J Clin Pharmacol xxxx;xx:x-x 785J Clin Pharmacol 2011;51:785-786 785

Thirty-four percent of surgical site infections are thought to be secondary to patients’ skin com-

mensals,1 and minimizing the peri-incisional micro-bial load is believed to reduce infections.1,2 As infection control gains ever-increasing momentum, the use of antimicrobials is commonplace.

Chlorhexidine (Chx) is a cationic base existing as an acetate or gluconate salt and demonstrates concen-tration-dependent, sustained antimicrobial proper-ties. Isopropyl alcohol is a fast-acting, broad-spectrum antimicrobial but lacks persistent activity.3,4 Combining these reagents synergizes their properties.4,5 Compli-cations associated with Chx have been reported, including urticaria and arthrotoxicity.6

A 74-year-old male, with no atopy or family his-tory of cutaneous disorders, was admitted for laparo-scopic anterior resection. Medical history included cholecystectomy and gastroscopies decades ago. The airway was grade 3 at laryngoscopy. The skin was prepared with a Chx-based solution. During abdomi-nal insufflation, the patient’s oxygen saturation and blood pressure acutely dropped, ensuing in cardio-vascular collapse that necessitated cardiopulmonary resuscitation on the operating table. The operation was abandoned and the patient transferred to the intensive care unit with a rash and hypotension

requiring inotropes. Dexamethasone was given for a grossly swollen tongue that prevented extubation.

The hypotension was initially attributed to spinal anesthesia or an allergy to coadministration with amoxiclav or atracurium. Post extubation, we ascer-tained that the patient had previously experienced episodes of lip tingling and a swollen throat after visiting the dentist. Subsequent skin testing showed no allergies to the penicillin panel or to anesthetic agents but a repeatable, positive response to Chx.

The patient was readmitted for operation, and prior to insertion of an intravenous cannula, a skin-cleansing wipe was used. Breathing difficulties and a rash promptly developed, and admission to the high-dependency unit was required. Residual Chx was postulated to have entered the circulation after the skin was cleansed. We later learned the patient had needed cetirizine for developing facial swell-ings after using certain toothpastes.

This case highlights the difficulty of evaluating the cause of allergic reactions during procedures involving the successive use of various chemicals and exemplifies the findings of a review of publica-tions covering 37 years undertaken by Thong and Yeow.7 The structure of Chx is known to facilitate the cross-linking of immunoglobulin E antibodies on the surfaces of basophils and mast cells, thus leading to histamine release in sensitized individuals.8,9 Allergy to Chx is considered among authorities to be grossly underreported partly because of underrecognition.8,10

In 1998, the US Food and Drug Administration11

issued a public health warning describing “the potential for serious hypersensitivity reactions to medical devices impregnated with chlorhexidine.” Relative to the widespread use of Chx, allergic

The potential dangers of chlorhexidine must be conveyed to the medical community. Health care professionals have little knowledge about the side effects and complications that may arise from this increasingly used compound. The suggestions in this case study may help to reduce the risk of adverse effects.

Keywords: Chlorhexidine; complications; anaphylaxis; sensitization; adverse reaction

Journal of Clinical Pharmacology, 2011;51:785-786© 2011 The Author(s)

From the University of Leicester, Leicester, United Kingdom (Dr Sivathasan) and Chesterfield Royal Hospital, Chesterfield, United Kingdom (Dr Goodfellow). Submitted for publication March 16, 2010; revised version accepted April 19, 2010. Address for correspondence: Niroshan Sivathasan, Apt 221 St George’s Mill, 9 Wimbledon Street, Leicester, LE1 1SZ United Kingdom; e-mail: niroshan.s@virgin.net.DOI:10.1177/0091270010372628

Skin Cleansers: The Risks of Chlorhexidine

Niroshan Sivathasan, BSc (Hons), MB,BS, (Lond), MRCS, (Eng), and Peter Bryan Goodfellow, MB,ChB, FRCSI, FRCS, (Gen)

786 • J Clin Pharmacol 2011;51:785-786

SIVATHASAN AND GOODFELLOW

contact dermatitis has been rarely reported12 although well documented, so it is likely that the general sensitization rate is low.10 Consequential circulatory compromise is rare but has been reported after intranasal and rectal exposure to Chx.13,14

As Chx is extensively used, medical staff must be aware of several issues:

1. Potential for anaphylactic responses to skin-cleansing agents

2. The widespread presence of Chx in medical prod-ucts, including skin wipes, urethral anesthetic lubricants (eg, Instillagel), central venous catheteri-zation sets (eg, ARROWg+ard Blue Catheter), and dental preparations (eg, Corsodyl mouthwash)

3. The presentation of a true allergy and the distinc-tion between anaphylactoid and anaphylactic reactions

4. Chx allergy in health care workers with work-related allergies

We suggest the following:

1. Warning labels should be placed on materials con-taining Chx.

2. Drug charts should be available that document aller-gies to skin cleansers, especially because Chx is present in common household items, such as tooth-paste, bandages, contact lens fluid, and food pre-servatives, thus increasing the possibility of sensitization in a large proportion of patients.15

3. Caution should be exercised when using cutaneous antiseptics in patients with a history of contact der-matitis.

4. Departments investigating patients for allergic reac-tions related to hospital episodes should test for Chx allergy.

Financial disclosure: None, including no funding received.

RefeRenCeS

1. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for prevention of surgical site infection, 1999. Centers

for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999;27:97-132.2. Surgical Site Infection (Clinical Guideline 74). London, United Kingdom: National Institute for Health and Clinical Excellence; 2008.3. Hemani ML, Lepor H. Skin preparation for the prevention of sur-gical site infection: which agent is best? Rev Urol. 2009;11:190-195.4. Digison MB. A review of anti-septic agents for pre-operative skin preparation. Plast Surg Nurs. 2007;27:185-8.5. Reichman DE, Greenberg JA. Reducing surgical site infections: a review. Rev Obstet Gynecol. 2009;2:212-221.6. Douw CM, Bulstra SK, Vandenbroucke J, Geesink RG, Vermeulen A. Clinical and pathological changes in the knee after accidental chlorhexidine irrigation during arthroscopy: case reports and review of the literature. J Bone Joint Surg Br. 1998;80:437-440.7. Thong BY, Yeow C. Anaphylaxis during surgical and interven-tional procedures. Ann Allergy Asthma Immunol. 2004;92:619-628.8. Jee R, Nel L, Gnanakumaran G, Williams A, Eren E. Four cases of anaphylaxis to chlorhexidine impregnated central venous cath-eters: a case cluster or the tip of the iceberg? Br J Anaesth. 2009;103:614-615.9. Pham NH, Weiner JM, Reisner GS, Baldo BA. Anaphylaxis to chlorhexidine: case report: implication of immunoglobulin E antibodies and identification of an allergenic determinant. Clin Exp Allergy. 2000;30:1001-1007.10. Lim KS, Kam PC. Chlorhexidine—pharmacology and clinical applications. Anaesth Intensive Care. 2008;36:502-512.11. Center for Devices and Radiological Health. FDA Public Health Notice: Potential Hypersensitivity Reactions To Chlorhexidine-Impregnated Medical Devices. Food and Drug Administration. http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/UCM062306. Published March 1998. Accessed May 18, 2010.12. Sharma A, Chopra H. Chlorhexidine urticaria: a rare occurrence with a common mouthwash. Indian J Dent Res. 2009;20:377-379.13. Chisholm DG, Calder I, Peterson D, Powell M, Moult P. Intranasal chlorhexidine resulting in anaphylactic circulatory arrest. BMJ. 1997;315:785.14. Bae YJ, Park CS, Lee JK, et al. A case of anaphylaxis to chlo-rhexidine during digital rectal examination. J Korean Med Sci. 2008;23:526-528.15. Ebo DG, Bridts CH, Stevens WJ. Anaphylaxis to an urethral lubricant: chlorhexidine as the “hidden” allergen. Acta Clin Belg. 2004;59:358-360.

For reprints and permission queries, please visit SAGE’s Web site at http://www.sagepub.com/journalsPermissions.nav.