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Abstract: Case Reports |

INTERFERON-INDUCED CENTRAL SLEEP APNEA FREE TO VIEW

Sireesha Gogineni, MD*; Rose A. Franco, MD
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Medical College of Wisconsin, Milwaukee, WI


Chest


Chest. 2007;132(4_MeetingAbstracts):721a-722. doi:10.1378/chest.132.4_MeetingAbstracts.721a
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INTRODUCTION:Interferon was the first cytokine implicated in sleep regulation. Early studies on mice demonstrated hypersomnia induced by the drug. There are no studies in literature indicating interferon can impact, control of respiration during sleep. This case report illustrates how interferon could induce central sleep apnea (CSA).

CASE PRESENTATION:A 55 year old man (BMI 26.8) presented with worsening snoring and witnessed apneic episodes. His past medical history included hypertension, rheumatoid arthritis, hepatitis-c, cirrhosis, and previous drug abuse history. Only medication was methadone.Polysomnography revealed 3 obstructive(OA) and 36 central apneas(CA), mostly during Non rapid eye movement(NREM) sleep, with an apnea-hypopnea index (AHI) of 21. He was placed on an auto-titrating CPAP device. Download after one month of use, showed residual AHI of 20 with good compliance. One month afterward, he was started on interferon for Hepatitis-C. He then reported worsened sleepiness and poor tolerance of CPAP.The second sleep study done while receiving interferon therapy was significantly worse with escalation in AHI to 62.9, 4 OA and 253 CA, majority in NREM sleep. Bipap trial at 14/10 showed no improvement. An echo done showed normal cardiac function and MRI of the brain showed no significant lesions. No new medications were started and no escalation in chronic methadone dose.

DISCUSSIONS:In our patient, there is clear evidence that he has opioid induced CSA, which worsened significantly after initiating interferon.Opioid induced CSA is a well known concept. Recognition of airway occlusion, hypoxia and breath by breath control of ventilation is mainly regulated by the carotid bodies during sleep, especially during NREM sleep. Mu-opioids depress respiration and blunt ventilatory responsiveness to hypercapnia and hypoxia by their direct effect on brainstem respiratory centers and carotid bodies. Ian Kronborg et al.in Chest 2005 article, “Central Sleep Apnea in Stable Methadone Maintenance Treatment (MMT) Patients”, confirmed that the AHI difference between MMT patients and normal subjects is mainly due to CSA events. As in our case, the events were primarily NREM sleep related but did not appear to be dose-dependent.Interferon has structural and functional similarities to opioids and may exert some direct effect on respiratory controller mechanisms but to-date there is no report in the literature of interferon directly suppressing the respiratory control mechanism. Another explanation is found by reviewing the systemic effects of interferon. This cytokine depresses the hepatic cytochrome p450- linked drug metabolizing system and increases the levels of substances cleared through that system. All opioids are cleared by hepatic cytochrome p450. Interferon, by inhibition of this pathway could increase the levels of opioids and prolong their effects. In animal models, this interaction has been verified resulting in opiate levels 2-3 times higher than prior to introducing interferon.

CONCLUSION:This case alerts us to a very real potential for CSA worsening in patients receiving interferon therapy and concurrent opiates. A significant number of hepatitis-C patients are on chronic opiate therapy. The exacerbation of CSA seen in our patient, with addition of interferon, may occur in many and remain undetected because of the accepted knowledge that interferon disrupts sleep. This may lead to Interferon dose adjustments or discontinuation, resulting in poor sleep/fatigue placing them at high risk for progressive liver failure. Recognizing CSA in this setting and modifying therapy (decreased methadone dosing or CPAP or adaptive ventilation) may result in improved interferon compliance and quality of life. This concept should be further explored with a systematic study of sleep and breathing, in patients being treated with interferon.

DISCLOSURE:Sireesha Gogineni, No Financial Disclosure Information; No Product/Research Disclosure Information

Wednesday, October 24, 2007

2:00 PM - 3:30 PM

References

Bettina B et al. Interferon modifies cortical EEG activity: dose-dependence and antagonism by naloxone.Journal of the Neurological Sciences,100(1990)22-26. [CrossRef]
 
Linda Crnic et al. Behavioral effects of mouse interferons-alpha in mice.Brain Research,590(1992)277-284. [CrossRef]
 

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References

Bettina B et al. Interferon modifies cortical EEG activity: dose-dependence and antagonism by naloxone.Journal of the Neurological Sciences,100(1990)22-26. [CrossRef]
 
Linda Crnic et al. Behavioral effects of mouse interferons-alpha in mice.Brain Research,590(1992)277-284. [CrossRef]
 
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