Medication Summary
Due to the heterogeneity of the central sleep apnea syndromes, different medications have been used under different circumstances. No single medication can be considered a drug of choice. [1] Several different medications aimed at improving central sleep apnea include acetazolamide, theophylline, and sedative-hypnotic agents.
Acetazolamide (Diamox)
Acetazolamide is a carbonic anhydrase inhibitor that causes bicarbaturia and metabolic acidosis, which presumably shifts the apneic threshold of PaCO2 to a lower level. It has been shown to be effective therapy in primary central sleep apnea and CSB in patients with heart failure and in the treatment of high-altitude periodic breathing.
Theophylline
This agent has been studied in patients with heart failure and was found to be effective in attenuating CSB. [41] It may also be effective for high-altitude periodic breathing.
Sedative hypnotics
These agents have been used successfully in treating nonhypercapnic central sleep apnea. Temazepam and zolpidem have been shown to be effective under these circumstances and are believed to work by consolidating the sleep pattern, thus minimizing the instability in ventilation induced by sleep-wake transitions. A case series showed zolpidem reduced central apneas, and the overall apnea-hypopnea index, without worsening obstructive events. [42]
Carbonic Anhydrase Inhibitor
Class Summary
These agents are used to induce metabolic acidosis and increase baseline ventilation.
Acetazolamide (Diamox)
Acetazolamide is a carbonic anhydrase inhibitor for acclimatization to altitude in high-altitude cerebral edema (HACE) and acute mountain sickness (AMS). It helps prevent AMS in forced rapid ascent or in patients with a history of repeated AMS. It improves symptomatic periodic breathing and hypoxia experienced at high altitudes. Acetazolamide is not indicated for general prophylaxis of AMS. Treatment of AMS may be discontinued when the patient is asymptomatic.
Benzodiazepines
Class Summary
These agents are used to promote deeper stages of sleep.
Temazepam (Restoril)
The intermediate rate of absorption and duration of action make this drug useful for treating initial and middle insomnia. Temazepam has no active metabolites, which reduces cognitive impairment and grogginess the following day.
Nonbenzodiazepine sedative hypnotic
Class Summary
These agents are used to consolidate sleep.
Zolpidem (Ambien)
Zolpidem is rapidly absorbed, with a fast onset of action (20-30 min), which makes this a good drug for sleep induction. The ER product (Ambien CR) consists of a coated 2-layer tablet and is useful for insomnia characterized by difficulties with sleep onset and/or sleep maintenance. The first layer releases drug content immediately to induce sleep, whereas second layer gradually releases additional drug to provide continuous sleep.
Phosphodiesterase inhibitor
Class Summary
These agents are respiratory stimulants.
Theophylline (Theo-dur)
Theophylline has a number of physiological effects, including increases in collateral ventilation, respiratory muscle function, mucociliary clearance, and central respiratory drive. It partially acts by inhibiting phosphodiesterase, elevating cellular cyclic AMP levels, or antagonizing adenosine receptors in the bronchi, resulting in relaxation of smooth muscle. However, clinical efficacy is controversial, especially in acute settings.
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The role of loop gain in determining respiratory instability. A) When loop gain is less than 1, the tendency for an overshoot of the corrective response to an apnea or hypopnea is lessened, and ventilation returns to a steady pattern. B) When loop gain is greater than or equal to 1, the vigorous responses to respiratory disturbances result in continuous oscillation between the events and the corrections, resulting in an unstable periodic breathing pattern. Adapted from White DP Pathogenesis of obstructive and central sleep apnea. Am J Respir Crit Care Med. Dec 1 2005;172(11):1363-70.
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This polysomnogram demonstrates central sleep apnea and Biot respiration in a patient receiving long-term morphine for chronic pain. The Biot pattern may be irregular without any type of periodicity, or it can consist of runs of similar-sized breaths alternating with central apneas.
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Obstructive sleep apnea (OSA): This polysomnogram demonstrates typical hypopneas occurring in OSA prior to continuous positive airway pressure titration. In OSA, airflow is absent or reduced, but ventilatory effort persists.
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Cheyne Stokes: This polysomnogram represents Cheyne Stokes breathing and occurred subsequent to continuous positive airway pressure titration for OSA in the same patient in the previous media file. Cheyne Stokes breathing has a classic crescendo-decrescendo breathing pattern.