Effects of Bedtime Dosing With Suvorexant and Zolpidem on Balance and Psychomotor Performance in Healthy Elderly Participants During the Night and in the Morning.

PURPOSE/BACKGROUND: This study was designed as an early assessment of the safety of the orexin receptor antagonist suvorexant, but also included exploratory assessments of balance and psychomotor performance that are the focus of this report. METHODS/PROCEDURES: This was a double-blind, randomized, 3-period, crossover, phase 1 study. Balance and psychomotor performance were evaluated during the night in 12 healthy elderly participants after bedtime administration of suvorexant 30 mg (a supratherapeutic dose), the GABAergic agonist zolpidem 5 mg (the recommended dose in the elderly), or placebo. Balance (body sway measured by platform stability) and psychomotor performance (measured by choice reaction time) were assessed predose and at 1.5, 4, and 8 hours postdose in each period. Memory (measured by word recall) was assessed predose and at 4 hours postdose. FINDINGS/RESULTS: At 1.5 hours after nighttime administration of each drug (the approximate time of their anticipated maximal plasma concentrations), both zolpidem and suvorexant increased body sway versus placebo, with a greater increase for zolpidem than suvorexant. Suvorexant increased choice reaction time compared with placebo or zolpidem at 1.5 hours. There were no treatment differences on body sway or choice reaction time at 4 or 8 hours, or on word recall at 4 hours. IMPLICATIONS/CONCLUSIONS: These exploratory data suggest that a 30-mg dose of suvorexant (supratherapeutic) and a 5-mg dose of zolpidem (recommended dose in the elderly) impaired balance at 1.5 hours in healthy elderly people, with potentially less impairment for suvorexant relative to zolpidem, but no treatment differences on body sway or psychomotor performance at 4 and 8 hours. Because of their exploratory nature, these findings and their clinical relevance, if any, require confirmation in a prospective study.

Heliox therapy in bronchiolitis: phase III multicenter double-blind randomized controlled trial.

BACKGROUND AND OBJECTIVE: Supportive care remains the mainstay of therapy in bronchiolitis. Earlier studies suggest that helium-oxygen therapy may be beneficial, but evidence is limited. We aimed to compare efficacy of 2 treatment gases, Heliox and Airox (21% oxygen + 79% helium or nitrogen, respectively), on length of hospital treatment for bronchiolitis. METHODS: This was a multicenter randomized blinded controlled trial of 319 bronchiolitic infant subjects randomly assigned to either gas; 281 subjects completed the study (140 Heliox, 141 Airox), whose data was analyzed. Treatment was delivered via facemask (nasal cannula, if the facemask intolerant) ± continuous positive airway pressure (CPAP). Severe bronchiolitics received CPAP from the start. Primary end point was length of treatment (LoT) required to alleviate hypoxia and respiratory distress. Secondary end-points were proportion of subjects needing CPAP; CPAP (LoT); and change in respiratory distress score. RESULTS: Analysis by intention to treat (all subjects); median LoT (inter-quartile range, days): Heliox 1.90 (1.08-3.17), Airox 1.87 (1.11-3.34), P = .41. Facemask tolerant subgroup: Heliox 1.46 (0.85-1.95), Airox 2.01 (0.93-2.86), P = .03. Nasal cannula subgroup: Heliox 2.51 (1.21-4.32), Airox 2.81 (1.45-4.78), P = .53. Subgroup started on CPAP: Heliox 1.55 (1.38-2.01), Airox 2.26 (1.84-2.73), P = .02. Proportion of subjects needing CPAP: Heliox 17%, Airox 19%, O.R. 0.87 (0.47-1.60), P = .76. Heliox reduced respiratory distress score after 8 hours (mixed models estimate, -0.1298; P < .001). The effect was greater for facemask compared with nasal cannula (mixed models estimate, 0.093; P = .04). CONCLUSIONS: Heliox therapy does not reduce LoT unless given via a tight-fitting facemask or CPAP. Nasal cannula heliox therapy is ineffective.

The effects of Heliox on the output and particle-size distribution of salbutamol using jet and vibrating mesh nebulizers.

There are theoretical benefits of delivering drug aerosols to patients with asthma and chronic obstructive pulmonary disease (COPD) using Heliox as a carrier gas. The objective of this study was to develop systems to allow bronchodilators nebulized by a breath enhanced jet nebulizer and a vibrating mesh nebulizer to be delivered to patients in Heliox. This was achieved by attaching a reservoir to the nebulizers to ensure inhaled Heliox was not diluted by entrained air. For the vibrating mesh nebulizer, the total output was significantly higher after 5 min of nebulization when Heliox rather than air was used as the delivery gas (p < 0.001). The proportion of drug in particles <5 microm was 58.1% for Heliox and 50.1% when air was entrained. When the breath enhanced nebulizer was used a much higher driving flow of Heliox, compared to air, was required to deliver a similar dose of drug (p < 0.05). The total amount of drug likely to be inhaled was significantly higher when the vibrating mesh nebulizer (Aerogen) was used compared to the breath enhanced jet nebulizer (Pari LC plus) (p < 0.001). The amount of drug likely to be inhaled was also significantly greater for the adult as opposed to pediatric breathing pattern for all nebulizers and flows tested with the exception of the Aeroneb and Heliox entrainment. In this case, total amounts were similar for both patterns but for the pediatric pattern, the time taken to reach this output was longer. Such information is required to allow appropriate interpretation of clinical trials of drug delivery using Heliox.