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Posts tagged Evidence based medicine.

Metoclopramide: it actually works!?

Metoclopramide had long been written off by many anesthetists and anesthesiologists, aware of trials and meta-analyses that show no or limited effect in treating or preventing nausea and vomiting – in particular limited ability to prevent post-operative nausea and vomiting (PONV). Most recently Henzi, Walder and Tramèr (1999) were able to show only very limited benefit for metoclopramide 10 mg in preventing vomiting and no significant effect in preventing nausea in adults.1,2,3

What is metoclopramide?

Metoclopromaide is a benzamide, predominately used for antiemesis and its gastric prokinetic effect. It is marketed under the names Maxalon®, Pramin® and Reglan® in various countries. Although considered an old drug its antiemetic action was first identified in 1964 by French doctors Justin-Besançon and Laville.3 (In contrast the analgesic tramadol is often considered a "modern" drug outside of Europe, but was launched by Grünenthal GmbH in 1977.)

Metoclopramide readily crosses the blood-brain barrier where it mediates anti-emetic effects primarily as a dopamine D2 antagonist in the chemoreceptor trigger zone (CTZ – located in the area postrema of the 4th ventricle). Metoclopramide also has mixed 5-HT3 receptor antagonist and 5-HT4 receptor agonist actions. The former may contribute to anti-emesis at higher doses and the later to its pro-kinetic effects. Muscarinic cholinergic actions have also been identified, both through increasing acetylcholine release and by increasing receptor sensitivity to acetylcholine in the upper GI tract – further contributing to the pro-kinetic effect.

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  1. Henzi I, Walder B, Tramèr MR. Metoclopramide in the prevention of postoperative nausea and vomiting: a quantitative systematic review of randomized, placebo-controlled studies. Br J Anaesth. 1999 Nov;83(5):761-71. 

  2. It's also interesting to note that there was no dose responsive effect regardless of route. NNT to prevent early (<6h) and late (<48h) vomiting were 9.1 (95% CI 5.5-27) and 10 (6-41) respectively. In children the best documented regimen was 0.25 mg/kg. NNT to prevent early vomiting was 5.8 (3.9-11); there was no effect on late vomiting. There was only a single documented case of extrapyramidal side effects out of 3260 patients, giving an incidence of 0.03%. 

  3. Justin-Besançon L, Laville C.C R Seances Soc Biol Fil. 1964;158:723-7. 

Critically appraising the evidence

It’s hard to keep up with the latest evidence. Not only is the sheer volume of newly published papers overwhelming and the variety of topics broad and wide, but then after finding a paper that piques your interest you are still faced with the tricky task of critically assessing the paper's quality and relevance. Metajournal aims to solve many of these problems, but sometimes you need to just sit down and drag that paper over the keel yourself.

One of the most useful tools I have found are checklists provided by the Critical Appraisal Skills Programme, a UK non-profit based in Oxford. CASP runs workshops that educate healthcare workers and others on how to appraised medical evidence — and they share online the great checklists they use during the workshop under a Creative Commons license.

Find → Appraise → Act

They provide a set of eight critical appraisal tools designed to be used when reading research, covering:

  1. Systematic Reviews
  2. Randomised Controlled Trials
  3. Cohort Studies
  4. Case Control Studies
  5. Economic Evaluations
  6. Diagnostic Studies
  7. Qualitative studies
  8. Clinical Prediction Rule

How to read a journal article

One of the great classic introductions to critical assessment of medical research is Trisha Greenhalgh’s series in the British Medical Journal ‘How to read a paper’. Although the practical aspects of critiquing a paper are better served by newer tools like CASP, Greenhalgh’s work has stood the test of time and is still worth recommending.

The best place to start is with ‘Getting your bearings — deciding what the paper is about’, and then have a look at ‘Assessing the methodological quality’, and ‘Statistics for the non-statistician I’ & ‘II’.

"It usually comes as a surprise ... to learn that some (perhaps most) published articles belong in the bin, and should certainly not be used to inform practice." — Trisha Greenhalgh.

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