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Three Part Question

In [undifferentiated adult patients presenting to the Emergency Department with nausea and/or vomiting], are [intravenous fluids] effective as an [antiemetic]?

Clinical Scenario

You see a middle age lady in the Emergency Department who has presented with nausea and vomiting. She continued vomiting despite ondansetron. One of the anaesthetists suggests that you try just intravenous fluids before giving further anti-emetics. You wonder if there is any evidence for this?

Search Strategy

A literature search of EMBASE (1980—week 2 February 2015), MEDLINE (1950—week 2 February 2015) and CINAHL (1981—week 2 February 2015) was conducted via NHS Evidence. The Cochrane database and Google Scholar were also searched.

Medline
[“emergency department*”.ti,ab OR ED.ti,ab OR "A and E".ti,ab OR exp EMERGENCY SERVICE, HOSPITAL/ OR undifferentiated.ti,ab] AND [nausea.ti,ab OR vomit*.ti,ab OR emesis.ti,ab OR exp VOMITING/] AND ["anti-emetic*".ti,ab OR antiemetic*.ti,ab OR exp ANTIEMETICS/] AND [saline.ti,ab OR hartman*.ti,ab OR intravenous fluid*".ti,ab OR exp PLACEBOS/ OR placebo*.ti,ab]

EMBASE

[“emergency department*”.ti,ab OR ED.ti,ab OR "A and E".ti,ab OR exp EMERGENCY HEALTH SERVICE/ OR undifferentiated.ti,ab] AND [nausea.ti,ab OR vomit*.ti,ab OR emesis.ti,ab OR exp VOMITING/] AND ["anti-emetic*".ti,ab OR antiemetic*.ti,ab OR exp ANTIEMETIC AGENT/] AND [saline.ti,ab OR hartman*.ti,ab OR "intravenous fluid*".ti,ab OR exp PLACEBOS/ OR placebo*.ti,ab]

All searches were limited to English language and adults.

Search Outcome

MEDLINE; 84 papers, EMBASE; 65 papers, Cochrane database; 0 papers, Google Scholar; 1 papers.

After removal of duplicates and exclusion of papers not relevant to the three part question after review of abstract, three relevant papers were identified for review. Three articles were reviewed for this BET.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Egerton-Warburton, D., Meek, R., Mee, MJ. et al. November 2014 Australia	270 adult patients (aged 18 or older) who, during their ED episode, suffered nausea OR vomiting for which the attending physician advised intravenous anti-emetics. Excluded: haemodynamic instability, patients requiring time critical intervention, pregnant or breast-feeding women, patients with Parkinson's disease, restless leg syndrome, anti-emetics in the previous 8 hours, prior IV fluids during the ED episode, motion related symptoms, vertigo, chemotherapy or radiotherapy patients, known allergy to metoclopramide or ondansetron, those unable to consent.	Multi-centre randomised controlled trial	Mean change in severity rating on VAS scale at 30minutes after drug administration	No statistically significant difference between ondansetron, metoclopramide and placebo (0.9% saline) groups	While all patients received IV fluids at 250ml/hour, and the placebo group received a further 4ml 0.9% saline, this study compares anti-emetics to a placebo rather than establishing the usefulness of intravenous fluid therapy in patients with nausea and vomiting. Owing to its rather pragmatic design, convenience sampling was used, resulting in a risk of sampling bias. The study was powered to detect a 30mm reduction in VAS score, despite a minimum clinically significant difference being defined as a reduction of 20mm. This risks type 2 error. The study compared 20mg metoclopramide with 4mg ondansetron and 0.9% saline. The dose of metoclopramide used potentially affects generalisation of results to UK EDs. The study has extensive exclusion criteria which resulted in the inclusion of only patients with opioid induced nausea and gastroenteritis. This potentially limits generalisation of the findings to the "undifferentiated" Emergency Department patient. Rescue anti-emetics were given after discussion between physician and patient, rather than according to a protocol or pre-defined symptom severity, making this apparently objective measurement quite subjective.
			Number requiring	Statistically significant difference between metoclopramide (17.9%) and ondansetron (34.5%) and placebo (36.3%)
Barrett TW, DiPersio DM, Jenkins CA et al. March 2011 USA	Convenience sample of 212 patients, all adults (age 18years or over) presenting with nausea and/or vomiting requiring intravenous antiemetics according to the treating physician. Excluded: haemodynamically unstable patients, allergy to any of the study medications, antiemetic given in last 24hrs, unable to complete assessment tool, patients with a baseline nausea rating less than 40mm on VAS.	Prospective, double-blind, randomised controlled trial	Reduction in VAS score at 30minutes post-antiemetic administration	No statistically significant difference between the groups	Although all patients received 500ml 0.9% saline during the 30minutes, this study does not specifically answer the three part question, addressing the issue of antiemetic compared to placebo rather than 0.9% saline as a treatment for undifferentiated nausea and vomiting. A convenience sample puts the study at risk of sampling bias. The sample size achieved failed to meet the sample size requirement calculated a priori risking type 2 error. There is a risk of co-intervention bias as other treatments e.g. opiates that were administered to patients were not recorded.
			Patients requesting additional antiemetics	22% in metoclopramide group compared to 40% in ondansetron, promethazine and placebo groups
Braude D, Soliz T, Crandall C et al. 2006 USA	100 adult patients (age 18-65) attending an urban teaching hospital ED with a primary or secondary complaint of nausea and/or vomiting and a baseline nausea VAS rating of at least 40mm. Excluded: mild symptoms, hypotension, more that 1litre IV fluid administration prior to enrollment, use of other antiemetic within the last 24hrs, cardiac failure, pregnancy, allergy to study medications.	A double-blind, randomised controlled trial comparing droperido, metoclopramide, and prochlorperazine with placebo (0.9% NaCl).	Improvement in nausea at 30minutes	Droperidol significantly better than metoclopramide, prochlorperazine or placebo (P = 0.04)	Patients were given IV fluids throughout the study period by "opening up the line to full" giving a mean dose of 739 +/- 445ml. There is therefore a significant difference in the amount of fluid received. This could have been improved by administering fluids at a pre-specified rate via a pump. The study was powered to detect a change in VAS nausea score of 20mm. Studies conducted more recently have used a score of 12mm as clinically significant, therefore this study risked type 2 error. The study failed to recruit the 104 participants calculated to be required a prior by the sample size calculation, again risking type 2 error. Droperidol, used in the study, has since been take off licence. Convenience sample risking bias and confounding.
			Need for rescue anti-emetic at 30minutes post treatment	No significant difference between the groups (P = 0.23)

Comment(s)

No randomised controlled trial has yet been conducted to compare specifically the use of intravenous fluid therapy with antiemetic treatment. The three studies detailed, however, all show no significant difference in the nausea scores of patients receiving currently used antiemetics compared to placebo. Of note, all of the studies gave background intravenous fluids during the study period, although at varying rates. As all patients in all groups, including the placebo group, improved, it may be that this was attributable to intravenous fluid therapy. It is therefore possible that intravenous fluid therapy may have a role in controlling the symptoms of nausea and vomiting in the Emergency Department.

Editor Comment

KMJ

Clinical Bottom Line

Further work is required to compare the use of intravenous fluid in significant volumes with anti-emetics, before any firm conclusions can be drawn. It seems, however, that intravenous fluid therapy may be of some use in controlling the symptoms of nausea and vomiting.

References

1. Egerton-Warburton, D., Meek, R., Mee, MJ. et al. Antiemetic use for nausea and vomiting in adult emergency department patients: randomized controlled trial comparing ondansetron, metoclopramide, and placebo Ann Emerg Med 2014; 64(5): 526-32
2. Barrett TW, DiPersio DM, Jenkins CA et al. A randomized, placebo-controlled trial of ondansetron, metoclopramide, and promethazine in adults Am J Emerg Med 2011; 29(3): 247-55
3. Braude D, Soliz T, Crandall C et al. Antieetics in the ED: a randomized controlled trial comparing 3 common agents Am J Emerg Med 2006; 24:177-182