Many cases of acute overdose in Korea are attributed to deliberate consumption of agricultural pesticides and herbicides as a means of suicide [1]. Bentazone is an acidic herbicide classified as moderately hazardous by the World Health Organization (WHO) [2]. Among the cases reported to date, only two have included fatal outcomes and muscle rigidity within a few hours [3,4]. We report a case of mortality after bentazone intoxication, with death occurring within 4 hours of ingestion.

A 65-year-old man visited the emergency department (ED) 40 minutes after ingesting approximately 75 mL of Basagran M60 (bentazone 33.6%, 25.2 g; FMC Corp) to commit suicide. The only co-ingestion was alcohol. He had no medical history.

The patient was alert and did not report any symptoms. His vital signs were as follows: blood pressure, 128/64 mmHg; heart rate, 106 beats/min; respiratory rate, 20 breaths/min; body temperature, 37.3 °C; and oxygen saturation, 94%. Results of his physical examination, including chest auscultation, were unremarkable.

Initial arterial blood gas analysis (ABGA) revealed respiratory alkalosis (pH, 7.482; PCO₂, 32.3 mmHg; PO₂, 68 mmHg; HCO₃, 24.2 mmol/L). Notably, his ionized calcium level was 1.4 mg/dL. Other abnormal laboratory results included lactic acid at 2.3 mmol/L, osmolality at 329 mOsmol/kg, and ammonia at 149 µg/dL. His serum potassium level was 3.9 mmol/L, and his creatine kinase concentration was 56 U/L. Additionally, his serum glucose concentration was 114 mg/dL, and his blood urea nitrogen and serum creatinine were 9 and 1.1 mg/dL, respectively. All other laboratory results were normal. Electrocardiography (ECG) revealed sinus tachycardia with significant QT prolongation (Fig. 1A). Findings on chest plain radiographs were normal. The patient was uncooperative, and it was not possible to perform gastric lavage or administer activated charcoal. Normal saline (500 mL) and sodium bicarbonate (60 mEq) were administered. Calcium replacement was not performed.

Approximately 90 minutes after ED admission, the patient had a body temperature of 38.7 °C. The patient was treated with evaporative external cooling and urinary bladder irrigation with cold saline. Acetaminophen (1,000 mg) was also intravenously injected. One hour later, his tachypnea was aggravated, with a respiratory rate exceeding 30 breaths/min and a rapid deterioration of mental status, with a Glasgow Coma Scale of 3 points. Subsequent ABGA revealed a pH of 7.555, PCO₂ of 24.2 mmHg, PO₂ of 81 mmHg, and HCO₃ of 21.0 mmol/L. Moreover, his lactate level had increased to 7.49 mmol/L. Brain computed tomography was performed because of his comatose state but showed no acute lesions. The patient's body temperature rose to 41.0 °C right after the computed tomography scan. An additional 1,000 mL of normal saline was administered.

After 163 minutes of ED admission, endotracheal intubation was performed for airway protection. The patient was intubated with 20 mg of etomidate without a neuromuscular blocker. At this time, he did not exhibit any muscle rigidity. His blood pressure subsequently decreased to 63/34 mmHg 5 minutes after endotracheal intubation. Despite the administration of norepinephrine up to 0.34 µg/kg/min, cardiac arrest occurred 10 minutes after endotracheal intubation, with the initial rhythm being pulseless electrical activity. ABGA before the arrest showed a pH of 7.237, PCO₂ of 56.7 mmHg, PO₂ of 90 mmHg, and HCO₃ of 24.1 mmol/L. His lactate level was 10.21 mmol/L, and an ionized calcium test yielded a result of <1.0 mg/dL. Also, his serum potassium level was 5.5 mmol/L, and his serum glucose concentration was 41 mg/dL. Finally, his blood urea nitrogen and serum creatinine levels were 12 and 1.3 mg/dL, respectively. Creatine kinase was not rechecked. ECG showed QRS widening and QT prolongation (Fig. 1B).

Two minutes after the cardiac arrest, asystole was observed in every cycle. Despite resuscitation efforts, the patient died. Muscle rigidity was observed throughout his body at the time of death (Fig. 2).

Bentazone, a herbicide of the thiadiazine group, interferes with photosynthesis by preventing carbon dioxide fixation [5]. It is widely used for the cultivation of rice, perilla, barley, and corn [6]. The WHO classifies bentazone as moderately hazardous, and fatal cases following exposure are very rare [2]. Muller et al. [7] previously suggested that a dose of 686 to 1,371 mg/kg is lethal in humans. Fatal cases of liver failure, kidney injury, and muscle rigidity with failed or delayed airway access have been reported [3–7]. Of the five fatal cases of acute bentazone intoxication reported to date, the smallest dose was 100 to 200 mL (48%), while all other cases involved doses >200 mL [3–7]. In the presented case, the dose was 364 mg/kg.

Previous studies reported delayed airway establishment due to muscle rigidity. Lee [3] and Turcant et al. [4] reported no improvement in rigidity despite succinylcholine administration, suggesting a need for early surgical airway. However, in this case, despite achieving a definite airway before muscle rigidity developed, the patient eventually expired. This suggests that the cause of death is something other than respiratory failure, and the recommendation of early advanced airway is questionable.

Neuroleptic malignant syndrome (NMS) and malignant hyperthermia (MH) are similar in that they cause symptoms such as fever, muscle rigidity, and autonomic dysfunction. Lin et al. [8] reported that bentazone intoxication mimics NMS. However, we propose that bentazone intoxication mimics MH rather than NMS. First, MH occurs in a small percentage of genetically susceptible individuals. While bentazone is classified as moderately hazardous, and most patients have an insidious course after consumption, a few patients have been reported to develop muscle rigidity and a fatal course. The reported fatal cases may have been genetically susceptible to bentazone. Second, hypocalcemia and QT prolongation in our patient were consistent with the pathophysiology of MH, which is based on calcium release from the sarcoplasmic reticulum and extracellular calcium influx. This indicates that bentazone may induce a potential influx of extracellular calcium. In this regard, patients with bentazone intoxication and an anticipated fatal course may be candidates for dantrolene. Dantrolene inhibits calcium ions release from the sarcoplasmic reticulum by antagonizing ryanodine receptors. Therefore, it is a key part of the treatment of MH and is also used in other conditions that cause muscle contraction and heat production, including NMS. Despite hypocalcemia, the benefit of calcium administration is questionable because it may increase the intracellular calcium concentration, which may lead to a fatal outcome. Also, since succinylcholine is one of the causes of MH, it should be avoided.

To our knowledge, this case report documents the lowest dose of bentazone that led to a fatal outcome to date. It is also the first to report hypocalcemia and ECG changes following bentazone intoxication. In addition, we suggest an association between bentazone intoxication and MH. A limitation of our case is that, although we propose dantrolene as a therapeutic candidate, it has not been applied in practice. Future studies are required to validate this therapeutic effect. Furthermore, it will be necessary to investigate the presence of ryanodine receptor mutations to confirm that those who have been fatally affected by bentazone intoxication indeed have MH.