Nancy E Epstein
  1. Clinical Professor of Neurosurgery, Schoold of Medicine, State University of New York at Stony Brook, NY and ℅ Dr. Marc Agulnick,1122 Franklin Avenue Suite 106, Garden City, NY 11530.

Correspondence Address:
Nancy E Epstein, MD, FACS, Clinical Professor of Neurosurgery, School of Medicine, State University of New Yorrk at Stony Brook, NY and ℅ Dr. Marc Agulnick, 1122 Franklin Avenue Suite 106, Garden City, NY 11530.


Copyright: © 2021 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Nancy E Epstein. Review: Perspective on ocular toxicity of presurgical skin preparations utilizing Chlorhexidine Gluconate/Hibiclens/Chloraprep. 06-Jul-2021;12:335

How to cite this URL: Nancy E Epstein. Review: Perspective on ocular toxicity of presurgical skin preparations utilizing Chlorhexidine Gluconate/Hibiclens/Chloraprep. 06-Jul-2021;12:335. Available from:

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Background: Chlorhexidine Gluconate (CHG), Hibiclens (4% CHG with 4% Isopropyl Alcohol Detergent), and Chloraprep (i.e. labeled CHG-based solutions), utilized as preoperative surgical preparatory solutions may all cause severe oculotoxicity and ototoxicity. Alternatively, 10% Povidone-Iodine (PI) solutions without detergent demonstrate minimal toxic effects on the eyes and ears.

Methods: Based on studies from 1984 to 2021, we compared the safety/efficacy of CHG-based versus PI-based solutions utilized for presurgical skin preparation near the cornea/eyes and ears (i.e., predominantly for cranial or cervical spine surgery).

Results: Some studies documented that even minimal exposure (i.e., “splash risk”) during face/neck skin preparation with CHG-based solutions could result in irreversible corneal injury and ototoxicity. Within minutes to hours, CHG-based non-detergent solutions posed the risks of; corneal epithelial edema, anterior stromal edema, conjunctival chemosis, bullous keratopathy, and de-epithelialization. Notably, even occlusive dressings like Tegaderm could not protect against CHG penetration. Alternatively, PI-based solutions posed no to minimal ocular and/or ototoxicity, while often demonstrating comparable protection against surgical site infections (SSI).

Conclusion: Chlorhexidine Gluconate (CHG), Hibiclens, and Chloraprep (i.e. CHG-based solutions) are often used as skin preparations near the face/eyes/spine (i.e., particularly anterior/posterior cervical procedures). However, if these solutions come in contact with the eyes, corneal irritation, abrasions, and even blindness may result. Alternatively, PI non-detergent solutions demonstrate safety/minimal oculotoxicity/ototoxicity, while frequently showing comparable efficacy against SSI.

Keywords: Chloraprep, Corneal toxicity, Hibiclens, Oculotoxicity, Ototoxicity, Povidone-iodine solution, Skin preparation


Chlorhexidine gluconate (CHG), Hibiclens (4% CHG and 4% Isopropyl Alcohol), and Chloraprep (i.e. CHG-based solutions) presurgical skin preparations have well-documented oculotoxicity and ototoxicity. Therefore, great care must be utilized to avoid eye and ear contact when utilizing these presurgical preparation solutions when performing cranial and/ or anterior or posterior cervical spine surgery, and occasionally, other procedures near the eyes/ears. Alternatively, Povidone-Iodine (PI) non-detergent solutions have demonstrated minimal eye/ear toxicity, while often showing comparable prophylaxis against surgical site infection (SSI). Here we reviewed the relative risks/benefits, and alternatives to CHG-based preoperative skin preparation solutions versus PI non-detergent solutions for patients undergoing procedures near the eyes/ears (i.e. cranial surgery, spinal surgery, and occasionally other procedures).


In 1984, Mac Rae et al. evaluated the corneal toxicity in rabbits of multiple skin preparations [ Table 1 ].[ 5 ] These included; tincture of iodine (2% iodine, 2.35% sodium iodine, 46% ethanol), Hibiclens (4% chlorhexidine; 4% isopropyl alcohol with detergent), PhisoHex (3% hexachlorophene/detergent), Lavacol (70% ethanol), 7.5% povidone iodine scrub (PIS plus detergent), and 10% PI solutions (PI without detergent). At 3 h, all skin preparations resulted in marked de-epithelialization, conjunctival chemosis, and/or anterior stromal edema except the 10% PI solution without detergent and 0.9% Normal Saline. They concluded that only the 10% PI solution without detergent and NS showed no significant toxicity, while all other skin preparations were ototoxic or oculotoxic (i.e., to the cornea).

Table 1:

Oculotoxicity of CHG-based versus PI-based solutions when used as a skin preparation. Near the eyes/ears (i.e., face) and cervical spine.



Multiple studies demonstrated significant corneal toxicity when using CHG-based preoperative skin preparation solutions for cranial, cataract, or spinal surgery [ Table 1 ].[ 6 , 9 ] Van Rij (1995) noted that mistakenly using CHG, Cetrimide or Cialit solutions for irrigation during cataract surgery resulted in acute corneal changes that included; epithelial edema, bullous keratopathy, loss of keratocytes, and loss of the endothelial cell layer.[ 9 ] In Murthy et al. (2002) case study, eye drops containing Topical CHG (0.0.2%) were utilized in a 45-year-old patient (2002).[ 6 ] Within 8 weeks, they encountered near complete loss of the corneal endothelium/epithelial cells resulting in ulcerative keratitis (i.e., later warranting a penetrating keratoplasty), and ulceration involving Bowman’s membrane.


Several studies documented that CHG-based versus PI-based skin preparation solutions provided comparable or superior prevention of SSI [ Table 1 ].[ 3 , 4 ] In 2010, Darouiche et al., in a study specifically designed to address the insertion of percutaneous catheters, found that CHG (409 patients) significantly reduced the risk of postoperative superficial and deep SSI at 30 postoperative days versus those receiving PI (440 patients).[ 3 ] Note, however, that the Centers for Disease Control did not issue a specific recommendation favoring CHG-based soutions over PI solutions to address other surgical procedures including spine operations (i.e., also approximately 27 million total operations performed/year in the US). In 2018, Ghobrial et al. compared the efficacy of the preoperative skin preparation with CHG versus PI solutions in 6959 consecutive patients undergoing a variety of spinal procedures (2011–2015); the infection rates were comparable for both types of skin preparations (i.e., 2 (0.1%) infections for minimally invasive surgical cases (total 885) and 1.1% for open procedures (67 of 6074 cases)) 6074 [ Table 1 ].[ 4 ]


Even tight or bio occlusive dressings (i.e. Tegaderm) did not adequately protect the eyes from dripping skin CHG-based preparations or “splashes” [ Table 1 ].[ 1 , 2 , 7 , 8 ] In 2016, Bever et al. noted that CHG (4%) skin preparations resulted in 2 cases of significant ocular toxicity even when a tight protective Tegaderm dressing was placed to protect the eyes during surgery.[ 1 ] They recommended using PI solutions as a safe/effective alternative. If CHG-based solutions had to be used, “tightly occlusive dressings” including “eye pads should be added to avoid eye exposure, but would/could not guarantee adequate eye protection”. Brodie et al., (2018) similarly found that although CHG-based solutions provided excellent protection against infection (2-4%), using Tegarm as a bio occlusive dressing did not adequately protect the closed eyes from injury.[ 2 ] In their 3 pronged study, the first in vitro prong involved a 5 min application of CHG versus water; the CHG-based solution pentrated the edges of the Tegaderm d while simple water; CHG penetrated the edges of the Tegaderm dressing, but ismple water did not. In the second arm, central penetration of a Tegaderm dressing at 90 min was tested with a CHG-based solution versus water; the Tegarerm was impermeable to both. However, in the third in vivo arm, CHG-based solutions penetrated the Tegaderm edges within 10 min while water did not. They concluded that Tegaderm did not provide a sufficient bio occlusive dressing against CHG-based solutions, and that PI solutions should be used instead. In 2017, Steinsapir and Woodward noted 11 sentinel cases of corneal toxicity due to CHG for presurgical skin preparation on the face.[ 8 ] CHG-based solutions, even including minimal “splashes”, were toxic to the cornea. PI-based solutions, therefore, provided a safer and more effective alternative. In Shive et al. (2021), CHG-based solutions were used in head and neck surgery.[ 7 ] They resulted in 14 cases of ototoxicity and 38 cases of ocular toxicity; 8 from direct contact, 17 from periocular skin preparation, 7 preparations to the face and 1 to the scalp, 2 drips/distant sites, and 3 that were not specified.[ 7 ]


Multiple studies have documented the safety/efficacy of PI-based solution skin preparations when used near the eyes, ears, face, and neck (i.e., cranial, cervical spine, cataract/ surgery, other). Alternatively, CHG-based solutions (i.e., including Hibiclens and Chloraprep) have proven both oculotoxic and ototoxic. As both products have shown nearly comparable SSI prevention, careful attention must be given when using CHG over PI solutions near the eyes or ears.

Declaration of patient consent

Patient’s consent not required as there are no patients in this study.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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2. Brodie F, Bever G, Hwang DG. Performance of bio-occlusive dressing as barrier protection from presurgical chlorhexidine skin preparation. Curr Eye Res. 2018. 5: 576-9

3. Darouiche RO, Wall MJ, Itani KM, Otterson MF, Webb AL, Carrick MM. Chlorhexidine-Alcohol versus Povidone-Iodine for Surgical-Site Antisepsis. N Engl J Med. 2010. 362: 18-26

4. Ghobrial G, Wang MY, Green BA, Leyene HB, Manzano G, Vanni S. Preoperative skin antisepsis with chlorhexidine gluconate versus povidone-iodine: A prospective analysis of 6959 consecutive spinal surgery patients. J Neurosurg Spine. 2018. 28: 209-14

5. Mac Rae SM, Brown B, Edelhauser HF. The corneal toxicity of presurgical skin antiseptics. Am J Ophthalmol. 1984. 97: 221-32

6. Murthy S, Hawksworth NR, Cree I. Progressive ulcerative keratitis related to the use of topical chlorhexidine gluconate (0.02%). Cornea. 2002. 21: 237-9

7. Shive M, Hou Z, Zachary C, Cohen J, Rivers JK. The use of chlorhexidine as a skin preparation on the head and neck: A systematic review of ocular and ototoxicity. Dermatol Surg. 2021. 47: 34-7

8. Steinsapir KD, Woodward JA. Chlorhexidine keratitis: Safety of chlorhexidine as a facial antiseptic. Dermatol Surg. 2017. 43: 1-6

9. van Rij G, Beekhuis WH, Eggink CA, Geerards AJ, Remeijer L, Peis EL. Toxic keratopathy due to the accidental use of chlorhexidine, cetrimide and cialit. Doc Ophthalmol. 1995. 90: 7-14

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