Iodine-Based Antiseptics and Hypersensitivity Reactions

Educational Objectives

The goal of this program is to improve management of hypersensitivity reactions to iodine-based antiseptics. After hearing and assimilating this program, the clinician will be better able to:

1. Assess the safety of povidone-iodine antisepsis for patients with previous reactions to iodine-based contrast dye and shellfish.
2. Use povidone-iodine for antisepsis before and during eye surgery.

Summary

Allergies to shellfish and contrast dye: patients may be labeled as having an iodine allergy because they have allergies to contrast agents or shellfish that contain iodine; Hinkle et al (2020) demonstrated greater rates of endophthalmitis in the absence of use of preoperative antiseptic products containing povidone-iodine (PI); studies in the 1970s proposed a link between allergies to iodine-containing contrast dye and allergies to shellfish; early studies show that 6% of patients with allergies to seafood have sensitivity to contrast dye; however, subsequent studies have shown no relationship between allergies to shellfish and reactions to radiocontrast dye

Reactions to contrast dye: related to the nature of the dyes; traditional contrast dyes are highly concentrated and hypertonic, which causes cells to rupture; rupture of cells containing histamine can cause a dose-dependent anaphylactoid reaction (not anaphylactic); therefore, administration of steroids is unlikely to be helpful; reactions are less common with newer, low-osmotic contrast agents

Shellfish allergy: a tropomyosin allergy; individuals may have allergies to other types of crustaceans and mollusks, but not scaled fish (allergies to scaled fish are caused by parvalbumin); chitins and arthropods (including dust mites) can release histamines; shellfish allergy can be potentiated by alcohol

Types of antiseptics: chlorhexidine — concentrated solutions are highly toxic to the epithelium in the cornea, particularly with long exposure times; preferred option for skin preparation, due to greater efficacy and staining power than PI, but not generally used around the eye or in ophthalmology due to risk for corneal perforation; available in alcohol or aqueous forms; povidone-iodine — highly effective against most common infectious agents seen in ophthalmology; concentration listed on the bottle is the concentration of the compound (not free iodine) and ranges from 6% to 20%; toxicity can occur, but window for effectiveness without toxicity is wide; relative concentration of free iodine in the solution increases as the concentration of PI is diluted; studies from Japan show that 0.0125% PI can be placed in the vitreous in cases of endophthalmitis and decreases the doubling time of the bacteria (this strategy is not currently used in the United States [US])

Rationale for use of PI before eye surgery: contamination of the anterior chamber occurs in ≤20% of cataract surgeries and are mostly derived from bacteria on the skin around the eye; most endophthalmitis isolates have multiple drug resistance, but PI is effective against most pathogens (ie, all bacteria, most viruses), with the exception of spores; PI is most effective at concentrations of 0.1% to 1.0%; PI was designed to penetrate skin and must be adequately concentrated to do so; surfactants in PI differ among countries (nonoxynol-9 is used in the US); iodine interacts with multiple biocidal targets and chemical bonds; therefore, no resistance has developed to PI; disinfection rate is related to concentration of free iodine; disinfection capacity is related to total iodine available and amount supplied; free iodine is used up in reactions with the intended target and fomites on the surface of the eye

Clinical pearls for use of PI

Timing: PI should be applied prior to adding lidocaine gel because lidocaine gel interferes with antisepsis; single application of 5% PI for 3 min is commonly used; multiple applications of lower concentration may minimize toxicity; Silas et al (2017) found that 3 applications of ≥0.7% PI given ≈1 min apart reduced bacteria load by ≥99.9% (cutoff required by the Food and Drug Administration for antiseptic agents); the study authors recommended 1% PI used 3 times over a period of ≈2 min; speaker prefers preservative-free 1% lidocaine for topical anesthesia because it is least likely to cause punctate epithelial erosions (which can promote bacterial adherence and postoperative infection)

Intraocular anesthetics with adrenergic drugs (eg, phenylephrine lidocaine, epi-Shugarcaine): highly effective for preventing intraoperative floppy iris syndrome; drugs can be redosed when switching from phacoemulsification to irrigation-aspiration, and this maintains anesthetic properties and dilation of the pupil; the drugs can be topically administered, which is convenient if surgery takes longer than expected; continue to add PI intraoperatively because squeezing of the eyelids causes meibum to exit the eye and removes the antisepsis applied preoperatively; at the end of surgery, speaker uses moxifloxacin at a 1 mg/mL concentration because obtaining the desired dose is more difficult with the 5 mg/mL concentration

Topical steroids: Shorstein et al (2020) recommends subconjunctival injection of 4 mg of triamcinolone ≥5 mm posterior to the limbus to permit sufficient distance from the canal of Schlemm (where the sclera is thinner) and avoid frequent spikes in intraocular pressure (IOP); topical steroids can be superiorly placed in high-risk cases, but acetate ptosis can occur over time and also lead to IOP spikes; 40 mg of triamcinolone can be injected into Tenon space without harmful effects

Topical nonsteroidal anti-inflammatory drugs: speaker does not use in most cases because adequate use of steroids blocks the cyclooxygenase pathway; they may be beneficial to minimize use of steroids in patients with glaucoma; agents are relatively expensive

Contraindications to PI: most sensitivity reactions are related to povidone or surfactants (not caused by iodine per se); use is not recommended early in pregnancy, although safety data are sparse; significant reactions can occur in patients who use lithium, are experiencing thyroid storm, or are experiencing herpetic skin disease; skin irritation is often caused by prolonged exposure and can be identified by a specialized allergist or dermatologist that specializes in contact allergy

Readings

Bottinor W, Polkampally P, Jovin I. Adverse reactions to iodinated contrast media. Int J Angiol. 2013;22(3):149-154. doi:10.1055/s-0033-1348885; Hinkle JW, Wykoff CC, Lim JI, et al. “Iodine allergy” and the use of povidone iodine for endophthalmitis prophylaxis. J Vitreoretin Dis. 2020;4(1):65-68. doi:10.1177/2474126419865991; Koerner JC, George MJ, Meyer DR, Rosco MG, Habib MM. Povidone-iodine concentration and dosing in cataract surgery. Surv Ophthalmol. 2018;63(6):862-868. doi:10.1016/j.survophthal.2018.05.002; Shorstein NH, Myers WG. Drop-free approaches for cataract surgery. Curr Opin Ophthalmol. 2020;31(1):67-73. doi:10.1097/ICU.0000000000000625; Silas MR, Schroeder RM, Thomson RB, Myers WG. Optimizing the antisepsis protocol: Effectiveness of 3 povidone-iodine 1.0% applications versus a single application of povidone-iodine 5.0. J Cataract Refract Surg. 2017;43(3):400-404. doi:10.1016/j.jcrs.2017.01.007.

Disclosures

For this program, the following relevant financial relationships were disclosed and mitigated to ensure that no commercial bias has been inserted into this content: Dr. Myers is a consultant for Carl Zeiss Meditec and Leiters. Members of the planning committee reported nothing relevant to disclose. Dr. Myers' lecture discusses information related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Myers was recorded at 36th Annual Scientific Meeting of the Ophthalmic Anesthesia Society, held September 9-11, 2022, in Baltimore, MD, and presented by Ophthalmic Anesthesia Society. For information on future CME activities from this presenter, please visit eyeanesthesia.org. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 1.00 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 1.00 CE contact hours.

Lecture ID:

OP611701

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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