Amy T. Bascom

Tetraplegia is a risk factor for central sleep apnea

Sleep-disordered breathing (SDB) is highly prevalent in patients with spinal cord injury (SCI); the exact mechanism(s) or the predictors of disease are unknown. We hypothesized that patients with cervical SCI (C-SCI) are more susceptible to central apnea than patients with thoracic SCI (T-SCI) or able-bodied controls. Sixteen patients with chronic SCI, level T6 or above (8 C-SCI, 8 T-SCI; age 42.5 ± 15.5 years; body mass index 25.9 ± 4.9 kg/m(2)) and 16 matched controls were studied. The hypocapnic apneic threshold and CO2 reserve were determined using noninvasive ventilation. For participants with spontaneous central apnea, CO2 was administered until central apnea was abolished, and CO2 reserve was measured as the difference in end-tidal CO2 (PetCO2) before and after. Steady-state plant gain (PG) was calculated from PetCO2 and VE ratio during stable sleep. Controller gain (CG) was defined as the ratio of change in VE between control and hypopnea or apnea to the ΔPetCO2. Central SDB was more common in C-SCI than T-SCI (63% vs. 13%, respectively; P < 0.05). Mean CO2 reserve for all participants was narrower in C-SCI than in T-SCI or control group (-0.4 ± 2.9 vs.-2.9 ± 3.3 vs. -3.0 ± 1.2 l·min(-1)·mmHg(-1), respectively; P < 0.05). PG was higher in C-SCI than in T-SCI or control groups (10.5 ± 2.4 vs. 5.9 ± 2.4 vs. 6.3 ± 1.6 mmHg·l(-1)·min(-1), respectively; P < 0.05) and CG was not significantly different. The CO2 reserve was an independent predictor of apnea-hypopnea index. In conclusion, C-SCI had higher rates of central SDB, indicating that tetraplegia is a risk factor for central sleep apnea. Sleep-related hypoventilation may play a significant role in the mechanism of SDB in higher SCI levels.

Identification and treatment of sleep-disordered breathing in chronic spinal cord injury

Study design:A follow up on an ongoing prospective cohort study.Objective:Spinal cord injury or disorder (SCI/D) patients have higher rates of sleep-disordered breathing (SDB) than the general population. The objectives of this study were to examine predictors of SDB diagnosis and to estimate rates of SDB treatment in SCI/D patients.Setting:A SCI clinical sleep research laboratory.Methods:Twenty-eight SCI/D patients (7 women, age 42.8±15.8 years; 16 cervical and 12 thoracic level injuries) completed a battery of questionnaires (Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Berlin questionnaire (BQ) and fatigue severity scale (FSS)) and had one night of attended laboratory polysomnography (PSG). Participants were then notified of the results of their PSG and were interviewed approximately 1 year later to assess clinical outcomes.Results:The majority of patients reported poor sleep quality on all questionnaires. On the basis of PSG, 22 (79%) patients had SDB (apnea-hypopnea index (AHI)⩾5 events per hour), and 17 (61%) had moderate/severe SDB (AHI⩾15 events per hour). Higher ESS scores were associated with a higher risk of AHI⩾5; however, other questionnaires did not distinguish between those with and without SDB using either AHI cutoff. In follow-up interviews, only 50% of patients had spoken to a health-care provider about SDB and only six patients with SDB were prescribed treatment, four of whom were using the treatment at follow-up.Conclusion:SDB is common and severe among SCI/D patients. Screening questionnaires do not appear to differentiate between those with and without SDB. Even when SDB was recognized, many patients remained untreated. The increased prevalence of cardiovascular disease in SCI/D patients could represent a consequence of untreated SDB, and improving diagnosis and management of SDB has the potential to improve outcomes for these patients.

Effects of theophylline on pulmonary function in patients with traumatic tetraplegia.

Abstract Background/Objectives: To assess the effects of theophylline on pulmonary function in patients with chronic traumatic tetraplegia, we conducted a double-blind placebo-controlled crossover study in 10 patients. Methods: The patients (age: 41 ± 3 years; time from injury: 16 ± 3 years; neurological levels: C3 to C7-T1) were randomized to receive oral theophylline or placebo for 6 weeks. After 2 months of washout, the patients received the medication not taken in the first trial for an additional 6 weeks. We measured lung volumes, expiratory flow rates, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) at both baseline and at the end of each treatment arm. Theophylline blood serum assays were measured during the first week of the treatment and on the day of respiratory measurements. Results: Mean theophylline level on the day of treatment completion was 12.6 ± 1.4 ng/mL. In analyzing the data from the group of 10 patients, the percent changes from baseline in total lung capacity, forced vital capacity, forced expiratory volume at 1 second, MIP, and MEP did not differ significantly between the two treatment arms (P > 0.05 in all). Conclusion: These data show that in this small group of 10 subjects with chronic tetraplegia, administration of oral theophylline did not improve pulmonary function.

Testosterone Conversion Blockade Increases Breathing Stability in Healthy Men during NREM Sleep

STUDY OBJECTIVES Gender differences in the prevalence of sleep apnea/hypopnea syndrome may be mediated via male sex hormones. Our objective was to determine the exact pathway for a testosterone-mediated increased propensity for central sleep apnea via blockade of the 5α-reductase pathway of testosterone conversion by finasteride. DESIGN Randomization to oral finasteride vs. sham, single-center study. SETTING Sleep research laboratory. PARTICIPANTS Fourteen healthy young males without sleep apnea. INTERVENTION Hypocapnia was induced via brief nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea. MEASUREMENTS AND RESULTS The apnea threshold (AT) was defined as the end-tidal CO₂(P(ET)CO₂) that demarcated the central apnea closest to the eupneic P(ET)CO₂. The CO₂ reserve was defined as the difference in P(ET)CO₂ between eupnea and AT. The apneic threshold and CO₂ reserve were measured at baseline and repeated after at a minimum of 1 month. Administration of finasteride resulted in decreased serum dihydrotestosterone. In the finasteride group, the eupneic ventilatory parameters were unchanged; however, the AT was decreased (38.9 ± 0.6 mm Hg vs.37.7 ± 0.9 mm Hg, P = 0.02) and the CO₂ reserve was increased (-2.5 ± 0.3 mm Hg vs. -3.8 ± 0.5 mm Hg, P = 0.003) at follow-up, with a significantly lower hypocapnic ventilatory response, thus indicating increased breathing stability during sleep. No significant changes were noted in the sham group on follow-up study. CONCLUSIONS Inhibition of testosterone action via the 5α-reductase pathway may be effective in alleviating breathing instability during sleep, presenting an opportunity for novel therapy for central sleep apnea in selected populations.

Tetraplegia is associated with enhanced peripheral chemoreflex sensitivity and ventilatory long-term facilitation.

Cardiorespiratory plasticity induced by acute intermittent hypoxia (AIH) may contribute to recovery following spinal cord injury (SCI). We hypothesized that patients with cervical SCI would demonstrate higher minute ventilation (V̇e) following AIH compared with subjects with thoracic SCI and able-bodied subjects who served as controls. Twenty-four volunteers (8 with cervical SCI, 8 with thoracic SCI, and 8 able-bodied) underwent an AIH protocol during wakefulness. Each subject experienced 15 episodes of isocapnic hypoxia using mixed gases of 100% nitrogen (N2), 8% O2, and 40% CO2 to achieve oxygen saturation ≤90% followed by room air (RA). Measurements were obtained before, during, and 40 min after AIH to obtain ventilation and heart rate variability data [R-R interval (RRI) and low-frequency/high-frequency power (LF/HF)]. AIH results were compared with those of sham studies conducted in RA during the same time period. Individuals with cervical SCI had higher V̇e after AIH compared with able-bodied controls (117.9 ± 23.2% vs. 97.9 ± 11.2%, P < 0.05). RRI decreased during hypoxia in all individuals (those with cervical SCI, from 1,009.3 ± 65.0 ms to 750.2 ± 65.0 ms; those with thoracic SCI, from 945.2 ± 65.0 ms to 674.9 ± 65.0 ms; and those who were able-bodied, from 949 ± 75.0 to 682.2 ± 69.5 ms; P < 0.05). LH/HF increased during recovery in individuals with thoracic SCI and those who were able-bodied (0.54 ± 0.22 vs. 1.34 ± 0.22 and 0.67 ± 0.23 vs. 1.82 ± 0.23, respectively; P < 0.05) but remained unchanged in the group with cervical SCI. Our conclusion is that patients with cervical SCI demonstrate ventilatory long-term facilitation following AIH compared with able-bodied controls. Heart rate responses to hypoxia are acutely present in patients with cervical SCI but are absent during posthypoxic recovery.

Sleep onset hypoventilation in chronic spinal cord injury

A high prevalence of sleep‐disordered breathing (SDB) after spinal cord injury (SCI) has been reported in the literature; however, the underlying mechanisms are not well understood. We sought to determine the effect of the withdrawal of the wakefulness drive to breathe on the degree of hypoventilation in SCI patients and able‐bodied controls. We studied 18 subjects with chronic cervical and thoracic SCI (10 cervical, 8 thoracic SCI; 11 males; age 42.4 ± 17.1 years; body mass index 26.3 ± 4.8 kg/m2) and 17 matched able‐bodied subjects. Subjects underwent polysomnography, which included quantitative measurement of ventilation, timing, and upper airway resistance (RUA) on a breath‐by‐breath basis during transitions from wake to stage N1 sleep. Compared to able‐bodied controls, SCI subjects had a significantly greater reduction in tidal volume during the transition from wake to N1 sleep (from 0.51 ± 0.21 to 0.32 ± 0.10 L vs. 0.47 ± 0.13 to 0.43 ± 0.12 L; respectively, P < 0.05). Moreover, end‐tidal CO2 and end‐tidal O2 were significantly altered from wake to sleep in SCI (38.9 ± 2.7 mmHg vs. 40.6 ± 3.4 mmHg; 94.1 ± 7.1 mmHg vs. 91.2 ± 8.3 mmHg; respectively, P < 0.05), but not in able‐bodied controls (39.5 ± 3.2 mmHg vs. 39.9 ± 3.2 mmHg; 99.4 ± 5.4 mmHg vs. 98.9 ± 6.1 mmHg; respectively, P = ns). RUA was not significantly altered in either group. In conclusion, individuals with SCI experience hypoventilation at sleep onset, which cannot be explained by upper airway mechanics. Sleep onset hypoventilation may contribute to the development SDB in the SCI population.

Upper airway mechanics in chronic spinal cord injury during sleep

Sleep-disordered breathing has been shown to be more prevalent in patients with spinal cord injury (SCI) than the general population. The pathogenesis of increased sleep-disordered breathing in individuals with chronic SCI is unknown. The purpose of this study is to determine whether SCI level affects upper airway (UA) collapsibility and neuromuscular compensatory responses to obstruction. Twenty-four participants (8 cervical SCI, 8 thoracic SCI, and 8 controls) were studied. The ventilation, timing, UA resistance, and pharyngeal collapsibility, defined by critical closing pressure, were determined during non-rapid eye movement sleep. Inspiratory duty cycle and minute ventilation were observed in response to increasing severity of UA obstruction. Compared with controls, both cervical and thoracic SCI participants demonstrated elevated passive critical closing pressure (0.5 ± 2.2 and 0.9 ± 2.7 vs. -2.5 ± 1.0 cmH2O, respectively; P = 0.01). No difference in UA resistance was observed between groups. Cervical and thoracic SCI individuals exhibited a similar degree of hypoventilation and dose-dependent increase in inspiratory duty cycle in response to UA obstruction. Passive UA collapsibility is increased in both cervical and thoracic SCI compared with control. The neuromuscular compensatory responses to UA obstruction during sleep are preserved in chronic SCI and are independent of the level of injury.

Spinal cord injury is associated with enhanced peripheral chemoreflex sensitivity.

Sleep‐disordered breathing (SDB) is prevalent in individuals with chronic spinal cord injury (SCI), but the exact mechanism is unknown. The aim of this study was to investigate whether peripheral chemoreceptors activity is enhanced in individuals with chronic SCI compared to abled‐bodied control subjects using CO2 and O2 chemical tests. In protocol (1) 30 subjects (8 cervical [cSCI], 7 thoracic [tSCI] and 15 able‐bodied [AB]) were studied to determine the ventilatory response to hyperoxia during wakefulness in the supine position. In protocol (2) 24 subjects (6 cSCI, 6 tSCI, and 12 AB subjects) were studied to determine the ventilatory response to a single breath of CO2 (SBCO2). The chemoreflex response to SBCO2 was calculated as ∆VE/∆CO2 (L/min/mmHg). The ventilatory response to hyperoxia was defined as the % change in VT following acute hyperoxia compared to preceding baseline. During hyperoxia SCI subjects had a significant decrease in VT and VE (63.4 ± 21.7% and 63.1 ± 23.0% baseline, respectively, P < 0.05) compared to AB (VT: 87.1 ± 14.3% and VE: 91.38 ± 15.1% baseline, respectively, P < 0.05). There was no significant difference between cSCI and tSCI in the VT or VE during hyperoxia (P = NS). There was no significant correlation between AHI and VE% baseline (r = −0.28) in SCI and AB (n = 30). SCI participants had a greater ventilatory response to an SBCO2 than AB (0.78 ± 0.42 L/min/mmHg vs. 0.26 ± 0.10 L/min/mmHg, respectively, P < 0.05). Peripheral ventilatory chemoresponsiveness is elevated in individuals with chronic SCI compared to able‐bodied individuals.

Nocturnal Swallowing and Arousal Threshold in Individuals with Chronic Spinal Cord Injury.

Respiratory complications are potential causes of death in patients with spinal cord injury (SCI). Nocturnal swallowing could be related to transient arousals and could lead to fragmented sleep in SCI patients. However, the impact of nocturnal swallowing on breathing and sleep physiology in SCI is unknown. The objectives of this study were 1) to determine whether nocturnal swallowing is more common in SCI than in able-bodied (AB) subjects, 2) to determine the role of nocturnal swallowing on arousal threshold (ArTh) in SCI individuals with sleep-disordered breathing (SDB), and 3) to determine the effect of continuous positive airway pressure (CPAP) treatment on nocturnal swallowing. A total of 16 SCI and 13 AB subjects with SDB completed in-laboratory polysomnography with a pharyngeal catheter. A swallowing event (SW) was defined as a positive spike in pharyngeal pressure and was used to calculate the swallow index (SI) defined as a number of SW/total sleep time. Each SW was assessed for a relationship to the sleep stages and respiratory cycle phases, and associated arousals and ArTh were calculated. SI was higher in the SCI group compared with AB subjects during wake and different sleep stages ( P < 0.05). SWs were found to be significantly higher in the late expiratory phase in the group with SCI compared with the other respiratory phases and were eliminated by CPAP ( P < 0.05). ArTh for the subjects with SCI was significantly lower ( P < 0.05) compared with the AB subjects. Nocturnal swallowing is more common in SCI than in AB individuals who have SDB, particularly during the expiratory phase. The ArTh is significantly lower in SCI (indicating increased arousal propensity), which may contribute to the mechanism of sleep disturbances in SCI. NEW & NOTEWORTHY Nocturnal swallowing is common in patients with chronic spinal cord injury (SCI) and is associated with frequent arousals from sleep. The lower arousal threshold during sleep in SCI may contribute to the mechanism of sleep disturbances that are commonly found in cervical and high thoracic SCI. Continuous positive airway pressure may play a therapeutic role in alleviating nocturnal swallowing, which may contribute to reduced risk of aspiration.

Sleep Disordered Breathing and Spinal Cord Injury- A State of the Art Review

&NA; Individuals living with spinal cord injury or disease (SCI/D) are at increased risk for sleep‐disordered breathing (SDB), with a prevalence that is three‐ to fourfold higher than the general population. The main features of SDB, including intermittent hypoxemia and sleep fragmentation, have been linked to adverse cardiovascular outcomes including nocturnal hypertension in patients with SCI/D. The relationship between SDB and SCI/D may be multifactorial in nature given that level and completeness of injury can affect central control of respiration and upper airway collapsibility differently, promoting central and/or obstructive types of SDB. Despite the strong association between SDB and SCI/D, access to diagnosis and management remains limited. This review explores the role of SCI/D in the pathogenesis of SDB, poor sleep quality, the barriers in diagnosing and managing SDB in SCI/D, and the alternative approaches and future directions in the treatment of SDB, such as novel pharmacologic and nonpharmacologic treatments.