Endotracheal tube cuffs filled with lidocaine as a drug delivery system: in vitro and in vivo investigations.
The purpose of this study was to examine if lidocaine diffusion across an endotracheal tube cuff could improve post-operative tolerance, especially sore throat. The in vitro release of lidocaine from tube cuffs filled with different lidocaine formulations (base form, hydrochloride form or alkalinized lidocaine hydrochloride) was investigated. A preliminary pilot clinical study in anaesthesia for spine surgery in smoker patients was carried out to examine the pharmacokinetic (i.e. systemic uptake) and pharmacodynamic effects (i.e. incidence of sore throat) obtained with the endotracheal tube cuff filled with lidocaine solution, compared to cuffs inflated only with air. From our in vitro experiment, only the hydrophobic neutral base form of lidocaine was able to diffuse (65.1+/-1.1% released after 6 h), while for the charged hydrochloride form, only a permeation phenomenon occurred concerning only 1% of the total drug. Alkalinization of lidocaine hydrochloride (the only form available as a drug) allows smaller amounts to be used compared to previous published studies (20-40 mg vs. 200-500 mg) and no lag time for diffusion. Such a system could provide a controlled release reservoir for lidocaine to adjacent tracheal tissue. This was shown in our pilot study with sustained plasmatic profiles and improved tolerance (decreased pain scores) in the rank order: air group<<lidocaine hydrochloride group<alkalinized lidocaine group.
Dollo
G
G
Laboratoire de Pharmacie Galénique et Biopharmacie, Université de Rennes I, 2 ave Pr Leon Bernard, 35043 Rennes, France. gilles.dollo@univ-rennes1.fr
Estebe
J P
JP
Le Corre
P
P
Chevanne
F
F
Ecoffey
C
C
Le Verge
R
R
D000328:Adult; D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D006801:Humans; D007202:Indicators and Reagents; D007442:Intubation, Intratracheal / Q000295:instrumentation*; D008012:Lidocaine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D010612:Pharyngitis / Q000517:prevention & control; D010865:Pilot Projects; D011183:Postoperative Complications / Q000517:prevention & control; D016684:Prone Position; D012907:Smoking / Q000473:pathology
D000779:Anesthetics, Local; D007202:Indicators and Reagents; D008012:Lidocaine