To the Editor
Thank you for the opportunity to respond to your readerÕs questions concerning the use of chlorhexidine-based solutions 1) with regional anesthesia, 2) near the eyes and ears, and 3) with routine IV catheter placement.
Chlorhexidine (CHG) or tinctures of CHG antiseptic solutions have been used extensively outside the United States for anesthesia procedures.1 Interestingly, the US Physician Desk Reference (PDR), as of 1984, warns that “chlorhexidine gluconate is for external use only. Keep out of eyes and ears and avoid contact with meninges.” Before 1984, the PDR did not have the “avoid contact with meninges” warning. There are two referenced articles for neurotoxicity, both of which are animal studies. One article, published in 1955, was a study with many chemicals and detergent compounds that were injected into the cerebral spinal fluid of monkeys; neurotoxicity was seen with all compounds.2 A second study published in 1984, based on a rat model, involved injecting a CHG solution into the anterior chamber of the eye. This study showed degeneration of adrenergic nerves and suggested that neurotoxic effects on thin myelinated fiber systems in the CNS should be investigated.3 Since the publication of the 1984 PDR warning, an article entitled “Use of a Chlorhexidine Dressing to Reduce Microbial Colonization of Epidural Catheters” from Anesthesiology, 1990, has been released with an epidural catheter study. This CHG-impregnated split dressing absorbs fluid, which allows the release of CHG to the site; in this study there were no cited adverse events.4 The literature states that this dressing is indicated for use with epidural catheters. In 2001, Kinirons and Mimoz published a study comparing a CHG-based antiseptic to povidone-iodine in the reduction of colonization in epidural catheters; interestingly, the patient population was children. Conclusion: CHG was superior to PVP-I.5
Deafness has been demonstrated in patients who have undergone vascular myringoplasty operations; the common factor was the use of 0.05% CHG in 70% alcohol for perioperative disinfection of the middle ear. It was thought that the solution had penetrated the membrane, entered the inner ear and caused damage to the cochlea. This direct exposure did result in permanent hearing loss.6 Animal model studies have demonstrated severe vestibular and cochlear damage; the extent of damage was related to the concentration and the duration of exposure.7,8 Other antiseptics with high levels of alcohol or detergent have had similar ototoxicity concerns.9
Dilute solutions of pure CHG have been used for eye irrigation (0.05%) and as a preservative for eye drops (0.01%). Solutions of higher concentrations and formulations that contain a vehicle for the drug delivery can cause eye damage. Direct application of a topical 2% CHG to the eye demonstrated no changes to the cornea by direct observation or light microscopy; additional studies demonstrated superficial epithelial changes examined by electron microscopy following application of 0.1% and 0.5% CHG solutions.10,11 Concentrations of 2% CHG or greater were clearly toxic to both the corneal epithelium and conjunctiva; a concentration of 1% produced no significant delay in epithelial healing but did cause mild conjunctivitis.12 Accidental splashes entering the eye during normal hand washing procedures using a 4% CHG-detergent based solution have caused irritation but have resolved completely following irrigation of the eye. From the information available, the detergents present in the handwash formulation, or possibly a combination of CHG and excipients are more likely to cause permanent ocular damage than the CHG alone. CHG solutions in an alcohol-base are not appropriate solutions for eye care.
Intravascular catheter placement is the most common procedure used in caring for hospitalized patients and often leads to catheter-related bloodstream infection (CR-BSI). The use of antiseptic solutions for skin disinfection prior to catheter insertion and site maintenance can help prevent infection, especially in the immunocompromised and intensive care patient (ICU). Catheter-related bloodstream infections double the number of ICU admissions, increase costs an estimated $40,000 per patient survivor, increase the average length of stay by 7 days, and demonstrate mortality rates of 35%.13 Povidone-iodine solution (PVP-I) is the most commonly used skin disinfectant in the US today. But the recent release of a meta-analysis evaluating PVP-I to CHG gluconate indicated that CHG is superior for vascular catheter site care.14
In evaluations of clinical efficacy and cost savings, the implementation of a CHG-based solution will improve patient outcomes and is economically feasible.
Cynthia T Crosby
Director, Clinical Affairs
Overland Park, KS
- Adam MN, Dinulescu T, Mathieu P, et al. Comparison of the efficacy of 2 antiseptic solutions in the prevention of infection from peridural catheters. Cah Anesthesiol 1996;44:465-7.
- Hurst EW. Adhesive arachnoiditis and vascular blockage caused by detergents and other chemical irritants: an experimental study. In: Stewart MJ, Cameron GR, Oakley CL, Collins DH, MacDonald A, eds. The Journal of Pathology and Bacteriology. London, Oliver and Boyd Ltd., 167-178, 1955.
- Henschen A, Olson L. Chlorhexidine-induced dengeneration of adrenergic nerves. Acta Neuropathol 1984;63:18-23.
- Shapiro JM, Bond EL, Garman JK. Use of a chlorhexidine dressing to reduce microbial colonization of epidural catheters. Anesthesiology 1990;73:625-31.
- Kinirons B, Mimoz O, Lafendi L, et al. Chlorhexidine versus povidone iodine in preventing colonization of continuous epidural catheters in children. Anesthesiology 2001;94:239-44.
- Bicknell PG. Sensorineural deafness following myringoplasty operations. J Laryngol Otol 1971;85:957-61.
- Morizono T, Johnstone BM, Hadjar E. The ototoxicity of antiseptic (preliminary report). J Otolaryngol Soc Aust 1973;3:550-3.
- Igarashi Y, Suzuki JI. Cochlear ototoxicity of chlorhexidine gluconate in cats. Arch Otorhinolaryngol 1985;242:167-76.
- Morizono T, Johnstone BM, Entjep H. Sensorineural deafness caused by perioperative antiseptics. Otologia Fukuoka 1974;20:97-9.
- Browne RK, Anderson AN, Charvez BW, Azzarello RJ. Ophthalmic response to chlorhexidine digluconated in rabbits. Toxicol Appl Pharmacol 1975;32:621-7.
- Dormans JA, van Logten MJ. The effect of ophthalmic preservatives on the corneal epithelium of the rabbit: A scanning electron microscopical study. Toxicol Appl Pharmacol 1982;62:251-61.
- Hamill MB, Osato MS, Wilhelmus KR. Experimental evaluation of chlorhexidine gluconate for ocular antisepsis. Antimicrob Agents Chemother 1984;26:793-6.
- Ross VM, Orr PA. Prevention of infections related to central venous catheters. Crit Care Nurs Q 1997;20:79-88.
- Chaiyakunapruk N, Veenstra DL, Lipsky BA, Saint S. Chlorhexidine compared with povidone-iodine solution for vascular catheter-site care: a meta-analysis. Ann Intern Med 2002;136:792-801.