Original article. Efficacy of intravenous dexamethasone for the prevention of vomiting associated with intrathecal chemotherapy and ketamine sedation in children: a randomized, double-blinded, crossover, placebocontrolled trial

Abstract

Background: Chemotherapy-induced nausea and vomiting remains a significant problem for children with leukemia. There is limited evidence to support using prophylactic antiemetic prior to the administration of intrathecal chemotherapy.

Objective: Determine whether vomiting and nausea associated with intravenous ketamine and intrathecal chemotherapy may be reduced by the addition of prophylactic dexamethasone in children.

Method:A randomized, double-blinded, crossover, placebo-controlled trial was completed in 33 children receiving intrathecal chemotherapy with methotrexate and ketamine sedation at Pharmongkutklao Hospital. Patients were randomly assigned in a double-blinded fashion to receive one of two interventions during the first period, either an infusion of normal saline or intravenous dexamethasone at 0.25 mg/kg/dose. Each patient acted as his or her own control, and each patient was studied at two time-points.

Results: Period effect, sequence effect, and carry over effect were not demonstrated. The absolute risk reduction of vomiting was significantly greater after infusion of dexamethasone than after placebo at 33.3 % (p=0.02). The number needed to treat was three to prevent one episode of vomiting. Fifteen patients in the treatment group reported nausea versus 26 patients in the placebo group (p= 0.007). In the group of patients treated with dexamethasone, five required antiemetic vs. 16 of those receiving placebo (p=0.02). There was no complication from dexamethasone.

Conclusion: Intravenous dexamethasone reduced vomiting associated with intrathecal chemotherapy and ketamine sedation, without significant side-effects. It may be recommended a reasonable option before intrathecal chemotherapy

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Onciu M. Acute lymphoblastic leukemia. Hematol Oncol Clin North Am. 2009; 23:655-74.

  • 2. Pui CH, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation N Engl J Med. 2009; 360:2730-41.

  • 3. Holdsworth MT, Raisch DW, Winter SS, Chavez CM. Assessment of the emetogenic potential of intrathecal chemotherapy and response to prophylactic treatment with ondansetron. Support Care Cancer. 1998; 6:132-8.

  • 4. Langston WT, Wathen JE, Roback M, Bajaj L. Effect of ondansetron on the incidence of vomiting associated with ketamine sedation in children: a double-blind, randomized, placebo-controlled trial. Ann Emerg Med. 2008; 52:30-4.

  • 5. Jordan K, Kasper C, Schmoll HJ. Chemotherapyinduced nausea and vomiting: Current and new standards in the antiemetic prophylaxis and treatment. Eur J Cancer. 2005; 41:199-205.

  • 6. Holdsworth MT, Raisch DW, Duncan MH, Chavez CM, Leasure MM. Assessment of chemotherapy-induced emesis and evaluation of a reduced-dose intravenous ondansetron regimen in pediatric outpatients with leukemia. Ann Pharmacother. 1995; 29:16-21.

  • 7. Jones B, Kenward MG. Design and Analysis of Cross- Over Trials. 1st ed. Chapman & Hall/CRC. 1989; p. 340.

  • 8. Senn SS. Cross-over Trials in Clinical Research. 2nd ed. Chichester:John Wiley & Sons. 2002; p. 345.

  • 9. Jayabose S, Levendoglu-Tugal O, Giamelli J, Grodin W, Cohn M, Sandoval C, et al. Intravenous anesthesia with propofol for painful procedures in children with cancer. J Pediatr Hematol Oncol. 2001; 23:290-3.

  • 10. Larsson S, Argeirsson B, Magnusson J. Propofolfentanyl anesthesia compared to thiopental-halothane with special reference to recovery and vomiting after pediatric strabismus surgery. Acta Anaesthsiol Scand. 1992; 36:182-6.

  • 11. Martin TM, Nicholson SC, Bargas MS. Propofol anesthesia reduces emesis and airway obstruction in pediatric outpatients. Anesth Analg. 1993; 76:144-8.

  • 12. Nagel K, Willan AR, Lappan J, Korz L, Buckley N, Barr RD. Pediatric oncology sedation trial (POST): A double-blind randomized study. Pediatr Blood Cancer. 2008; 51:634-8.

  • 13. Parker RI, Prakash D, Mahan RA, Giugliano DM, Atlas MP. Randomized, double-blind, crossover, placebo-controlled trial of intravenous ondansetron for the prevention of intrathecal chemotherapy-induced vomiting in children. J Pediatr Hematol Oncol. 2001; 23: 578-81.

  • 14. Pitetti RD, Singh S, Peirce MC. Safe and efficacious use of procedural sedation and analgesia by non anesthesiologists in a pediatric emergency department. Arch Pediatr Adolesc Med. 2003; 157:1090-6.

  • 15. Aapro MS, Alberts DS. Dexamethasone as an antiemetic in patients treated with cisplatin. N Engl J Med. 1981; 305:520.

  • 16. Markman M, Sheidler V, Ettinger DS, Quaskey SA, Mellits ED. Antiemetic efficacy of dexamethasone. Randomized, double-blind, crossover study with prochlorperazine in patients receiving cancer chemotherapy. N Engl J Med. 1984; 311:549-52.

  • 17. Holte K, Kehlet H. Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications. J Am Coll Surg. 2000; 195: 694-712.

  • 18. Olver I, Clark-Snow RA, Ballatori E, Espersen BT, Bria E, Jordan K. Guidelines for the control of nausea and vomiting with chemotherapy of low or minimal emetic potential. Support Care Cancer. 2011; 19:33-6.

  • 19. Bisgaard T, Klarskov B, Kehlet H, Rosenberg J. Preoperative dexamethasone improves surgical outcome after laparoscopic cholecystectomy: a randomized double-blind placebo-controlled trial. Ann Surg. 2003; 238:651-60.

  • 20. Apfel CC, Korttila K, Abdalla M, Kerger H, Turan A, Vedder I, et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med. 2004; 350:2441-51.

  • 21. Subramaniam B, Madan R, Sadhasivam S, Sennaraj B, Tamilselvan P, Rajeshwari S, et al. Dexamethasone is a cost-efective alternative to ondansetron in preventing PONV after paediatric strabismus repair. Br J Anaesth. 2001; 86:84-9.

  • 22. Hesketh PJ, Kris MG, Grunberg SM, Beck T, Hainsworth JD, Harker G, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol. 1997; 15:103-9.

  • 23. Tanihata S, Oda S, Nakai S, Uchiyama T. Antiemetic effect of dexamethasone on cisplatin-induced early and delayed emesis in the pigeon. Eur J Pharmacol. 2004; 484:311-21.

  • 24. Green SM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation in children. Ann Emerg Med. 2004; 44:460-71.

  • 25. Janinis J, Giannakakis T, Athanasiades A, Fountzilas G, Bafaloukos D, Kosmidis P, et al. A randomized open-label parallelgroup study comparing ondansetron with ondansetron plus dexamethasone in patients with metastatic breast cancer receiving high-dose epirubicin. A Hellenic Cooperative Oncology Group study. Tumori. 2000; 86:37-41.

  • 26. Lopez-Olaondo L, Carrascosa F, Pueyo FJ, Monedero P, Busto N, Saez A. Combination of ondansetron and dexamethasone in the prophylaxis of postoperative nausea and vomiting. Br J Anaesth. 1996; 76: 835-40.

  • 27. Henzi I, Walder B, Tramer MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg. 2000; 90:186-94.

  • 28. Madan R, Bhatia A, Chakithandy S, Subramaniam R, Rammohan G, Deshpande S, et al. Prophylactic dexamethasone for postoperative nausea and vomiting in pediatric strabismus surgery: a dose ranging and safety evaluation study. Anesth Analg. 2005; 100:1622-6.

  • 29. Liechti M, Feurer R, Gross D, Schmitz A, Stutz K, Gerber A, et al. Prevention of postoperative nausea and vomiting in children following adenotonsillectomy, using tropisetron with or without low-dose dexamethasone. J Anesth. 2007; 21:311-6.

  • 30. Mathew PJ, Madan R, Subramaniam R, Bhatia A, Mala CG, Soodan A, et al. Efficacy of low-dose dexamethasone for preventing postoperative nausea and vomiting following strabismus repair in children. Anaesth Intensive Care. 2004; 32:372-6.

  • 31. Ng WL, Della-Fiorentina SA. The efficacy of oral ondansetron and dexamethasone for the prevention of acute chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapya retrospective audit. Eur J Cancer Care (Engl). 2010; 19:403-7.

OPEN ACCESS

Journal + Issues

Search