Results from 404 drug-induced sleep endoscopies with probability ramp control: lessons for pharmacokinetic design of DISE protocols. Issue 3 (22nd August 2020)

• Record Type: Journal Article
• Authors: Mandel, Jeff E.; Atkins, Joshua H.
• Is Part Of: Journal of head & neck anesthesia. Volume 4:Issue 3(2020)
• Page Start: e27
• Page End: e27
• Publication Date: 2020-08-22
• Subjects: Drug-induced sleep endoscopy -- Propofol -- Pharmacokinetics
• DOI: 10.1097/HN9.0000000000000027
• Languages: English
• ISSNs: 2475-5028

Abstract

Abstract : Introduction: Drug-induced sleep endoscopy (DISE) employs a drug such as propofol to allow observation of airway collapse to predict success in surgical interventions for obstructive sleep apnea. A number of protocols have been published for the administration of propofol during DISE, but these protocols do not make use of pharmacokinetic modeling to estimate the propofol concentration at airway collapse and the probability distribution for this quantity. We hypothesized that this information could be used to improve the delivery of propofol during DISE. Methods: Deidentified data from 404 patients sedated with Probability Ramp Control was analyzed. The estimated effect site concentration at the time of airway collapse (ECac ) was fit to a gamma distribution. Correlation between ECac and age/weight were performed using Spearman ρ. This probability distribution was utilized to assess the ability of a published protocol to produce airway collapse in a reasonable duration in a representative cohort of patients. Results: The parameters of the gamma distribution were a=8.3 (95% confidence interval, 7.2–9.5), b=0.58 (95% confidence interval, 0.51–0.67). The mean ECac was 4.8±1.7 µg/mL; 95% of ECac fell in the range 2.4–8.5 µg/mL. ECac was uncorrelated with age (ρ=−0.06, P =0.27) and weight (ρ=−0.11, P =0.03). The previously published protocol displayed variability across the cohort and failed to achieve effect site concentrations sufficient for the least sensitive patients in our cohort. Conclusions: Effect site propofol concentrations at the time of airway collapse during DISE span a wide range with a skewed distribution. The lack of correlation with either age or weight suggests that the pharmacokinetic model is sufficient for describing the effect of age and weight on propofol dosing. The impact of these factors on propofol dosing during DISE is examined, and workable solutions to this clinical challenge are proposed.