Joseph M. Gabriel

Relationship of pharyngeal water content and jugular volume with severity of obstructive sleep apnea in renal failure

BACKGROUND In patients with end-stage renal disease (ESRD), fluid overload may contribute to their high prevalence of obstructive sleep apnea (OSA) by increasing the amount of fluid displaced from the legs into the neck overnight, and possibly compressing the upper airway (UA). Indeed, in ESRD patients, the amount of overnight rostral fluid displacement from the legs is related to the frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index, AHI). We, therefore, hypothesized that in ESRD patients, the greater the UA-mucosal water content (UA-MWC) and internal jugular vein volume (IJVVol), the higher the AHI. METHODS We studied 20 patients with ESRD on thrice weekly hemodialysis who had undergone diagnostic polysomnography (age 41.0 ± 12.3 years, with a body mass index (BMI) of 25.8 ± 6.3 kg/m(2) and an AHI of 20.2 ± 26.8). The leg fluid volume (LFV) was measured by bioelectric impedance. The IJVVol and MWC were measured by UA magnetic resonance imaging (MRI). RESULTS The only significant independent correlates of the AHI were IJVVol (r = 0.801, P < 0.0001) and UA-MWC (r = 0.720, P = 0.0005) which together explained 72% of its variability. CONCLUSIONS These data suggest that fluid overload via increased IJVVol, and UA-MWC, contributes to the pathogenesis of OSA in patients with ESRD. These findings help us to explain the high prevalence of OSA in ESRD patients, and attenuation of OSA in association with nocturnal dialysis. They also suggest the need for randomized trials to determine whether more aggressive fluid removal in ESRD patients will alleviate OSA.

Inverse relationship of subjective daytime sleepiness to sympathetic activity in patients with heart failure and obstructive sleep apnea.

BACKGROUND Patients with heart failure (HF) and obstructive sleep apnea (OSA) are less sleepy than patients with OSA but without HF. Furthermore, unlike the non-HF population, in the HF population, the degree of daytime sleepiness is not related to the apnea-hypopnea index (AHI). The sympathetic nervous system plays a critical role in alertness. HF and OSA both increase sympathetic nervous system activity (SNA) during wakefulness. We hypothesized that in patients with HF and OSA, the degree of subjective daytime sleepiness would be inversely related to SNA. METHODS Daytime muscle SNA (MSNA) was recorded in patients with HF and OSA. Subjective daytime sleepiness was assessed by the Epworth Sleepiness Scale (ESS). RESULTS We studied 27 patients with HF and OSA and divided them into two groups based on the median ESS score: a less sleepy group, with an ESS score < 6 (n = 13), and a sleepier group, with an ESS score ≥ 6 (n = 14). The less sleepy group had higher MSNA than did the sleepier group (82.5 ± 9.9 bursts/100 cardiac cycles vs 69.3 ± 18.6 bursts/100 cardiac cycles; P = .037) and a longer sleep-onset latency (33 ± 29 min vs 14 ± 13 min; P = .039). The ESS score was inversely related to MSNA (r = -0.63; P < .001) but not to the AHI, arousal index, or indices of oxygen desaturation. CONCLUSIONS In patients with HF and OSA, the degree of subjective daytime sleepiness is inversely related to MSNA. This relationship is likely mediated via central adrenergic alerting mechanisms. These findings help to explain the previously reported lack of daytime hypersomnolence in patients with HF and OSA.

Contrasting Effects of Lower Body Positive Pressure on Upper Airways Resistance and Partial Pressure of Carbon Dioxide in Men With Heart Failure and Obstructive or Central Sleep Apnea

OBJECTIVES This study sought to test the effects of rostral fluid displacement from the legs on transpharyngeal resistance (Rph), minute volume of ventilation (Vmin), and partial pressure of carbon dioxide (PCO2) in men with heart failure (HF) and either obstructive (OSA) or central sleep apnea (CSA). BACKGROUND Overnight rostral fluid shift relates to severity of OSA and CSA in men with HF. Rostral fluid displacement may facilitate OSA if it shifts into the neck and increases Rph, because pharyngeal obstruction causes OSA. Rostral fluid displacement may also facilitate CSA if it shifts into the lungs and induces reflex augmentation of ventilation and reduces PCO2, because a decrease in PCO2 below the apnea threshold causes CSA. METHODS Men with HF were divided into those with mainly OSA (obstructive-dominant, n = 18) and those with mainly CSA (central-dominant, n = 10). While patients were supine, antishock trousers were deflated (control) or inflated for 15 min (lower body positive pressure [LBPP]) in random order. RESULTS LBPP reduced leg fluid volume and increased neck circumference in both obstructive- and central-dominant groups. However, in contrast to the obstructive-dominant group in whom LBPP induced an increase in Rph, a decrease in Vmin, and an increase in PCO2, in the central-dominant group, LBPP induced a reduction in Rph, an increase in Vmin, and a reduction in PCO2. CONCLUSIONS These findings suggest mechanisms by which rostral fluid shift contributes to the pathogenesis of OSA and CSA in men with HF. Rostral fluid shift could facilitate OSA if it induces pharyngeal obstruction, but could also facilitate CSA if it augments ventilation and lowers PCO2.

Relationship of heart rate variability to sleepiness in patients with obstructive sleep apnea with and without heart failure.

BACKGROUND Many patients with severe obstructive sleep apnea (OSA) do not complain of excessive daytime sleepiness (EDS), possibly due to increased sympathetic nervous activity (SNA) and accompanying heightened alertness. We hypothesized that in patients with OSA, those without subjective EDS (Epworth Sleepiness Scale, ESS score < 11) would have higher very low frequency (VLF) heart rate variability (HRV) during sleep, reflecting greater sympathetic heart rate modulation than patients with an ESS score ≥ 11. METHODS Patients with severe OSA (AHI ≥ 30: 26 with and 65 without heart failure) were divided into those with and without EDS. Heart rate (HR) signals were acquired in stage 2 sleep during periods of recurrent apneas and hypopneas and submitted to coarse graining spectral analysis, which extracts harmonic, neurally mediated contributions to HRV from total spectral power. Because the apnea-hyperpnea cycle entrains muscle SNA at VLF (0 to 0.04 Hz), VLF power was our principal between-group comparison. RESULTS Subjects without EDS had higher harmonic VLF power (944 ± 839 vs 447 ± 461 msec(2), p = 0.003) than those with EDS, irrespective of the presence or absence of heart failure (1218 ± 944 vs 426 ± 299 msec(2), p = 0.043, and 1029 ± 873 vs 503 ± 533 msec(2), p = 0.003, respectively). ESS scores correlated inversely with VLF power in all (r = -0.294, p = 0.005) and in heart failure subjects (r = -0.468, p = 0.016). CONCLUSIONS Patients with severe OSA but without EDS have higher VLF-HRV than those with EDS. This finding suggests that patients with severe OSA but without EDS have greater sympathetic modulation of HRV than those with EDS that may reflect elevated adrenergically mediated alertness. CITATION Taranto Montemurro L; Floras JS; Picton P; Kasai T; Alshaer H; Gabriel JM; Bradley TD. Relationship of heart rate variability to sleepiness in patients with obstructive sleep apnea with and without heart failure.

Influence of rostral fluid shift on upper airway size and mucosal water content.

STUDY OBJECTIVE Fluid displacement from the legs during recumbency while in bed might narrow the upper airway (UA) in association with nuchal fluid accumulation that may contribute to the pathogenesis of obstructive sleep apnea (OSA). The aim of this study was to test the hypothesis that rostral fluid displacement from the legs causes a greater decrease in UA cross-sectional area (UA-XSA) and a greater increase in UA mucosal water content (UA-MWC) and internal jugular venous volume (IJVVol) in subjects with OSA than in those without OSA. METHODS Subjects underwent baseline assessment of leg fluid volume (LFV) measured by bio-electrical impedance, as well as UA-XSA and UA-MWC by magnetic resonance imaging. They were then randomly assigned to a 20-min period either with or without application of lower body positive pressure (LBPP) of 40 mm Hg, followed by a 15-min washout period, after which they crossed over to the other arm of the study. Measurements of LFV, UA-MWC, and UA-XSA were repeated after each arm of the study. RESULTS In 12 subjects without sleep apnea, UA-XSA increased and UA-MWC decreased significantly, whereas in 12 subjects with OSA, UA-XSA decreased and UA-MWC increased significantly in response to LBPP. The changes in UA-XSA and UA-MWC in response to LBPP differed significantly between the 2 groups (p = 0.006 and p < 0.001, respectively), despite similar changes in LFV and IJVVol. CONCLUSIONS Our results suggest that rostral fluid shift may contribute to the pathogenesis of OSA at least partly through narrowing of the UA due to transudation of fluid into the UA mucosa.

Factors predisposing to worsening of sleep apnea in response to fluid overload in men

OBJECTIVES Obstructive sleep apnea (OSA) is highly prevalent in patients with fluid-retaining conditions. Using bioimpedance measurements, previous studies have shown that the greater the amount of fluid redistributed from the legs to the neck overnight, the greater the severity of OSA. Our objective was to investigate factors that predispose the development or worsening of OSA in response to experimental fluid overload. METHODS Fifteen normotensive and non-obese adult men with and without OSA underwent polysomnography (PSG) during which normal saline was infused intravenously at a minimal rate to keep the vein open (control) or as a bolus of 22 ml/kg body weight (approximately 2 L) in a random order and crossed over after a week. RESULTS AND CONCLUSIONS Before and after sleep, neck circumference and bioimpedance were measured to calculate neck resistance, reactance, phase angle, and fluid volume. Subjects who experienced more than a twofold increase in apnea-hypopnea index (AHI) or obstructive AHI from control to intervention and had an AHI>10 during intervention were considered susceptible to the development or worsening of OSA. Baseline neck circumference and phase angle before saline infusion were independently associated with increased susceptibility to developing or worsening OSA in response to saline infusion. In non-obese men, a larger neck circumference and bioimpedance phase angle of the neck, which may be associated with larger pharyngeal tissue content, is associated with increased susceptibility for worsening of OSA in response to fluid overloading.