic irrigation and based on the risk of emerging antimicrobial resistance associated with the unnecessary use of antibiotics, irrigation with antibiotic solution should be avoided. Low-quality evidence suggests benefit from incisional wound irrigation with aqueous povidone–iodine. New high-quality RCTs are needed but might not have priority, considering the relatively large effect of prophylactic incisional wound irrigation using aqueous povidone–iodine. A combined approach of several interventions to reduce SSIs may be more favorable because it has become apparent that a bundle approach has been successful in some studies [62 -64].

Footnotes

Acknowledgments

This review was conducted in line with the development of the Global Guidelines for Prevention of Surgical Site Infections commissioned by the World Health Organisation (WHO) in Geneva. We received no funding to perform this research.

S.W. de Jonge, Q.J.J. Boldingh, J.S. Solomkin, B. Allegranzi, and M. Egger declare no conflicts of interest.

E.P. Dellinger reports personal fees from Merck, Ortho-McNeil, Targanta, Schering-Plough, Astellas, Allergan, Care Fusion, Durata, Pfizer, Applied Medical, Rib-X, Affinium, Tetraphase, Televancin, R-Pharm, Cubist, Melinta, and 3M and grants from Motif for research outside the submitted work.

M.A. Boermeester reports institutional grants from J&J/Ethicon, Acelity/KCI, Allergan/LifeCell, Ipsen, Baxter, Mylan, Bard, advisory board member of J&J/Ethicon, Acelity/KCI, and Allergan/LifeCell for research outside the submitted work.

Author Disclosure Statement

No competing financial interests exist.

References

Magill

, Edwards

, Bamberg

, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med, 2014; 370:1198–1208.

Allegranzi

, Bagheri Nejad

, Combescure

, et al. Burden of endemic health-care-associated infection in developing countries: Systematic review and meta-analysis. Lancet, 2011; 377:228–241.

Griškevičienė

. European Centre for Disease Prevention and Control. Surveillance of Surgical Site Infections in Europe 2010–2011. Stockholm. ECDC. 2013.

de Lissovoy

, Fraeman

, Hutchins

, et al. Surgical site infection: Incidence and impact on hospital utilization and treatment costs. Am J Infect Control, 2009; 37:387–397.

Kirkland

, Briggs

, Trivette

, et al. The impact of surgical-site infections in the 1990s: Attributable mortality, excess length of hospitalization, and extra costs. Infect Control Hosp Epidemiol, 1999; 20:725–730.

Whiteside

, Tytherleigh

, Thrush

, et al. Intra-operative peritoneal lavage: Who does it and why?. Ann R Coll Surg Engl, 2005; 87:255–258.

Pivot

, Tiv

, Luu

, et al. Survey of intraoperative povidone–iodine application to prevent surgical site infection in a French region. J Hosp Infect, 2011; 77:363–364.

Mueller

, Loos

, Haller

, et al. Intra-operative wound irrigation to reduce surgical site infections after abdominal surgery: A systematic review and meta-analysis. Langenbecks Arch Surg, 2015; 400:167–181.

Leaper

, Burman-Roy

, Palanca

, et al. Prevention and treatment of surgical site infection: Summary of NICE guidance. BMJ, 2008; 337:a1924.

10.

Anderson

, Podgorny

, Berrios-Torres

, et al. Strategies to prevent surgical site infections in acute care hospitals: 2014 update. Infect Control Hosp Epidemiol, 2014; 35:605–627.

11.

Barnes

, Spencer

, Graham

, et al. Surgical wound irrigation: A call for evidence-based standardization of practice. Am J Infect Control, 2014; 42:525–529.

12.

Allegranzi

, Bischoff

, de Jonge

, et al. New WHO recommendations on preoperative measures for surgical site infection prevention: An evidence-based global perspective. Lancet Infect Dis, 2016; 16:e276–e287.

13.

Allegranzi

, Zayed

, Bischoff

, et al. New WHO recommendations on intraoperative and postoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect Dis, 2016; 16:e288–e303.

14.

Moher

, Liberati

, Tetzlaff

, et al. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. BMJ, 2009; 339:b2535.

15.

Mangram

, Horan

, Pearson

, et al. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control, 1999; 27:97–132.

16.

Higgins

, Green

. Cochrane Handbook for Systematic Reviews of Interventions 2011. London U.K. 2011.

17.

Egger

, Davey Smith

, Schneider

, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ, 1997; 315:629–634.

18.

Guyatt

, Oxman

, Akl

, et al. GRADE guidelines 1: Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol, 2011; 64:383–394.

19.

DerSimonian

, Laird

. Meta-analysis in clinical trials. Control Clin Trials, 1986; 7:177–188.

20.

Tanaka

, Matsuo

, Kawaguchi

, et al. Randomized clinical trial of peritoneal lavage for preventing surgical site infection in elective liver surgery. J Hepatobiliary Pancreat Sci, 2015; 22:446–453.

21.

Baker

, Jones

, Nguyen-Van-Tam

, et al. Taurolidine peritoneal lavage as prophylaxis against infection after elective colorectal surgery. Br J Surg, 1994; 81:1054–1056.

22.

Freischlag

, McGrattan

, Busuttil

. Topical versus systemic cephalosporin administration in elective biliary operations. Surgery. 1984; 96(4):686–93.

23.

Silverman

, Ambrose

, Youngs

. The effect of peritoneal lavage with tetracycline solution of postoperative infection: A prospective, randomized, clinical trial. Dis Colon Rectum, 1986; 29:165–169.

24.

Ruiz-Tovar

, Santos

, Arroyo

, et al. Effect of peritoneal lavage with clindamycin–gentamicin solution on infections after elective colorectal cancer surgery. J Am Coll Surg, 2012; 214:202–207.

25.

Al-Ramahi

, Bata

, Sumreen

, et al. Saline irrigation and wound infection in abdominal gynecologic surgery. Int J Gynaecol Obstet, 2006; 94:33–36.

26.

Cervantes-Sánchez

, Gutiérrez-Vega

, Vázquez-Carpizo

, et al. Syringe pressure irrigation of subdermic tissue after appendectomy to decrease the incidence of postoperative wound infection. World J Surg, 2000; 24:38–41.

27.

Hargrove

, Ridgeway

, Russell

, et al. Does pulse lavage reduce hip hemiarthroplasty infection rates?. J Hosp Infect, 2006; 62:446–449.

28.

Nikfarjam

, Weinberg

, Fink

, et al. Pressurized pulse irrigation with saline reduces surgical-site infections following major hepatobiliary and pancreatic surgery: Randomized controlled trial. World J Surg, 2014; 38:447–455.

29.

Rogers

, Blouin

, O'Leary

. Povidone–iodine wound irrigation and wound sepsis. Surg Gynecol Obstet, 1983; 157:426–430.

30.

Sindelar

, Mason

. Irrigation of subcutaneous tissue with povidone–iodine solution for prevention of surgical wound infections. Surg Gynecol Obstet, 1979; 148:227–231.

31.

Sindelar

, Brower

, Merkel

, et al. Randomised trial of intraperitoneal irrigation with low molecular weight povidone–iodine solution to reduce intra-abdominal infectious complications. J Hosp Infect, 1985; 6(Suppl A):103–114.

32.

Lau

, Fan

, Chu

, et al. Combined topical povidone–iodine and systemic antibiotics in postappendicectomy wound sepsis. Br J Surg, 1986; 73:958–960.

33.

Chang

, Chang

, Wang

, et al. Can povidone–iodine solution be used safely in a spinal surgery?. Eur Spine J, 2006; 15:1005–1014.

34.

Cheng

, Chang

, Wang

, et al. Efficacy of dilute Betadine solution irrigation in the prevention of postoperative infection of spinal surgery. Spine, 2005; 30:1689–1693.

35.

Kokavec

, Fristáková

. (Efficacy of antiseptics in the prevention of post-operative infections of the proximal femur, hip and pelvis regions in orthopedic pediatric patients: Analysis of the first results) [Czech]. Acta Chir Orthop Traumatol Cech, 2008; 75:106–109.

36.

Juul

, Merrild

, Kronborg

. Topical ampicillin in addition to a systemic antibiotic prophylaxis in elective colorectal surgery: A prospective randomized study. Dis Colon Rectum, 1985; 28:804–806.

37.

Moesgaard

, Nielsen

, Hjortrup

, et al. Intraincisional antibiotic in addition to systemic antibiotic treatment fails to reduce wound infection rates in contaminated abdominal surgery: A controlled clinical trial. Dis Colon Rectum, 1989; 32:36–38.

38.

Pitt

, Postier

, MacGowan

, et al. Prophylactic antibiotics in vascular surgery: Topical, systemic, or both?. Ann Surg, 1980; 192:356–364.

39.

Ruiz-Tovar

, Cansado

, Perez-Soler

, et al. Effect of gentamicin lavage of the axillary surgical bed after lymph node dissection on drainage discharge volume. Breast, 2013; 22:874–878.

40.

, Lazenby

, Zelano

, et al. Effects of shaving methods and intraoperative irrigation on suppurative mediastinitis after bypass operations. Ann Thorac Surg, 1992; 53:301–305.

41.

Sindelar

, Mason

. Intraperitoneal irrigation with povidone–iodine solution for the prevention of intra-abdominal abscesses in the bacterially contaminated abdomen. Surg Gynecol Obstet, 1979; 148:409–411.

42.

BusinessWire. Survey Conducted at AORN Congress Reveals Need for New and Better Surgical Site Infection Prevention Strategies. 2013 [Available at: www.businesswire.com/news/home/20130311005412/en/Survey-Conducted-AORN-Congress-Reveals-Surgical-Site

43.

Galland

, Saunders

, Mosley

, et al. Prevention of wound infection in abdominal operations by peroperative antibiotics or povidone–iodine: A controlled trial. Lancet, 1977; 2:1043–1045.

44.

Edmiston

Jr , Bruden

, Rucinski

, et al. Reducing the risk of surgical site infections: Does chlorhexidine gluconate provide a risk reduction benefit?. Am J Infect Control, 2013; 41(5 Suppl):S49–S55.

45.

Haley

, Marling-Cason

, Smith

, et al. Bactericidal activity of antiseptics against methicillin-resistant Staphylococcus aureus. J Clin Microbiol, 1985; 21:991–992.

46.

Berkelman

, Holland

, Anderson

. Increased bactericidal activity of dilute preparations of povidone–iodine solutions. J Clin Microbiol, 1982; 15:635–639.

47.

Lineaweaver

, McMorris

, Soucy

, et al. Cellular and bacterial toxicities of topical antimicrobials. Plast Reconstr Surg, 1985; 75:394–396.

48.

Cooper

, Laxer

, Hansbrough

. The cytotoxic effects of commonly used topical antimicrobial agents on human fibroblasts and keratinocytes. J Trauma, 1991; 31:775–782.

49.

Kaysinger

, Nicholson

, Ramp

, et al. Toxic effects of wound irrigation solutions on cultured tibiae and osteoblasts. J Orthop Trauma, 1995; 9:303–311.

50.

Lavelle

, Doedens

, Kleit

, et al. Iodine absorption in burn patients treated topically with povidone-iodine. Clin Pharmacol Ther, 1975; 17:355–362.

51.

Pietsch

, Meakins

. Complications of povidone–iodine absorption in topically treated burn patients. Lancet, 1976; 1:280–282.

52.

Aiba

, Ninomiya

, Furuya

, et al. Induction of a critical elevation of povidone–iodine absorption in the treatment of a burn patient: Report of a case. Surg Today, 1999; 29:157–159.

53.

Damm

. Intraoperative anaphylaxis associated with bacitracin irrigation. Am J Health Syst Pharm, 2011; 68:323–327.

54.

WHO. The evolving threat of antimicrobial resistance: Options for action. Geneva. World Health Organization. 2012 [Available at: http://apps.who.int/iris/bitstream/10665/44812/1/9789241503181_eng.pdf

55.

Holmes

, Moore

, Sundsfjord

, et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet, 2016; 387:176–187.

56.

Laxminarayan

, Duse

, Wattal

, et al. Antibiotic resistance: The need for global solutions. Lancet Infect Dis, 2013; 13:1057–1098.

57.

Sheldon

Jr.

Antiseptic “resistance”: Real or perceived threat?. Clin Infect Dis, 2005; 40:1650–1656.

58.

Leaper

, McBain

, Kramer

, et al. Healthcare associated infection: Novel strategies and antimicrobial implants to prevent surgical site infection. Ann R Coll Surg Engl, 2010; 92:453–458.

59.

Edmiston

Jr , Bruden

, Rucinski

, et al. Reducing the risk of surgical site infections: Does chlorhexidine gluconate provide a risk reduction benefit?. Am J Infect Control, 2013; 41:S49–S55.

60.

Platt

, Bucknall

. An experimental evaluation of antiseptic wound irrigation. J Hosp Infect, 1984; 5:181–188.

61.

Fournel

, Tiv

, Soulias

, et al. Meta-analysis of intraoperative povidone–iodine application to prevent surgical-site infection. Br J Surg, 2010; 97:1603–1613.

62.

Keenan

, Speicher

, Thacker

, et al. The preventive surgical site infection bundle in colorectal surgery: An effective approach to surgical site infection reduction and health care cost savings. JAMA Surg, 2014; 149:1045–1052.

63.

Bull

, Wilson

, Worth

, et al. A bundle of care to reduce colorectal surgical infections: An Australian experience. J Hosp Infect, 2011; 78:297–301.

64.

Cima

, Dankbar

, Lovely

, et al. Colorectal surgery surgical site infection reduction program: A National Surgical Quality Improvement Program-driven multidisciplinary single-institution experience. J Am Coll Surg, 2013; 216:23–33.

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