Severe Acute Pipazethate <scp>HCl</scp> Poisoning: A Case Report

Abstract

Pipazethate hydrochloride is a phenothiazine-derived antitussive drug used for nonproductive coughs, particularly in developing countries, because of its affordability and low sedative effect. It is licensed in Egypt, and a lot of countries in Asia (India, Pakistan, Bangladesh, Malaysia and Japan), Europe (Germany, Italy, Belgium, Switzerland and others in Eastern/Western Europe) and Latin America (Argentina, Brazil, Chile and Peru). While Pipazethate hydrochloride has been used in many countries, it is not currently approved or used in the United States. Nonetheless, safety concerns, especially in children, have reduced its use in high-income nations [1]. Overdoses can cause severe neurological, respiratory and cardiac complications, including QT prolongation and life-threatening arrhythmias due to quinidine-like sodium channel blockade [2]. Although acute poisoning is rare, paediatric cases often result in coma, seizures or death. Early reports by Antonio da Silva and Bonavita [3, 4] documented fatalities, whereas Abdelnaby et al. [5] demonstrated the utility of lidocaine in managing arrhythmias. Pipazethate's antitussive efficacy, initially validated in clinical trials [4], underscores its historical use despite modern safety challenges. This report details a near-fatal Pipazethate overdose in a 28-month-old child, emphasising clinical management and advocating for improved safety protocols. A 28-month-old male child with no significant medical or surgical history was brought to the Ain Shams Poison Control Center on February 12, 2009, approximately 2 h after accidentally ingesting approximately 7.5 mL (half of a 15 mL bottle) of Pipazethate hydrochloride oral drops (Selgon, EIPICO, Egypt; 40 mg/mL), totaling approximately 300 mg. The medication had been inadvertently left within reach at home. According to the caregiver, the child developed lethargy shortly after ingestion. On arrival at the center—approximately 2 h post-ingestion—the child presented with generalised tonic–clonic seizures, apnea, cyanosis, undetectable blood pressure and severe bradycardia (20 beats per minute). Due to the postictal state and need for immediate resuscitation, Glasgow Coma Scale (GCS) assessment was not performed. Immediate resuscitative measures were initiated. Seizures were controlled with intravenous diazepam (0.3 mg/kg/dose, repeated once), followed by endotracheal intubation and mechanical ventilation to secure the airway. Hemodynamic support was provided with rapid infusion of normal saline (20 mL/kg bolus). Gastric lavage was performed 3 h post-ingestion, followed by the administration of activated charcoal (1 g/kg) to bind any residual drug. Approximately 1 h after admission (3 h post-ingestion), cardiac monitoring revealed significant arrhythmia. The initial electrocardiogram (ECG) revealed torsades de pointes progressing to monomorphic ventricular tachycardia at a rate of 200 beats per minute (Figure 1A). Antiarrhythmic therapy was initiated via a bolus of lidocaine (1 mg/kg) followed by continuous infusion (20–50 mcg/kg/min). Synchronised direct current (DC) cardioversion (2 J/kg) successfully restored normal sinus rhythm (Figure 1B). Arterial blood gas (ABG) analysis at admission revealed severe metabolic acidosis (pH 7.11), hypoxia (pO2 40.5 mmHg), an elevated anion gap (26.3 mmol/L) and hyperlactatemia (5.8 mmol/L). Electrolyte abnormalities included hyponatremia, hypochloremia and hyperglycemia. Blood urea and serum creatinine levels were within normal range on admission and after improvement. Liver enzymes were mildly elevated. The complete blood count (CBC) revealed leukocytosis, anemia, microcytosis and anisocytosis (Table 1). Within 8 h of admission, the child's condition improved significantly. Hemodynamic stability was achieved (blood pressure: 90/60 mmHg; heart rate: 110 bpm) and repeat ECG confirmed persistent normal sinus rhythm (Figure 1B). Follow-up laboratory tests revealed resolution of metabolic acidosis, normalisation of the anion gap, improved oxygenation, and normalisation of electrolytes and liver enzymes. No Pipazethate blood level estimation was performed due to unavailability of this test at our facility. The patient was successfully extubated 24 h post-admission with intact neurological function and was discharged on the following day. At the one-week follow-up, no residual cardiac or neurological complications were observed. Pipazethate's narrow therapeutic index, particularly in children, stems from its dual action as a sodium channel blocker and QT interval prolonging agent, mechanisms that mirror class I antiarrhythmics [5, 6]. At toxic doses, the drug inhibits myocardial sodium influx during Phase 0 of the action potential, delaying ventricular repolarisation and fostering re-entrant circuits—key drivers of torsades de pointes and monomorphic ventricular tachycardia [6]. The ingestion of 300 mg (15× the paediatric dose) in a 28-month-old patient resulted in coma, seizures and hemodynamic collapse, which is consistent with prior reports of sodium channel toxicity [3, 5]. Metabolic acidosis (pH 7.11, lactate 5.8 mmol/L) exacerbates these effects by impairing ion channel function and myocardial contractility, creating a vicious cycle of arrhythmogenesis [1, 3]. Management adhered to toxidrome-specific protocols. Diazepam, a GABA-A receptor agonist, terminated seizures by enhancing inhibitory neurotransmission, mitigating secondary hypoxic injury [5]. Patients who have consumed potentially deadly levels of poison for no more than an hour earlier are advised to use activated charcoal as a stomach decontamination technique [7]. However, in clinical settings, the impact of charcoal given after 1 h of intoxication is unclear [7, 8]. When compared to individuals treated with activated charcoal alone, research conducted on poisoned patients has not demonstrated that the combination of gastric lavage and activated charcoal improves the patient's outcome [9, 10]. Only one study has demonstrated a slightly improved clinical outcome for a small subset of patients who received the combination treatment. Nevertheless, the conclusions that can be made are limited by the small sample size and retrospective stratification [11]. Based on these results, and on a few experimental studies, gastric lavage continues to be recommended for patients with significant, possibly fatal overdoses; if they show symptoms within 1 h of intake [12]. Consequently, it is uncertain whether lavage should be followed by activated charcoal or charcoal should be used alone. To the best of our knowledge, only one study has examined how well lavage and charcoal work together to prevent drug absorption in a controlled environment as opposed to charcoal alone. In this regard, therapeutic doses of three distinct medications were utilised [13] and no differences were found between combination treatment versus activated charcoal alone. Lidocaine, a class IB antiarrhythmic agent, has been prioritised over alternatives (e.g., amiodarone) because of its rapid sodium channel dissociation kinetics, which counteracts blockade without exacerbating repolarisation delays [6]. Synchronised cardioversion (50 J) restored sinus rhythm after lidocaine alone failed, which aligns with a report by Abdelnaby et al. [5], who emphasised combined antiarrhythmic and electrical therapies. It is to be noted that the patient was normotensive at the time of lidocaine administration, and we recommend co-administration of lidocaine and cardioversion in such cases. Sodium bicarbonate has been shown to correct acidosis, stabilise myocardial membranes and reduce susceptibility to arrhythmia [1, 3]. This patient's survival contrasts with fatal outcomes in cases such as those reported by Soto et al. [14], and Antonio da Silva's 1977 [3], where delayed hospitalisation (> 6 h post-ingestion) precluded effective intervention. Bonavita and Crinò's case [4] further highlights the lethality of untreated Pipazethate-induced arrhythmias. The absence of antidotes underscores the need for pharmacokinetic studies to explore extracorporeal removal, as current guidelines rely solely on supportive care [5]. Preventive measures are critical. Child-resistant packaging, which has been proven to reduce accidental ingestions of high-risk medications by 80% [1], must be mandated for Pipazethate in endemic regions. Caregivers' education on secure storage and early symptom recognition (e.g., lethargy, palpitations) can bridge gaps in healthcare access. Regulatory shifts toward safer alternatives such as dextromethorphan, which lacks cardiotoxicity, are urgently needed [14]. Pipazethate overdose demands prompt lidocaine therapy, seizure control and acidosis correction. Survival hinges on early intervention, underscoring the need for global guidelines, child-resistant packaging and caregiver education. Pharmacokinetic research and safer antitussives must be prioritised to mitigate risks in regions where Pipazethate usage remains prevalent. Mohamed F. Abbas: conceptualisation, case management oversight, investigation, analysis and manuscript drafting. Amin A. Alamin: clinical data interpretation, manuscript editing and final approval. Melad Gad Paulis: case management oversight, validation and critical revision. Ahmad H. Abbas: case management oversight, validation and critical revision. Sayed F. Abdelwahab: validation, manuscript editing and critical revision. All authors reviewed and approved the last version of the manuscript and agreed to be accountable for all aspects of the work. The authors have nothing to report. Ethical approval was not required for this case report. Written informed consent was obtained from the child's guardian for the publication of the clinical details. All identifying information has been omitted to ensure confidentiality. Assent was not applicable due to the patient's age. The authors declare that the research presented in this manuscript adheres to the ethical principles outlined by Ain Shams University. All procedures involving human participants were conducted in accordance with the ethical standards of Ain Shams University and the Declaration of Helsinki (1964), as revised in 2013. The authors declare no conflicts of interest. Data supporting the findings of this report are available from the corresponding author upon a reasonable request.