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And Long-Term Outcomes of Children with Cyclic Vomiting Syndrome

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And Long-Term Outcomes of Children with Cyclic Vomiting Syndrome Short- and Long-Term Outcomes of Children with Cyclic Vomiting Syndrome Suporn Treepongkaruna MD*, Chaowapong Jarasvaraparn MD*, Pornthep Tanpowpong MD, MPH*, Chatmanee Lertudomphonwanit MD* * Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Objective: To determine the efficacy of prophylactic pharmacotherapy on the short- and long-term outcomes of children with cyclic vomiting syndrome (CVS). Material and Method: Medical records were reviewed in 32 children who were diagnosed with CVS between 2000 and 2013. Efficacy of prophylactic medications was classified as good vs. no response after treatment for three to six months. Long-term outcome was evaluated in patients who had been diagnosed for ≥2 years and classified as 1) excellent: no episode, 2) good: one to two episodes, and 3) poor: three episodes or more during the past year. Results: At three to six months after treatment, good response to amitriptyline was significantly higher than propranolol (73% vs. 36%, p = 0.04). Of the 24 CVS patients who had been diagnosed ≥2 years, data was available in 19 patients (mean age, 11.34.9; and mean duration from diagnosis to follow-up, 6.33.3 years). Excellent outcome was achieved in seven, good in seven, and poor in five children. Overall, the favorable long-term outcome (good and excellent) was 74%. Most children (86%) who had favorable long-term outcome had good response to the prophylactic medications in the early period of treatment. Conclusion: Amitriptyline may be more effective than propranolol for prophylaxis of CVS. However, a randomized controlled trial is required to confirm this result. Children with CVS have a relatively favorable long-term outcome, particularly those who initially responded well to the prophylactic medications. Keywords: Cyclic vomiting syndrome, Functional gastrointestinal disorder, Migraine, Vomiting J Med Assoc Thai 2014; 97 (10): 1077-83 Full text. e-Journal: http://www.jmatonline.com Cyclic vomiting syndrome (CVS) is a There are no specific diagnostic investigations for disorder characterized by recurrent episodes of severe CVS; therefore, diagnosis is based on characteristic vomiting with symptom-free intervals between the clinical manifestations(6,10,11). Although CVS is a episodes and stereotypic pattern within individuals(1). functional gastrointestinal disorder(10,11), patients and CVS can involve all age groups including adults(2) their family usually suffer from repetitive severe but commonly presents in childhood and occurs symptoms, frequent admissions to hospital and approximately 2% of school-aged children(3,4). A school absenteeism(5,6). Moreover, delayed diagnosis population-based study in Ireland has shown the is common, typically two years from the disease onset, incidence of 3.1 per 100,000 children per year(5). The resulting in treatment delay(6,12,13). etiologic mechanisms of CVS remain unknown but Key management of CVS includes supportive likely due to mitochondrial dysfunction, hypothalamic- treatment during acute episodes and prophylactic pituitary-adrenal axis stimulation and autonomic therapy(1). The most commonly used prophylactic dysfunction(6). Many studies have suggested that CVS medications are antimigraine agents including is associated with migraine headache, as many patients cyproheptadine, propranolol, and amitriptyline(1,14,15). develop migraine headache during adolescence, and However, only few studies compared the efficacy of family history of migraine headache is common(7-9). these medications for CVS in children(13,16,17). The efficacy of other drugs including phenobarbital, Correspondence to: sodium valproate, erythromycin, co-enzyme Q10 and Treepongkaruna S, Division of Gastroenterology, Department of L-carnitine has been reported in small studies(18-22). Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol Moreover, there have been only few studies on the University, Rama VI Road, Bangkok 10400, Thailand. (12,23-25) Phone: 0-2201-1446, Fax 0-2201-1446 long-term outcome of CVS in children . The E-mail: [email protected], [email protected] objectives of the present study were to determine the J Med Assoc Thai Vol. 97 No. 10 2014 1077 efficacy of prophylactic pharmacotherapy on the was considered statistically significant. Stata 13 short- and long-term outcomes of children with CVS. (StataCorp, College Station, TX, USA) was used for calculation and statistical analyses. Study design Retrospective cohort study. Results Between January 2000 and December 2013, Material and Method 40 pediatric patients were diagnosed with CVS, but Patients younger than 18 years who were only 32 medical records were available for study. diagnosed with CVS at Ramathibodi Hospital between Baseline characteristics are shown in Table 1. Blood January 2000 and December 2013 were enrolled. tests for complete blood count, electrolytes, blood Medical records were comprehensively reviewed to sugar, ammonia, urinalysis, and upper GI series gather demographic data, clinical manifestations, with or without small bowel follow-through were associated symptoms, medical conditions, investigations, and prophylactic medications including outcome after the initiation of treatment. In the short-term evaluation, Table 1. Demographic and clinical data of the study patients clinical response to prophylactic medications was (n = 32) evaluated at three to six months after initiation of treatment and categorized as: 1) good response: Characteristic Mean (SD) or numbers (%) either remission (no attacks after treatment) or markedly improvement, and 2) no response: decreased Male, n (%) 17 (53.1) approximately <50% in the frequency of attack. The Age at onset (years) 3.9 (SD 2.6) authors evaluated all patients who took medications Age at diagnosis (years) 6.1 (SD 3.7) for at least three months including those who received Duration between onset to diagnosis (years) 2.2 (SD 2.8) alternatives to the first-line medication. Additional Duration of each episode (days) 4.5 (SD 2.3) medications were not evaluated if they were used as combination therapy. Severity at the time of diagnosis, n (%) Interval ≤4 weeks 22 (68.7) Long-term outcome was evaluated in the Interval >4 to ≤8 weeks 7 (21.8) patients who were diagnosed with CVS for ≥2 years. Interval >8 to ≤12 weeks 1 (3.1) For those who were lost to follow-up, a questionnaire Interval >12 weeks 2 (6.2) was sent to the child’s guardian to verify current Associated symptoms during episodes, n (%) 27 (84.4) clinical status, severity and frequency of vomiting, Abdominal pain 19 (59.4) age of outgrowing from CVS, an occurrence of Lethargy 9 (28.1) migraine headache, and current medications. Long-term Headache 6 (18.8) outcome was classified by the frequency of vomiting Hypertension 7 (21.9) as 1) excellent (resolution): no episode, 2) good: one Pallor 2 (6.3) or two episodes, and 3) poor: three episodes or more Dizziness 1 (3.1) during the past year. Patients who had no attacks in the Fever 1 (3.1) past year but remained on prophylactic medications Hematemesis 8 (25.0) were classified as good. Migraine headache was Identified triggering factors, n (%) 18 (54.5) diagnosed based on the third International Classification Physical stress 7 (21.9) of Headache Disorder(26). Psychological stress/excitement 7 (21.9) Illness 6 (18.8) The study was approved by the Ethic Menstruation 1 (3.1) Committee of the Faculty of Medicine, Ramathibodi Hospital, Mahidol University, and conformed to the Coexisting conditions, n (%) 10 (31.3) Mental retardation 2 (6.2) Declaration of Helsinki 1995 (revised in Seoul 2008). Developmental delay 3 (9.4) Asthma 3 (9.4) Statistical analysis Allergic rhinitis 3 (9.4) Subjects were described using descriptive Growth hormone deficiency 1 (3.1) statistics, such as mean (standard deviation, SD), Others (Cornelia de Lange, Noonan 3 (9.4) median (interquartile range, IQR). For the continuous syndrome, Ehlers-Danlos syndrome) variables, we used student t-tests. The p-value of <0.05 Family history of migraine, n (%) 9 (28.1) 1078 J Med Assoc Thai Vol. 97 No. 10 2014 performed in all patients. Other investigations including upper gastrointestinal endoscopy, abdominal ultrasonography, computerized tomography or magnetic resonance imaging of the brain, and investigations for metabolic diseases were performed if clinically indicated. The study flow chart is shown in Fig. 1. Short-term outcome of prophylactic pharmacotherapy Prophylactic medications were given in 29 patients (90%) and the first-line medications were propranolol (n = 11), cyproheptadine (n = 4), and amitriptyline (n = 14) with the recommended dosages(1). We noted 18 out of 29 patients received only the first-line treatment, while 11 patients required alternatives which four required more than two changes in 46 treatment events. The reason for changing the Fig. 1 Flow chart of the study. medications was poor response in all except one patient who experienced an adverse reaction. Ten treatments were excluded from the analysis due to treatment Seven patients (37%) had excellent outcome, duration shorter than three months (amitriptyline 5, while seven patients (37%) had good, and five (26%) propranolol 1, topiramate 1) and the additional drugs had poor outcome. The favorable long-term outcome for a combination therapy (valproate 1, co-enzyme (excellent combined with good outcomes) was then Q10/L-carnitine 2). Response to treatment (Table 2) documented in 74% in this cohort. Three patients with was evaluated in the
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