Oral pseudoephedrine decreases the rate of transmucosal nitrous oxide exchange for the middle ear

Abstract

Objective Determine if oral pretreatment with a vasoconstrictor decreases the blood to middle-ear exchange-rate of the perfusion-limited gas, Nitrous Oxide (N2O). Study Design Randomized, double-blind, crossover study. Methods Ten adult subjects with and 10 without past middle-ear disease completed paired experimental sessions, identical but for oral pretreatment with either pseudoephedrine HCL or lactose placebo. At each session, subjects were fitted with a non-rebreathing mask and breathed room air for 20 minutes (acclimation period), 50% N2O:50% O2 for 20 minutes (experimental period) and 100% O2 for 10 minutes (recovery period). Throughout, heart-rate, blood-pressure and O2 saturation were monitored and bilateral middle-ear pressures were recorded by tympanometry every minute. The primary outcome was the slope of the middle-ear pressure-time function for the experimental period which estimates the volume N2O exchange-rate. Using repeated measures ANOVA, the effects of Group (disease history), Treatment (active vs. placebo) and Period (1 vs. 2) on the recorded vital signs, and of Group, Treatment and Ear (left/right) on the middle-ear pressure-time slope were evaluated for statistical significance. Results Statistically significant effects of Period on O2 saturation (Period 2>Period 1) and of Treatment on heart-rate (Active>Placebo) were documented. Only Treatment was statistically significant for the middle-ear pressure-time slope with a shallower slope characterizing the active treatment session. Conclusion The volume exchange-rate across the middle-ear mucosa of perfusion-limited gases can be modulated pharmacologically. Theoretically, similar drugs can be used to reduce the requisite Eustachian tube opening efficiency for adequate middle-ear pressure regulation.

A formal description of middle ear pressure-regulation

“…Simulations 5 and 6 predict that a downgraded ET opening efficiency will be expressed as a less efficient MEPR for those periods which is accompanied by a consequent negative shift in the EV-MEEPG, effects validated by the change in MEEPG (tympanometric pressure) observed for children and adults during natural and experimental upper respiratory viral infections (Antonio et al, 2002; Buchman et al, 1995; Moody et al, 1998). In addition, emergent features of the model such as physiologic ME species-pressures (Simulation 6), the negative EV-MEEPG for all ET opening efficiencies not equal to 1 (Simulation 3), and the perfusion-limitation on the rate of MEEPG change (Simulations 2, 3) are consistent with clinical measurement (Antonio et al, 2002; Felding et al, 1987; Hergils et al, 1990; Hergils et al, 1997; Moody et al, 1998; Sade et al, 1993) and experimental results (Buchman et al, 1995; Teixeira et al, 2015; Teixeira et al, 2016). …”

Oxymetazoline Applied Topically to the Nasal Mucosa Decreases Trans-Mucosal Nitrous Oxide Exchange for the Middle Ear

“…This model shows that downgraded MEPR caused by low, but not 0, ET opening efficiency can be partly restored by an intervention that decreases the transMEM inert gas exchange-rate as for, example, treatment with vasoactive drugs 12 . While provocative, the introduction of any such treatment to improve MEPR with the goal of reducing the morbidity burden attributable to hearing loss and ME pathology in “at risk” populations defined by constitutively low ET opening efficiency is premature and overly ambitious.…”

“…One recently published human experiment showed that pharmacologically induced mucosal vasoconstriction decreased the ME gas demand and, specifically, that oral administration of a single standard dose of pseudoephedrine HCL, a drug with well characterized vasoconstrictive effects, decreased the basal transMEM N 2 O exchange-rate by approximately 33% 12 . That effect was attributed to a decreased ME mucosal blood perfusion rate consequent to the decreased ME mucosal blood volume under conditions of drug-induced vasoconstriction.…”

“…Consequently, it is expected that, at a fixed ET opening frequency and conductance, MEPR efficiency can be modulated by interventions that affect mucosal blood-perfusion, either upgraded by decreasing perfusion or downgraded by increasing perfusion. This possibility was explored in a recent study that reported a decrease in the transMEM conductance of the inert gas, N 2 O, following systemic administration of the vasoconstrictor, pseudoephedrine HCL, to adults 12 .…”

Histamine Applied Topically to the Nasal Mucosa Increases the Transmucosal Nitrous Oxide Exchange for the Middle Ear

“…This was a randomized, double-blind, placebo-controlled, cross-over study requiring that participants complete paired N 2 O breathing sessions at a minimum 1-week interval 12,13 . Prior to subject entry, a pharmacist prepared the two challenge materials according to a randomization code and supplied them to the investigators as identical intranasal atomization devices (LMA MAD Nasal, Wolfe-Tory Medical Inc, Salt Lake City, UT) labeled only with session and subject numbers.…”