Review article: cyclic vomiting syndrome in adults--rediscovering and redefining an old entity.

BACKGROUND: Cyclic vomiting syndrome is a disorder characterised by recurrent episodes of severe nausea and vomiting separated by symptom-free periods. AIMS: To review the history, epidemiology, clinical aspects, pathophysiology, diagnosis and treatments of adult cyclic vomiting syndrome as well as to identify areas for further clinical research and the unanswered questions in this field. METHODS: We conducted a PubMed search using such keywords as cyclic vomiting syndrome; nausea; vomiting; pathophysiology; diagnosis; treatment; trigger factors; gastric emptying test; autonomic nerve function test; gastrointestinal hormones; outcome and natural history and combined this information with the knowledge and extensive clinical research and publications from the authors. RESULTS: Available data show that in adult cyclic vomiting syndrome, severe epigastric and sometimes diffuse abdominal pain accompanies most cycles of nausea and vomiting interspersed with periods of symptomatic remission. Psychological disorders, specifically anxiety and depression are common, and gastric emptying is actually rapid in approximately 60% of patients and normal in the remainder. There is an impressive and sustained response to high-dose tricyclic antidepressants. In up to 15% who are regarded as poor responders to tricyclic antidepressants, a predictable profile can be identified related to co-existing psychological disorders, marijuana use, poorly controlled migraine headache or chronic narcotic use. CONCLUSIONS: Cyclic vomiting syndrome in adults is an entity that is being increasingly recognised, but the need to educate Internists, Gastroenterologists and Emergency Department staff remains an ongoing challenge.

Autonomic nerve function in adult patients with cyclic vomiting syndrome.

BACKGROUND: Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea and vomiting separated by symptom-free periods. Autonomic dysfunction has been a postulated mechanism for the pathogenesis of this disorder in children but has not been explored in adults. METHODS: Our goals were to investigate autonomic nerve function in adult patients with CVS. The sympathetic nervous system was evaluated through postural changes in heart rate and blood pressure and sympathetic skin response in the hand and foot. The parasympathetic nervous system was tested through heart rate response to deep breathing [expiration/inspiration (E/I)], Valsalva and postural indices (30 : 15 ratio). All patients had a 4-h standard isotope labeled egg beater meal gastric emptying test (GET). KEY RESULTS: Twenty-two adult (18 female), mean age 35 ± 11 (range 19-61 years), who met Rome III criteria for CVS were included. History of migraine headache was reported in three patients. Five (23%) had pediatric onset. Of 21 patients who completed the test, nine patients had 21 abnormalities detected in their autonomic nerve testing profile and the remaining 12 had normal autonomic function results. Orthostatic tachycardia was observed in two (mean heart rate increase 39 beats min(-1)) and a decline in blood pressure (BP) in three patients (mean BP drop 30/14 mmHg). Parasympathetic abnormalities were elicited in six patients with an abnormal response to deep breathing and E/I index <1.25. Sympathetic nerve dysfunction was reported in seven patients with absent sympathetic skin response in the foot and/or hand. Twelve (57%) of CVS group had rapid GET (<50% retention at 1 h). The frequency of abnormal autonomic nerve function was not significantly higher in rapid GET subgroup. CONCLUSIONS & INFERENCES: (i) Autonomic nerve dysfunction is common in adult CVS patients, being observed in 43% of our cohort; (ii) Sympathetic abnormalities dominate; and (iii) Rapid gastric emptying, present in 57% of patients, did not correlate with autonomic testing results. These new data provide more insight into the pathophysiology of CVS in adults and help explain the spectrum of clinical manifestations observed in this entity.

Spectrum of gastric emptying patterns in adult patients with cyclic vomiting syndrome.

BACKGROUND: Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea, vomiting and abdominal pain separated by symptom-free intervals. Both rapid and delayed gastric emptying (GE) have been observed but the reports involved small numbers of CVS patients. METHODS: We performed a retrospective study of 92 adult patients who met Rome Ш diagnostic criteria for CVS between 2003 and 2009 at the Kansas University Medical Center. Gastric emptying was measured by a standardized scintigraphic method involving a low fat (2%) isotope labeled egg white meal of 250 Kcal, with anterior and posterior gastric imaging in the standing position obtained at 0, 1, 2, 4 h after meal ingestion. Rapid GE was defined as <50% isotope retention at 1st h and/or <30% at 2nd h and delayed GE as >10% at 4 h. KEY RESULTS: Ninety two patients were analyzed: 47 males and 45 females mean of age 37 ± 12 years (range: 20-68 years). There were 27 patients with a personal history of migraine headache, 30 with history of marijuana use, 12 had diabetes mellitus (DM) and 10 had irritable bowel syndrome (IBS) as an accompanying diagnosis. Fifty four patients (59%) met criteria for rapid GE, 25 (27%) had normal GE and 13 (14%) had slow GE. Eighty percent of patients with co-existing IBS symptoms were identified as rapid. The subset with delayed emptying was often associated with narcotics use, DM and marijuana use (P < 0.05). CONCLUSIONS & INFERENCES: (i) In adult CVS patients, GE is generally either rapid or normal. (ii) Cyclic vomiting syndrome is an important new etiology to explain the finding of rapid GE on a radionuclide test. (iii) The small subset of CVS patients (14%) whose GE was slow were explained by the role of narcotics and/or marijuana.

Who are the nonresponders to standard treatment with tricyclic antidepressant agents for cyclic vomiting syndrome in adults?

BACKGROUND: Cyclic vomiting syndrome in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea and vomiting separated by symptom-free periods. AIMS: To investigate the demographic and clinical characteristics of adult cyclic vomiting syndrome patients not responding to standard tricyclic antidepressant (TCA) therapy. METHODS: A total of 132 adults (62 men) with cyclic vomiting syndrome were followed for a mean of 1.6 years. Of these, 17 (eight men) patients were identified as nonresponders based on the criteria of unchanged, increased or minimally changed (<25%) frequency/duration of episodes and/or emergency department visits/hospitalizations. Demographic and clinical characteristics at baseline and annually up to 4 years were investigated. RESULTS: The nonresponders were receiving TCAs at an average dose of 90 mg/day compared to a mean dose of 85 mg/day in responders. Compared with the responders, the nonresponders were significantly more likely to have a history of migraine (P < 0.05); co-existing psychological disorders (P < 0.05); chronic marijuana use (P < 0.05) and reliance on narcotics for pain control between cyclic vomiting syndrome episodes (P < 0.05). CONCLUSIONS: (1) Nonresponse to standard therapy in adult cyclic vomiting syndrome patients occurs in approximately 13% and is not explained by under dosing with TCA therapy. (2) The main risk factors for nonresponse are: co-existing migraine headache, psychiatric disorder, chronic narcotic and marijuana use, which should be addressed aggressively when symptom exacerbations continue during attempts to induce remission in cyclic vomiting syndrome with high-dose TCA therapy.