Anuj Chandra, MD, DABSM
Deepak Shrivastava, MD, DABSM, RPSGT
Cindy M. Simmons, PA-C, MMSc
Some patients visiting the sleep lab will exhibit a form of “mixed apnea,” where obstructive sleep apnea hypopnea syndrome (OSAHS) will change to central sleep apnea (CSA) with a switch in body position or use of continuous positive airway pressure.
Many sleep specialists have witnessed this clinical phenomenon, but it wasn’t specifically defined until a group of researchers at the Mayo Clinic Sleep Disorders Center in Rochester, Minn., studied complex sleep apnea in detail.1
They found that when patients with complex sleep apnea develop frequent central apneas or a Cheyne-Stokes respiratory pattern after initial application of CPAP, their sleep often remains severely fragmented by the persistent or emergent breathing abnormalities.
In a case series involving similar patients who at first appeared to have OSAHS, but developed significant CSA or Cheyne-Stokes respiration after application of CPAP, another research team concluded no satisfactory CPAP pressure may be found in these patients.2 At the best pressures, they still had a respiratory disturbance index of approximately 60 events per hour.
The investigators have advocated recognition of “complexity” through the use of time-series analysis, usually beyond the clinically available techniques. Further, they acknowledge that such complexity may not be unmasked until application of CPAP.
These patients don’t respond well to CPAP and, in particular, may not be appropriate candidates for auto-titration devices, so it would be useful to clinically identify such patients and anticipate alternate therapeutic approaches. A clinical profile also may help in understanding the pathophysiology involved in the development of unstable breathing patterns.
Non-hypercapnic repetitive central apneas and hypopneas are most commonly found in patients with concurrent cardiac disease. Multivariate analysis indicates that in such people referred to a sleep lab, symptoms such as snoring, a clinical indicator of upper airway instability, or body mass index aren’t predictive of OSAHS over Cheyne-Stokes breathing syndrome.
Instead, risk factors for Cheyne-Stokes included male sex, age over 65 years, lower ejection fractions on echocardiographic examination, and atrial fibrillation.
A closer look
The Mayo group, lead by Timothy Morgenthaler, MD, retrospectively recorded data on history, BMI, hypertension, diabetes, polysomnography data, and treatment recommendations on consecutive adult patients (age 18 and older) referred to its sleep disorders center during January 2004.
Two hundred fifty-one patients had polysomnography performed; 223 were diagnosed with a sleep-related breathing disorder. Among these patients, only one had CSA.
In order to enrich their study population with more patients having CSA, they searched all polysomnography results from February through June 2004 to identify 20 additional individuals with CSA. Thus, they examined the clinical and polysomnography data for 243 patients.
Then they excluded all patients with a clinical history of congestive heart failure or a left ventricular ejection fraction of 40 percent or less, leaving 219 for analysis.
Patients were diagnosed with OSAHS if they had five or more obstructive apneas and hypopneas per hour, or if they complained of sleepiness and had 10 or more respiratory-related arousals per hour (consistent with upper airway resistance syndrome).
They considered the patients to have CSA when they observed a central apnea index of more than five events per hour and at least 50 percent of the total apnea-hypopnea index was purely central in origin, that is, without obstructive components.
The researchers determined patients to have complex sleep apnea if CPAP titration eliminated events defining OSAHS, but the residual central apnea index was five or more per hour or Cheyne-Stokes respiratory pattern became prominent and disruptive.
When patients with apparent OSAHS have a poor response to CPAP, one must question whether an adequate CPAP titration was performed, they stated. In clinical trials evaluating various aspects of CPAP efficacy in patients with OSAHS, residual AHI is typically less than 10.
The residual obstructive apnea index in their patients with complex sleep apnea was very low (0.93) but higher than in the patients with OSAHS. This was probably due to their CPAP-titration scheme.
When central apneas and hypopneas emerge on CPAP, they often become more frequent with higher CPAP pressures. When this is encountered by the sleep technologist, after first trying higher pressures, he should lower CPAP to find the best compromise between central and obstructive abnormalities.
After excluding patients with congestive heart failure or left ventricular ejection fraction of 40 percent or less, the researchers observed only small clinical differences between their patient groups.
Similar to findings in other reports, their OSAHS patients tended to be heavier and to have less sleep-maintenance insomnia than their CSA patients. Elevated BMI has been a consistent risk factor for OSAHS. Obesity is thought to increase the likelihood of developing OSA by its deleterious effect on airway configuration and on respiratory control.
Their patients with complex sleep apnea had a mean BMI intermediate between that of patients with OSAHS and CSA, yet it wasn’t statistically different from either.
The researchers had hypothesized the clinical profile of patients with complex sleep apnea would most nearly resemble that of patients with CSA. Simplistically, they thought patients with complex sleep apnea might be patients with CSA who had accumulated risk factors for OSAHS such as obesity or hypertension combining aspects of respiratory-control instability with airway compromise.
They found the relationships to be more complicated.
Apart from a higher proportion of men, little distinguished patients with complex sleep apnea from those with OSAHS on clinical grounds. Their hypothesis wasn’t supported, and they had to consider other factors to explain why fairly similar patients respond differently to CPAP.
Patients who have complex sleep apnea initially are treated with CPAP, but the problem begins when there seems to be no pressure that will resolve their apnea episodes completely. This “complexity” isn’t generally found until the patient is treated with CPAP.2
The Mayo researchers were attempting to clinically define patients with complex sleep apnea so alternative therapeutic approaches could be identified. “A clinical profile may also help in understanding the pathophysiology involved in the development of unstable breathing patterns,” they wrote.1
In their retrospective study, 15 percent of patients with sleep-disordered breathing had complex sleep apnea. The complex sleep apnea patients had longer apnea duration than those with OSAHS, which indicated a difference in feedback or respiratory chemo-reflex gain that allowed the variations in response to CPAP.
They also noted that theoretically CPAP in some patients may induce hypocapnia by “suddenly relieving the work of breathing or by improving physiologic shunt.”1
The Mayo researchers defined complex sleep apnea as, “The emergence of problematic CSA and Cheyne-Stokes respirations with CPAP application sufficient of eliminating obstructive apneas and hypopneas.”1
Patients with complex sleep apnea had clinical features that placed it between OSAHS and CSA. It seems to be more like OSAHS until CPAP is applied, and then it appears more like CSA. Also, complex sleep apnea patients have less sleep-maintenance insomnias.
They concluded complex sleep apnea looks like a separate entity from OSAHS and CSA, optimal treatment is still undetermined, and more research is needed.1
1. Morgenthaler TI, Kagramanov V, Hanak V, Decker PA. Complex sleep apnea syndrome: is it a unique clinical syndrome? Sleep. 2006;29(9):1203-9.
2. Gilmartin GS, Daly RW, Thomas RJ. Recognition and management of complex sleep-disordered breathing. Curr Opin Pulm Med. 2005;11(6):485-93.
Anuj Chandra, MD, DABSM, is chairman at the Advanced Center for Sleep Disorders, Chattanooga, Tenn.
Deepak Shrivastava, MD, DABSM, RPSGT, is director of the Sleep Diagnostics Center at San Joaquin General Hospital, Stockton, Calif., and professor of medicine at UC Davis School of Medicine, Sacramento, Calif.
Cindy M. Simmons, PA-C, MMSc, is physician assistant at the Advanced Center for Sleep Disorders.
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