Intranasal oxytocin increases respiratory rate and reduces obstructive event duration and oxygen desaturation in obstructive sleep apnea patients: a randomized double blinded placebo controlled study.

BACKGROUND: Activation of the oxytocin network has shown benefits in animal models of Obstructive Sleep Apnea (OSA) as well as other cardiorespiratory diseases. We sought to determine if nocturnal intranasal oxytocin administration could have beneficial effects in reducing the duration and/or frequency of obstructive events in obstructive sleep apnea subjects. METHODS: Two sequential standard "in-lab" polysomnogram (PSG) sleep studies were performed in patients diagnosed with OSA that were randomly assigned to initially receive either placebo or oxytocin (40 i.u.) administered intranasally in this double blinded randomized placebo controlled study. Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated bradycardias, arterial oxygen desaturation and respiratory rate were assessed in 2 h epochs following sleep onset. Oxytocin significantly decreased the duration of obstructive events, as well as the oxygen desaturations and incidence of bradycardia that were associated with these events. Notably, oxytocin increased respiratory rate during non-obstructive periods. There were no significant changes in sleep architecture and no adverse effects were reported. CONCLUSIONS: Oxytocin administration can benefit OSA subjects by reducing the duration and adverse consequences of obstructive events. Oxytocin could also be beneficial in situations involving respiratory depression as oxytocin increased respiratory rate. Additional studies are needed to further understand the mechanisms by which oxytocin promotes these changes in cardiorespiratory function. The long-term efficacy and optimal dose of intranasal oxytocin treatment should also be determined in OSA subjects. ClinicalTrials.gov NCT03148899.

Benefits of oxytocin administration in obstructive sleep apnea.

Activation of oxytocin receptors has shown benefits in animal models of obstructive sleep apnea (OSA). We tested if nocturnal oxytocin administration could have beneficial effects in OSA patients. Eight patients diagnosed with OSA were administered intranasal oxytocin (40 IU). Changes in cardiorespiratory events during sleep, including apnea and hypopnea durations and frequency, risk of event-associated arousals, and heart rate variability, were assessed. Oxytocin significantly increased indexes of parasympathetic activity, including heart rate variability, total sleep time, and the postpolysommogram sleep assessment score, an index of self-reported sleep satisfaction. Although the apnea-hypopnea index was not significantly changed with oxytocin administration, when apnea and hypopnea events were compared independently, the frequency of hypopneas, but not apneas, was significantly (P ≤ 0.005) decreased with oxytocin treatment. Both apneas and hypopneas were significantly shortened in duration with oxytocin treatment. Oxytocin treatment significantly decreased the percent of apnea and hypopnea events that were accompanied with an arousal. Oxytocin administration has the potential to restore cardiorespiratory homeostasis and reduce some clinically important (objective and patient-reported) adverse events that occur with OSA. Additional studies are needed to further understand the mechanisms by which oxytocin promotes these changes in cardiorespiratory and autonomic function in OSA patients.

Respiratory rate variability in sleeping adults without obstructive sleep apnea.

Characterizing respiratory rate variability (RRV) in humans during sleep is challenging, since it requires the analysis of respiratory signals over a period of several hours. These signals are easily distorted by movement and volitional inputs. We applied the method of spectral analysis to the nasal pressure transducer signal in 38 adults with no obstructive sleep apnea, defined by an apnea-hypopnea index <5, who underwent all-night polysomnography (PSG). Our aim was to detect and quantitate RRV during the various sleep stages, including wakefulness. The nasal pressure transducer signal was acquired at 100 Hz and consecutive frequency spectra were generated for the length of the PSG with the Fast Fourier Transform. For each spectrum, we computed the amplitude ratio of the first harmonic peak to the zero frequency peak (H1/DC), and defined as RRV as (100 - H1/DC) %. RRV was greater during wakefulness compared to any sleep stage, including rapid-eye-movement. Furthermore, RRV correlated with the depth of sleep, being lowest during N3. Patients spent most their sleep time supine, but we found no correlation between RRV and body position. There was a correlation between respiratory rate and sleep stage, being greater in wakefulness than in any sleep stage. We conclude that RRV varies according to sleep stage. Moreover, spectral analysis of nasal pressure signal appears to provide a valid measure of RRV during sleep. It remains to be seen if the method can differentiate normal from pathological sleep patterns.

Respiratory Inductance Plethysmography Improved Diagnostic Sensitivity and Specificity of Obstructive Sleep Apnea.

BACKGROUND: Respiratory inductance plethysmography (RIP) is a tool used during a polysomnogram (PSG), which serves as a surrogate of respiratory effort and can help detect inspiratory air-flow limitation. We hypothesize that RIP can improve the sensitivity and specificity of scoring hypopneas when compared with both the recommended and acceptable criteria of the American Academy of Sleep Medicine. METHODS: We retrospectively analyzed a cohort of 12 subjects who had no obstructive sleep apnea (OSA) or mild OSA on PSG when scored by the American Academy of Sleep Medicine acceptable criteria for hypopneas but had high clinical suspicion for a diagnosis of OSA. These subjects were rescored using the American Academy of Sleep Medicine recommended criteria as well as RIP. Hypopnea was scored when there was a 50% decrease in the amplitude of the RIP sum channel (which combined input from chest and abdominal belts). OSA was diagnosed if the subjects had >5 respiratory events/h of sleep. The subject's response to CPAP was assessed by using a short questionnaire called the post-PSG sleep assessment. which evaluated subjective sleep quality. A positive response was considered an improvement in the post-PSG sleep assessment score after CPAP use. RESULTS: When scored using the American Academy of Sleep Medicine acceptable criteria, 10 subjects had a negative study, and 2 subjects had mild OSA for a sensitivity of 11% and specificity of 50%. When scored using the recommended criteria, 10 subjects had OSA, and 2 were negative, for a sensitivity of 78% and specificity of 70%. By RIP scoring, all 12 subjects had >5 respiratory events/h for a sensitivity of 100% and specificity of 75%. CONCLUSIONS: This small retrospective pilot study showed improved sensitivity and specificity when scoring hypopneas by RIP sum channel.