Central Apneas In Patients Research Articles

Central Apnea in Patients with COVID-19 Infection

Background: The Coronavirus Disease 2019 (COVID-19) is a global pandemic that has killed over 1.5 million people worldwide. A constellation of multisystem involvement with SARS-CoV-2 has been reported. COVID-19 has been shown to affect the human nervous system, however, both the extent and severity of involvement have yet to be fully elucidated. In this manuscript, we aimed to better understand the effect of COVID-19 on neuro-respiratory status by studying COVID-19 patients who presented with central apnea. Methodology: We analyzed patient characteristics, clinical outcomes, laboratory results, and imaging results of three patients with symptomatic, PCR-proven COVID-19 and episodes of central apnea. Results: Of the three patients included in this study, two patients developed new central apnea, and one patient developed an exacerbation of underlying central apnea despite COVID-19 treatments with systemic steroids and remdesivir. All occurred, on average, 15 days after the onset of COVID-19 symptoms. At 1-year follow-up, all patients experienced complete resolution of apneic breathing. Conclusions: Physicians should be vigilant for the presentation of COVID-19 with central apnea. Central apnea may be a complication in patients with severe COVID-19 infection. More research is warranted to further understand this association.

Effect of Zolpidem on nocturnal arousals and susceptibility to central sleep apnea.

Arousals may contribute to the pathogenesis of sleep-disordered breathing (SDB) and central sleep apnea (CSA). We aimed to determine the effect of the nonbenzodiazepine hypnoticzolpidemon the frequency of respiratory-related arousals and central apneain patients withmoderate-to-severe SDB.We hypothesized thatzolpidemdecreasesthe severity of SDB by decreasingthe frequency ofrespiratory-related arousals. Patients with apnea-hypopnea index ≥ 15 events/hour and central apnea-hypopnea index ≥ 5 events/hour underwent a sleep study on zolpidem 5mg and a sleep study with no medication in a randomized order. The respiratory arousal index was compared between the two studies using a randomized crossover design. Sleep, respiratory, and physiologic parameters, including the CO2 reserve and the respiratory arousal threshold, were also compared. Eleven participants completed the study. Compared to no treatment, zolpidem reduced the respiratory arousal index (39.7 ± 7.7 vs. 23.3 ± 4.4 events/h, P = 0.031). Zolpidem also lowered the total apnea-hypopnea index (55.6 ± 8.5 vs. 41.3 ± 7.5 events/hour, P = 0.033) but did not affect other clinical and physiologic parameters. Compared to control, zolpidem did not widen CO2 reserve (- 0.44 ± 1.47 vs. - 0.63 ± 0.86mmHg, P = 0.81). The respiratory arousal threshold did not show a significant change on zolpidem compared to control (- 8.72 ± 2.1 vs. - 8.25 ± 2.81 cmH2O, P = 0.41). Nocturnal arousals and overall SDB severity were reduced with a single dose of zolpidem in patients with moderate-to-severe sleep-disordered breathing with increased susceptibility for central apnea. Zolpidem did not widen the CO2 reserve or increase the arousal threshold. Clinicaltrials.gov. Sleep and Breathing in the General Population - Chemical Stimuli (NCT04720547).

Central apnea-hypopnea syndrome and Chiari malformation type 1: pre and post-surgical studies

• Central apneas in children with Chiari malformation are frequently described. In adults however they are uncommon. • Central apneas in patients with Chiari type 1 have a poor response to non-invasive ventilation. • Surgery in Chiari type 1 in adults should be considered.

Sacubitril–valsartan treatment is associated with decrease in central apneas in patients with heart failure with reduced ejection fraction

BackgroundTo assess the impact of sacubitril-valsartan on apneic burden in patients with heart failure with reduced ejection fraction (HFrEF), 51 stable HFrEF patients planned for switching from an ACE-i/ARB to sacubitril-valsartan were prospectively enrolled. Methods and resultsAt baseline and after 6 months of treatment, all patients underwent echocardiography, 24-h cardiorespiratory monitoring, neurohormonal evaluation, and cardiopulmonary exercise testing. At baseline 29% and 65% of patients presented with obstructive and central apneas, respectively. After 6 months, sacubitril-valsartan was associated with a decrease in NT-proBNP, improvement in LV function, functional capacity and ventilatory efficiency. After treatment, the apnea-hypopnea index (AHI) decreased across the 24-h period (p < 0.001), as well as at daytime (p < 0.001) and at nighttime (p = 0.026), proportionally to baseline severity. When subgrouping according to the type of apneas, daytime, nighttime and 24-h AHI decreased in patients with central apneas (all p < 0.01). Conversely, in patients with obstructive apneas, the effect of drug administration was neutral at nighttime, with significant decrease only in daytime events (p = 0.007), mainly driven by reduction in hypopneas. ConclusionsSacubitril-valsartan on top of medical treatment is associated with a reduction in the apneic burden among a real-life cohort of HFrEF patients. The most marked reduction was observed for central apneas.

Sacubitril/valsartan improves ventilation stability in patients with chronic heart failure

Abstract Background Sacubitril/valsartan (SV) ameliorates symptoms and prognosis in patients with heart failure and reduced ejection fraction (HFrEF), but the reasons for such effects are unclear. The impact of SV on ventilation has never been investigated. In HFrEF, apneas are highly prevalent both at daytime and nighttime and are associated with increased mortality. Purpose We hypothesize that treatment with SV could favourably stabilize ventilation by reducing the severity of central apneas in patients with HFrEF. Methods 51 patients with HFrEF (mean age 67±9 years, mean left ventricular ejection fraction, LVEF 27±7%) and apneas defined by an apnea-hypopnea index, AHI≥5 (median 16, interquartile range 8–28) events/hour, eligible to treatment with SV and previously on optimal medical therapy for HFrEF, were enrolled. An extensive evaluation including cardiac ultrasound and a 24-hour cardiorespiratory monitoring was performed. Results After six months of treatment with SV, left ventricle systolic and diastolic function, mitral regurgitation (MR), left atrial volume (LAVI) and systolic pulmonary artery pressure (sPAP) were improved. Severity of apneas was reduced by 50%, 65% and 36% throughout the 24-hour, at daytime and nighttime, respectively. Conclusion Besides its known efficacy on cardiac remodeling, SV positively decreases the apneic burden in patients with HFrEF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Roche Diagnostics unrestricted grant

Buspirone decreases susceptibility to hypocapnic central sleep apnea in chronic SCI patients.

Spinal cord injury (SCI) is a risk factor for central sleep apnea (CSA). Previous studies in animal models with SCI have demonstrated a promising recovery in respiratory and phrenic nerve activity post-injury induced by the systemic and local administration of serotonin receptor agonists such as Buspirone and Trazodone. Human trials must be performed to determine whether individuals with SCI respond similarly. We hypothesized that Buspirone and Trazodone would decrease the propensity to hypocapnic CSA during sleep. We studied eight males with chronic SCI and sleep-disordered breathing (SDB) [age: 48.8 ± 14.2 yr; apnea-hypopnea index (AHI): 44.9 ± 23.1] in a single-blind crossover design. For 13 days, participants were randomly assigned either Buspirone (7.5-15 mg twice daily), Trazodone (100 mg), or a placebo followed by a 14-day washout period before crossing over to the other interventions. Study nights included polysomnography and induction of CSA using a noninvasive ventilation protocol. We assessed indexes of SDB, CO2 reserve, apneic threshold (AT), controller gain (CG), plant gain (PG), and ventilatory parameters. CO2 reserve was significantly widened on Buspirone (-3.6 ± 0.9 mmHg) compared with both Trazodone (-2.5 ± 1.0 mmHg, P = 0.009) and placebo (-1.8 ± 1.5 mmHg, P < 0.001) but not on Trazodone vs. placebo (P = 0.061). CG was significantly decreased on Buspirone compared with placebo (1.8 ± 0.4 vs. 4.0 ± 2.0 L/(mmHg·min), P = 0.025) but not on Trazodone compared with placebo (2.5 ± 1.1 vs. 4.0 ± 2.0 L/(mmHg·min); P = 0.065). There were no significant differences for PG, AT, or any SDB indexes (AHI, obstructive apnea index, central apnea index, oxygen desaturation index). The administration of Buspirone decreased the susceptibility to induced hypocapnic central apnea by reducing chemosensitivity and increasing CO2 reserve in chronic SCI patients.NEW & NOTEWORTHY This research study is novel as it is the first study in a humans that we are aware of that demonstrates the ability of Buspirone to increase CO2 reserve and hence decrease susceptibility to hypocapnic central apnea in patients with spinal cord injury.

Effects of central apneas on sympathovagal balance and hemodynamics at night: impact of underlying systolic heart failure

BackgroundIncreased sympathetic drive is the key determinant of systolic heart failure progression, being associated with worse functional status, arrhythmias, and increased mortality. Central sleep apnea is highly prevalent in systolic heart failure, and its effects on sympathovagal balance (SVB) and hemodynamics might depend on relative phase duration and background pathophysiology.ObjectiveThis study compared the effects of central apneas in patients with and without systolic heart failure on SVB and hemodynamics during sleep.MethodsDuring polysomnography, measures of SVB (heart rate and diastolic blood pressure variability) were non-invasively recorded and analyzed along with baroreceptor reflex sensitivity and hemodynamic parameters (stroke volume index, cardiac index, total peripheral resistance index). Data analysis focused on stable non-rapid eye movement N2 sleep, comparing normal breathing with central sleep apnea in subjects with and without systolic heart failure.ResultsTen patients were enrolled per group. In heart failure patients, central apneas had neutral effects on SVB (all p > 0.05 for the high, low, and very low frequency components of heart rate and diastolic blood pressure variability). Patients without heart failure showed an increase in very low and low frequency components of diastolic blood pressure variability in response to central apneas (63 ± 18 vs. 39 ± 9%; p = 0.001, 43 ± 12 vs. 31 ± 15%; p = 0.002). In all patients, central apneas had neutral hemodynamic effects when analyzed over a period of 10 min, but had significant acute hemodynamic effects.ConclusionEffects of central apneas on SVB during sleep depend on underlying systolic heart failure, with neutral effects in heart failure and increased sympathetic drive in idiopathic central apneas.

A safety trial of sodium oxybate in patients with obstructive sleep apnea: Acute effects on sleep-disordered breathing

Objective Sodium oxybate (SXB) is an approved drug for the treatment of excessive daytime sleepiness (EDS) and cataplexy in narcolepsy. Obstructive sleep apnea syndrome (OSAS) is a condition that frequently co-occurs with narcolepsy. Given the known central nervous system (CNS) depressant effects of SXB, this study aimed to examine its effects on sleep-disordered breathing (SDB) and sleep architecture in patients with OSAS. Methods Sixty patients with a history of mild to moderate OSAS (apnea-hypopnea index [AHI] ⩾ 10 and ⩽40, mean oxygen saturation [SaO 2] ⩾ 75%) received one of four treatments of the following: (1) 9 g SXB, (2) 9 g SXB/modafinil 200 mg, (3) zolpidem 10 mg, and (4) placebo (PBO) in a randomized, crossover design on four consecutive nights followed by overnight polysomnography. Results Forty-two patients (70%) completed the study. The mean change from baseline in AHI and mean SaO 2 was not significantly different among groups following treatment. Central apneas in patients treated with SXB increased, and clinically significant oxygen desaturations were seen in three patients with SXB treatment. The most common treatment related adverse events were headache and nausea. Conclusion These results suggest that nighttime administration of 9 g SXB in patients with mild to moderate OSAS does not negatively impact SDB, as measured by mean change from baseline in AHI and SaO 2, but might increase central apneas and cause oxygen desaturation in some individuals and should be used with caution.

Increased Propensity for Central Apnea in Patients with Obstructive Sleep Apnea

There is increasing evidence of increased ventilatory instability in patients with obstructive sleep apnea (OSA), but previous investigations have not studied whether the hypocapnic apneic threshold is altered in this group. To compare the apneic threshold, CO2 reserve, and controller gain between subjects with and without OSA matched for age, sex, and body mass index. Hypocapnia was induced via nasal mechanical ventilation for 3 minutes. Cessation of mechanical ventilation resulted in hypocapnic central hypopnea or apnea depending upon the magnitude of the hypocapnia. The apnea threshold (Pet(CO2)-AT) was defined as the measured Pet(CO2) at which the apnea closest to the last hypopnea occurred. The CO2 reserve was defined as the change in Pet(CO2) between eupneic Pet(CO2) and Pet(CO2)-AT. Controller gain was defined as the ratio of change in Ve between control and hypopnea or apnea to the DeltaPet(CO2). Eleven pairs of subjects were studied. There was no difference in the Pet(CO2)-AT between the two groups. However, the CO2 reserve was smaller in the subjects with OSA (2.2 +/- 0.6 mm Hg) compared with the control subjects (4.5 +/- 1.4 mm Hg; P < 0.001). The controller gain was increased in the subjects with OSA (3.7 +/- 1.3 L/min/mm Hg) compared with the control subjects (1.6 +/- 0.5 L/min/mm Hg; P < 0.001). Controller gain decreased and CO2 reserve increased in seven subjects restudied after using continuous positive airway pressure for 1 month. Ventilatory instability is increased in subjects with OSA and is reversible with the use of continuous positive airway pressure.

Overnight shift from obstructive to central apneas in patients with heart failure: role of PCO2 and circulatory delay.

Obstructive (OSA) and central sleep apnea (CSA) can coexist in patients with congestive heart failure (CHF). However, the reason why OSA events occur at one time and CSA events at another has not been determined. We hypothesized that a change in PCO(2) would be associated with an alteration in apnea type: a decrease in PCO(2) should lead to CSA. To test this hypothesis, we evaluated minute ventilation (V(I)), transcutaneous PCO(2) (PtcCO(2)), circulation time, and periodic breathing cycle length during overnight polysomnography in 12 patients with CHF and coexisting OSA and CSA. V(I) was significantly greater (mean+/-SEM, 9.4+/-1.3 versus 8.0+/-0.9 L/min; P:<0.05) and PtcCO(2) was lower (39.4+/-1.0 versus 41.9+/-1.1 mm Hg, P:<0.01) during episodes of CSA than of OSA. These changes were associated with significant lengthening of circulation time (23.6+/-3.7 versus 21.1+/-3.6 seconds, P:<0.01) and periodic breathing cycle length (53.7+/-3.5 versus 49.6+/-2.9 seconds, P:<0.01). In addition, the proportion of obstructive events decreased (from 68.5+/-11.4% to 22.5+/-7.2%, P:<0.001) and of CSA events increased (from 31.5+/-11.4% to 77.5+/-7.2%, P:<0.001) from the first to the last quarter of the night in association with a significant decrease in PtcCO(2) (from 42.6+/-0.9 to 40.8+/-0.9 mm Hg, P:<0.01). In patients with CHF, the shift from OSA to CSA is associated with a reduction in PCO(2). This appears to be related to an overnight deterioration in cardiac function as suggested by the concurrent lengthening of circulation time. Therefore, in CHF patients, alterations in cardiac function may influence apnea type.

Effects of inhaled carbon dioxide and oxygen on cheyne-stokes respiration in patients with heart failure.

We hypothesized that in patients with congestive heart failure (CHF), reductions in PaCO2 sensed at the peripheral chemoreceptors trigger central apneas during Cheyne-Stokes respiration (CSR-CSA), and that raising PaCO2 by inhalation of a CO2 would eliminate these events. The effects of CO2 inhalation on the frequency of apneas and hypopneas during stage 2 (S2) sleep were studied in 10 CHF patients with CSR-CSA. The time from the breath with the minimal end tidal fraction of CO2 (FETCO2) during hyperpnea until the onset of apnea correlated strongly with the lung to ear circulation time (LECT) (r2 = 0.90, p < 0.0001), a measure of lung to carotid body circulatory delay. Among the six patients who also inhaled O2, CO2 inhalation increased transcutaneous PCO2 (PtcCO2) (36.4 +/- 4.6 mm Hg versus 38 +/- 4.4 mm Hg, p < 0.002), abolished central apneas and hypopneas (43.0 +/- 8.4 per hour on air versus 1.6 +/- 2.6 per hour on CO2, p < 0.0001), and increased SaO2. In contrast, O2 inhalation causing a similar rise in SaO2 had no significant impact on either PtcCO2 or the frequency of central events. We conclude that central apneas in patients with CHF are triggered by a low PaCO2 most likely sensed at the peripheral chemoreceptors, and that inhalation of CO2 reverses central apneas by raising PaCO2.

Pharyngeal narrowing/occlusion during central sleep apnea

We hypothesized that subatmospheric intraluminal pressure is not required for pharyngeal occlusion during sleep. Six normal subjects and six subjects with sleep apnea or hypopnea (SAH) were studied during non-rapid-eye-movement sleep. Pharyngeal patency was determined by using fiber-optic nasopharyngoscopy during spontaneous central sleep apnea (n = 4) and induced hypocapnic central apnea via nasal mechanical ventilation (n = 10). Complete pharyngeal occlusion occurred in 146 of 160 spontaneously occurring central apneas in patients with central sleep apnea syndrome. During induced hypocapnic central apnea, gradual progressive pharyngeal narrowing occurred. More pronounced narrowing was noted at the velopharynx relative to the oropharynx and in subjects with SAH relative to normals. Complete pharyngeal occlusion frequently occurred in subjects with SAH (31 of 44 apneas) but rarely occurred in normals (3 of 25 apneas). Resumption of inspiratory effort was associated with persistent narrowing or complete occlusion unless electroencephalogram signs of arousal were noted. Thus pharyngeal cross-sectional area is reduced during central apnea in the absence of inspiratory effort. Velopharyngeal narrowing consistently occurs during induced hypocapnic central apnea even in normal subjects. Complete pharyngeal occlusion occurs during spontaneous or induced central apnea in patients with SAH. We conclude that subatmospheric intraluminal pressure is not required for pharyngeal occlusion to occur. Pharyngeal narrowing or occlusion during central apnea may be due to passive collapse or active constriction.

Interaction of hyperventilation and arousal in the pathogenesis of idiopathic central sleep apnea.

Central apneas during sleep may arise as a result of reduction in PaCO2 below the apnea threshold. We therefore hypothesized that hyperventilation and arousals from sleep interact to cause hypocapnia and subsequent central apneas in patients with idiopathic central sleep apnea (ICSA). Accordingly, the relationships among preapneic ventilation, arousal from sleep, and the onset and duration of subsequent central apneas were examined during Stage 2 non-REM sleep in eight patients with ICSA (mean +/- SEM, 45.4 +/- 4.7 central apneas and hypopneas/h of sleep). During Stage 2 sleep, all episodes of periodic breathing with central apneas were triggered by hyperventilation. Minute ventilation (VI) was greater (6.3 +/- 0.7 versus 5.4 +/- 0.8 L/min, p < 0.05) and mean transcutaneous PCO2 (PtcCO2) was lower (37.8 +/- 1.3 versus 38.9 +/- 1.6 mm Hg, p < 0.05) during periodic breathing than during stable breathing. VI during the ventilatory phase of the periodic breathing cycle increased progressively with increasing grades of associated arousals from Grade 0 (no arousal) (10.3 +/- 1.4 L/min) to Grade 1 (EEG arousal) (12.6 +/- 1.6 L/min) to Grade 2 (movement arousal) (14.1 +/- 1.6 L/min, p < 0.01). There was a corresponding progressive increase in central apnea length following the ventilatory period from no arousal (14.1 +/- 2.0) to EEG arousal (16.4 +/- 1.8) to movement arousal (18.1 +/- 2.0 s, p < 0.01). We conclude that arousals and hyperventilation interact to trigger hypocapnia and central apneas in ICSA.