Neurol Med Chir (Tokyo) 46, 421¿428, 2006Effect of Fasudil Hydrochloride, a Protein Kinase Inhibitor,on Cerebral Vasospasm and Delayed Cerebral—Results of a Randomized Trial of Fasudil HydrochlorideJizong ZHAO, Dingbiao ZHOU*, Jing GUO**, Zyuan REN***, Liangfu ZHOU†,Shuo WANG, Bainan XU*, and Renzhi WANG***Department of Neurosurgery, Capital Medical University Affiliated Beijing Tiantan
Jets_jan-april_2009.inddFull Text Online @ www.onlinejets.org
Use of antiemetics in children with acute gastroenteritis: Are they safe and effective? Henry Ford Hospital, 2799 W. Grand Blvd, Detroit, MI 48201, USA ABSTRACT
The use of antiemetics is a controversial topic in treatment of pediatric gastroenteritis. Although not recommended by the American Academy of Pediatrics, antiemetics are commonly prescribed by physicians. A review of the literature shows side effects of promethazine, prochlorperazine, and metoclopramide are common and potentially dangerous. Ondansetron has recently been studied as an adjunct to oral rehydration therapy in treatment of acute gastroenteritis with mild to moderate dehydration. Although studies are limited, early research suggests the medication is safe when used in a single dose and can be effective to prevent vomiting, the need for intravenous fluids, and hospital admission.
Key Words: Antiemetics, gastroenteritis, pediatrics A 2-year-old female presents to the emergency department (ED) 220,000 hospitalizations each year. The cost of each admission is from family practice clinic with a 2 day history of vomiting, approximately $1900. Four hundred deaths per year are attributed diarrhea, and a failed attempt at oral rehydration in the clinic. The to the dehydration caused by gastroenteritis. Over 60% of cases mother states she herself recently got over the “stomach ß u.” of AGE which present to the ED are of viral cause, with the She has had six wet diapers today. On physical examination, she is non-toxic, appearing restless in her mothers arms, crying with tears, and has vital signs within normal limits for her age. Her PATHOPHYSIOLOGY
lips appear dry, but her tongue is moist and her abdomen is soft and non-tender. The working diagnosis is acute gastroenteritis The mechanism of vomiting in gastroenteritis is not completely with mild dehydration and you explain the process of oral understood. One of the proposed mechanisms is thought to rehydration to the mother and give reassurance. The mother is be initiated by serotonin stimulation of 5HT-3 receptors in the hesitant to take her child home because she vomited in the clinic stomach and small intestine as well as the vagus nerve. These and that is why she was sent to the ED. The patient is given 50 receptors send afferent nerve impulses to the chemoreceptor ml of an oral rehydration solution to drink slowly, which she trigger zone (CTZ) and the vomiting center (VC) in the brain keeps down, the nurse brings the patient’s discharge paperwork stem which cause the diaphragm, abdominal muscles, and visceral and the girl vomits again. Should the ED physician continue with plans for discharge? Should the physician order a bolus of intravenous normal saline and/or consider admission? Are DEHYDRATION AND ORAL REHYDRATION THERAPY
there any medications that may aid in oral rehydration that are safe and effective? Children are more susceptible to the effects of ß uid loss and electrolyte abnormalities because of physical size. There is EPIDEMIOLOGY
no widely accepted classiÞ cation system for dehydration in children. Most physicians use clinical judgment based on a Acute gastroenteritis (AGE) in the pediatric population is a series of physical exam Þ ndings to determine the severity of common problem in the emergency department and accounts for dehydration [Table 1]. Oral rehydration therapy (ORT) as at least 1.5 million visits to primary care providers each year in the United States. It accounts for approximately 10% of all hospital determined by the World Health Organization (WHO) has been admissions for children under the age of 5 and approximately shown to be safe and effective for ß uid repletion in infants and children with AGE and mild to moderate volume depletion. Address for correspondence:
ORT can be instituted if the patient continues to vomit or have Dr. Jacob Manteuffel, E-mail: firstname.lastname@example.org diarrhea. There are a number of oral rehydration solutions Journal of Emergencies, Trauma and Shock I 2:1 I Jan - Apr 2009
Manteuffel: Antiemetics in acute gastroenteritis Table 1: Example physical exam findings in dehydration
Normal or mild dehydration
COPYRIGHT 2006 MASSACHUSETTS MEDICAL SOCIETY. ALL RIGHTS RESERVED. (ORS) to choose from, the most common of which is Pedialyte, Prochlorperazine (Compazine) was Þ rst introduced as an anti- (Abbot Nutrition, Columbus OH) which is slightly hypotonic psychotic in the 1950s, and subsequently found to be effective to intravascular ß uid. The protocol for ORT is to establish the to control vomiting. It is a weak dopamine receptor blocker degree of dehydration, and use 50 ml/kg of ORS for mildly and depresses the CTZ. Akathisia and dystonia are the most dehydrated children and 100 ml/kg for moderately dehydrated common reported side effects in adults and children in up to children. Twenty Þ ve percent of the established volume is 44% of patients administered this medication.[2,11-13] administered each hour for a four-hour period. If the patient fails this therapy intravenous ß uids (IVF) are indicated. Metoclopramide (Reglan) is a dopamine receptor antagonist which acts both centrally and peripherally, increases gastric AAP GUIDELINES
motility and decreasing afferent impulses to the CTZ. A review of the pediatric literature reports akathisia and dystonia in up to The American Academy of Pediatrics (AAP) recommends ORT 25% of children receiving this medication. as the treatment of choice in the mild to moderate dehydration and is as effective as IV therapy. They recommend starting an RECENT RESEARCH
age-appropriate diet as soon as the patient is rehydrated. The routine use of anti-diarrhea agents is not recommended because Ondansetron (Zofran) has been proven safe and effective in of potential side effects. There is no mention of antiemetic use chemotherapy induced and post operative vomiting. It is a selective serotonin 5HT-3 receptor blocker and inhibits the initiation of the vomiting reß ex in the periphery. In 1997, Cubeddu was the CLINICAL PRACTICE
Þ rst to demonstrate the antiemetic effects of ondansetron in AGE. Reeves, 2002, also demonstrated the antiemetic properties Review of the literature shows clinicians commonly use and of ondansetron and a decreased hospital admission rate in those prescribe antiemetics for vomiting in children with AGE. A with a serum CO >15 mEq/L. Ramsook, 2002, was the Þ rst retrospective study of 20,000 children with AGE showed 9% of to compare oral ondansetron to placebo again demonstrating its patients had a prescription Þ lled for an antiemetic. In addition, antiemetic effect and also a decreased need for IVF and hospital 5% of patients under the age of 2 had a prescription Þ lled for admission. SigniÞ cantly higher rates of diarrhea were reported an antiemetic, the most common of which was promethazine in this study related to ondansetron as additional doses of this (Phenergan). A survey of Italian pediatricians reported a 79% medication were given at discharge. In 2006, Freedman published use of antiemetics for AGE. A survey of emergency medicine a study in the New England Journal of Medicine (NEJM) (EM), Pediatrics, and Pediatrics/EM boarded physicians demonstrating the antiemetic properties of oral ondansetron with reported a 61% use of antiemetics at least once in the past year. a number needed to treat (NNT) of 5 to prevent vomiting and a Promethazine per rectum was the most common medication NNT of 6 to prevent the need for IVF. This medication was given MEDICATIONS
Roslund, 2008, demonstrated an improved success rate of ORT, a decreased need for IVF, and a decreased hospitalization rate in Promethazine is a H1 receptor antihistamine which inhibits the patients with AGE treated with a single dose of oral ondansetron, VC from peripheral stimulants. The most common side effect of who initially failed ORT in the ED. Rates of diarrhea on follow promethazine is respiratory depression and sedation which caused up were similar to placebo. This study again suggests when the FDA in 2004 to issue a “boxed warning” contraindicating ondansetron is used in a single dose there appear to be no side the medication for children less than 2 years old. Numerous case reports detail other extra pyramidal side effects including torticollis in therapeutic doses of promethazine. Another study showed a higher incidence of promethazine use in SIDS related cases. Prochlorperazine, promethazine, and metoclopramide have a Journal of Emergencies, Trauma and Shock I 2:1 I Jan - Apr 2009
Manteuffel: Antiemetics in acute gastroenteritis REFERENCES
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Albano F, Bruzzese E, Spagnuolo MI, De Marco G. Antiemetics for chil- dren with gastroenteritis: off-label but still on in clinical practice. J Pediatr COPYRIGHT 2006 MASSACHUSETTS MEDICAL SOCIETY. ALL RIGHTS RESERVED. Starke PR, Weaver J, Chowdhury BA. Boxed warning added to prometha-zine labeling for pediatric use. N Engl J Med 2005;352:2653.
DeGrandi T, Simon JE. Promethazine-induced dystonic reaction. Pediatr high incidence of side effects and should be avoided in patients less than 2 years old and used with extreme caution in children 10. Kahn A, Blum D. Phenothiazines and sudden infant death syndrome. older than 2 years.[2,8-13] In limited studies, ondansetron when used as a single dose has shown to be safe in children with acute 11. Ernst AA, Weiss SJ, Park S, Takakuwa KM, Diercks DB. Prochlorperazine gastroenteritis. In addition, ondansetron has recently become versus promethazine for uncomplicated nausea and vomiting in the emer- generic and cost is no longer a barrier to routine use in the ED. gency department: A randomized, double-blind clinical trial. Ann Emerg Oral ondansetron could be a consideration for children with AGE who fail ORT to prevent the need for IVF, or as an adjunct 12. Drotts DL, Vinson DR. Prochlorperazine induces akathisia in emergency to IVF to help facilitate ORT and prevent admission. The dose patients. Ann Emerg Med 1999;34:469-75.
of this medication can be weight based, approximately 0.1 mg/ 13. Olsen JC, Keng JA, Clark JA. Frequency of adverse reactions to prochlor- kg.[4,16] If an ED physician decides to use ondansetron it should perazine in the ED. Am J Emerg Med 2000;18:609-11.
only be given as a single dose in the ED, as further doses have 14. Reeves JJ, Shannon MW, Fleisher GR. Ondansetron decreases vomiting associated with acute gastroenteritis: A randomized, controlled trial. Pe- shown to cause persistent diarrhea. Presently in the literature there are Þ ve studies which examine the safety and effectiveness 15. Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D. of ondansetron in pediatric patients with AGE.[3-4,14-16] Therefore, A randomized clinical trial comparing oral ondansetron with placebo further studies and a subsequent meta-analysis are required to in children with vomiting from acute gastroenteritis. Ann Emerg Med determine whether ondansetron is an effective adjunct therapy 16. Roslund G, Hepps TS, McQuillen KK. The role of oral ondansetron in children with vomiting as a result of acute gastritis/gastroenteritis who RESOLUTION OF CASE
have failed oral rehydration therapy: A randomized controlled trial. Ann Emerg Med 2008;52:22-9e6.
In the case of the 2 year old with vomiting and diarrhea, the girl was given a 2 mg ondansetron oral dissolving tablet and observed How to cite this article: Manteuffel J. Use of antiemetics in children
in the emergency department for 2 h. She was able to tolerate with acute gastroenteritis: Are they safe and effective? J Emerg 10 ml/kg of pedialyte every 10 min without vomiting. At this point, the patient was discharged with her mother to continue Received: 29.07.08. Accepted: 18.09.08.
ORT for 2 h, then to resume regular diet.
Source of Support: Nil. Confl ict of Interest: None declared.
Journal of Emergencies, Trauma and Shock I 2:1 I Jan - Apr 2009
22 september 2006 • Pharmaceutisch Weekblad nr. 38Farmakundigen passen in een maatschapApothekers moeten investeren in ondernemerschap. Volgens minister Hoogervorst kan de farmakundige daarbij ondersteunen. Veertig farmakundigen zijn inmiddels afgestudeerd. Ze werken bij apotheekketens, zorgverzekeraars en in de industrie, maar niet in de apotheek. De gemiddelde apotheek blijkt te klein, maar