Research in Review

Pain Res Manag. 2004 Winter;9(4):209-11.

Treatment of pediatric chronic pain with tramadol hydrochloride: siblings with Ehlers-Danlos syndrome - Hypermobility type.

Brown SC, Stinson J.

Department of Anaesthesia, The Hospital for Sick Children, Toronto, Ontario. stephen.brown@sickkids.ca

OBJECTIVE: To evaluate the effectiveness of tramadol hydrochloride for the treatment of chronic pain refractory to previous treatment in two pediatric patients.

METHODS: Tramadol hydrochloride was administered (50 mg/day to 150 mg/day) to two siblings with Ehlers-Danlos syndrome - Hypermobility type refractory to previous pharmacological treatments, and changes in pain intensity and physical activity were assessed.

RESULTS: Pain intensity decreased and physical activity improved within days of starting therapy. Positive results have been maintained for 30 months.

CONCLUSIONS: Tramadol hydrochloride was a safe and effective treatment for relieving chronic pain in two pediatric patients suffering from the hypermobility type of Ehlers-Danlos syndrome. No morbidity or side effects were noted during the 30-month follow-up.

PMID: 15605135

J Pediatr Gastroenterol Nutr. 2005 Apr;40(4):425-8.

Gastrointestinal symptoms associated with orthostatic intolerance.

Sullivan SD, Hanauer J, Rowe PC, Barron DF, Darbari A, Oliva-Hemker M.

Departments of Pediatric Gastroenterology and Nutrition and Pediatrics, The Johns Hopkins University School of Medicine, The Johns Hopkins University, Baltimore, Maryland.

BACKGROUND: The term orthostatic intolerance is used to describe symptoms of hemodynamic instability such as lightheadedness, fatigue, impaired cognition and syncope that develop on assuming an upright posture. Common forms of orthostatic intolerance in childhood include postural tachycardia syndrome and neurally mediated hypotension.

OBJECTIVE: A descriptive report of the clinical characteristics of patients presenting with gastrointestinal symptoms who are ultimately found to have orthostatic intolerance.

METHODS: A medical record review of all patients referred to the pediatric gastroenterology service at the Johns Hopkins Children's Center who had an abnormal tilt table test between June 1996 and December 2000.

RESULTS: Of 24 eligible subjects aged 9-17 years (mean, 14.3 years), four had postural tachycardia syndrome, eight had both postural tachycardia and neurally mediated hypotension, and 12 had neurally mediated hypotension alone. The most common presenting gastrointestinal symptoms were abdominal pain, nausea and vomiting. Median number of gastrointestinal symptoms per patient was 3 (range, 1-7), and 87% of the patients experienced gastrointestinal symptoms for more than 1 year and 48% experienced gastrointestinal symptoms for more than 3 years. Follow-up information was available on 18 patients. Seventy-eight percent of patients (14 of 18) had complete resolution of symptoms with treatment of orthostatic intolerance.

CONCLUSION: Pediatric patients with chronic upper gastrointestinal symptoms may have underlying orthostatic intolerance. In patients with upper gastrointestinal symptoms and orthostatic intolerance, treatment of orthostatic intolerance may result in resolution of gastrointestinal symptoms.

PMID: 15795588

Circulation. 2005 Apr 5;111(13):1574-82. Epub 2005 Mar 21.

Renin-aldosterone paradox and perturbed blood volume regulation underlying postural tachycardia syndrome.

Raj SR, Biaggioni I, Yamhure PC, Black BK, Paranjape SY, Byrne DW, Robertson D.

Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tenn 37232-2195, USA. satish.raj@vanderbilt.edu

BACKGROUND: Patients with postural tachycardia syndrome (POTS) experience considerable disability, but in most, the pathophysiology remains obscure. Plasma volume disturbances have been implicated in some patients. We prospectively tested the hypothesis that patients with POTS are hypovolemic compared with healthy controls and explored the role of plasma renin activity and aldosterone in the regulation of plasma volume.

METHODS AND RESULTS: Patients with POTS (n=15) and healthy controls (n=14) underwent investigation. Heart rate (HR), blood pressure (BP), plasma renin activity, and aldosterone were measured with patients both supine and upright. Blood volumes were measured with 131I-labeled albumin and hematocrit. Patients with POTS had a higher orthostatic increase in HR than controls (51+/-18 versus 16+/-10 bpm, P<0.001). Patients with POTS had a greater deficit in plasma volume (334+/-187 versus 10+/-250 mL, P<0.001), red blood cell volume (356+/-128 versus 218+/-140 mL, P=0.010), and total blood volume (689+/-270 versus 228+/-353 mL, P<0.001) than controls. Despite the lower plasma volume in patients with POTS, there was not a compensatory increase in plasma renin activity (0.79+/-0.58 versus 0.79+/-0.74 ng x mL(-1) x h(-1), P=0.996). There was a paradoxically low level of aldosterone in the patients with POTS (190+/-140 pmol/L versus 380+/-230 pmol/L; P=0.017).

CONCLUSIONS: Patients with POTS have paradoxically unchanged plasma renin activity and low aldosterone given their marked reduction in plasma volume. These patients also have a significant red blood cell volume deficit, which is regulated by the renal hormone erythropoietin. These abnormalities suggest that the kidney may play a key role in the pathophysiology of POTS.

PMID: 15781744

Hypertension. 2005 Mar;45(3):385-90. Epub 2005 Feb 14.

Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders.

Shibao C, Arzubiaga C, Roberts LJ 2nd, Raj S, Black B, Harris P, Biaggioni I.

Division of Clinical Pharmacology, Department of Medicine and Pharmacology, and the Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, Tenn 37212, USA.

Postural tachycardia syndrome (POTS) is a disabling condition that commonly affects otherwise normal young females. Because these patients can present with a flushing disorder, we hypothesized that mast cell activation (MCA) can contribute to its pathogenesis. Here we describe POTS patients with MCA (MCA+POTS), diagnosed by episodes of flushing and abnormal increases in urine methylhistamine, and compared them to POTS patients with episodic flushing but normal urine methylhistamine and to normal healthy age-matched female controls. MCA+POTS patients were characterized by episodes of flushing, shortness of breath, headache, lightheadedness, excessive diuresis, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Triggering events include long-term standing, exercise, premenstrual cycle, meals, and sexual intercourse. In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79+/-4 to 114+/-6 bpm), increased systolic blood pressure on standing (from 117+/-5 to 126+/-7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157+/-12 versus 117+/-9 in normal controls and 119+/-7 mm Hg in POTS; P=0.048), and an exaggerated phase IV blood pressure overshoot (50+/-10 versus 17+/-3 mm Hg in normal controls; P<0.05). In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but beta-blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.

PMID: 15710782

Research abstracts obtained from PubMed

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