Effectiveness of surgical skin preparation solutions in orthopaedic surgery: A systematic review of the current comparative literature

Table 1 Surgical skin preparation demographics and results of studies evaluating more than one anatomical area

Ref.	Level of evidence	Surgery type	Sample size (n)	Interventions	Comparisons	Key findings
Beber et al[24], 2022, United States	Retrospective cohort (level 3)	Pediatric sports/UE, pediatric trauma, pediatric hip and LE	1416	2% chlorhexidine gluconate in 70% isopropyl alcohol (U); povidone-iodine (U, concentration unspecified)	SSI between the two cohorts	No difference in SSI was noted for all procedures between the two cohorts; no difference in SSI was noted for spine or hip/LE procedures between the two cohorts; in sports/UE procedures, povidone-iodine had a significantly lower rate of SSI (P = 0.005)
Sprague et al[25], 2024, United States	Randomized crossover trial (level 1)	Open upper and lower extremity fractures	1638	Aqueous 4% chlorhexidine gluconate (P); aqueous 10% povidone-iodine (P)	Comparing SSI between the preparation cohorts	No statistical difference in SSI between the two preparation cohorts
Sprague et al[25], 2024, United States	Randomized control trial (level 1)	Closed pelvis/acetabulum and lower extremity fractures, open upper and lower extremity fractures	8485	2% chlorhexidine gluconate in 70% isopropyl alcohol (S); 0.7% iodine povacrylex in 74% isopropyl alcohol (S)	Comparing SSI between the preparation cohorts	Closed fractures using iodine povacrylex resulted in lower odds of an SSI when compared with the chlorhexidine group (P = 0.049); in open fractures, there was no difference in SSI between the two preparation cohorts

UE: Upper extremity; LE: Lower extremity; S: Stick application; P: Paint application; U: Unspecified application method; SSI: Surgical site infection.

Table 2 Surgical skin preparation demographics and results of studies evaluating lower extremity surgery

Ref.	Level of evidence	Surgery type	Sample size (n)	Interventions	Comparisons	Key findings
Cho et al[27], 2023, China	Randomized control trial (level 1)	Total knee arthroplasty	150 (50 per group)	10% povidone-iodine scrub-and-paint (P); 2% chlorhexidine gluconate in 72% ethanol paint after povidone-iodine scrub (P); 10% povidone-iodine paint after 2% chlorhexidine gluconate in 72% ethanol scrub (P)	Post preparation culture swabs between the groups	Povidone-iodine scrub-and-paint group had positive cultures in 12% of patients; chlorhexidine gluconate paint after povidone-iodine scrub had positive cultures in 2%; povidone-iodine paint after chlorhexidine gluconate had positive cultures in 2%; isolated povidone-iodine scrub-and-paint had a significantly higher number of positive cultures (P = 0.037)
Droll et al[28], 2022, Canada	Randomized control trial (level 1)	Total hip arthroplasty	105	2% chlorhexidine gluconate in 70% isopropyl alcohol (S); 0.7% iodophor in 74% isopropyl alcohol (S)	Comparison of cultures pre-preparation and post-preparation	The pre-preparation chlorhexidine group had positive cultures in 93% of patients, and the iodophor group had positive cultures in 94% of patients; after preparation, the iodophor had a lower relative risk of a positive culture than the chlorhexidine group (RR = 0.40, 95%CI: 0.18-0.85)
Rouquette et al[29], 2020, France	Prospective cohort study (level 2)	Thigh sampling of lower extremity volunteers	30	5% povidone-iodine in 95% ethanol with adhesive polyester draping (U); 5% povidone-iodine in 95% ethanol with adhesive iodine draping (U); 0.5% chlorhexidine in 90% ethanol with adhesive polyester draping (U); 0.5% chlorhexidine in 90% ethanol with adhesive iodine draping (U)	Culture growth at 30 minutes intervals up to 90 minutes after draping	No protocols demonstrated superiority in reducing bacterial load
Morrison et al[30], 2016, United States	Randomized control trial (level 1)	Total joint arthroplasty	600	7.5% povidone-iodine scrub, followed by 10% iodine paint, and 75% isopropyl alcohol (P); preparation of group one plus 0.7% iodine povacrylex in 74% isopropyl alcohol after draping (S)	Rate of SSI and blistering between the groups	The intervention group with the additional intervention after draping had significantly lower superficial SSI (P = 0.02); the intervention group had lower rates of blistering, but this was not statistically significant
Peel et al[31], 2019, Australia	Randomized control trial (level 1)	Total joint arthroplasty	780	0.5% chlorhexidine gluconate in 70% ethanol (S); 1% iodine in 70% ethanol (S)	Postoperative SSI and superficial wound complications	No difference in superficial wound complications between the chlorhexidine and iodine-based groups; significantly higher odds of SSI in the chlorhexidine group when compared with the iodine group (OR = 3.55; 95%CI: 1.20-10.44; P = 0.022)
Ritter et al[32], 2020, Germany	Randomized control trial (level 1)	Lower limb fractures	279	2% chlorhexidine in 70% isopropyl alcohol (S); 1% povidone-iodine in 50% 2-propanol (S)	Postoperative SSI and wound healing disorders	The povidone-iodine group had significantly higher rates of SSI and wound healing disorders than the chlorhexidine group (P = 0.022)

S: Stick application; P: Paint application; U: Unspecified application method; SSI: Surgical site infection; RR: Risk ratio; CI: Confidence interval; OR: Odds ratio.

Table 3 Surgical skin preparation demographics and results of studies in foot and ankle surgery

Ref.	Level of evidence	Surgery type	Sample size (n)	Interventions	Comparisons	Key findings
Becerro de Bengoa Vallejo et al[33], 2009, Spain	Prospective randomized comparative study (level 2)	Foot	28	4% chlorhexidine gluconate scrub for 5 minutes + 70% isopropyl alcohol paint (P); 7.5% povidone-iodine scrub for 5 minutes + 10% povidone-iodine paint (P); prewash with 70% isopropyl alcohol for 3 minutes + 7.5% povidone-iodine scrub for 5 minutes + 10% povidone-iodine paint (P); 4% chlorhexidine gluconate immersion + prewash with 70% isopropyl alcohol for 3 minutes + 7.5% povidone-iodine scrub for 5 minutes + 10% povidone-iodine paint (P)	Culture growth of nail fold and first web space	The nailfold remained contaminated regardless of preparation type; the addition of alcohol may reduce the bacterial load in foot surgery, however, study results are limited due to lack of measurement of clinical infections
Cheng et al[34], 2009, United Kingdom	Randomized control trial (level 1)	Forefoot surgery	50	0.5% chlorhexidine gluconate in 70% isopropyl alcohol (S); 1% povidone-iodine in 23% isopropyl alcohol (S)	Culture growth before and after skin preparation	No significant difference in colony growth between skin preparation methods
Hunter et al[35], 2016, United States	Randomized control trial (level 1)	Foot and ankle surgeries	95	4% chlorhexidine application followed by 70% isopropyl alcohol rinse (P); 70% isopropyl alcohol followed by 4% chlorhexidine (P)	Cultures and postoperative SSI between the cohorts	The alcohol followed by chlorhexidine group showed a significant difference in positive cultures after draping (P = 0.02) and postoperatively (P = 0.05); there was no difference in SSI between the two cohorts
Keblish et al[36], 2005, United States	Randomized control trial (level 1)	Foot and ankle of volunteers	50	10% povidone-iodine alone (P); 10% povidone-iodine alone and 70% isopropyl alcohol pre-wash (P); 10% povidone-iodine and scrubbing with bristled brush (P); 70% isopropyl alcohol and scrubbing with bristled brush (N/A)	Cultures of hallux nailfold, interdigital web spaces, and anterior ankle	1.70% isopropyl alcohol and scrubbing with bristled brush showed a significant reduction in positive cultures from the nail-fold when compared with other preparation methods (P < 0.001); quantitative analysis found that bristled brushes had a significant decrease in heavy growth when compared to no bristles (P < 0.01)
Mehraban et al[37], 2021, United States	Randomized control trial (level 1)	Foot and ankle surgery	242	70% isopropyl alcohol followed by 2% chlorhexidine in 70% isopropyl alcohol (S); 7.5% povidone-iodine followed by 70% isopropyl alcohol followed by 2% chlorhexidine in 70% isopropyl alcohol (P + S)	Culture taken from the hallux nailfold	There was no significant difference in culture rate between cohorts
Ostrander et al[38], 2005, United States	Randomized control trial (level 1)	Foot and ankle surgery	125	2% chlorhexidine gluconate in 70% isopropyl alcohol (S); 0.7% iodine in 74% isopropyl alcohol (S); 3% chloroxylenol (S)	Culture at the toe and hallux sites	The chlorhexidine culture was significantly lower at both hallux (P = 0.01) and small toe site (P = 0.05) than the iodine group, and the iodine group was significantly lower than chloroxylenol (P = 0.001)
Rugpolmuang et al[39], 2012, Thailand	Randomized control trial (level 1)	Foot of volunteers	20	4% chlorhexidine gluconate scrub then painted with 2% chlorhexidine in 70% alcohol (P + S); 7.5% povidone-iodine scrub then painted with 10% povidone-iodine (P)	Cultures taken from toes, nail fold, interdigital spaces	There was no significant difference in culture rate between cohorts
Shadid et al[40], 2019, Netherlands	Randomized control trial (level 1)	Foot surgery	49	0.5% chlorhexidine with 70% isopropyl alcohol (S); 1% iodine with 70% isopropyl alcohol (S)	Cultures, complications and postoperative SSI between cohorts	There was no significant difference in SSI, complications or cultures between cohorts
Talhaoğlu and Çürük[41], 2023, Türkiye	Randomized trial (level 1)	Diabetic foot debridement	60	0.05% chlorhexidine gluconate before and after debridement, 10% povidone iodine (P + S); 10% povidone iodine (P)	Cultures taken after debridement	Microbial growth was 46.7% in the chlorhexidine group after debridement and 83.3% in the iodine alone group (P = 0.05); the mean number of species per foot was reduced in the chlorhexidine group (P = 0.05)

S: Stick application; P: Paint application; P + S: Paint and stick; N/A: Not applicable; SSI: Surgical site infection.

Table 4 Surgical skin preparation demographics and results of studies evaluating upper extremity surgery

Ref.	Level of evidence	Surgery type	Sample size (n)	Interventions	Comparisons	Key findings
Blonna et al[42], 2018, Italy	Prospective comparative study (level 2)	Proximal humerus fracture	40	1% povidone iodine in 50% isopropyl alcohol (P); 4% chlorhexidine followed by 1% povidone iodine in 50% isopropyl alcohol (P)	Comparison of positive culture rates	The 4% chlorhexidine followed by 1% povidone iodine in 50% isopropyl alcohol produced a significant decrease in positive coagulase-negative Staphylococci cultures when compared to the single preparation (P < 0.001)
Crutcher et al[43], 2024, United States	Randomized control trial (level 1)	Shoulders of volunteers	72	2% chlorhexidine in 70% isopropyl alcohol alone (S); 3% hydrogen peroxide followed by 2% chlorhexidine in 70% isopropyl alcohol (S)	Comparison of culture growth for C. acnes	No statistically significant difference in culture rate between the two interventions
Dörfel et al[44], 2021, Germany	Prospective crossover (level 2)	Shoulders of volunteers	16	2% chlorhexidine in 70% isopropyl alcohol (S); 3.24% povidone-iodine in 38.9% isopropyl alcohol and 37.3% ethanol (P)	Comparison of culture growth for aerobic and anaerobic bacteria	Aerobic skin flora was significantly reduced by povidone-iodine at 2.5 minutes of application than chlorhexidine (P = 0.04), but not at thirty minutes or three hours; anaerobic skin flora was significantly reduced by povidone-iodine at 2.5 minutes (P < 0.01) and 30 minutes (P < 0.01) of application than chlorhexidine, but not at three hours
Hancock et al[45], 2018, New Zealand	Randomized control trial (level 1)	Shoulder of volunteers	22	Two applications of 2% chlorhexidine in alcohol (S); 5% benzoyl peroxidase wash + 2% chlorhexidine in alcohol (S)	Comparison of culture growth for C. acnes of the anterior deltoid and axilla	No statistically significant difference in culture growth between the two groups
Mizels et al[46], 2024, United States	Prospective comparative study (level 3)	Total shoulder arthroplasty	61	70% ethyl alcohol followed by two applications of 2% chlorhexidine in 70% isopropyl alcohol (S); 70% ethyl alcohol followed by hydrogen peroxide followed by two applications of 2% chlorhexidine in 70% isopropyl alcohol (S)	Comparison of patient reported outcomes, infection rate, and revision surgeries	No statistical difference was found in patient reported outcomes between groups; no statistical difference was found in revision or infection rate between groups
Saltzman et al[47], 2009, United States	Randomized control trial (level 1)	All shoulder surgeries	150	2% chlorhexidine gluconate in 70% isopropyl alcohol (S); 0.7% iodophor 74% isopropyl alcohol (S); 0.75% iodine scrub and 1.0% iodine paint (P)	Comparing positive culture rate of the different preparation methods	The positive culture rate was significantly lower in the chlorhexidine group than the iodophor (P = 0.01) or iodine paint (P < 0.001) groups; chlorhexidine and iodophor significantly reduced positive coagulase-negative Staphylococcus cultures (P < 0.001 for both groups); no significant difference noted for positive C. acnes cultures between the groups
Wade et al[51], 2021, United Kingdom	Prospective cohort (level 2)	Upper limb surgeries	2454	Aqueous or alcoholic chlorhexidine (P) (concentration unspecified); aqueous or alcoholic povidone-iodine (P) (concentration unspecified)	Comparison of 90 days SSI between the two groups	Alcoholic povidone iodine produced a decreased risk of SSI in emergency upper extremity surgery (HR = 0.15; 95%CI: 0.02-0.94); alcoholic chlorhexidine produced a decreased risk of SSI in elective upper extremity surgery (HR = 0.30; 95%CI: 0.11-0.83)
Xu et al[49], 2017, United States	Randomized control trial (level 1)	Hand surgery	240	10% povidone-iodine (P); 2% chlorhexidine gluconate in 70% isopropyl alcohol (S); 0.7% iodine in 74% isopropyl alcohol (S)	Comparison of positive cultures	1.2% chlorhexidine gluconate and 70% isopropyl alcohol had higher rates of positive cultures than the 10% povidone-iodine and 0.7% iodine and 74% isopropyl alcohol groups (P < 0.001)
Yamakado[50], 2021, Japan	Randomized control trial (level 1)	Arthroscopic rotator cuff repair	151	1% chlorhexidine gluconate in 70% isopropyl alcohol (S); chlorhexidine alcohol with 3% hydrogen peroxide (S)	Comparison of the cultures of cut arthroscopic sutures and SSI	There was no statistically significant difference in the positive culture rate for C. acnes or number of SSI between the two groups

S: Stick application; P: Paint application; SSI: Surgical site infection; C. acnes: Cutibacterium acnes; HR: Hazard ratio; CI: Confidence interval.

Table 5 Surgical skin preparation demographics and results of studies evaluating spine surgery

Ref.	Level of evidence	Surgery type	Sample size (n)	Interventions	Comparisons	Key findings
Dromzee et al[52], 2012, France	Randomized clinical trial (level 1)	Pediatric scoliosis	56	Cyanoacrylate liquid (N/A); no cyanoacrylate liquid	Comparison of surgical site infection	No statistically significant difference in surgical site infection
Ghobrial et al[53], 2018, United States	Prospective cohort (level 2)	All spine cases	6959	2% chlorhexidine gluconate and 70% isopropyl alcohol (S); 7.5% povidone iodine solution (P)	Comparing culture rates and surgical site infections	There was no statistically significant difference between cohorts for culture growth or surgical site infections
Madariaga et al[54], 2024, United States	Retrospective comparative study (level 2)	Cervical spine	86	0.7% iodine povacrylex in 74% isopropyl alcohol (S); 0.77% iodine povacrylex in 74% isopropyl alcohol and 3% hydrogen peroxide (S)	Comparing post prep C. acnes culture and surgical site infection	There was no statistically significant difference in culture rate between cohorts
Savage et al[55], 2012, United States	Randomized control trial (level 1)	Lumbar spine surgery	100	2% chlorhexidine gluconate in 70% isopropyl alcohol (S); 0.7% available iodine in 74% isopropyl alcohol (S)	Comparing post prep culture rates and surgical site infection	There was no statistically significant difference in positive culture rate between cohorts
Yoshii et al[56], 2018, Japan	Prospective comparative study (level 2)	Posterior spine surgery	190	0.5% chlorhexidine in 79% ethanol (S); 10% povidone iodine (P)	Comparing culture rate and surgical site infection	There was no significant difference in culture rates immediately after skin preparation (P = 0.49); the positive culture rate after wound closure was significantly lower in the chlorhexidine group than the iodine group (P = 0.046)

N/A: Not applicable; S: Stick application; P: Paint application; C. acnes: Cutibacterium acnes.

Table 6 Methodological index for non-randomized studies criteria of comparative studies

MINORS criteria quality assessment
Ref.	Beber et al[24], 2022	Becerro de Bengoa Vallejo et al[33], 2009	Blonna et al[42], 2018	Dörfel et al[44], 2021	Ghobrial et al[53], 2018	Madariaga et al[54], 2024	Mizels et al[46], 2024	Rouquette et al[29], 2020	Wade et al[51], 2021	Yoshii et al[56], 2018
Clearly stated aim	2	2	2	2	2	2	2	2	2	2
Inclusion of consecutive patients	2	2	2	2	2	2	2	2	2	2
Prospective collection of data	2	2	2	2	2	2	2	2	2	2
Appropriate endpoints	2	1	2	2	2	2	2	2	2	2
Unbiased assessment endpoints	1	1	1	1	2	2	2	1	2	2
Appropriate follow-up	2	2	2	2	2	2	2	2	2	2
Loss to follow-up	2	2	2	2	2	2	2	2	1	2
Prospective calculation of study size	2	0	2	2	2	2	0	0	0	0
Adequate control group	2	1	2	1	2	2	2	2	1	2
Contemporary groups	2	1	1	1	2	2	2	2	1	2
Baseline equivalence of groups	2	1	1	1	2	2	2	2	1	2
Adequate statistical analysis	2	2	2	2	2	2	2	2	2	2
Cumulative MINORS score	23	17	21	20	24	24	22	21	18	22

MINORS: Methodological index for non-randomized studies; 0: Not reported; 1: Reported but inadequate; 2: Reported and adequate.