What is Chlorhexidine digluconate?

Chlorhexidine digluconate (CHG) , is a disinfectant and antiseptic that is used for skin disinfection before surgery and to sterilize surgical instruments. It may be used both to disinfect the skin of the patient and the hands of the healthcare providers. It is also used for cleaning wounds, preventing dental plaque, treating yeast infections of the mouth, and to keep urinary catheters from blocking. It is used as a liquid or powder.

Chlorhexidine came into medical use in the 1950s. Chlorhexidine is available over the counter (OTC) in the United States. It is on the World Health Organization's List of Essential Medicines. In 2017, it was the 286th most commonly prescribed medication in the United States, with more than one million prescriptions. 1,6-Di(4 -chlorophenyldiguanido)hexane gluconate (Hibiclens)is the most effective of a series of antibacterial biguanides originallydeveloped in Great Britain.

Biguanides

The antimicrobial properties of the biguanides were discoveredas a result of earlier testing of these compounds aspossible antimalarial agents. Although thebiguanides are technically not bisquaternary ammoniumcompounds and, therefore, should probably be classifiedseparately, they share many physical, chemical, and antimicrobialproperties with the cationic surfactants. Thebiguanides are strongly basic, and they exist as dications atphysiological pH. In chlorhexidine, the positive charges arecounterbalanced by gluconate anions (not shown). Likecationic surfactants, these undergo inactivation when mixed with anionic detergents and complex anions such as phosphate,carbonate, and silicate.

Solution Form

Chlorhexidine digluconate solution is a bis(biguanide) family cationic broad spectrum antibiotic that is available in a range of concentrations and has been safely used for over 40 years for a variety of health-related applications; but its specific use for umbilical cord care was uniquely tested in three clinical trials in Nepal, Bangladesh, and Pakistan, in the form of 7.1% chlorhexidine digluconate (CHX). Given the promising results of the trials, in 2013 the World Health Organization (WHO) added CHX to its Model List of Essential Medicines for Children; and in 2014 the WHO issued a new guideline on umbilical cord care, which included a formal recommendation on the use of chlorhexidine.

Uses

Chlorhexidine has broad-spectrum antibacterial activitybut is not active against acid-fast bacteria, spores, orviruses. It has been used for such topical uses as preoperativeskin disinfection, wound irrigation, mouthwashes, andgeneral sanitization. Chlorhexidine is not absorbedthrough skin or mucous membranes and does not causesystemic toxicity.

Chlorhexidine is used in disinfectants (disinfection of the skin and hands), cosmetics (additive to creams, toothpaste, deodorants, and antiperspirants), and pharmaceutical products (preservative in eye drops, active substance in wound dressings and antiseptic mouthwashes).[9] A 2019 Cochrane review concluded that based on very low certainty evidence in those who are critically ill "it is not clear whether bathing with chlorhexidine reduces hospital‐acquired infections, mortality, or length of stay in the ICU, or whether the use of chlorhexidine results in more skin reactions.

In endodontics, chlorhexidine is used for root canal irrigation and as an intracanal dressing, but has been replaced by the use of sodium hypochlorite bleach in much of the developed world.

Mechanism of Action

Chlorhexidine digluconate is a broad spectrum antiseptic. Its mechanism of action involves destabilization of the outer bacterial membrane. It is effective on both Gram-positive and Gram-negative bacteria, although it is less effective with some Gram-negative bacteria.It has both bactericidal and bacteriostatic mechanisms of action, the mechanism of action being membrane disruption, not ATPase inactivation as previously thought.It is also useful against fungi and enveloped viruses, though this has not been extensively investigated. Chlorhexidine is harmful in high concentrations, but is used safely in low concentrations in many products, such as mouthwash and contact lens solutions.

Side effects

CHG is ototoxic; if put into an ear canal which has a ruptured eardrum, it can lead to deafness.

CHG does not meet current European specifications for a hand disinfectant. Under the test conditions of the European Standard EN 1499, no significant difference in the efficacy was found between a 4% solution of chlorhexidine digluconate and soap.[17] In the U.S., between 2007 and 2009, Hunter Holmes McGuire Veterans Administration Medical Center conducted a cluster-randomized trial and concluded that daily bathing of patients in intensive care units with washcloths saturated with chlorhexidine gluconate reduced the risk of hospital-acquired infections.

Whether prolonged exposure over many years may have carcinogenic potential is still not clear. The US Food and Drug Administration recommendation is to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months.

When ingested, CHG is poorly absorbed in the gastrointestinal tract and can cause stomach irritation or nausea. If aspirated into the lungs at high enough concentration, as reported in one case, it can be fatal due to the high risk of acute respiratory distress syndrome.

Manufacturing Process

35 parts of hexamethylene bis-dicyandiamide, 35 parts of p-chloroaniline hydrochloride and 250 parts of β-etoxyethanol are stirred together at 130- 140°C for 2 hours under reflux. The mixture is then cooled and filtered. The solid is washed with water and crystallised from 50% aqueous acetic acid. 1,1'-Hexamethylene bis(5-(p-chlorophenyl)biguanide) is obtained as colorless plates, melting point 258-260°C. By addition of D-gluconic acid to aqueous solution of chlorhexidine base is prepared 1,1'-hexamethylenebis(5-(pchlorophenyl)biguanide)digluconate (1:2).