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58 Digestive Disorders FAMILY P RACTICE N EWS • May 15, 2006 Ondansetron Cuts Vomiting, Surgery Still Top Tx for Need for IV in Enterocutaneous Fistulas BY JEFF EVANS complications occurred with the BY SHERRY BOSCHERT consent had not been obtained before randomiza- Senior Writer use of VAC and fistula output did San Francisco Bureau tion, said Dr. Freedman, of the University of Toron- not increase, Dr. Draus noted. to, and his associates (N. Engl. J. Med. L OUISVILLE, KY. — Treat- VAC should be used in the single oral dose of the antiemetic on- 2006;354:1698-705). Ondansetron also significantly ment of enterocutaneous fistu- subset of patients whose dansetron significantly reduced vomiting reduced the mean number of episodes of vomit- las continues to rely primarily on wounds are free of active infec- Aand mild to moderate dehydration in chil- ing, compared with placebo (0.18 vs. 0.65 episodes, surgery, augmented in some cas- tion, have no exposed bowel, dren treated in a pediatric emergency department respectively). Significantly fewer children in the on- es by octreotide or vacuum-as- and have a healthy layer of sur- for gastroenteritis, allowing more children to be re- dansetron group received intravenous rehydra- sisted closure, according to a re- rounding soft tissue, he advised. hydrated orally rather than intravenously, Dr. tion—14%, versus 31% in the placebo group. view of 106 patients. The application of fibrin glue Stephen B. Freedman reported. Among the children who did not vomit during The management of entero- resulted in only one completely A prospective, double-blind study randomized oral rehydration in either group, intravenous flu- cutaneous fistulas continues to healed fistula among eight pa- 215 children aged 6 months through 10 years to re- ids were started in 5% given ondansetron and 17% be a problem because of 5%- tients, all of whom had small ceive a disintegrating tablet of oral ondansetron given placebo, a significant difference. 15% mortality, a spontaneous bowel fistulas with high output. (Zofran) or placebo administered by a nurse while Contrary to a study that looked at multiple dos- healing rate of less than 30%, The glue transiently healed one the physicians and research assistants were out of es, the single dose of ondansetron did not cause any and an overall healing rate hov- patient’s fistula for 11 days. the room. Five seconds af- significant adverse events, ering around 80%-90%, Dr. John Of 24 patients who received ter placing the tablet on and the groups did not dif- M. Draus said at the annual treatment with octreotide, 8 re- the patient’s tongue, the Treatment Group Less Likely fer in the rate of return vis- meeting of the Central Surgical sponded with at least a 50% de- nurse asked or helped the To Need IV Rehydration its to the emergency de- Association. crease in fistula output within 3 child to swallow. Children partment (19% with He and his colleagues in the days; 4 of these 8 patients healed who vomited within 15 31% ondansetron and 22% with surgery department at the Uni- without an operation. minutes received a second placebo). The ondansetron versity of Louisville, Ky., re- “Octreotide responders ap- dose. Fifteen minutes later, group did have more viewed cases of gastrointestinal- pear more likely to heal their fis- clinicians started a 1-hour episodes of during cutaneous fistulas that occurred tula without operation” than period of intense oral re- the oral rehydration than from 1997 to 2005 at two large those who receive other nonop- hydration, and oral rehy- the placebo group—1.4 vs. teaching hospitals. The investi- erative modalities, Dr. Draus

14% EWS dration could be continued N 0.5 episodes—but this dif- gators excluded patients with in- said. He recommended that until the patient was sent ference was not significant. flammatory bowel disease and most patients with an enterocu- home or admitted. After EDICAL GlaxoSmithKline, which those with esophageal, pancre- taneous fistula be given at least the first hour of oral rehy- M makes ondansetron, pro- atic, or anorectal fistulas. a 3-day trial of octreotide. If Ondansetron Placebo dration, the treating physi- LOBAL vided the tablets but had Among the 106 patients, fis- there isn’t a dramatic decrease in cian could choose to give Note: Based on a study of 215 children. G no other role in the study, tulas most often resulted from a fistula output by the end of 3 intravenous fluids. Source: Dr. Freedman and the investigators did previous operation (81) and orig- days, there is probably not much LSEVIER

The investigators pri- E not report any other po- inated from the small bowel benefit in continuing octreotide, marily assessed how many tential conflicts of interest. (67), colon (26), stomach (8), or he suggested. Most patients in children vomited during The ondansetron dosing was 2 mg for children (5). These operations the study began receiving 100 by conducting phone interviews with the families weighing 8-15 kg, 4 mg for those weighing 16-30 were performed to treat cancer, mcg of octreotide three times 3-7 days later and reviewing patients’ records. kg, and 8 mg for heavier children. adhesions, small bowel obstruc- per day, but the dose was in- Among 107 children in the ondansetron group, At a cost of $35.75 per 4-mg tablet, the on- tion, gynecologic problems, or creased to 500 mcg three times 14% vomited while receiving oral rehydration ther- dansetron in the study cost a total of $3,825 but ventral . Other fistula eti- per day in one patient. apy, compared with 35% of 107 children in the saved the hospital $4,145 by avoiding insertion of ologies included trauma (15), Audience member Dr. Bruce placebo group. One child in the ondansetron group intravenous catheters (at a cost of $124.74/child) mesh erosion (6), diverti- A. Harms of the University of was not included in the analysis because parental and hospitalizations ($1,900/admission). ■ culitis (2), and radiation (2). Wisconsin, Madison, found this The group of patients com- recommendation to be “a little prised 31 with high-output fis- bit of a stretch” in light of the tulas (leaking more than 200 fact that there is no hard effica- Blood Test Predicts in Patients mL/day), 44 with low-output cy data to back up Dr. Draus’ fistulas (less than 200 mL/day), advice. Octreotide should fall Who Have Nonalcoholic Fatty Disease and 31 whose fistula output was into the category of an ancillary managed with a single gauze treatment, said Dr. Harms. ATLANTA — A blood test can cutoff value of 395 U/L was borderline NASH, and two had dressing. The analysis showed Of 77 patients who had a predict nonalcoholic steatohep- 99.9% sensitive and 85.7% spe- alternative diagnoses, which left that the rate of healing or need planned operation, 69 (90%) atitis in patients with nonalco- cific in predicting nonalcoholic 39 evaluable patients. for operation did not differ healed. The average time from holic fatty , according steatohepatitis (NASH). Caspase activation was signif- among patients with low- or fistula formation to operation to results of a study presented at “A is the only reli- icantly elevated in patients with high-output fistulas. was 12 weeks. Some audience a meeting sponsored by the able method to differentiate sim- definitive NASH, with median In general, the initial treat- members said that 12 weeks was American Association for the ple from NASH and cytokeratin-18 levels of 767 U/L, ment plan for each of the pa- too short of an interval to wait Study of Liver Diseases. stage disease severity,” noted compared with 202 U/L in pa- tients consisted of the correction to repair the fistulas, but Dr. apoptosis is study author Dr. Anna Wieck- tients with simple steatosis. After of fluid and electrolyte imbal- Draus noted that the operation known to mediate liver injury in owska of the Cleveland Clinic. adjustment for confounding ances, nutritional support occurred after 3-6 months in nonalcoholic However, biopsy has inherent variables, including AST/ALT through total parenteral or en- about half of the patients. (NAFLD). The activation of cas- risks and is not practical to per- ratio and , cy- teral feeding, wound care, diag- “It is frustrating that in 2006 pases that mediate apoptosis can form multiple times. Her group tokeratin-18 levels were inde- nostic imaging, early recogni- we still have made so little be measured in the plasma, thus thus evaluated a caspase activity pendently predictive of NASH, tion of sepsis, drainage of progress in treating fistulas with allowing an indirect evaluation blood test in 44 consecutive pa- with a positive predictive value abscesses, and an operation nothing but an operation,” said of liver damage. tients with suspected NAFLD. of 99.9% and a negative predic- when necessary. audience member Dr. Merril Caspase activation was de- They measured caspase activity tive value of 85.7%. Among 13 patients who re- Dayton of the State University tected in the plasma using an en- in plasma samples obtained at Dr. Keith D. Lindor of the ceived treatment with vacuum- of New York at Buffalo. zyme-linked immunosorbent as- liver biopsy and then correlated Mayo Clinic in Rochester, Minn., assisted closure (VAC), all had Fistulas healed in 82% of pa- say for cytokeratin-18 fragments, the blood test results with noted that “a noninvasive way to improved wound care and over- tients regardless of which treat- which are a byproduct of cas- histopathologic features. Five pa- accurately predict mild degrees of all healing, but only 1 patient had ment was used. Seven of the pa- pase activation. In the study, cas- tients were excluded due to a would allow us to select complete healing that was at- tients in the study died as a result pase activation was strongly as- hemolyzed blood sample, two patients for treatment trials.” tributed to VAC. The other 12 re- of continued sepsis or persistent sociated with disease severity; a were excluded because they had —Melinda Tanzola quired an operation. No septic cancer. ■

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