Corresponding author : Sunil Sharma, M.D, DíABSM, Assistant Professor of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, Brody School of Medicine, 600 Moye Boulevard, 3E-149, East Carolina University, Greenville, NC 27834, USA, Tel: 252-744-4653; Fax: 252-744-4887; E-mail: firstname.lastname@example.org
Received: August 02, 2012 Accepted: August 18, 2012 Published: August 22, 2012
Citation:Islam MM, Albustami O, Judy J, Boettger PC, Liles DK, et al. (2012) Opioid Induced Sleep Disordered Breathing in Sickle Cell Patient. J Sleep Disor: Treat Care 1:1. doi:10.4172/2325-9639.1000101
Chronic opioid use is a risk factor for sleep disordered
breathing (SDB) like obstructive sleep apnea (OSA), Biotís or ataxic
breathing, central sleep apnea and sleep related hypoventilation.
Withdrawal of opioids may be the optimal management but it is
not always feasible. Continuous positive airway pressure (CPAP)
therapy, which is effective treatment for OSA, may not resolve
central events. Opioid induced sleep disordered breathing has
been described mostly in patients with chronic back pain on
narcotics. We present a case of sickle cell disease who is a 37
year old male on short and long acting Morphine presenting with
excessive daytime sleepiness, fatigue and memory loss. Baseline
nocturnal polysomnography (NPSG) showed central sleep apnea
(Biotís breathing) with AHI of 27. After initial failure of CPAP, ASV
at IPAPmax/ EPAPmin (inspiratory and expiratory positive airway
pressures) of 25/7 cm of H2O with a pressure support setting of
0-15 and auto back-up rate was applied with complete resolution of
Biotís breathing and symptoms. This case highlights the increased
risk of central sleep apnea induced by opioids in a population with
improving life expectancy and chronic use of narcotics. It also adds
to the small but growing body of evidence suggesting the beneficial
role of ASV in opioid induced sleep disordered breathing where
narcotics /opioids cannot be discontinued.
Biot’s or ataxic breathing is a type of opioid induced nonobstructive
sleep disordered breathing (SDB) seen in patients who use
opioid for a long time . Management of opioid related disordered
breathing is important for improvement of the quality of life and it
may alleviate sleep-related morbidity and mortality . Most cases
have been described in patients with chronic back pain (reference).
Recently published studies and case reports showed mixed results
related to the effectiveness of adaptive servo-ventilation (ASV) in
controlling SDB [2-4]. Whether there is any morbidity or mortality
benefit by treating SDB due to long term opioid use with positive airway pressure devices is unknown . We report a case of opioid
induced sleep disordered breathing in a patient with sickle cell disease
that resolved with the use of ASV.
A 37 year old man presented to our sleep center with excessive
day time sleepiness, fatigue and memory loss. His Epworth sleepiness
scale (ESS) was 13/24. Medical history was significant for OSA
diagnosed several years ago. He reported feeling worse on Bilevel
positive airway therapy (BiPAP) therapy and discontinued use
within a few months. He has not been on any treatment since that
time. Patient has sickle cell anemia (Hg SS) with chronic bone pain
on Morphine IR 30 mg po every 4-6 hours as needed and scheduled
Morphine SR 100 mg po twice daily. He was also taking scheduled
Ibuprofen 800 mg po three times daily with meals. The patient also
has type 2 diabetes mellitus essential hypertension, dyslipidemia and
a remote history of transient ischemic attack during a sickle cell crisis
from which he had recovered completely. His medications included
lisinopril; metformin XR, insulin and glipizide; rosuvastatin. He also
had migraine headaches for which he was taking zolmitriptan as
needed. The patient had a normal thyroid function test.
Physical examination showed normal vital signs, body mass index
of 33.2 kg/m2 and neck circumference of 16.5 inches.
Polysomnography included ECG, EEG, continuous oronasal
air-flow recording with thermister and pressure transducer,
chest wall and abdomen movement recording using respiratory
inductive plethysmography belts, transcutaneous oximetry, and chin
electromyography. All sleep studies were performed at American
Academy of Sleep Medicine (AASM) accredited university sleep
disorder center (Easy III PSG system, Cadwell: Kennewick, WA,
An overnight polysomnogram demonstrated central events
(Biot’s breathing with a central index of 27) and few obstructive
events with obstructive index of 1. No periodic leg movements were
noted and sleep efficiency was 86%. The patient spent 2% (normal
5%) of total sleep time in Stage 1 sleep, 86% (normal 50%) in Stage
2 sleep, 2% (normal 20%) in Stage 3 sleep, and 10% (normal 25%) in
REM (Figure 1).
Figure 1: A 5-minute epoch of baseline polysomnogram displaying central events.
Subsequently, a trial of ASV titration was attempted. EPAP was
titrated upto 7 cm of H2O pressure and IPAP IPAPmax /EPAPmin
of 25/7 cm of H2O with a pressure support setting of 0-15 and auto
back-up rate which was well tolerated by the patient and completely
resolved his Biot’s breathing and symptoms (Figure 2).
Figure 2: A 5-minute epoch of polysomnogram with ASV displaying resolution of central events at IPAPmax of 25 cm of H2O and EPAPmin of 7 cm of H2O.
We are not aware of any report describing opioid induced sleep
disordered breathing (Biot’s) in the setting of sickle cell disease. Our
patient demonstrated moderate sleep disordered breathing (AHI=27)
and responded well to ASV therapy.
Biot’s breathing was first described by Dr. Camille Biot, in
1876. He described the breathing pattern as irregular and rapid,
with rhythmical pauses lasting 10–30 seconds but sometimes with alternating periods of apnea and tachypnea. This breathing pattern lacked the crescendo–decrescendo cycles attributed to Cheyne–Stokes breathing and was completely irregular with varying periods of apnoea .
The use of opioids has increased for the management of nonmalignant pain and increases the risk of development of sleep disordered breathing [1-4,6]. Biot’s breathing to our knowledge has never been described in sickle cell disease. It is possible that the increasing life expectancy in sickle cell disease has unmasked this phenomenon due to longer opioid exposure in this population .
Appropriate management of central apnea associated with chronic opioid use is still not well defined. Optimal management would be to discontinue the offending agent; however that is not always practical in light of chronic pain issues as is the case in sickle cell disease. The patients who develop central sleep apnea / Biot’s breathing do not respond well to CPAP or Bilevel Positive Airway Pressure ventilation [3,4,8,9]. Few reports on effectiveness of ASV have shown conflicting results. One report showed that ASV is effective therapy and another did not show any benefit of using ASV in patients with opioid induced central SDB [3,4]. In another case report, ASV was effective but the patient did not tolerate it; however he was successfully weaned of the opioids and resulted in resolution of Biot’s breathing .
Our patient showed complete resolution of opioid induced central apneas, along with improvement clinically with excellent tolerance of ASV.
We speculate that since patients with sickle cell disease are living longer and are exposed to extended use of narcotics, the prevalence of opioid induced sleep disordered breathing may increase. Physicians taking care of this population need to be aware of this possibility as it may be misdiagnosed as OSA (as that is what has historically been reported in sickle cell and appears to have been in our case). Secondly, this type of sleep disordered breathing does not respond to traditional CPAP/BIPAP and may get worse on CPAP/BIPAP (again our patient had reported that he felt worse with it and discontinued therapy after few weeks).