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1/81. The use of oral vasopressors in the management of autonomic dysfunction and orthostatic hypotension.

    OBJECTIVE: To describe a patient with hypotension secondary to autonomic dysfunction who was successfully treated with oral vasopressors. CASE SUMMARY: A 76-year-old African-American man with a history of cerebrovascular accident with right hemiparesis 30 years prior to admission was admitted from another hospital four days after a new posterior inferior cerebellar artery occlusion and poor distal flow as manifested by weakness and hypotension. This was treated with intravenous fluids and dopamine. The dopamine was weaned and changed to phenylephrine to maintain systolic blood pressure >80 mm Hg. fludrocortisone 0.3 mg orally once daily was initiated; pressure support garments were used for the management of orthostatic hypotension. ephedrine 25 mg po tid was added and titrated up to 50 mg p.o. tid. yohimbine 5.4 mg po every eight hours was added due to continued dependence on phenylephrine to maintain adequate blood pressure. yohimbine was titrated up to 10.8 mg p.o. tid in an unsuccessful effort to wean the patient from phenylephrine. fludrocortisone was decreased to 0.1 mg po tid and the phenylephrine was tapered off. The patient developed a pan-sensitive escherichia coli urinary tract infection that was treated with oral trimethoprim/sulfamethoxazole. Over the subsequent days, an 80% left subclavian stenosis was detected; yohimbine and pressure support garments were discontinued. Subsequently, oral ephedrine was tapered off over two days, and fludrocortisone was tapered to 0.1 mg p.o. bid. The patient was transferred in a stable normotensive condition to an inpatient rehabilitation unit. The fludrocortisone was later discontinued with no further hypotension or orthostatic symptoms. DISCUSSION: In this case, orthostatic hypotension associated with autonomic dysfunction was successfully managed with a combination of intravenous vasopressors and hydration, pressure support garments, oral mineralocorticoids, and oral vasopressors. Oral vasopressors and mineralocorticoids are effective treatment options in the management of the vasopressor-dependent patient. In our patient the adverse effects were tolerable. After continued therapy, the oral vasopressors were withdrawn without a return of orthostatic symptoms. CONCLUSIONS: Orthostatic hypotension due to autonomic dysfunction may be successfully managed with combination oral therapy after initial treatment with intravenous vasopressors as evidenced by the absence of orthostasis.
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2/81. A case of sinus arrest and vagal overactivity during REM sleep.

    A young man presented with tachycardia and faintness after an episode of influenza. He underwent 24-h heart rate recordings, each of which documented episodes of sinus arrest lasting up to 7.2 seconds. All episodes occurred in the second half of the night and were always accompanied by severe bradycardia. Cardiac function tests failed to disclose anything abnormal. Two polysomnographic recordings demonstrated that the sinus arrests occurred during REM sleep. Power spectral analysis of heart rate variability showed that during the second half of the night there was an abnormal prevalence of vagal activity, particularly during REM sleep stages, presumably responsible for the bradycardia and fall in blood pressure. We speculate that the episodes of sinus arrest are linked to a central mechanism that triggers the autonomic imbalance during REM sleep.
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3/81. Acute dysautonomia secondary to autoimmune diseases: efficacy of intravenous immunoglobulin and correlation with a stimulation of plasma norepinephrine levels.

    Acute dysautonomia is a disorder characterized by severe sympathetic and parasympathetic failure with relative preservation of motor and sensory function. The disease is considered to be idiopathic in most cases, but there is now a trend towards considering the disorder as an uncommon variant of Guillain Barre syndrome. We report two cases of acute dysautonomia which did not fulfill the criteria of the idiopathic form. The first case was associated with sjogren's syndrome and the second with thyroiditis and antiganglioside antibodies which were correlated with the severity of the disease. Intravenous gammaglobulin (IVGG) was effective in both cases, as has been reported for the idiopathic form, and in one case the treatment was associated with an increase in the supine and standing plasma norepinephrine levels, thus substantiating the positive effects of IVGG on the orthostatic blood pressure and heart rate. We conclude that the spectrum of acute dysautonomia is superimposable on that of the inflammatory peripheric neuropathies and should include both the idiopathic form and dysautonomia with autoimmune associated disorders. IVGG are effective and seems to act by increasing plasma norepinephrine levels.
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4/81. Severe gamma-hydroxybutyrate withdrawal: a case report and literature review.

    We report a case of gamma-hydroxybutyrate (GHB) withdrawal resulting in severe agitation, mental status changes, elevated blood pressure, and tachycardia hours after stopping chronic use of GHB. The patient admitted to substantial GHB abuse on a daily basis for 2.5 years. Previous attempts at cessation reportedly resulted in diaphoresis, tremors, and agitation. The patient's symptoms, negative polypharmacy history, and negative urine and blood toxicological analysis for alcohol, benzodiazepines, sedative-hypnotics, or other substances suggested the diagnosis of GHB withdrawal. Later analysis of a patient drug sample confirmed the presence of GHB. The patient required 507 mg of lorazepam and 120 mg of diazepam over 90 h to control agitation. This is one of the few reported cases of GHB withdrawal and one of the most severe. Given the increasing use of GHB, more cases of severe GHB withdrawal should be anticipated.
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5/81. Clinico-pathological features of postural hypotension in diabetic autonomic neuropathy.

    We report the clinico-pathological features and management of a 49-year-old male with a 30-year history of Type 1 diabetes mellitus who had nephropathy (proteinuria 1.81 g/24 h, creatinine 136 micromol/l), proliferative retinopathy and severe somatic and autonomic neuropathy. A sural nerve biopsy demonstrated marked myelinated fibre loss with unmyelinated fibre degeneration and regeneration combined with extensive endoneurial microangiopathy. The management of the patient's blood pressure problems (supine hypertension) and symptomatic postural hypotension is discussed.
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6/81. Hormonal and cardiovascular reflex assessment in a female patient with pure autonomic failure.

    We report the case of a 72-year-old female with pure autonomic failure, a rare entity, whose diagnosis of autonomic dysfunction was determined with a series of complementary tests. For approximately 2 years, the patient has been experiencing dizziness and a tendency to fall, a significant weight loss, generalized weakness, dysphagia, intestinal constipation, blurred vision, dry mouth, and changes in her voice. She underwent clinical assessment and laboratory tests (biochemical tests, chest X-ray, digestive endoscopy, colonoscopy, chest computed tomography, abdomen and pelvis computed tomography, abdominal ultrasound, and ambulatory blood pressure monitoring). Measurements of catecholamine and plasmatic renin activity were performed at rest and after physical exercise. Finally the patient underwent physiological and pharmacological autonomic tests that better diagnosed dysautonomia.
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7/81. Endogenous circulating sympatholytic factor in orthostatic intolerance.

    Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.
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8/81. Hypotensive akathisia: autonomic failure associated with leg fidgeting while sitting.

    The author describes a distinct clinical syndrome in six patients with autonomic failure who manifested habitual, voluntary, transiently suppressible, yet irresistible leg movements occurring only in the sitting position. Keeping the legs still brought on vague symptoms of fatigue, lightheadedness, or apprehension. Repetitive leg crossing, muscle tensing, foot twirling or wiggling, or heel or toe floor tapping while sitting may have compensated for orthostatic hypotension and raised systolic blood pressure by a mean of 28 mm Hg and diastolic pressure by a mean of 11 mm Hg.
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9/81. Severe cardiovascular autonomic dysfunction in a patient with guillain-barre syndrome: a case report.

    Autonomic dysfunction is a frequent and severe complication of guillain-barre syndrome. It is often responsible for cardiovascular abnormalities, even cardiac arrest. We report a 49-year-old patient, who suffered from guillain-barre syndrome necessitating mechanical ventilation. He showed wide fluctuations of blood pressure and heart rate spontaneously or in relation with medical procedures. Though heart rate variability (HRV) and baroreflex sensitivity (BRS) values derived from different methods were extremely low, vigorous stimuli, like eyeball pressure test and carotid sinus massage, produced exaggerated responses, like severe bradycardias, hypotension and cardiac arrest. Despite the plasma exchange and supportive therapies, the patient finally developed adult respiratory distress syndrome (ARDS), sepsis and died due to septic shock.
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10/81. Assessment of coronary morphology and flow in a patient with guillain-barre syndrome and ST-segment elevation.

    patients with guillain-barre syndrome often have cardiac disturbances as a manifestation of autonomic dysfunction. Such abnormalities consist of arrhythmias and disturbances of heart rate and blood pressure. We report a case of a patient with guillain-barre syndrome who developed ST-segment elevation in the inferolateral leads, suggestive of an acute coronary syndrome. cardiac catheterization revealed angiographically normal coronary arteries. Intracoronary ultrasound was also normal. Intracoronary Doppler flow measurements revealed an elevated baseline coronary flow velocity of up to 41 cm/s and decreased coronary flow reserve, particularly in the left circumflex artery. Myopericarditis as cause of the electrocardiographic changes could be ruled out by echocardiography and endomyocardial biopsy. We postulate that the intracoronary Doppler findings are caused by autonomic dysfunction with decrease of coronary resistance and redistribution of the transmural myocardial blood flow.
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