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Patient Safety Tip of the Week

November 15, 2022

Which Antiseptic?



When we evaluate a medication or a procedure or any intervention, we look at both benefits and risks. When it comes to skin disinfectants, the obvious benefit is avoidance of infection. The most serious potential risk is flammability and risk of surgical fire.


Chlorhexidine is the most widely used skin disinfectant in surgery. It is an alcohol-based preparation. In our May 19, 2015 Patient Safety Tip of the Week “Dueling Chlorhexidine Studies” we discussed a series of studies on chlorhexidine for a number of purposes, some of which were pro, and others con. The issue, of course, was complicated by patient safety’s infamous “first scandal”, in which the editor of the Journal of Patient Safety lobbied the National Quality Foundation to include verbiage favorable to chlorhexidine in its recommendations, at a time when he had an undisclosed financial conflict of interest. (He was subsequently removed from NQF committees and his post as editor of the Journal of Patient Safety.)


But chlorhexidine has largely remained the #1 skin disinfectant now for many years. The newest AORN guidelines (AORN 2022) states that rapid, persistent, and cumulative action can be achieved by selecting a surgical skin preparation agent that combines alcohol with another antiseptic. Further, “the collective evidence supports that alcohol-based skin antiseptics are more effective than aqueous-based skin antiseptics in reducing SSI incidence. Use an alcohol-based skin antiseptic for surgical site preparation unless contraindicated.” It does discuss contraindications to alcohol-based antiseptics, such as proximity to areas of mucosa, open wounds, or the patient’s cornea or ear, or if dry-time is likely to be inefficient or unachievable due to large amounts of hair, of which removal may not be feasible or desired. It says that selection of an alcohol-based antiseptic should be based on individual patient assessment, including consideration of allergies or sensitivities and the location of the surgical site to which it will be applied.


Two recent studies, published in two Lancet journals, add to our knowledge base of efficacy of skin disinfectants.


Jalalzadeh and colleagues (Jalalzadeh 2022) did a systematic review and network meta-analysis comparing different preoperative skin antiseptics in the prevention of SSI;s in adult patients undergoing surgery of any wound classification. They looked at studies that directly compared two or more antiseptic agents (ie, chlorhexidine, iodine, or olanexidine) or concentrations in aqueous and alcohol-based solutions. Their study was published in The Lancet Microbe. 33 studies were eligible for the systematic review, and 27 studies with 17,735 patients reporting 2144 SSI’s were included in the quantitative analysis. Only 2.0-2.5% chlorhexidine in alcohol (relative risk 0·75) and 1.5% olanexidine (RR 0.49) significantly reduced the rate of SSI’s compared with aqueous iodine. But bias was evident in many of the studies. Seven of the RCT’s (randomized controlled trials) were at high risk of bias, 24 had some concerns, and two had low risk of bias. Heterogeneity across the studies was moderate. But overall, in line with previous research, they found a benefit of chlorhexidine in alcohol over both aqueous iodine and iodine in alcohol for the prevention of SSI’s in all wound classifications, particularly 2.0-2.5% chlorhexidine in alcohol. In contrast to a previous network meta-analysis, they found no additional benefit from 4.0% chlorhexidine in alcohol. The efficacy of olanexidine was established by a single randomized trial, so further investigation is needed. Of note, the studies that mentioned adverse events noted only mild events and none reported a substantial difference in adverse events between groups.


Most comparative studies have been performed in patients undergoing clean surgery. What about those with open wounds? Many surgeons avoid alcohol-based solutions for antisepsis of open wounds because of the potential for tissue toxicity and the risk of electrocautery fire or chemical burn hazard from alcohol pooling in the wound or beneath a surgical tourniquet. So investigators (PREP-IT Investigators 2022) conducted a cluster-randomized, crossover trial at 14 hospitals in Canada, Spain, and the USA on adults aged 18 years or older with an open extremity fracture were treated with a surgical fixation implant. Participating sites were randomly assigned (1:1) to use either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate immediately before surgical incision; sites then alternated between the study interventions every 2 months. Participants, health-care providers, and study personnel were aware of the treatment assignment due to the color of the solutions, but the outcome adjudicators and data analysts were masked to treatment allocation. The primary outcome was surgical site infection. An SSI occurred in 7% of 787 participants in the povidone-iodine group and 7% of 784 in the chlorhexidine gluconate group. The report does not specify adverse events. The researchers concluded that, for patients who require surgical fixation of an open fracture, either aqueous 10% povidone-iodine or aqueous 4% chlorhexidine gluconate can be selected for skin antisepsis on the basis of solution availability, patient contraindications, or product cost.


We’ve previously noted that chlorhexidine preparations with alcohol are typically flammable and have been implicated in some surgical fires (see our Patient Safety Tips of the Week for December 13, 2011 “Surgical Fires Again”, August 12, 2014 “Surgical Fires Back in the News”, and December 16, 2014 “More on Each Element of the Surgical Fire Triad”). After a case described in the latter column a hospital implemented a policy prohibiting alcohol-based skin preps in any emergency surgery that does not allow sufficient drying time (usually 3 minutes or longer). Instead, they went back to non-alcohol-based preps like Betadine for such emergency cases. And in our April 24, 2012 Patient Safety Tip of the Week “Fire Hazard of Skin Preps, Oxygen” we noted a hospital in New Zealand switched from alcohol-based skin disinfectants to aqueous-based skin preps for ob/gyn procedures after a surgical fire during a C-section. We’ve also noted problems with “the fine print” on package inserts and labels in some cases. In several of our prior columns (see our January 10, 2017 Patient Safety Tip of the Week “The 26-ml Applicator Strikes Again!”) we noted another surgical fire in which a hospital had switched from the 10.5 ml Chloraprep applicator, which did not have the warning to avoid use in head and neck surgery, to the 26 ml applicator which did have the warning. It was actually quite predictable that staff would assume the new supplies were the same as the old and not “read the fine print”.


Skin disinfectants are important in avoiding surgical site infections. Be sure you choose the most appropriate one, based on the type and location of surgery. And make sure you follow recommended procedures for use of each type of disinfectant.






AORN (Association of periOperative Registered Nurses). Key Takeaways: New Recommendation: Guideline for Patient Skin Antisepsis. Periop Today 2022; Publish Date: October 12, 2022



Jalalzadeh H, Groenen H, Buis DR, et al. Efficacy of different preoperative skin antiseptics on the incidence of surgical site infections: a systematic review, GRADE assessment, and network meta-analysis. Lancet Microbe 2022; Published Online First August 16, 2022



PREP-IT Investigators. Aqueous skin antisepsis before surgical fixation of open fractures (Aqueous-PREP): a multiple-period, cluster-randomised, crossover trial. The Lancet 2022; 400(10360): 1334-1344 October 15, 2022





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