A healthy two-year-old, American Society of Anaesthesiologists class 1 child presented for circumcision. He had no allergies, was appropriately fasted and weighed 13.8kg. Inhalational induction of general anaesthesia was performed with sevoflurane and maintained with desflurane. He was intubated with a size 4 cuffed endotracheal tube. Penile block was performed with lignocaine and levobupivicaine. Intraoperatively, he received 15μg fentanyl, 1.5mg dexamethasone, 1.3mg ondansetron and 25mg tramadol intravenously. He was also given paracetamol and diclofenac suppositories. Surgery was successful and the patient was extubated awake. 

 On emergence from anaesthesia, the child presented with generalised rigidity and bradykinesia. On examination, he had upper limb rigidity and masked, Parkinsonian facies. Horizontal nystagmus was evident on eye examination. A broad differential diagnosis was considered. Notably, there were no signs of opioid toxicity, hypoglycaemia or seizure activity. Blood glucose was 8.6mmol/L, respiratory rate was 22/min, there were no focal neurological signs, the patient was responsive, and his pupils were normal in size and reactive. During the episode, the child was easily distractable and redirectable with no post-ictal period. Symptoms persisted and a diagnosis of a drug-induced extrapyramidal reaction was made. This reaction was likely related to ondansetron. Procyclidine 2mg was administered intravenously, with resolution of symptoms over the next 10 minutes. 

Extrapyramidal symptoms (EPS) comprise a set of movement disorders characterised by dystonia, akathisia, bradykinesia and tremor. Most commonly these reactions are caused by dopamine D2 receptor antagonists, classically the typical antipsychotics. Anti-dopaminergic antiemetics, such as metoclopramide, are also potentially offending drugs.¹ The leading theory for the pathophysiology of EPS involves an imbalance of dopaminergic-cholinergic balance in the nigrostriatum. D2 receptor blockade leaves striatal cholinergic output unopposed, leading to disinhibition of the indirect pathway of the basal ganglia, causing unintentional movement.² This theory is supported by observations that anticholinergics (such as procyclidine) can cause resolution of EPS. However, it has become evident in recent years that this model is incomplete, as antidepressants that act via serotonin and noradrenaline reuptake inhibition have also been reported to cause EPS.^3,4

Ondansetron is a highly selective 5-HT3 receptor antagonist that is widely used in children for the treatment and prophylaxis of nausea and vomiting. Extrapyramidal adverse effects from ondansetron are unusual but have been reported, with most cases occurring at high doses and in adults receiving chemotherapeutic agents.^{5,6,7,8,9,10,11,12} Few cases have been reported in the perioperative period,⁵ and only one similar case has been reported in a child under five years of age.⁷ A regulatory role of serotonergic innervation to the basal ganglia on dopaminergic motor inhibition has been demonstrated, which is the potential mechanism by which ondansetron precipitates extrapyramidal symptoms.¹³

The aetiology of peri-operative EPS is difficult to pin down due to polypharmacy. Of note, there exists one case report in the literature of a dystonic reaction to sevoflurane on induction.¹⁴ It has also been suggested that ondansetron may interact with other medications, precipitating EPS.⁶ While there are no reported cases of EPS after tramadol administration, tramadol causes inhibition of serotonin and noradrenaline reuptake,¹⁵ and could theoretically contribute to EPS in a similar way to antidepressants.

We must further elucidate the potential neurological side effects of drugs that are given during anaesthesia. In the case of ondansetron, there is a growing volume of case reports linking it to EPS. This case gives cause to carefully consider the paediatric safety profile of ondansetron, especially when given to children at low risk of postoperative nausea and vomiting. 

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