title: A Randomized, Prospective, Double-Blinded Study of Physostigmine to Prevent Sedation-Induced Ventilatory Arrhythmias.
abstract: BACKGROUND
  Physostigmine, a centrally acting acetylcholinesterase inhibitor, is most commonly used by anesthesiologists in the postanesthetic setting to reverse confusion caused by central anticholinergic medication effects. It has also been proposed as a treatment for sleep-disordered breathing. We investigated whether physostigmine was effective in decreasing the frequency of ventilatory arrhythmias produced during moderate sedation with midazolam and remifentanil during the conditions of breathing room air or 2 L/min nasal O2.
  
  
  METHODS
  Ten healthy male volunteers participated in this randomized, double-blind control trial of physostigmine (0.24 µg·kg·min) versus placebo. Moderate sedation was achieved with infusions of midazolam and remifentanil and monitored with full and processed electroencephalogram. Analgesia was quantified with subjective pain score to thermal stimulation. Ventilatory arrhythmias, as measured by the sedation apnea-hypopnea index (S-AHI), were scored as the number of apneas and hypopneas during two 1-hour periods on room air or 2 L/min nasal O2.
  
  
  RESULTS
  All subjects tolerated the sedation and physostigmine without significant adverse effects. Sedation during placebo infusion resulted in clinically significant (S-AHI > 15) ventilatory arrhythmias in 5 conditions in 3 subjects (2 on room air and then O2, and 1 on O2 only). Physostigmine did not significantly (P > 0.46) reduce the total number of ventilatory arrhythmias on either room air or O2 (13.4 ± 18.8 events/h [mean ± SEM], 95% confidence interval [CI] = -9.9 to 62.7; and 6.2 ± 8.0, 95% CI = -3.1 to 28.7, respectively). Physostigmine did reduce the S-AHI in all 5 instances of clinically significant ventilatory arrhythmias (S-AHI decreased by 67.0 ± 22.2; CI = 29.2-111.7; P = 0.04).
  
  
  CONCLUSIONS
  Physostigmine does not appear to be useful as a pretreatment to prevent ventilatory arrhythmias during moderate sedation. However, it may be useful as a treatment for clinically significant ventilatory arrhythmias during moderate sedation.
authors.affiliation: From the Departments of Anesthesiology, Neurology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, New York.
authors.forename: Suzanne B
authors.initials: SB
authors.lastname: Karan
authors.forename: Elia
authors.initials: E
authors.lastname: Rackovsky
authors.forename: William A
authors.initials: WA
authors.lastname: Voter
authors.forename: Jason A
authors.initials: JA
authors.lastname: Kanel
authors.forename: Nick
authors.initials: N
authors.lastname: Farris
authors.forename: Joshua
authors.initials: J
authors.lastname: Jensen
authors.forename: Lynn
authors.initials: L
authors.lastname: Liu
authors.forename: Denham S
authors.initials: DS
authors.lastname: Ward
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000517:prevention & control*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage; D016292:Procedural Sedation / Q000009:adverse effects / Q000379:methods*; D004311:Double-Blind Method; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008297:Male; D010830:Physostigmine / Q000008:administration & dosage*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D002800:Cholinesterase Inhibitors; D006993:Hypnotics and Sedatives; D010830:Physostigmine