Hrev_master Abstract Ondansetron, a 5-HT3 serotonin receptor antagonist, is widely used to manage nausea and vomiting, particularly in postoperative recovery, chemotherapy, and paediatric gastroenteritis. Although it is well-tolerated, recent reports have raised concerns regarding dystonic reactions associated with its use, particularly in children. A 9-year-old boy (24 kg) developed acute dystonia after receiving a 2mg intravenous dose of ondansetron followed by a 4mg oral dose for symptomatic relief of acute gastroenteritis. Several hours post-administration, he exhibited abnormal muscle movement. Clinical examination showed dystonia and a positive Babinski’s sign. The patient was diagnosed with ondansetron-induced acute dystonia and was successfully treated with oral trihexyphenidyl and clonazepam. Emerging evidence indicates that ondansetron may disrupt dopaminergic-cholinergic balance in the basal ganglia, potentially triggering dystonic reactions. The Naranjo scale classi- fied this reaction as “probable”, further supporting ondansetron as the causative agent. Although rare, dystonic reactions can occur with ondansetron, especially in paediatric populations. Clinicians should remain vigilant when prescribing ondansetron, especially in children. Introduction Ondansetron is a selective 5-HT3 serotonin receptor antago- nist, and is widely used for its antiemetic properties in clinical set- tings. It is primarily prescribed for the management of nausea and vomiting associated with Postoperative Nausea and Vomiting (PONV) and chemotherapy, as approved by FDA.1 Ondansetron exerts its therapeutic effect by blocking the 5-HT3 receptors, lever- aging its structural similarity to serotonin, to provide effective symptom relief. Its application has expanded to include poediatric patients, especially in the treatment of acute gastroenteritis. Ondansetron has few adverse effects and is generally well tolerat- ed.2 Generally well-tolerated, ondansetron is associated with mini- mal side effects.2 Compared to dopamine antagonist antiemetics, it has a lower risk of extrapyramidal side effects due to its weak affinity for dopamine receptors. This reduces the likelihood of dis- rupting the dopaminergic-cholinergic balance that regulates pos- ture and involuntary motor functions via acetylcholine, dopamine, and Gamma-Aminobutyric Acid (GABA) within the extrapyrami- dal tracts. Consequently, symptoms such as rigidity, tremors, and bradykinesia—commonly seen with potent dopamine antago- nists—are less frequent. However, caution remains necessary, par- ticularly for patients with pre-existing neurological conditions.3,4 Recent research has focused on dystonic reactions associated with ondansetron use, especially as it remains the first-line antiemetic for acute gastroenteritis in paediatric patients. Reported adverse effects range from isolated upper extremity chorea to severe whole-body jerking movements.5 Case Report A 9-year-old boy weighing 24 kg presented to the emergency department with the onset of dystonia. He had a prior diagnosis of acute gastroenteritis and had initially reported two episodes of non-bilious, non-projectile vomiting, giddiness and abdominal pain localized to the umbilical region starting the day before admission. He was taken to a local health centre where he received the following medications: Inj. Ondansetron 2 mg (0.08 mg/kg), Emergency Care Journal 2025; volume 21:13771 [Emergency Care Journal 2025; 21:13771] [page 41] Severe acute dystonia induced by ondansetron in a paediatric patient: a case report Kishore Nagaraju,1 Roshni Balachandran,1 Srilakshmi Ravindra Bhat,1 Venkatesh Karkada Srinivas,2 Srinivasan Ranganathan1 1Department of Pharmacy Practice, PESU Institute of Pharmacy - Pes University, Bengaluru; 2Department of Paediatrics, PESUIMSR, Bengaluru, India Correspondence: Kishore Nagaraju, Department of Pharmacy Practice, PESU Institute of Pharmacy, PES University, Bengaluru 560100, India. E-mail: nkishore2468@gmail.com Key words: Ondansetron, dystonia, acute gastroenteritis, extrapyra- midal symptoms, 5-hydroxytryptamine (5-HT3) receptor antagonist. Ethics approval and consent to participate: no ethical committee approval was required for this case report by the Department, because this article does not contain any studies with human partic- ipants or animals. Informed consent was obtained from the patient included in this study. Patient consent for publication: the patient’s guardians gave their written consent to use the patient’s personal data for the publication of this case report and any accompanying images. Availability of data and materials: all data underlying the findings are fully available. Received: 25 February 2025. Accepted: 22 May 2025. Early view: 4 July 2025. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright: the Author(s), 2025 Licensee PAGEPress, Italy Emergency Care Journal 2025; 21:13771 doi:10.4081/ecj.2025.13771 Publisher's note: all claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Inj. pantoprazole 40 mg, tablet dicyclomine 20 mg and acetaminophen 500 mg and Intravenous Fluid (IVF) 0.9% Dextrose Normal Saline (DNS). Within a few hours, the patient experienced abnormal body movements, prompting his referral to our institution. The patient had no past history of adverse reactions and was not taking any herbal or indigenous drugs. He developed deviation of the mouth towards the left side, rigidity of lower limbs, abnormal neck posture, and brisk reflexes. These symptoms were episodic. Initially, he was alert, conscious, and oriented to time, place, and person. Upon evaluation, his temperature, blood pressure, blood glucose, respiration, and pulse rate were within normal ranges, with no indications of dehydration. There were no focal neurological deficits as per the CT scan performed. However, Babinski’s sign was positive (Figure 1) and hypertonia was observed. Serum electrolytes, urine routine analysis, renal function test, complete blood count, and liver function tests were all within nor- mal limits. At one week of follow-up, the patient remained healthy with no recurrence of dystonic episodes. Based on the Naranjo scale, ondansetron was classified as the probable cause of the acute dystonia. On admission, the patient received an immediate dose of oral trihexyphenidyl 5 mg, oral clonazepam 0.25mg, which allevi- ated the lower limb stiffness and mouth deviation (Figure 2). The patient was closely monitored for symptoms and potential drug- related adverse effects were assessed. Medication adjustments or additional therapies were considered based on the patient’s clinical response. The patient demonstrated significant symptomatic improvement following 72 hours of treatment, therefore all the medications were withdrawn and oral trihexyphenidyl was gradu- ally tapered.The patient has been discharged after exhibiting notable progress.A follow-up appointment was scheduled one week later, during which investigations revealed no abnormalities and no recurrence of dystonic episodes. Discussion Ondansetron, a selective 5-HT3 receptor antagonist, prevents nausea and vomiting by blocking serotonergic transmission. It acts at the nucleus tractus solitarius and the chemoreceptor trigger zone in the brain, as well as on vagal nerve terminals in the gastrointesti- nal tract.6,7 Clinical studies have demonstrated the efficacy of ondansetron in managing paediatric gastroenteritis. In a study by Cubeddu et al.,8 children treated with ondansetron or metoclopramide experi- enced significantly fewer emetic episodes compared to those administered a saline placebo (p < 0.05). Similarly, Reeves et al.9 reported that children receiving ondansetron with intravenous flu- ids were more likely to stop vomiting completely than those who received IV fluids and placebo (70% vs. 51%; p=0.04). Furthermore,ondansetron has a relatively mild side effect profile compared to dopamine antagonists and anticholinergics.10 Though initially believed not to cause extrapyramidal side effects, case reports have documented instances of ondansetron-induced dys- tonic reactions.11 This may result from ondansetron’s interaction with serotonergic pathways that influence dopaminergic transmis- sion in the basal ganglia and limbic system.12 By blocking 5-HT3 receptors, ondansetron may indirectly alter dopamine and acetyl- choline activity, leading to an imbalance that triggers dystonia.13,14 The first documented case of ondansetron-induced extrapyramidal symptoms was reported by Dobrow et al.,15 and Diaz-Parlet et al. described a severe dystonic reaction requiring intensive care sup- port.16 Management of ondansetron-induced dystonia involves early symptom recognition and pharmacologic intervention. Anticholinergic agents such as trihexyphenidyl, are effective in alleviating dystonic symptoms by restoring the dopamine-acetyl- choline balance.17 Additionally, benzodiazepines like clonazepam, have shown efficacy in reducing muscle rigidity and associated anxiety in extrapyramidal reactions.18 Case Report Figure 1. Babinski’s sign was positive in this patient after admin- istration with Ondansetron. Figure 2. Deviation of mouth was observed in this patient after administration of ondansetron. [page 42] [Emergency Care Journal 2025; 21:13771] Furthermore, the probability that ondansetron caused the dys- tonic reaction was assessed using Naranjo’s Adverse Drug Reaction Probability Scale, a validated instrument for assessing causality by taking into account variables like the patient’s response to dechallenge and rechallenge, the known side effect profile of the drug, and the temporal relationship between drug administration and the adverse event. The classification of the reaction as “probable” based on this evaluation supported the the- ory that ondansetron was the most likely cause of the dystonia.19 Further investigation is warranted due to the striking similarity between this case and previously reported instances in which ondansetron was associated with dystonic reactions. References 1. Griddine A, Bush JS. Ondansetron. [Updated 2023 Feb 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi. nlm.nih.gov/books/NBK499839/ 2. Baigent AV, Morris EAJ. Severe acute drug-induced dystonia in the post-operative period requiring tracheal re-intubation. Anaesth Rep 2023;11:e12258 3. Schramm BM, Orser BA. Dystonic reaction to propofol atten- uated by benztropine (cogentin). Anesth Analg 2002;94:1237- 40. 4. Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. Anesthesiology 1992;77: 162-84. 5. Manteuffel J. 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