Tetraplegia is a risk factor for central sleep apnea

Abstract

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.

Keywords: apnea; cervical; sleep; spinal; tetraplegia.

Fig. 1.

A representative polygraph from one spinal cord injured (SCI) patient during non-rapid eye movement (REM) sleep depicting the noninvasive ventilation (NIV) protocol to induce central apnea. Left: baseline ventilation preceding NIV trial. NIV is performed for 3 min; termination of NIV resulted in central apnea. P_SG, supraglottic pressure; Pet_CO2, end-tidal CO₂; P_mask, mask pressure.

Fig. 2.

A representative polygraph from one cervical SCI patient who had spontaneous central apnea and breathing instability associated with fluctuations in Pet_CO2 and O₂ saturation during sleep. Fi_O2, fractional inspired O_2.

Fig. 3.

A summary of data to compare the controller gain (top), steady-state plant gain (middle) and CO₂ reserve (bottom) in the cervical, thoracic and able-bodied control groups. Data are expressed as mean ± SE. *P < 0.05 for cervical vs. control; +P < 0.05 for cervical (C)-SCI vs. thoracic (T)-SCI. Note that the steady-state plant gain and controller gain analysis included only NIV protocol to induce central apnea (5 C-SCI and 6 T-SCI).

Fig. 4.

A summary data to compare the CO₂ reserve in the cervical (n = 5) and thoracic (n = 6) subgroups that underwent NIV protocol to induce central apnea. Data are expressed as mean ± SE. *P < 0.05 for cervical vs. thoracic.

Fig. 5.

A plot box represents the summary data to compare the eupneic Pco₂ and hypocapnic apneic threshold (dotted lines) in the cervical, thoracic and able-bodied control groups. CO₂ reserve is indicated by parentheses for cervical (A), control (B), and thoracic (C), respectively. Data are expressed as mean ± SE for SCI and as means for control group.

Fig. 6.

A schematic diagram depicting the ventilatory responsiveness to CO₂ below eupnea in C-SCI and T-SCI patients for a given isometabolic hyperbolae. This illustration depicts 2 examples of C-SCI and T-SCI with similar chemoreflex sensitivity slopes (solid and dotted lines; respectively). Note that in C-SCI example (solid lines) a smaller change in Pet_CO2 (from 42.8 mmHg at baseline to 40.8 mmHg) in response to hyperventilation is required to cross the apneic threshold (A) and results in an apnea. In T-SCI case (dotted lines), however, a larger change in Pet_CO2 (from 40.0 mmHg at baseline to 36.6 mmHg) in response to hyperventilation is required to cross the apneic threshold (B) and develop an apnea. Note that the T-SCI example is at higher point (Y) on the isometabolic hyperbolae than C-SCI example (X) despite similar chemoreflex sensitivity. Slopes indicate similar chemoreflex sensitivity below eupnea in the thoracic and cervical groups. The solid line and arrow in T-SCI example indicate the estimated change in Pet_CO2 (from 40.0 mmHg at baseline to 38.5 mmHg) for the same change in ventilation, which is noted in C-SCI example in response to hyperventilation reaching (C) point without crossing the apneic threshold (B).