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Metoclopramide versus Ondansetron
- John Moyle (20 November 2007)
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New drug to Old: Aren't we going backwards?
- Tarun Bhalla, S.Suresh, MD, Children's Memorial Hospital, Chicago, IL, USA (26 October 2007)
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John Moyle
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To prove that this Senior Fellow still reads the BJA I would like to comment upon Bolton et al Randomized, double-blind study comparing the efficacy of moderate dose metoclopramide and ondansetron . Yet another paper comparing a gastrokinetic and a 5HT3 –blocker. There are three criticisms that I would put forward: 1. There is no description of the vomit. Ingested blood is an irritant in the stomach and nothing will stop emesis recurring until it has been evacuated at which time the vomiting will cease without anti-emetics. 2. Gastrokinesis by metoclopromide is obtunded by concurrent administration of an anti-cholinergic (in this case atropine) or any other drug with anti-cholinergic side-effects. 3. There is no anti-emesis provided at the vomiting centre Sadly there is still a >20% incidence of post-operative nausea and vomiting which in the main may be due to the way which anaesthetists choose anti-emetics. I spent 25 years as an anaesthetist, the last 18 or so with palliative medicine as a sub-specialty. Anaesthetists and palliative care physicians approach the treatment and prophylaxis of emesis in different ways. Most anaesthetists use one anti-emetic based on randomized trials and statistics. The palliative care physician’s approach is to assess the likely cause of any nausea and vomiting in each individual, consider the physiology and likely neurotransmitters involved and then choose one or a combination of anti-emetic drugs to block those neurotransmitters. This method requires knowledge of pathophysiology and pharmacology of N/V and has a success rate of >90%. The aetiology of N/V following tonsillectomy may be classified: Surgical: • Pharyngeal irritation via the glossopharyngeal nerve to the vomiting centre (emesis pattern generator) • Ingested blood as an irritant in the stomach probably by vagal afferent nerves to the vomiting centre • Pain acting centrally on the vomiting centre Anaesthetic: • Gaseous distension of stomach via vagal afferents • Drugs acting upon the chemoreceptor trigger zone (CTZ) Recovery phase: • Motion in the form of multiple ‘turns’ using a ‘PatSlide’ • Drugs acting on the CTZ Neither ondansetron nor metoclopramide have anti-emetic effects at the vomiting centre. The most appropriate anti-emetics at the vomiting centre are either anti-histamines or anticholinergics both of which must be able to cross the blood brain barrier. Common choices are cyclizine or hyoscine hydrobromide. The main receptors involved in the CTZ are dopamine D2 and to a lesser extent 5HT3. The most appropriate anti-emetic is a dopamine-blocker although a 5HT3–blocker could be an expensive alternative. 5HT3- blockers are of maximum benefit when 5HT3 in excess is the cause of emesis for example with chemotherapy. As there is no definitive dopaminergic- blocker use has to be made of the anti-dopaminergic side effect of phenothiazines or butyrophenones. The best choice would be a very low dose of haloperidol which provides very good anti-emesis against many drugs including opioids for 24 hours. Droperidol which is no longer available in the UK was as good but its anti-emesis only lasted for about 4 hours. Metoclopramide is a dopamine receptor antagonist with complex pharmacoclogy. Although at higher doses there is a marked anti- dopaminergic effect at the CTZ, the most useful anti-emetic effect is by gastrokinesis, thus emptying the stomach in the correct direction. The mechanism of this gastrokinesis is by blocking dopamine pre-synaptic inhibition of the terminal parasympathetic neurones controlling the smooth muscle of the gastrointestinal tract thus increasing the acetylcholine released. The effect of this is of course reversed by simultaneous administration of anti-cholinergics and drugs with anticholinergic side effects. My choice as the best anti-emetic combination for ENT surgery would be hyoscine hydrobromide (available as a tablet called Kwik-Kwells for a child) and a surgeon who does not fill the stomach with blood! In an adult the addition of haloperidol 3mg orally preoperatively would also cover the CTZ John Moyle Milton Keynes john@moyle.demon.co.uk Conflict of Interest:None declared |
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Tarun Bhalla, Resident, Anesthesiology Northwestern University, Chicago, IL, USA, S.Suresh, MD, Children's Memorial Hospital, Chicago, IL, USA
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I commend the authors for their comparison of ondansetron to metaclopramide in children undergoing tonsillectomy. All children received dexamethasone which could have altered their results. I would have rather preferred the comparison of metaclopramide with ondansetron with the elimination of a muscle relaxant which requires the use of reversal agents that are potent emetics. Ondansetron is so widely used in pediatric practice that old drugs like metaclopramide have been side- lined. As the use of these newer drugs increase, we are only going to see a shift in the cost basis for the drug. The surrogate importance of 'vomiting' is offset by the cost savings in hospitalization as well as early discharge. Conflict of Interest:None declared |
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