E M O R Y U N I V E R S I T Y D E P A R T M E N T O F S U R G E R Y REPAIR SYSTEM (APTUS DEVICE), AN INVESTIGATIONAL DEVICE, USED IN THE TREATMENT OF ABDOMINAL AORT THORACIC ENDOPROSTHESIS IN SUBJECTS W/DESCENDING THORACIC AORTIC ANEURSYMS INVESTIGATIONAL DEVICE FOR INTRA-BRONCHIAL TREATMENT LONG-TERM SAFETY, AND TOLERABILITY OF TACROLIMUS IN STABLE PEDIATRIC LIVER TRANSPLANT PATIENTS CONVERTE
Oral ondansetron for gastroenteritis in a pediatric emergency departmentT h e n e w e n g l a n d j o u r n a l o f m e d i c i n e Oral Ondansetron for Gastroenteritis in a Stephen B. Freedman, M.D.C.M., Mark Adler, M.D., Roopa Seshadri, Ph.D., and Elizabeth C. Powell, M.D., M.P.H.
From the Division of Pediatric Emergency Vomiting limits the success of oral rehydration in children with gastroenteritis. We Medicine, Hospital for Sick Children, Uni- conducted a double-blind trial to determine whether a single oral dose of ondanse- versity of Toronto, Toronto (S.B.F.); the
Division of Pediatric Emergency Medicine tron, an antiemetic, would improve outcomes in children with gastroenteritis.
(M.A., E.C.P.) and the Mary Ann and
J. Milburn Smith Child Health Research Methods
Program (R.S.), Children’s Memorial Re-
search Center, Children’s Memorial Hospi-
We enrolled 215 children 6 months through 10 years of age who were treated in a tal, Chicago; and the Departments of Pedi- pediatric emergency department for gastroenteritis and dehydration. After being ran- atrics (M.A., R.S., E.C.P.) and Preventive domly assigned to treatment with orally disintegrating ondansetron tablets or placebo, Medicine (R.S.), Feinberg School of Medi-cine, Northwestern University, Chicago. the children received oral-rehydration therapy according to a standardized proto-Address reprint requests to Dr. Freedman col. The primary outcome was the proportion who vomited while receiving oral at the Division of Pediatric Emergency rehydration. The secondary outcomes were the number of episodes of vomiting and Medicine, Hospital for Sick Children, 555 University Ave., Toronto ON M5G 1X8, the proportions who were treated with intravenous rehydration or hospitalized.
Canada, or at email@example.com.
As compared with children who received placebo, children who received ondanse- Copyright 2006 Massachusetts Medical Society. tron were less likely to vomit (14 percent vs. 35 percent; relative risk, 0.40; 95 percent confidence interval, 0.26 to 0.61), vomited less often (mean number of episodes per child, 0.18 vs. 0.65; P<0.001), had greater oral intake (239 ml vs. 196 ml, P = 0.001), and were less likely to be treated by intravenous rehydration (14 percent vs. 31 per-cent; relative risk, 0.46; 95 percent confidence interval, 0.26 to 0.79). Although the mean length of stay in the emergency department was reduced by 12 percent in the ondansetron group, as compared with the placebo group (P = 0.02), the rates of hospi-talization (4 percent and 5 percent, respectively; P = 1.00) and of return visits to the emergency department (19 percent and 22 percent, P = 0.73) did not differ signifi-cantly between groups.
In children with gastroenteritis and dehydration, a single dose of oral ondansetron reduces vomiting and facilitates oral rehydration and may thus be well suited for use in the emergency department. Downloaded from nejm.org on October 10, 2011. For personal use only. No other uses without permission. Copyright 2006 Massachusetts Medical Society. All rights reserved. effic ac y of or a l onda nse t ron in pedi at r ic g a s t roen t er i t is In the united states, gastroenteritis the study, a research assistant was contacted. Re- accounts for more than 1.5 million pediatric search assistants were on call from 8 a.m. until outpatient visits and 200,000 hospitalizations midnight, and overnight coverage was provided annually.1 Although oral-rehydration therapy is by the principal investigator. A log was kept of recommended for children with mild-to-moder- all children asked to enroll in the study, and any ate dehydration,1 it remains underused. Clinicians reasons for refusal were recorded. Written in-who provide care in emergency departments are formed consent was obtained from the parents more likely to choose intravenous over oral rehy- or guardians of all children. All 33 supervising dration when vomiting is a major symptom.2 In physicians working in the emergency department one survey, 36 percent of pediatricians reported participated in screening, and 10 research assis-that vomiting was a contraindication to oral rehy- tants were involved in the project.
dration.3 Thus, a safe and effective method of con- A baseline dehydration score (Table 1) was trolling vomiting is likely to increase the use and assigned to all children. The score could range success rate of oral rehydration.
from 6 to 21, with higher scores indicating more In a previous study of oral ondansetron (Zofran, severe dehydration. Children under 24 months GlaxoSmithKline) in children with gastroenteritis, of age were evaluated for all seven items used to six doses of oral elixir or placebo were admin- determine the score, and those 24 months of age istered over a period of 48 hours.4 Although vom- or older were evaluated for six (their ability to iting was reduced among children receiving on- produce tears was not evaluated).7-14 It was de-dansetron in the emergency department, the rates termined a priori that children under 24 months of diarrhea and return visits to the emergency department were increased.4 We conducted a study to determine whether the administration of a single Table 1. Dehydration Score.*
orally disintegrating ondansetron tablet to chil- Normal or Mild
dren with vomiting and dehydration as a result of Dehydration
gastroenteritis would control vomiting with mini- Variable
The study was a prospective, double-blind, ran- domized comparison of ondansetron and place- bo to control vomiting among children 6 months through 10 years of age. The trial was conducted in the emergency department of Children’s Me- morial Hospital in Chicago from January 1, 2004, through April 11, 2005. The study was approved Normal amount Reduced amount None passed by the hospital’s institutional review board. All children with symptoms consistent with gastroenteritis were screened for eligibility by the supervising physician. Eligible children had at least one reported episode of nonbilious, non- * Higher scores indicate more severe dehydration. Scores range from 7 to 21 bloody vomiting within the four hours preced- for children under 24 months of age and from 6 to 18 for children 24 months ing triage, at least one episode of diarrhea dur- of age or older. Children under 24 months of age with scores of 10 to 17 and those 24 months of age or older with scores of 8 to 15 were considered to ing the illness, and mild-to-moderate dehydration have mild-to-moderate dehydration. Those under 24 months of age with (Table 1). The exclusion criteria were a body weight scores of 18 or more and those 24 months of age or older with scores of 16 of less than 8 kg, severe dehydration, underlying or more were considered to be severely dehydrated.
† To assess pinch-retraction time, the examiner pinches a small fold of skin on disease that could affect the assessment of hy- the lateral abdominal wall at the level of the umbilicus and estimates the time dration (such as renal failure or hypoalbumin- it takes for the skin to resume its normal shape.5 emia), a history of abdominal surgery, hypersen- ‡ Only children under 24 months of age were evaluated for tears.
§ The normal heart rate was based on values published by Davignon et al.6 sitivity to ondansetron, and previous enrollment ¶ The amount and color of the urine were reported by the parent.
in the study. If the child was deemed eligible for Downloaded from nejm.org on October 10, 2011. For personal use only. No other uses without permission. Copyright 2006 Massachusetts Medical Society. All rights reserved. T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e of age with scores of 10 to 17 and those 24 months the protocol specified the administration of 20-ml
of age or older with scores of 8 to 15 would be boluses of 0.9 percent normal saline per kilo-
considered to have mild-to-moderate dehydration gram of body weight, each given over a period of
and to be in need of rehydration. For analysis, 30 minutes.
dehydration scores for children 24 months of age
or older were standardized so that they were on Follow-up
the same scale as those for children under 24 On days 3 and 7 after randomization, a research
months of age.
assistant telephoned the child’s family and asked, using a standard script, whether the child had re- Randomization
turned to an emergency department, had received The patients were randomly assigned in blocks of intravenous-fluid treatment, had had any addi-
six to receive ondansetron or placebo and were tional symptoms, or had been hospitalized. The
stratified according to the dose of medication. An records of Children’s Memorial Hospital were
independent statistician provided the code to the reviewed to confirm caregivers’ reports. If the re-
pharmacy, which dispensed in an opaque bag a search assistant was unable to reach a caregiver on
weight-appropriate dose of active drug or a pla- the designated day, attempts were continued daily
cebo of similar taste and appearance. The weight- for two weeks after enrollment of the child.
based dose was 2 mg for children weighing 8 to
15 kg, 4 mg for children weighing more than Outcome Measures
15 kg and up to 30 kg, and 8 mg for children The primary outcome was the proportion of chil-
weighing more than 30 kg. GlaxoSmithKline sup- dren in each group who vomited while receiving
plied the tablets but had no role in the conception, oral-rehydration therapy. A vomiting episode was
design, or conduct of the study or in the analysis recorded by the research assistant when the force-
or interpretation of the data.
ful expulsion of stomach contents occurred. Epi-sodes separated by no more than two minutes were Study Intervention
counted as a single episode. Nonproductive retch- The bedside nurse administered the medication ing, spilling of oral contents, and drooling were
while the research assistant was outside the room not considered vomiting. The secondary outcomes
to ensure that the research assistant, physician, were the number of episodes of vomiting during
child, and caregivers remained unaware of the oral-rehydration therapy and the rates of intrave-
treatment assignment. A tablet was placed on the nous rehydration and hospitalization.
top of each child’s tongue, and the child was in-
structed to swallow five seconds later. Children who Adverse Events
were unable to adhere to these instructions were The research assistant, treating physician, and
assisted by the nurse until they swallowed. Since the nurses monitored patients for adverse events from
tablet dissolves in seconds and does not require the enrollment to disposition from the emergency
coadministration of liquids, aspiration was not con- department. A treatment-related adverse event was
sidered to be a risk. Children who vomited within 15 one considered by at least two of the three phy-
minutes after receiving the medication were giv- sician investigators to be possibly, probably, or
en a second dose. A 1-hour period of intense definitely related to the study drug. Although a
oral rehydration was initiated 15 minutes after significantly increased frequency of diarrhea in
administration of the medication; the oral rehy- the emergency department was considered an
dration period then continued until disposition adverse event, generalized symptoms related to
was determined (i.e., whether the child was ad- the underlying illness (fever, vomiting after dis-
mitted or sent home). In keeping with the World charge, diarrhea, or fatigue) were not considered to
Health Organization (WHO) recommendations be adverse events. A data and safety monitoring
on oral rehydration, the caregivers were instruct- board reviewed adverse outcomes in a blinded
ed to limit the amount of fluid given to 30 ml of fashion.
oral electrolyte solution (Enfalyte, Mead Johnson
Nutritionals) every five minutes.15 After the oral- Statistical Analysis
rehydration period was completed, the treating We estimated that the enrollment of 214 children
physician resumed management. If the treating would provide the study with a statistical power
physician chose to administer intravenous fluids, of 90 percent to detect a change from 35 percent
Downloaded from nejm.org on October 10, 2011. For personal use only. No other uses without permission. Copyright 2006 Massachusetts Medical Society. All rights reserved. effic ac y of or a l onda nse t ron in pedi at r ic g a s t roen t er i t is in the control group to 15 percent in the treat-ment group in the proportion of children who vomited during oral rehydration, given a two-sided type I error of 0.05. The calculation included a 10 percent adjustment for nonadherence of the care-giver to the therapy.16 Baseline characteristics of the two groups were compared by the chi-square or Fisher’s exact test for proportions and the t-test for continuous vari-ables. We used generalized estimating equations to account for the random effect that decision making by individual physicians might have had on the outcomes of interest, since the assump- tion of independence might not have been true for all outcomes.17 Logistic models were used for the dichotomous outcomes of vomiting and intrave- nous hydration. A cumulative logit model was used for the ordinal outcome of the number of vomit-ing episodes, with the number of episodes de-fined as zero, one, two, or greater than or equal to three.17 Since only nine children were hospital-ized, Fisher’s exact test was used to compare pro-portions between groups.
Because the child’s age, race, and sex, the time of day, the presence or absence of fever, the hy-dration score, and the amount of fluid adminis- tered could influence the response to the study medication, these factors were included in all models. Other variables that were included when appropriate were the number of episodes of vom-iting and diarrhea during oral-rehydration ther-apy and, in the 24 hours before triage, weight change, length of stay in the emergency depart- ment, and the type of physician caring for the child (pediatric emergency physician vs. urgent care physician). Because of sample-size limita- tions, the effect of each of these variables was determined individually. Those with a significant effect at the 0.2 level were included in multiple- Figure 1. Enrollment and Outcomes.
predictor models. The treatment group (ondanse- The primary outcome was vomiting during oral rehydration in the emergen- tron or placebo) was included in all models. For cy department after the receipt of ondansetron or placebo. The secondary outcomes were the mean number of episodes of vomiting, the rate of treat- the primary outcome of vomiting, the best four- ment with intravenous rehydration, and the rate of hospitalization.
predictor model based on deviance statistics was determined. Poisson models were used for length of stay in the emergency department and the num- come of vomiting, the mixed-effects models for ber of episodes of diarrhea in the emergency outcomes based on physician’s decision making, department. A mixed-effects linear regression and the rule for including multiple predictors in model was used for the outcomes of volume of regression models were specified in advance. For oral-rehydration fluid and volume of intravenous the number of vomiting episodes, we initially pro-fluid administered, with the physician as the ran- posed using a Poisson model, but data analysis dom effect. Variables with significant interactions revealed that the Poisson distribution did not pro-were considered together.18 vide a good fit and that a cumulative logit model The statistical model used for the primary out- was more appropriate.
Downloaded from nejm.org on October 10, 2011. For personal use only. No other uses without permission. Copyright 2006 Massachusetts Medical Society. All rights reserved. T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e cians (Fig. 1). One child did not meet the criteria Table 2. Baseline Characteristics of the Patients.*
for dehydration after evaluation by the research Ondansetron
assistant, and one child was withdrawn by the Characteristic
Group (N = 107)
supervising physician because of severe dehy- dration. The caregivers of 26 children declined to participate. A total of 215 children were ran- domly assigned to treatment, 108 to ondansetron and 107 to placebo. There were no significant dif- ferences in baseline characteristics between the Three children in the ondansetron group were withdrawn before receiving study medication. Database analysis revealed that one child in the placebo group did not meet the eligibility crite-ria. The only patient whose data were not ana- lyzed was a child who was accidentally assigned to ondansetron before parental consent had been obtained and whose family chose not to par- Vomiting — no. of episodes in preceding Five children who received ondansetron vom- Diarrhea — no. of episodes in preceding ited within 15 minutes. Each of these children was given a second dose, which was tolerated. Three children who received placebo vomited within 15 minutes. The parents of two of these children refused to allow a second dose to be given; the remaining child was given a second dose, which Of the 107 children in each group whose data * Plus–minus values are means ±SD. There were no significant differences be- were analyzed, 15 who received ondansetron vom- ited while receiving oral-rehydration therapy, as † Higher values indicate more severe dehydration.
compared with 37 who received placebo (14 per- ‡ A total of 100 urine samples were obtained for analysis. Urinary ketone values are reported as 0 to 4+, with higher values indicating increasing ketonuria.
cent vs. 35 percent, P<0.001) (Table 3). After ad- § The measurements were performed on serum samples obtained at the time justment for the type of physician providing care, of insertion of the intravenous catheter in 48 patients (15 in the ondansetron the relative risk was 0.40 (95 percent confidence group and 33 in the placebo group). To convert values for blood urea nitrogen to millimoles per liter, multiply by 0.357. To convert values for creatinine to interval, 0.26 to 0.61). The mean number of epi- millimoles per liter, multiply by 88.4. To convert values for glucose to milli- sodes of vomiting was significantly lower among moles per liter, multiply by 0.05551.
children who received ondansetron than among those who received placebo (0.18 vs. 0.65, P<0.001). Relative risks and 95 percent confidence in- This difference remained significant after ad- tervals are presented for all results. Analyses were justment for the type of physician providing care performed with SAS software (version 9.1) accord- (relative risk, 0.30; 95 percent confidence inter-ing to the intention-to-treat principle. All P values val, 0.18 to 0.50).
are two-sided, with a P value of less than 0.05 used Fifteen children in the ondansetron group (14 to indicate statistical significance, without ad- percent) and 33 in the placebo group (31 percent) justment for multiple comparisons.
received intravenous rehydration (P = 0.003). The interaction effect between treatment group and whether a child vomited was significant (P = 0.009); thus, separate models were used for children who Participants
vomited and those who did not. Among the 92 During the study period, 243 potentially eligible children in the ondansetron group and the 70 chil-patients were identified by the supervising physi- dren in the placebo group who did not vomit, in- Downloaded from nejm.org on October 10, 2011. For personal use only. No other uses without permission. Copyright 2006 Massachusetts Medical Society. All rights reserved. effic ac y of or a l onda nse t ron in pedi at r ic g a s t roen t er i t is Table 3. Outcome Measures.*
Group (N = 107)
Vomited during oral rehydration — no. (%) Vomiting episodes per patient — no. (%) Length of stay in emergency department — min * Plus–minus values are means ±SD. † The adjusted relative risk is reported for dichotomous outcomes. CI denotes confidence interval.
‡ All reported P values were adjusted as described in the text. travenous hydration was less common in the on- was well tolerated and resulted in a reduction of dansetron group (5 percent vs. 17 percent; P = 0.01; more than 50 percent in both the proportion of relative risk, 0.32; 95 percent confidence inter- children who vomited during oral rehydration val, 0.13 to 0.77). Although, overall, children in and the proportion treated with intravenous flu-the ondansetron group received a larger volume ids. As compared with children who received pla-of oral-rehydration fluid and a smaller volume cebo, children who received ondansetron had few-of intravenous fluid and had a shorter stay in the er episodes of vomiting, greater oral intake of emergency department, hospital admission rates fluids, and a shorter stay in the emergency de-were similar in the two groups.
To prevent vomiting in 1 child, 5 children had Adverse Events
to receive ondansetron (95 percent confidence No cardiovascular or respiratory events occurred. interval, 3.2 to 10.6); to prevent 1 child from hav-Urticaria developed in one child in the placebo ing to be treated by intravenous rehydration, 6 had group. Children who received ondansetron had to receive ondansetron (95 percent confidence more episodes of diarrhea while undergoing oral interval, 3.6 to 17.0). These benefits were also re-rehydration than those who received placebo (1.4 ported in a previous study, which found that the vs. 0.5, P<0.001), even after adjustment for the administration of liquid ondansetron three times number of episodes occurring before arrival. Fol- daily for two days reduced vomiting in the emer-low-up, which was completed for 96 percent of gency department, the use of intravenous fluids, the children (Table 4), did not reveal any additional and the need for hospitalization among children.4 adverse events. Kawasaki’s disease was diagnosed However, that study did not report a reduction in in one child in the ondansetron group six days vomiting after discharge, and children who were after randomization. The disease was not attrib- given ondansetron had significantly more episodes uted to treatment.
of diarrhea and return visits to the emergency department. We found that a single dose of oral ondansetron reduced vomiting and the need for intravenous fluids without any clinically signifi- We found that a single dose of ondansetron im- cant adverse events.
proves the success of oral rehydration in dehy- Although there are no established criteria in- drated children with gastroenteritis. The oral dose dicative of a need for intravenous rehydration, we Downloaded from nejm.org on October 10, 2011. For personal use only. No other uses without permission. Copyright 2006 Massachusetts Medical Society. All rights reserved. T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e may reduce overall costs while providing individ- Table 4. Follow-up Data.*
A total of 19 percent of children in the on- Variable
Group (N = 107) Group (N = 107)
dansetron group and 22 percent of those in the placebo group returned to the emergency depart- Completed follow-up — no./total no. (%) 107/107 (100) ment. Although these rates are higher than previ- ously reported rates,4,19 only about half of those who returned received intravenous f luids. We Return visit to emergency department — chose to analyze the data from children who be- came dehydrated and presented to the emergency department for care and not to focus on children who sought additional care from a primary care Other antiemetic agents used in the treatment Completed follow-up — no./total no. (%) 105/107 (98) of pediatric gastroenteritis, although frequently prescribed,20 either have substantial side effects or have not been well studied. A review of a phar- maceutical database revealed that promethazine accounted for 92 percent of all antiemetic pre- scriptions filled for gastroenteritis.20 Adverse events associated with promethazine include drowsiness (71 percent) and respiratory depression, dystonia, and neuroleptic malignant syndrome.21-24 Nei- ther promethazine nor prochlorperazine has been studied in children with gastroenteritis. However, in adults, promethazine is less effective than pro- * There were no significant differences between the groups.
chlorperazine.24 Data from adults suggest that drowsiness (38 percent)24 and akathisia (44 per- found that fewer children in the ondansetron group cent)25 are common adverse events. Other agents, than in the placebo group received intravenous such as trimethobenzamide, metoclopramide, and fluids. Since the decision to administer intrave- dimenhydrinate, either have been shown to be in-nous fluids was made by the supervising physi- effective26 or have never been evaluated in children cian, who was unaware of patients’ treatment as- with gastroenteritis.23signments, we believe this difference represents Our data suggest that it is safe to administer oral ondansetron to children with gastroenteri- Ondansetron did not reduce the hospitaliza- tis, with diarrhea being the most notable side ef- tion rate (4 percent overall). The failure to find fect. Since culture of specimens for viral and bacte-a reduction in the hospitalization rate might be rial causes is not routinely performed in children due to a lack of statistical power. Our study was with gastroenteritis, we cannot rule out the pos-powered, on the basis of previous data, to detect sibility that viruses or bacteria may explain the a reduction from 15 percent to 3 percent.4,19 Thus, differences in the frequency of diarrhea between the detection of a significant effect of ondanse- groups. However, this is unlikely, given the simi-tron on the rate of hospitalization might be more lar baseline characteristics of the two groups and likely in settings in which this rate was higher.4,19 the fact that Ramsook et al.4 also noted an in- The total cost of the ondansetron used in this creased rate of diarrhea among children given study, based on actual costs of $35.75 per 4-mg ondansetron.
orally disintegrating tablet at Children’s Memo- We used an unvalidated scale for dehydration rial Hospital, would have been $3,825. The re- because of the lack of an externally validated scale duction in cost resulting from the avoidance of and the conclusion of a recent meta-analysis that the insertion of intravenous catheters ($124.74 individual signs of dehydration are imprecise and per child) and hospitalization ($1,900 per admis- inaccurate.5 Thus, we grouped commonly used sion)19 was $4,145. Thus, the use of ondansetron signs and symptoms7-9 to improve the diagnostic Downloaded from nejm.org on October 10, 2011. For personal use only. No other uses without permission. Copyright 2006 Massachusetts Medical Society. All rights reserved. effic ac y of or a l onda nse t ron in pedi at r ic g a s t roen t er i t is characteristics in order to identify children with tion therapy might have been deemed successful evidence of dehydration. The dehydration score in some of the children in whom it was consid-was successful in this regard, since the ratio of ered to have failed if they had been observed for blood urea nitrogen to creatinine exceeded 20 in four hours, as recommended by the WHO.1596 percent of the children who underwent veni- We found that treatment with orally disinte- puncture. A similar result was obtained in a previ- grating ondansetron tablets was beneficial in ous study of intravenous rehydration: 82 percent children with vomiting and dehydration due to of the children had a ratio of blood urea nitrogen gastroenteritis. The ondansetron tablet is easy to creatinine of more than 20.19 to administer, has few side effects, and is safe We chose not to use the WHO classification and effective. Therefore, it may be a useful thera- of dehydration (no dehydration, some dehydra- py in the emergency department for children with tion, and severe dehydration),15 because it does vomiting and mild-to-moderate dehydration as a not work well as a research tool in settings in result of gastroenteritis.
which very few children are severely dehydrated. Supported by grants from the National Center for Research It would not have allowed us to distinguish chil- Resources of the National Institutes of Health (M01 RR-00048) dren with some dehydration who needed only No potential conflict of interest relevant to this article was reassurance and minimal rehydration from chil- reported.
dren with some dehydration who required rehy- We are indebted to the emergency department nurses, clerical staff, and physicians at Children’s Memorial Hospital for their assistance with patient recruitment and adherence to the proto- The oral-rehydration period in the emergency col; to the pharmacy staff for promptly supplying the study medi- department was limited to one hour to mimic cation; to the research assistants for their instrumental role in patient enrollment; to Nancy Ryan for her administrative sup- routine clinical practice, in which prolonged peri- port; and to Dr. Jennifer Thull-Freedman for her assistance ods of observation are impractical. Oral-rehydra- throughout the study.
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1ère CIRCONSCRIPTION - Vannes / La Roche-BernardARRADON - ILE AUX MOINES - ILE D'ARZ - LARMOR BADEN VANNES 1 - PALAIS DES ARTS ET DES CONGRESVANNES 2 - PALAIS DES ARTS ET DES CONGRES VANNES 3 - PALAIS DES ARTS ET DES CONGRES VANNES 4 - PALAIS DES ARTS ET DES CONGRESVANNES - Bureaux 1 - 2 - 5 - 10 - 25 - 26 VANNES 5 - PALAIS DES ARTS ET DES CONGRESVANNES - Bureaux 11 - 12 - 13 - 14 - 27 -