Therapeutics
Neither ondansetron nor metoclopramide reduced nausea and vomiting in the emergency department
Egerton-Warburton D, Meek R, Mee MJ, Braitberg G. Antiemetic use for nausea and vomiting in adult emergency department patients: randomized controlled trial comparing ondansetron, metoclopramide, and placebo. Ann Emerg Med. 2014 May 9. [Epub ahead of print]
Clinical impact rating: E ★★★★★★✩ Question In adults in the emergency department (ED) with undifferentiated nausea and vomiting, what are the relative efficacies of ondansetron and metoclopramide?
Methods Design: Randomized placebo-controlled trial. Australian Clinical Trials Registry ACTRN 12609000549224. Allocation: {Concealed}*.† Blinding: Blinded† (patients, clinicians, {data collectors, and outcome assessors}*).
0 vs 0 vs 0). The metoclopramide group used less rescue medication than the placebo group (relative risk reduction [RRR] 51%, 95% CI 16 to 71) and the ondansetron group (RRR 48%, CI 12 to 70).
Conclusion In adults presenting to the emergency department with undifferentiated nausea and vomiting, neither ondansetron nor metoclopramide reduced severity of nausea. *Information provided by author. †See Glossary.
Follow-up period: Median 35 minutes.
Source of funding: No external funding.
Setting: 2 EDs in Australia.
For correspondence: Dr. R. Meek, Monash Health, Melbourne, Victoria, Australia. E-mail [email protected]. ■
Patients: 270 adults ≥ 18 years of age (median age 42 y, 66% women) who presented to the ED with nausea or vomiting and had IV antiemetic medication recommended by the attending physician. Exclusion criteria included use of antiemetic medication in the past 8 hours or IV fluids during the ED episode of care, hemodynamic instability or primary diagnosis requiring time-critical treatment, pregnancy or lactation, nausea or vomiting related to motion or vertigo, or current treatment with chemotherapy or radiotherapy. Intervention: IV metoclopramide, 20 mg (n = 88 included in analyses), ondansetron, 4 mg (n = 87 included in analyses), or placebo (n = 83 included in analyses). Outcomes: Change in nausea severity measured on a 100-mm visual analogue scale (VAS). Secondary outcomes included change in nausea severity measured on a numeric scale (ranging from 0 [no nausea] to 10 [worst nausea imaginable]) and by an adjectival scale (“a lot less,”“a little less,”“the same,”“a little more,” and “a lot more”), change in the number of self-reported vomiting episodes, and use of rescue medication. 80 patients per group were needed to detect a VAS score reduction ≥ 30 mm (α = 0.05). Patient follow-up: 96% (modified intention-to-treat analysis of patients with both baseline and follow-up nausea VAS severity measurements).
Main results Ondansetron, metoclopramide, and placebo did not differ for reduction in nausea severity measured by VAS (Table), numeric scale (median reduction 2 vs 2 vs 1), or adjectival descriptions (72% vs 78% vs 64% indicated symptoms improved “a lot” or “a little”); or for reduction in number of vomiting episodes (median reduction Reduction in nausea severity with ondansetron vs metoclopramide vs placebo for undifferentiated nausea and vomiting in the emergency department‡ Mean VAS score§ reduction (mm) (95% CI) at a median 35 min Ondansetron Metoclopramide Placebo 27 (22 to 33)
28 (22 to 34)
23 (16 to 30)
‡VAS = visual analogue scale; CI defined in Glossary. §VAS was a 100-mm scale; greater reduction in score equals greater reduction in nausea.
16 December 2014 | ACP Journal Club | Volume 161 • Number 12
Commentary The trial by Egerton-Warburton and colleagues found no difference between metoclopramide and ondansetron for nausea in the ED and, surprisingly, no difference between either drug and placebo. The study was rigorously compliant with the Consolidated Standards of Reporting Trials guidelines and was powered to detect a clinically significant difference in VAS score reductions. Should this alter our practice in the ED? It would be a great leap to base such a major practice change on the results. First, these antiemetics have a benefit in selected patients with severe nausea from single causes, such as cancer chemotherapy (1), unlike the grab-bag of causes in the ED. Second, it is possible to move the goal posts after a study. Unsavory examples of this would be studies that report favorable subgroups that had not been chosen a priori (2). Another way to hedge your bets is to look beyond the negative primary outcome at secondary endpoints. In this case (Table 3 of the article), neither antiemetic had persuasive evidence of benefit over placebo, except for 1 of the 5 outcomes—use of rescue medication (defined as a single dose of ondansetron, 8 mg, if no response to the unidentified study drug). This secondary outcome was more favorable for metoclopramide (but not ondansetron) over placebo, with an NNT of 6 (CI 4 to 21). Of course, with multiple hypotheses it would be good form to reduce the P value threshold or, equivalently, increase confidence interval coverage. This post hoc emphasis on rescue drugs does have a justification in the critical appraisal armamentarium: Equality of treatment after randomization should be reported. The lower use of rescue drugs with metoclopramide is indirect evidence of benefit, like increased use of steroids in the placebo groups of bronchodilator trials for asthma (3). Stephen R. Pitts, MD, MPH Emory University School of Medicine Atlanta, Georgia, USA References 1. Billio A, Morello E, Clarke MJ. Cochrane Database Syst Rev. 2010;1: CD006272. 2. Sun X, Ioannidis JP, Agoritsas T, Alba AC, Guyatt G. JAMA. 2014; 311:405-11. 3. Griffiths B, Ducharme FM. Cochrane Database Syst Rev. 2013;8: CD000060. © 2014 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/931809/ by a NYU Medical Center Library User on 02/22/2017
JC3
Neither ondansetron nor metoclopramide reduced nausea and vomiting in the emergency department
Egerton-Warburton D, Meek R, Mee MJ, Braitberg G. Antiemetic use for nausea and vomiting in adult emergency department patients: randomized controlled trial comparing ondansetron, metoclopramide, and placebo. Ann Emerg Med. 2014 May 9. [Epub ahead of print]
Clinical impact rating: E ★★★★★★✩ Question In adults in the emergency department (ED) with undifferentiated nausea and vomiting, what are the relative efficacies of ondansetron and metoclopramide?
Methods Design: Randomized placebo-controlled trial. Australian Clinical Trials Registry ACTRN 12609000549224. Allocation: {Concealed}*.† Blinding: Blinded† (patients, clinicians, {data collectors, and outcome assessors}*).
0 vs 0 vs 0). The metoclopramide group used less rescue medication than the placebo group (relative risk reduction [RRR] 51%, 95% CI 16 to 71) and the ondansetron group (RRR 48%, CI 12 to 70).
Conclusion In adults presenting to the emergency department with undifferentiated nausea and vomiting, neither ondansetron nor metoclopramide reduced severity of nausea. *Information provided by author. †See Glossary.
Follow-up period: Median 35 minutes.
Source of funding: No external funding.
Setting: 2 EDs in Australia.
For correspondence: Dr. R. Meek, Monash Health, Melbourne, Victoria, Australia. E-mail [email protected]. ■
Patients: 270 adults ≥ 18 years of age (median age 42 y, 66% women) who presented to the ED with nausea or vomiting and had IV antiemetic medication recommended by the attending physician. Exclusion criteria included use of antiemetic medication in the past 8 hours or IV fluids during the ED episode of care, hemodynamic instability or primary diagnosis requiring time-critical treatment, pregnancy or lactation, nausea or vomiting related to motion or vertigo, or current treatment with chemotherapy or radiotherapy. Intervention: IV metoclopramide, 20 mg (n = 88 included in analyses), ondansetron, 4 mg (n = 87 included in analyses), or placebo (n = 83 included in analyses). Outcomes: Change in nausea severity measured on a 100-mm visual analogue scale (VAS). Secondary outcomes included change in nausea severity measured on a numeric scale (ranging from 0 [no nausea] to 10 [worst nausea imaginable]) and by an adjectival scale (“a lot less,”“a little less,”“the same,”“a little more,” and “a lot more”), change in the number of self-reported vomiting episodes, and use of rescue medication. 80 patients per group were needed to detect a VAS score reduction ≥ 30 mm (α = 0.05). Patient follow-up: 96% (modified intention-to-treat analysis of patients with both baseline and follow-up nausea VAS severity measurements).
Main results Ondansetron, metoclopramide, and placebo did not differ for reduction in nausea severity measured by VAS (Table), numeric scale (median reduction 2 vs 2 vs 1), or adjectival descriptions (72% vs 78% vs 64% indicated symptoms improved “a lot” or “a little”); or for reduction in number of vomiting episodes (median reduction Reduction in nausea severity with ondansetron vs metoclopramide vs placebo for undifferentiated nausea and vomiting in the emergency department‡ Mean VAS score§ reduction (mm) (95% CI) at a median 35 min Ondansetron Metoclopramide Placebo 27 (22 to 33)
28 (22 to 34)
23 (16 to 30)
‡VAS = visual analogue scale; CI defined in Glossary. §VAS was a 100-mm scale; greater reduction in score equals greater reduction in nausea.
16 December 2014 | ACP Journal Club | Volume 161 • Number 12
Commentary The trial by Egerton-Warburton and colleagues found no difference between metoclopramide and ondansetron for nausea in the ED and, surprisingly, no difference between either drug and placebo. The study was rigorously compliant with the Consolidated Standards of Reporting Trials guidelines and was powered to detect a clinically significant difference in VAS score reductions. Should this alter our practice in the ED? It would be a great leap to base such a major practice change on the results. First, these antiemetics have a benefit in selected patients with severe nausea from single causes, such as cancer chemotherapy (1), unlike the grab-bag of causes in the ED. Second, it is possible to move the goal posts after a study. Unsavory examples of this would be studies that report favorable subgroups that had not been chosen a priori (2). Another way to hedge your bets is to look beyond the negative primary outcome at secondary endpoints. In this case (Table 3 of the article), neither antiemetic had persuasive evidence of benefit over placebo, except for 1 of the 5 outcomes—use of rescue medication (defined as a single dose of ondansetron, 8 mg, if no response to the unidentified study drug). This secondary outcome was more favorable for metoclopramide (but not ondansetron) over placebo, with an NNT of 6 (CI 4 to 21). Of course, with multiple hypotheses it would be good form to reduce the P value threshold or, equivalently, increase confidence interval coverage. This post hoc emphasis on rescue drugs does have a justification in the critical appraisal armamentarium: Equality of treatment after randomization should be reported. The lower use of rescue drugs with metoclopramide is indirect evidence of benefit, like increased use of steroids in the placebo groups of bronchodilator trials for asthma (3). Stephen R. Pitts, MD, MPH Emory University School of Medicine Atlanta, Georgia, USA References 1. Billio A, Morello E, Clarke MJ. Cochrane Database Syst Rev. 2010;1: CD006272. 2. Sun X, Ioannidis JP, Agoritsas T, Alba AC, Guyatt G. JAMA. 2014; 311:405-11. 3. Griffiths B, Ducharme FM. Cochrane Database Syst Rev. 2013;8: CD000060. © 2014 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/931809/ by a NYU Medical Center Library User on 02/22/2017
JC3
