title: Measurements of chlorhexidine, p-chloroaniline, and p-chloronitrobenzene in saliva after mouth wash before and after operation with 0.2% chlorhexidine digluconate in maxillofacial surgery: a randomised controlled trial.
abstract: Chlorhexidine gluconate is used to prevent the accumulation of dental plaque and gingivitis, infection of the surgical site, and ventilator-associated pneumonia in maxillofacial surgery, but it is not clear whether the metabolites of chlorhexidine are detectable in the patient's saliva at clinically relevant concentrations. Forty-three patients who had orofacial operations were randomised to use a 0.2% chlorhexidine gluconate (n=23), or an octenidine-based, chlorhexidine-free (n=20), mouthwash once preoperatively and three times daily for five postoperative days. After the first, 8.7 (23.3) mg/L chlorhexidine (0.7%-2.5% of the total amount used) was measured in saliva. The concentration increased to 15.2 (6.2) mg/L after the second rinse (first postoperative day), and peaked at 29.4 (11.2) mg/L on the fourth postoperative day. It remained detectable for up to 12hours after the last one, but was not detectable in serum or urine at any time. The potentially carcinogenic metabolite p-chloroaniline was detectable in saliva at higher concentrations in the chlorhexidine group (0.55mg/L) than the octenidine group (0.21mg/L), and p-chloronitrobenzene was detected in both groups in only minimal concentrations (0.001-0.21mg/L). Chlorhexidine gluconate mouthwashes do increase the concentration of p-chloroaniline, but a single use seems to be safe. Whether prolonged exposure over many years may have carcinogenic potential is still not clear. Based on the hitherto unknown kinetics of p-chloroaniline in saliva, the recent recommendation of the Federal Drug Administration (FDA) in the USA to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months seems to be justified.
authors: Institute of Hygiene and Environmental Medicine, University Medicine Greifswald, Germany.
authors: H
authors: H
authors: Below
authors: Institute of Skin Integrity and Infection Prevention, School of Human & Health Sciences, University of Huddersfield, United Kingdom. Electronic address: o.assadian@hud.ac.uk.
authors: O
authors: O
authors: Assadian
authors: Institute of Hygiene and Environmental Medicine, University Medicine Greifswald, Germany.
authors: R
authors: R
authors: Baguhl
authors: Institute of Hygiene and Environmental Medicine, University Medicine Greifswald, Germany.
authors: U
authors: U
authors: Hildebrandt
authors: Institute of Biometry and Medical Computer Science, University Medicine Greifswald, Germany.
authors: B
authors: B
authors: Jäger
authors: Department of Anaesthesiology and Intensive Medicine, University Medicine Greifswald, Germany.
authors: K
authors: K
authors: Meissner
authors: Institute of Skin Integrity and Infection Prevention, School of Human & Health Sciences, University of Huddersfield, United Kingdom.
authors: D J
authors: DJ
authors: Leaper
authors: Institute of Hygiene and Environmental Medicine, University Medicine Greifswald, Germany.
authors: A
authors: A
authors: Kramer
mesh_terms: D000328:Adult; D000814:Aniline Compounds / Q000032:analysis*; D002710:Chlorhexidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009067:Mouthwashes; D009578:Nitrobenzenes / Q000032:analysis*; D019647:Oral Surgical Procedures; D012463:Saliva / Q000737:chemistry*; D016037:Single-Blind Method
chemical_list: D000814:Aniline Compounds; D009067:Mouthwashes; D009578:Nitrobenzenes; C010407:4-chloronitrobenzene; C010882:chlorhexidine gluconate; D002710:Chlorhexidine; C004658:4-chloroaniline
keywords: Chlorhexidine; absorption; antiseptic mouthwash; p-chloroaniline; saliva