Surgical site infections (SSIs) are the most common complication affecting one third of patients that undergo surgery globally [1]. Surgical site preparation immediately prior to surgery reduces the microbial burden on the surgical site prior to surgery and reduces the risk of SSIs [1,2]. Over time surgical site antiseptic preparations have undergone an evolution with increasing use of combination agents. Combination alcohol-based surgical site preparations were approved by the Food and Drug Administration (FDA) in 1998 (0.83 % povidone-iodine (PVP-I) with 72.5 % isopropyl alcohol (Prevail-FX)), 2002 (0.7 % iodine povacrylex and 74 % isopropyl alcohol (Duraprep)), and 2005 (2 % chlorhexidine gluconate (CHG) in 70 % isopropyl alcohol (Chloraprep)). Combination alcohol-based surgical site preparations have since been compared with aqueous solutions in multiple randomized controlled trials (RCTs) [[3], [4], [5], [6]]. Meta-analysis of these trials by the World Health Organization (WHO) found that combination alcohol-based antiseptic solutions reduce the risk of SSIs by 40 % compared with single agent aqueous solutions [1]. Based on this evidence, both the WHO and the Centers for Disease Control and Prevention (CDC) recommend surgical site preparation with an alcohol-based combination agent unless contraindicated [1,2].

In head and neck surgery, the anatomic proximity to the airway and oxygen increases the risk of surgical fire, contraindicating the use of alcohol-based antiseptic solutions. Furthermore, CHG-based surgical site preparations are absorbed through mucosal surfaces and should not be used when prepping the eyes, nose, or mouth. It remains unclear how best to adapt recent evidence on the effectiveness of different surgical site antiseptic solutions to head and neck surgery.

In patients undergoing head and neck surgery, is there an optimal antiseptic skin preparation that effectively prevents surgical site infections compared to those that have contraindications in head and neck surgery? What is the evidence available to support an optimal antiseptic surgical site preparation for head and neck surgery when relevant and associated contraindications are considered? With contraindications to alcohol due to fire risk and chlorhexidine due to toxicity, it is hypothesized that aqueous povidone‑iodine would be the ideal agent in reducing surgical site infections while avoiding contraindications specific to head and neck surgery.

In this article, we review the evidence on surgical site antiseptic solutions focusing on head and neck surgery. We highlight the indications and contraindications regarding antiseptic solutions in head and neck surgery and summarize major randomized clinical trials comparing different surgical site preparation agents. With this scoping review, we recommend options for surgical site preparation.

Povidone-iodine (PVP-I) is a complex of a polymer polyvinylpyrrolidone and iodine. The polyvinylpyrrolidone component of PVP-I has an affinity for cell membranes, which allows the delivery of iodine directly to the bacterial cell surface. Iodine penetrates into bacteria targeting proteins, nucleotides, and fatty acids in the cytoplasm and cytoplasmic membrane, which leads to the inactivation of molecules necessary for survival and, ultimately, bacterial cell death [7,8].

Aqueous 10 % PVP-I is available from multiple manufactures (examples include Betadine and Aplicare). High concentrations of PVP-I are toxic to the cornea [9]. Aqueous 5 % PVP-I (Betadine 5 %, Alcon) is FDA approved for surgical site preparation of the periocular region. Table 1 summarizes the instructions for use and warnings for PVP-I.

Chlorhexidine gluconate's (CHG) antibacterial effects are through destabilizing bacterial cell membranes. CHG initially damages the outer cell layers then crosses the cell wall or outer membrane resulting in damage to the cytoplasmic (inner) membrane. This leads to the leakage of intracellular components and cell death [8]. It works optimally at normal skin pH (5.0–7.0), and there is no evidence of absorption through intact skin.

Aqueous CHG 4.0 % (ex. Hibiclens) solution should be applied liberally to the surgical site twice for at least 2 min then dried with a sterile towel. This agent should not be used for general cleansing unless reduction of the bacterial population on the skin is necessary, and it should not be routinely used to treat wounds that involve more than the superficial layer of the skin. Dilute CHG (0.12 %, Peridex) is an FDA-approved antiseptic for mucosal surfaces in the mouth. Unique toxicities of CHG and PVP-I are summarized in Table 2.

The antimicrobial action of alcohol is most likely related to denaturation of proteins [8]. Alcohol has been combined with CHG and PVP-I in several single-step surgical site antiseptic solutions to simplify application and improve efficacy.

Iodine povacrylex (0.7 % available iodine) in 74 % isopropyl alcohol (ex. DuraPrep) combines dilute PVP-I and alcohol. The 26-mL applicator designed for surgical site preparation should not be used for head and neck surgery due to the risk of surgical fire. If there is any contact with the eyes, ears, or mouth, flush with cold water right away due to risk of serious injury if allowed to sit and remain.

2 % CHG with 70 % isopropyl alcohol (ex. ChloraPrep) combines CHG and alcohol. For head and neck surgery specifically, the 26-mL applicator also carries a written warning label recommending against its use (Table 1).