Treatment of Central Sleep Apnea Syndrome with low-pressure nasal continuous positive airway pressure and rebreathing.

Central sleep apnea syndrome (CSAS) is characterized by recurrent central
apneas during sleep. A central apnea is a cessation of airflow for at least ten
seconds without respiratory efforts. The syndrome is often accompanied by a
disturbed sleeping pattern and excessive daytime sleepiness. Treatment of CSAS
is difficult. Continuous positive airway pressure (CPAP), bi-level positive
airway pressure (BIPAP), oxygen and several drugs have been applied with
variable success. Additional CO2 can prevent apneas since the arterial CO2
pressure (PaCO2) is continually held above the apnea- threshold. This is the
PaCO2 below which breathing is no longer stimulated by CO2. When during sleep
PaCO2 drops below the apnea-threshold because of deep breathing, a central
apnea occurs. This can be prevented by adding CO2. With a rebreathing/dead
space mask, the patient breathes CO2 he has produced himself, and doesn*t need
a CO2 gas cylinder. Preliminary studies show that a rebreathing/dead space mask
may be effective in both CSAS and in Cheyne-Stokes breathing in heart failure.

Primary objective:
To show that addition of dead space to low-pressure nCPAP (which is usually not
effective but can be relatively well tolerated) makes the therapy effective and
diminishes the apnea hypopnea index with >10/hour in patients with CSAS.

Secondary Objective:
To show that addition of dead space to low-pressure nCPAP in patients with CSAS
improves sleep structure.

To show that addition of dead space to low-pressure nCPAP in patients with
CSAS improves blood pressure.

To show that addition of dead space to low-pressure nCPAP in patient with CSAS
improves the quality of sleep(Groningen Sleep Quality Scale)

To show that addition of dead space to low-pressure nCPAP in patients with CSAS
improves the heartrate variability.

Series of n of 1 studies.
Each patient acts as his or her own control and receives 5 pairs of treatments.
Each pair consists of a one night period of treatment with dead space and
low-pressure nCPAP and one night of treatment with low-pressure nCPAP only. The
latter is considered a placebo therapy since the pressure of 4 cm H2O is
considered ineffective. For each pair of treatments the order of low-pressure
nCPAP and low-pressure nCPAP with added dead space will be randomized. The
random sequence will be prepared in advance by a pulmonary function technician
for each patient separately. The patient and the investigator are unaware of
the sequence of treatment.

Each patient acts as his or her own control and receives 5 Pairs of treatments.
Each pair consist of one night treatment with low pressure CPAP with added dead
space(rebreathing) and a one night treatment with low pressure CPAP only. For
each pair of treatments the order of dead space with low pressure CPAP or low
pressure CPAP only was randomized.

Benefit is adequate treatment for CSAS in the future. The advantage of the n of
1 study is that we can investigate if this treatment is beneficial in this
specific person. The risk of participating in this study is low. Patients could
have a raise in their PaCO2 that is more than expected. This is prevented by
adjusting the dead space volume in such a way that the end-tidal CO2 does not
raise more than 5mmHg. The first time of sleeping with added dead
space(rebreathing) to low-pressure nCPAP will be monitored in hospital for
safety reasons. Furthermore It can be expected that patients with adequately
functioning chemoreflexes (normocapnic during daytime) increase their tidal
volumes during sleep to such an extent that severe hypercapnia will not occur.
Every day polygraphy and capnography will be performed at the patients home.
When a patient feels short of breath, this can be solved by breathing through
the mouth instead of the nose. Patients have to sleep in hospital 2 times and
visit the out-patient clinic 2 times. A researcher will visit the patients home
every day for 10 days. In a recent study 204 patients were treated with added
dead space to cpap and no patient experienced headache because of hypercapnia.