Critical Reading: Treatment of Vomiting

APPROACH TO THE PROBLEM

Although oral rehydration therapy is recommended for children with mild to moderate dehydration, it remains underused. Doctors in the emergency department are more likely to choose the intravenous route during oral rehydration when vomiting is a major symptom. In one survey, 36% of paediatricians reported that vomiting was a contraindication to oral rehydration. Therefore, a safe and effective method of controlling vomiting is likely to increase the utilisation rate and success of oral rehydration. This speeds up the approach in the emergency department and reduces the pressure in these units by discharging the child more quickly and safely.

One of the most popular medications due to its powerful antiemetic effect is ondansetron. However, several studies questioned its prescription in paediatric patients, due to its potential to generate heart arrhythmias and cause diarrhoea, among others, which becomes a relative contraindication in cases where diarrhoea is the predominant symptom, coupled with vomiting. This situation is very common in the approach to acute gastroenteritis in both paediatric and adult emergency departments.

In view of the foregoing, is ondansetron the reference drug to address acute gastroenteritis in paediatric emergencies? (Freedman, Adler, Seshadri, & Powell, 2006). Table 1:

LET’S ANSWER THE QUESTION

Based on that question, we searched for evidence in reference sources and found the article by Freedman (Freedman et al., 2006)(Freedman et al., 2006), published in a very high-impact journal. This author has continued to publish studies in this line of research and has been included in several systematic reviews, including the systematic review of the AAP.

A quick reading of the article focusing on the abstract suggests some very promising conclusions that seem to suit our question: “In children with gastroenteritis and dehydration, a single dose of oral ondansetron reduces vomiting and facilitates oral rehydration and may thus be well suited for use in the emergency department.” However, the methods section states: “We enrolled 215 children 6 months through 10 years of age who were treated in a pediatric emergency department for gastroenteritis and dehydration. After being randomly assigned to treatment with orally disintegrating ondansetron tablets or placebo…”. Additionally, the results section indicates: “As compared with children who received placebo, children who received ondansetron were less likely to vomit (14 percent vs. 35 percent; relative risk, 0.40; 95 percent confidence interval, 0.26 to 0.61), vomited less often (mean number of episodes per child, 0.18 vs. 0.65; P <0.001), had greater oral intake (239 ml vs. 196 ml, P=0.001), and were less likely to be treated by intravenous rehydration (14 percent vs. 31 percent; relative risk, 0.46; 95 percent confidence interval, 0.26 to 0.79).”

There is therefore a clear difference in favour of this medication compared to placebo. Is this the answer we are looking for?

UNPRETENTIOUS CRITICAL READING

The “overall quality” of a clinical research study is a complex concept that includes three elements:

One of the key aspects that has been pointed out as “uncertain” in the reading is COMPARISON. This is very much the practical and ethical domain of the RCT. From the practising clinician’s point of view, it only makes sense to compare new interventions with interventions with already proven effects, or at least with the usual treatments. This reproduces the real possible decision-making dilemma, i.e. new treatment versus usual treatment. Not using proven treatments in these comparisons would therefore be maleficent.

Comparative interventions reflect the point of friction between two different dialectic styles, i.e. that of clinical practice and that of clinical research. Comparative interventions are therefore a vital issue that determines the study design in a number of ways.

Firstly, comparative interventions require an explicit knowledge of the state of the art of the treatments available for the health condition or clinical setting in question (preferably by means of a systematic review). Secondly, the existence of effective treatments limits the use of placebo as a research technique and makes it necessary to include effective treatments in comparisons.

And here is the question: Are there other well-known and frequently used antiemetic treatments for the proposed scenario?

Comparisons with placebo inevitably lead to a selection bias regarding the asymmetric comparison between an effective drug and a passive element (or an element from which no outcomes are expected). In addition, this type of comparison may lead to an overestimation of the drug’s results in terms of the proposed objective, which is to be prescribed as an element that reduces the presence of an event (in this case, vomiting) in the chosen population and setting.

As a result, the correction of the model clashes with the relevance of the chosen comparison model.

The most widespread review tool for clinical trials (CONSORT) does not point to evident shortcomings in the article. See Image 1. Sample checklist of information to include when reporting a randomised clinical trial.

A FINAL THOUGHT

The Declaration of Helsinski specifies when placebo can be used in clinical research: “The benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic, and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists.”

Ondansetron may be a first-line drug in the clinical setting in question (Higgins & Green, 2011), but it is no less true that the comparison method chosen is quite unfortunate.

Choosing these comparison models is not uncommon, even in prestigious and international studies. There is an example where a bizarre title shows how this practice is prevalent in scientific studies. Using a correct methodology is not enough to ensure quality (Tomasik et al., 2016)

See Image 2 Critical reading Table 2. Critical reading Translation.

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It is also worth noting that, at the end of the selected article, in the section on conflicts of interest and acknowledgements, it is indicated that the study had been supported, among other institutions, by GlaxoSmithKline, the company that developed the molecule under the commercial name of Zofran®.

Thus, the use of ondansetron for these clinical features in question would require a review comparing the efficacy of ondansetron with other drugs, as there are numerous alternatives that have yielded positive results and are safe and widely used (Meredith, Murray, & McMurray, 2004)

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