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Volume 15 No. 03
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Case Reports

Central Sleep Apnea With Sodium Oxybate in a Pediatric Patient

Arezou Heshmati, MD
Columbia University Medical Center, New York, New York


A 12-year-old girl with normal neurodevelopment and narcolepsy type 1 presented with unexpected central apneas in response to sodium oxybate (SO). The patient underwent overnight polysomnography on SO (2.75 + 2.5 grams) which showed an apnea-hypopnea index of 4.3 events/h, and all the events were central apneas. A majority of central apneas clustered at about 1.5 hours after the first dose of SO. Remarkably, after a second dose of SO that was 0.25 grams smaller, she did not exhibit clusters of central sleep apneas. However, she did experience similar but milder breathing abnormalities that did not meet criteria to be scored as central apneas or hypopneas. Based on this observation, there may be an association between SO treatment and the development of central apnea. Further polysomnographic research on pediatric patients taking SO would help determine if there is a significant association between SO treatment and the development of central apnea in the pediatric population.


Heshmati A. Central sleep apnea with sodium oxybate in a pediatric patient. J Clin Sleep Med. 2019;15(3):515–517.


Central nervous system suppression and respiratory depression are known side effects of sodium oxybate (SO).1 SO comes with a warning that in clinical trials, adult patients taking recommended doses of SO experienced mental obtundation and clinically significant respiratory depression. However, sleep specialists commonly consider the recommended therapeutic dose of SO to be safe in patients without respiratory disorders as long as it is not combined with another central nervous system suppressant. Although clinicians are advised to remain vigilant when prescribing this medication to patients with underlying respiratory disorders, there are no clear guidelines for monitoring the respiratory function of patients taking SO.26

SO has been widely used off-label to treat symptoms in children and adolescents with narcolepsy type 1. Current therapy and dose are based on empirical data reported by pediatric sleep disorders experts.7,8


This case illustrates a rather unusual reaction to two slightly different doses of SO. A 12-year-old girl with normal neuro-development, a history of excessive daytime sleepiness for one year, and the diagnosis of narcolepsy type 1 came to the sleep clinic for a second opinion. Her past medical history included a tonsillectomy and adenoidectomy. Her initial workup at a different institution showed normal magnetic resonance imaging (MRI) and magnetic resonance angiography of the brain, normal electroencephalography, and positive HLA DQA1*01:02 and DQB1*06:02.

Her first sleep study and subsequent Multiple Sleep Latency Test (MSLT) showed four sleep-onset REM periods in four naps and a mean sleep latency of 1.6 minutes, consistent with the diagnosis of narcolepsy. The apnea-hypopnea index (AHI) on the overnight sleep study preceding the MSLT was 0.9 events/h.

Four months later, she underwent repeat polysomnography (PSG) at another institution, revealing severe obstructive sleep apnea (OSA) with an AHI of 32.2 events/h; there were no central apneas reported in this study. She was sick with an upper respiratory tract infection (URI) during this study. Given the normal AHI in the first study only a few months earlier, the absence of body weight changes between the two studies, and the fact that she had a URI, the finding of OSA was dismissed, and the treating physician proceeded with SO treatment. The dose of SO was gradually increased to 9 grams per night. On this dose, the patient exhibited side effects of nausea, vomiting, and depression, and as per her family's request, the dose was gradually decreased.

When she presented to our clinic, she was taking total 5.25 (2.75 + 2.5) grams of SO per night. She was also concurrently taking venlafaxine. The patient underwent an overnight PSG while taking SO to evaluate the current dose's safety and its potential effects on her breathing. During this overnight PSG on SO of 2.75 + 2.5 grams, she had an AHI of 4.3 events/h, and all the events were central apneas (Figure 1). Although the total AHI falls within normal limits, the cluster of central apneas at about 1.5 hours (Figure 1) after the first dose of SO suggested a relationship between the first dose of SO and the central apneas. Surprisingly, she did not show the clustered central sleep apneas after the second dose of SO, which was only lower by 0.25 grams. However, she did have similar but milder breathing abnormalities that did not meet the criteria to be scored as central apneas or hypopneas. After seeing this pattern of breathing, we reviewed the medication history with the patient's mother and found no reported deviation from her usual pattern of medication intake on the night of the sleep study.

Central apneas cluster about 1.5 hours after the first dose of sodium oxybate while the patient is in prolonged slow wave sleep.


Figure 1

Central apneas cluster about 1.5 hours after the first dose of sodium oxybate while the patient is in prolonged slow wave sleep.

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Given that the overall AHI was within normal limits, we decided to continue the current dose of SO without any further increase. About 2 months later, the patient discontinued the medication because she did not feel like herself and reported symptoms of depression. The patient was started on methylphenidate and venlafaxine, which provided satisfactory control of cataplexy and excessive daytime sleepiness while resolving depressive symptoms. After discontinuing SO for a year, a follow-up PSG showed an AHI of 2.5 events/h and a central apnea index of 1.2 events/h, both of which fell within normal limits (Table 1).

Sleep study parameters and relevant clinical information across two PSG studies.


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Table 1

Sleep study parameters and relevant clinical information across two PSG studies.

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SO is an FDA-approved medicine for the treatment of narcolepsy type 1 in adult patients. The manufacturer discloses that in clinical trials with recommended doses of SO, adult patients underwent mental obtundation and clinically significant respiratory depression; however, clinicians have no guidelines to monitor respiratory depression. In pediatric patients, the absence of a clear recommended dose compounds the problem.

There are multiple case reports of central sleep apnea in adult patients treated with SO, but no such case has been reported in pediatric patients.6,910 In this reported case, clusters of central apneas may have been related to the first dose of SO, but it is hard to explain why the second dose, which was only 0.25 grams lower, did not produce the same effect on the patient's breathing pattern. Generally, the plasma concentration of SO is higher after the second dose than after the first dose, mainly due to a lower food effect on the second dose. These findings may be explained by distinct pharmacokinetics of SO in children or simply by the fact that the second dose of SO was 0.25 grams lower.

All other potential causes of and contributors to central sleep apnea, including anatomical brain or brainstem abnormalities (eg, Arnold-Chiari malformation, foramen magnum stenosis, brain tumor), genetic conditions (eg, Prader-Willi syndrome, Rett syndrome), neuromuscular disorders, obesity, and congestive heart failure were ruled out because the patient was a developmentally normal girl with healthy general and neurological examination, normal brain MRI, and normal body mass index. Hypothyroidism is another potential cause of central sleep apnea, but the patient had normal thyroid function tests. She did not have OSA, another potential contributor to central sleep apnea. The central sleep apneas were not consistent with physiologic central sleep apneas since they did not occur during sleep onset, post-arousal periods, post-sigh periods, or REM sleep. Her only other concurrent medication was venlafaxine, which is not known to cause sleep apnea; moreover, the patient was on venlafaxine during the follow-up PSG, which did not show central sleep apnea.

Based on this patient's PSG tests, there may be an association between SO and the development of central apnea. As this patient's study did not show sleep fragmentation, oxygen desaturation, or persistent central apnea, the clinical significance of this patient's experience is unknown. It is possible that even small dose increases may affect respiratory drive, but a definitive conclusion cannot be drawn from this case report. Further PSG research on pediatric patients taking SO would reveal a potential association between SO and the development of central apnea in the pediatric population. It may also identify which groups (dose-dependent, pre-pubertal, taking other medications, or known neurologic disorder) may require repeat PSG tests.


Work for this study was performed at Columbia University Medical Center, New York, NY. This study includes off-label or investigational use of sodium oxybate in pediatric patients. The author reports no conflicts of interest.



apnea-hypopnea index


magnetic resonance imaging


Multiple Sleep Latency Test




sodium oxybate


upper respiratory tract infection



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