Respiratory arrest requiring resuscitation as a rare presentation of obstructive sleep apnoea and hypothyroidism

Abstract

A 79-year-old man, who had significant cardiovascular morbidities, presented with out-of-hospital respiratory arrest. He regained breathing after brief cardiopulmonary resuscitation by his paramedic son. After meticulous investigations, acute cardiovascular events and metabolic causes were ruled out while features of obstructive sleep apnoea were elicited. The findings on in-laboratory polysomnography were compatible with severe obstructive sleep apnoea, with unusually prolonged apnoea duration of up to 2.7 min which most likely accounts for the presentation as ‘respiratory arrest’. Thyroid function test for investigation of his weight gain confirmed hypothyroidism. His symptoms improved gradually after positive airway pressure therapy with bi-level support and thyroxine replacement. On further evaluation, his hypothyroidism is believed to be a complication of long-term amiodarone exposure. The case highlights that the combination of obstructive sleep apnoea and hypothyroidism can lead to catastrophic manifestation and the unusually long apnoea could be a feature prompting further workup for possible hypothyroidism.

Background

Obstructive sleep apnoea (OSA) and hypothyroidism are common medical problems and present similarly with somnolence. Both conditions may coexist, and the prevalence of clinical hypothyroidism is reported to be 1%–2% among the OSA subjects which is similar to the general population. Universal screening of thyroid function in OSA patients is controversial. Concomitant hypothyroidism may represent a distinct subset among OSA patients and limited data are available on their presentations and complications. The case reports underpin the importance of high index of suspicion among physicians to check for thyroid function in OSA patients with unusual features including excessively prolonged apnoea duration.

Common polysomnographic variables such as apnoea–hypopnoea index (AHI) cannot reflect on the duration of individual apneic event, which is of clinical importance. This case demonstrates a dreadful manifestation as respiratory arrest from prolonged apnoea related to the co-occurrence of these two common diseases.

Case presentation

A 79-year-old man was found unconscious with weak pulse and absent breathing lying supine on the recliner sofa in his living room. There was return of spontaneous breathing after a minute of cardiopulmonary resuscitation by his son. He had diabetes mellitus for 20 years, second degree heart block on a pacemaker and ischaemic heart disease. He was found to have a few episodes of non-sustained ventricular tachycardia prior to percutaneous transluminal coronary angioplasty 10 years ago, and was put on amiodarone 100 mg daily since then. He was on multiple medications: aspirin, pantoprazole, insulin subcutaneous injection, simvastatin, isosorbide mononitrate, amlodipine and perindopril. He was not on any self-acquired medications. On further questioning, he was watching television during the incident and did not have any choking episodes. His family reported that he dozed off easily and had a weight gain of 12 kg over the past 2 years. There was no particular change in his habitual activities to account for the weight change. There were no other particular symptoms on systemic enquiry. He was an ex-smoker and non-drinker.

At the emergency department, he was alert. His temperature was 36°C, blood pressure was 148/77 mm Hg, pulse 59/min, oxygen saturation was 99% on oxygen at 2 L/min and blood glucose was 7.0 mmol/L. Physical examinations were unremarkable other than central obesity with body mass index of 36 kg/m².

Investigations

ECG showed no evidence of acute ischaemia. Troponin-I and electrolytes were normal. Creatine kinase was high: 1286 U/L (reference range: 65–355 U/L). Arterial blood gas on oxygen 2 L/min showed pH 7.46, arterial partial pressure of oxygen (pO₂) 168 mm Hg, arterial partial pressure of carbon dioxide (pCO₂) 29 mm Hg and bicarbonate 23 mmol/L. His chest X-ray (CXR) was unremarkable other than the in situ pacemaker and mild cardiomegaly. Echocardiogram found left ventricular ejection fraction of 55%, mild diastolic dysfunction and structurally normal valves. Pacemaker interrogation showed ventricular pacing of 99% with no evidence of arrhythmias.

In view of his morbid obesity and excessive sleepiness, attended in-laboratory polysomnography (PSG) was performed. (figures 1 and 2). Arterial blood gas repeated after PSG found normal pCO₂ value. PSG showed highly fragmented sleep with sleep efficiency of 56%, and paucity of rapid eye movement stage (4% of total sleep time). There were repetitive periods of prolonged severe desaturation. His respiratory disturbance index, obstructive apnoea index and central apnoea index were 55/hour, 53/hour and 0.4/hour, respectively. He did not have respiratory effort-related arousals. The minimum oxygen saturation was 8% and the longest apnoea–hypoponea duration was 2.7 min. The ECG showed pacemaker rhythm throughout the night. During the PSG, oxygen supplement at 2 L/min was administered at around 01:00 by the attending technician after the finding of profound hypoxia episodes. His apnoea persisted despite oxygen. Thyroid stimulating hormone (TSH) was 66 mIU/L (reference range: 0.35–4.8 mIU/L) and free thyroxine level was 6.6 pmol/L (reference range: 12–23 pmol/L). The working diagnosis was severe OSA and hypothyroidism. The thyroid antibodies were negative and the hypothyroidism was believed to be related to amiodarone exposure.

Figure 1.

Hypnogram with evidence of severe obstructive sleep apnoea and repeated episodes of profound hypoxia.

Figure 2.

5-min epoch showing prolonged obstructive sleep apnoea and marked oxygen desaturation.

Treatment

Continuous positive airway pressure (PAP) was started but high pressure was required to control his sleep apnoea. He was subsequently stabilised on bilevel PAP which he tolerated well. Inspiratory and expiratory pressures levels were set at 20 cm H₂O and 14 cm H₂O, respectively, with a backup rate of 10/min. Thyroxine replacement was also started.

Outcome and follow-up

On follow-up in 6 months, compliance data showed residual AHI of 10/hour with good tolerance and compliance. Overnight oximetry on bilevel PAP showed his oxygen saturation was maintained above 88%. His sleep apnoea was well controlled and somnolence improved. His thyroid function is normalised with replacement and he is now having regular follow-up at our sleep clinic.

Discussion

OSA and hypothyroidism manifest similarly with somnolence and weight gain. Life threatening presentation is rare in either of the two conditions. Our case report describes the sinister presentation with respiratory arrest when both conditions coexist. The apnoea duration is unusually prolonged with profound hypoxaemia, which can lead to major adverse cardiovascular consequences.

Up to half of the hypothyroid patients have sleep apnoea. The prevalence of hypothyroidism varies from 1.6% to 11% among sleep clinic referrals.¹ Clinical hypothyroidism is present in 1%–2% among those with confirmed OSA, which is similar to the non-OSA counterpart.^{2 3}

In hypothyroidism, anatomical changes in the upper airway and the alteration in ventilation control predispose to OSA.⁴ Other than obesity as a risk factor for OSA, mucopolysaccharides deposition related to hypothyroidism leads to macroglossia, thickening of vocal cords and narrowing of airway calibre, all of which contribute to the anatomical propensity of having sleep apnoea. Hypothyroid myopathy affecting the pharyngeal dilator muscles predisposes to upper airway collapse, while the dysfunctional respiratory muscles compensate less effectively for ventilation insufficiency. The chemoreceptor sensitivity to blood gas changes and neuronal output to airway musculature are both blunted in overtly hypothyroid state.⁵

TSH level is reported to be positively correlated with the mean apnoea–hypoponea duration (MAD).⁶ In hypothyroid state, impairment of arousal response and disturbance of regulatory pharyngeal dilator muscles may contribute to the prolonged MAD. Of note, MAD is poorly reflected by the AHI or oxygen desaturation index, the usual indices of OSA severity. Longer MAD was associated with lower nadir oxygen saturation. The profound intermittent hypoxia can trigger a cascade of adverse vascular events, in particular in patients who had known cardiac-metabolic morbidities. Therefore, MAD, in addition to AHI, may be evaluated as an index of severity in patients with concomitant OSA and hypothyroidism.

In addition to controlling the OSA with PAP, replacing thyroid hormone was required in hypothyroidism.⁷ The effect of thyroxine replacement on alleviating OSA is inconsistent in the literature, and is often delayed to months or years later.^{7 8} The anatomical factors, including obesity, and soft tissue redundancy improve with thyroxine treatment, though it is unknown if the non-anatomical elements are readily reversible. In addition, sleep apnoea may persist as a result of factors unrelated to hypothyroidism.

Routine screening for hypothyroidism in sleep referrals is controversial.⁹ There is no clear evidence that hypothyroidism occurs at a higher frequency in patients with OSA. Of note, severe OSA can reciprocally lead to non-thyroidal illness syndrome (or sick euthyroid syndrome) which is reversible with PAP treatment.¹⁰ MAD may allow risk stratification, and its potential value in the selection for thyroid function screening will be an objective requiring further research.

Patient’s perspective.

It was lost when I woke up, and my son was pressing hard on my chest. It was painful. I did not know why he did so, as I thought I was just falling asleep during the boring television series. Watching television had been my major leisure activity, since the diagnosis of heart diseases and my retirement 20 years ago. I occasionally dozed off on the sofa, which was too comfortable, and admittedly I dozed off more frequently in recent years which I initially attributed to the flavourless programmes shown on the television. My waist got doubled since retirement, which I thought was quite usual for man at my age. It was to my surprise that I almost died during the ‘sleep’, and my son had saved me. I had never thought that snoring, or sleep, and now I knew that it was called obstructive sleep apnoea, could kill. My doctor said that I did not merely suffer from sleep apnoea, but also lack thyroid hormone and this might be the cause of my weight gain. The use of breathing device everyday was difficult to accept initially, the wind was too strong to bear. After switching to the two-pressure device, I felt better with more energy and now it was my regular ‘sleep mate’. I was hoping the hormone treatment might help me lose some weight.

His son’s perspective

It was a nightmare to me and my mother. We were in the terror of losing my dad at that juncture. What a big relief when he woke up.

Doctor had explained to me that my father suffered from a condition called obstructive sleep apnoea, and hypothyroidism. I was glad to know that both diseases were readily treatable and could prevent similar events from happening in the future. I would make sure that my father used the breathing device whenever he slept, and be compliant to the medications he required.

Finally, I was also grateful to have received training on basic life support, as a prerequisite of my job as a fireman.

Learning points.

• Obstructive sleep apnoea (OSA) and hypothyroidism present similarly, and both conditions may coexist and give rise to serious manifestations and complications.

• Hypothyroidism is closely linked to OSA, and the relationship is probably bidirectional.

• Unusually prolonged apnoea events and low nadir oxygen saturation characterise OSA in patients with hypothyroidism.