title: A randomised, double blind trial of N-Acetylcysteine for hearing protection during stapes surgery.
abstract: BACKGROUND
  Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies.
  
  
  METHODS
  We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight) or matching placebo (1:1 ratio), starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo.
  
  
  RESULTS
  One year after surgery, high-frequency hearing had improved 2.7 ± 3.8 dB in the placebo group (67 patients analysed) and 2.4 ± 3.7 dB in the treated group (72 patients; means ± 95% confidence interval, p = 0.54; linear mixed model). Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting.
  
  
  CONCLUSIONS
  N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00525551.
authors.affiliation: Center for Hearing and Communication Research, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; Department of Otolaryngology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Bagger-Sjöbäck
authors.affiliation: Department of Otolaryngology, Academic Hospital, SE-751 85 Uppsala, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Strömbäck
authors.affiliation: Center for Hearing and Communication Research, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Pierre
authors.initials: P
authors.lastname: Hakizimana
authors.affiliation: Department of Physical Geography and Quaternary Geology, Stockholm University, SE-106 91 Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Plue
authors.affiliation: Department of Otolaryngology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Christina
authors.initials: C
authors.lastname: Larsson
authors.affiliation: Center for Hearing and Communication Research, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; Department of Otolaryngology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Malou
authors.initials: M
authors.lastname: Hultcrantz
authors.affiliation: Department of Otolaryngology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Georgios
authors.initials: G
authors.lastname: Papatziamos
authors.affiliation: Center for Hearing and Communication Research, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; Department of Otolaryngology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Smeds
authors.affiliation: Department of Otolaryngology, Academic Hospital, SE-751 85 Uppsala, Sweden.
authors.forename: Niklas
authors.initials: N
authors.lastname: Danckwardt-Lillieström
authors.affiliation: Center for Hearing and Communication Research, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; Department of Audiology and Neurotology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Hellström
authors.affiliation: Department of Audiology and Neurotology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Ann
authors.initials: A
authors.lastname: Johansson
authors.affiliation: Department of Otolaryngology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Tideholm
authors.affiliation: Center for Hearing and Communication Research, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, SE-171 77 Stockholm, Sweden; Department of Clinical and Experimental Medicine, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Fridberger
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage* / Q000627:therapeutic use; D061605:Administration, Intravenous; D000975:Antioxidants / Q000008:administration & dosage* / Q000627:therapeutic use; D001301:Audiometry, Pure-Tone; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013506:Otologic Surgical Procedures / Q000009:adverse effects*; D010040:Otosclerosis / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D013201:Stapes Surgery; D014012:Tinnitus / Q000517:prevention & control*; D016896:Treatment Outcome; D014717:Vertigo / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D000111:Acetylcysteine