At least 5% of patients with vasovagal syncope also have Sleep Syncope. Patients awake from
sleep with profound malaise and gastrointestinal vagal symptoms. About 75% have severe nausea
and about 40% have lower abdominal cramps. Some faint while supine, but most find their
symptoms so severe that they rise quickly and hurry to the bathroom. Sometime either on the
way to the toilet, near it, or shortly afterwards they faint. The nausea is followed by
vomiting, and the cramps by watery diarrhea. After relief the patients remain presyncopal,
diaphoretic, and tired. Almost all patients also have clinical vasovagal syncope during
daytime hours.
The cause of this is unknown. Orthostatic stress cannot be a factor in triggering the event,
and in isolated case reports it occurs during non-REM sleep. There is no classic provocative
situation of pain, the sight of trauma, or the presence of medical settings. These suggest
the importance of central processes and the reduced likelihood that strategies that target
maintaining preload (such as with midodrine and fludrocortisone) would be helpful. As well,
midodrine is avoided during the night.
Recently the investigators reasoned that if the investigators could rapidly suppress the
nausea patients could remain supine, wait out the nausea, and not faint with orthostatic
stress. Ondansetron is a potent anti-nausea medication that has rapidly dissolving
preparations. Nine patients were instructed to keep one at the bedside, insert it upon waking
up with nausea, remain in bed, and raise their legs (if possible). There was partial success
with ondansetron 4 mg and complete success with ondansetron 8 mg. This remarkable but
anecdotal observation requires formal testing.
Research Objectives: the investigators will test the hypothesis that ondansetron 8 mg prn
sublingually on awakening with moderate to severe nausea prevents loss of consciousness in
patients with prior Sleep Syncope who awaken with malaise and nausea.
Study Design & Methodology: The main study will be a placebo-controlled, double-blind,
randomized, crossover clinical trial. The primary outcome will be the progression of
awakening with nausea to syncope. Thirty patients with Sleep Syncope will be randomized 1:1
to receive packages of either ondansetron 8 mg sublingual tablets or matching placebo. They
will each receive 3 boxes of 10 tabs, with refills available if needed. Each crossover period
will last 6 months.
In a substudy the investigators will test whether the predominant disturbed physiology is
bradycardia, decreased venous return, or decreased systemic vascular resistance. This will be
assessed using a unique, small, wearable blood pressure sensor that can be rapidly donned on
the ear. It records heart rate and beat-to-beat waveforms, which permit estimating stroke
volume, systemic vascular resistance, and cardiac output. the investigators will record these
variables in all patients continuously from when the device is put on until 30 minutes
afterwards. the investigators hypothesize that unlike during syncope provoked by head-up tilt
testing, here there will be no decrease in preload until patients arise, and that the main
physiologic disturbance during syncope is hypotension due to decreased preload superimposed
on heart rate collapse.
Anticipated Outcomes: If successful, this research would be i) the first to report a
well-tolerated and highly effective treatment for most sleep syncope, and ii) the first to
report the physiology of brain-initiated vasovagal syncope in the community outside a
laboratory environment.