Treatment of obstructive sleep apnea syndrome with a Kampo-formula, San’o-shashin-to: A case report

INTRODUCTION

We report on a patient with obstructive sleep apnea syndrome (OSAS) which improved with administration of a Kampo-formula. The patient was treated with San’o-shashin-to (Formula medicamentorum tres ad dispellendi cordis), based on Sho (the way of diagnosis based upon the pathophysiology concept of Kampo-medicine).¹ Before and after administration of San’o-shashin-to, polysomnography (PSG) was performed for an objective evaluation of OSAS.

CASE REPORT

A 76-year-old male was seen at our outpatient department. At the age of 74, he underwent amputation of the left crus, because of malignant melanoma of the left sole. A month prior to referral, he was admitted to the department of dermatology in our hospital for postoperative periodic examinations. During admission, heavy snoring and sleep walking episodes were noted, so he was referred to our outpatient department.

He was 156.0 cm in height and 49.7 kg in weight (body mass index (BMI): 20.4 kg/m²). No pharyngeal narrowing was observed on the physical examination. His general condition was good without any remarkable symptoms of dementia. Constipation developed and glycerine enemas were used twice or three times a week. He complained of nocturnal pollakisuria and decreased amounts of sleep. He also had hypertension and prostatic hypertrophy and was treated with manidipine hydrochloride (10 mg/day), tamsulosin hydrochloride (0.2 mg/day) and chlormadinone acetate (50 mg/day). Carbocisteine (750 mg/day) and Hochu-ekki-to (Formula repletiouis et auxilium vis vitalis, instant powder (TJ-41), 7.5 g/day) were also used. Resting wakeful electroencephalogram was normal. Whole brain magnetic resonance imaging (MRI) revealed mild diffuse cerebral atrophy and multiple lacunar infarctions in the substantia alba, which, however, were age-related normal findings. Abnormalities such as brain metastasis of malignant melanoma were not found.

Polysomnography confirmed a diagnosis of OSAS (Table 1). The apnea index (AI) was 11.1 events/hour, the apnea plus hypopnea index (AHI) was 18.4 events/hour, and events of sleep apnea and hypopnea were mostly noted during a non-rapid eye movement (NREM) sleep. About 40 min after falling asleep, an episode of large movements of arms, which followed an apnea-related arousal, was observed. Soon after that episode, he woke up completely and urinated using a urinal at his bedside. Then he was admitted to our department for the treatment with Kampo-formulas.

Table 1. . Number of sleep apnea and hypopnea before and after treatment with San’o-shashin-to

Clinical findings from the viewpoint of Japanese-Oriental (Kampo) medicine such as a relatively strong physique, thick, dry yellow fur overlaying the tongue, pulse of excess-type, and increased abdominal tension indicate Yang-excess state.¹ Marked redness of the tongue reflects a condition of Yang-excess of the heart.¹ According to the conditions classified as Yang-excess state and Yang-excess of the heart with constipation and flexible resistance, tenderness by pressure on the epigastric region, San’o-shashin-to is applied.¹ Therefore treatment was started with San’o-shashin-to, which was added to the preceding prescriptions for the complications mentioned above. He made a complete recovery from constipation after a week, and claimed to sleep more deeply. After 16 days, sleep walking was noted once, but no abnormal behavior during sleep had been observed since that episode. Polysomnography was performed again after a month (Table 1). The AI was reduced to 4.1 events/hour, and AHI to 10.7 events/hour. Snoring also diminished compared with the preceding PSG recording. No side effects occured.

DISCUSSION

In this patient, no remarkable abnormality was found by brain MRI. Polysomnography data showed no epoch of stage 1-REM with tonic EMG, which is often seen in delirium.² Sleep walking episodes were considered to be one of the clinical symptoms of OSAS.

San’o-shashin-to is a Kampo-formula based on the Kinki-yoryaku,³ an ancient book of classical Chinese medicine. The components of San’o-shashin-to are Scutellariae Radix (Ogon), Coptitis Rhizoma (Oren), and Rhei Rhizoma (Daio). San’o-shashin-to is also used for insomnia. There is, however, no report on the treatment of OSAS with San’o-shashin-to, to our knowledge, and moreover no reference to sleep apnea is found in the books of classical Chinese and Japanese-Oriental medicine.

Inagawa reported improvement of snoring with Dai-saiko-to (Formula bupleuri major).⁴ In that report, however, the objective evaluation, PSG was not performed. According to his report, the patient was overweight (BMI: 31.5 kg/m²). Dai-saiko-to is mostly used for strong patients with a tendency to obesity.¹ In contrast, our patient was normo-weight (BMI: 20.4 kg/m²). Kohta reported improvement of sleep-disordered breathing with Hochu-ekki-to.⁵ In his report, PSG was not performed, but continuous overnight monitoring of oxygen saturation of arterial blood (SaO₂) was done. In that case, the patient was in the condition of deficiency. Hochu-ekki-to is applied to weak patients, and is useful in cases of muscular weakness.¹ Our patient had already been treated with Hochu-ekki-to before administration of San’o-shashin-to, but OSAS still remained. After administration of San’o-shashin-to, the number of events of obstructive sleep hypopnea was not remarkably reduced, however AI improved from 11.1 events/hour to 4.1 events/hour, and moreover the abnormal behavior during sleep completely disappeared. We suppose that San’o-shashin-to may have some alleviating effects on the upper airway resistance during sleep. However, additional studies of other cases are needed.

Our patient had to be treated with San’o-shashin-to for the complication of severe constipation, even though he had no OSAS. It is significant to adopt the Kampo-formula based on Sho, because several different disorders are expected to be improved simultaneously with administration of only one Kampo-formula.