Abstract

Children with chronic unexplained nausea have a high incidence of cardiovascular instability (~ 75%) manifesting as orthostatic intolerance (OI), with exaggerated suppression of baroreflexes upon standing. Because vasopressin (AVP) causes nausea and may be triggered by a fall in blood pressure (BP), we aimed to determine the relationship between AVP and tilt-induced changes in BP in children with OI. Forty-eight patients (mean age [range] of 15.2 [10-18] years) (36 females, 12 males) underwent tilt table testing for symptoms of OI and nausea. Subjects were maintained supine for 15 min before 45 min upright tilt (from 0 to 70 degrees). Plasma AVP was measured in blood sampled immediately before and 15 min into upright tilt. Of the 48 tilt tests: 9 were normal and 39 abnormal. Abnormal tests were classified as: postural orthostatic tachycardia syndrome (POTS, heart rate >120 bpm or increase by 30 bpm during first 10 min of tilt; n = 15), neutrally mediated hypotension (NMH, decrease in systolic BP [SBP] >25 mmHg during first 10 min of tilt; n = 2), and neurocardiogenic syncope (NCS, hypotension followed by syncope; n = 22). Mean supine SBP of normal subjects was 129 ± 9 mmHg and diastolic BP [DBP] was 64 ± 3 mm Hg (mean ± SEM). There were no differences in supine BPs among groups. Supine AVP levels were 4 ± 2 and 2 ± 1 in abnormal vs normal subjects (p = NS) There was a positive correlation between SBP and AVP in the supine position before tilt (0.34, p = 0.02). AVP increased by 44 ± 13 pg/mL vs. 1 ± 1 pg/mL for subjects with abnormal vs. normal tilt tests (p = 0.002), by 43 ± 17 pg/mL for NCS alone vs. normal (p = 0.02), and by 37 ± 20 pg/mL for POTS vs. normal (p = NS). There was a negative correlation between AVP and both SBP and DBP during tilt (-0.3, p = 0.035 and -0.4, p = 0.005, respectively). Hypotension and syncope upon tilt are associated with acute increases in AVP in subjects with OI and nausea. The increase in AVP may serve as a compensatory mechanism in the face of impaired autonomic reflexes. It is not known whether the increase in AVP contributes to the nausea observed during tilt, but better understanding of this relationship may allow for more effective treatment options for the management of nausea in these subjects.

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