Capsule Summary

Intentional ingestion of agricultural pesticides and herbicides for suicide accounts for most of the cases of acute overdose in hospital emergency departments (EDs) in Korea [1]. Such cases differ in toxicological epidemiology from those reported in other developed countries. The World Health Organization classifies bentazone as a moderately hazardous (class II) herbicide [2]. Although fatal cases of acute bentazone overdose have been reported in other countries [3-6], a surgical airway such as cricothyroidotomy during cardiopulmonary resuscitation (CPR) for the victim has not yet been reported. We report a fatal case of acute bentazone overdose despite cricothyroidotomy during CPR.

A 53-year-old Korean woman was brought to the ED of a community hospital that had 250 in-patient beds by the 119 emergency medical services ambulance crew owing to pesticide poisoning. The 119 is a universal telephone code for fire, emergency medical services, and disaster in Korea. About an hour earlier, the patient attempted suicide at home by ingesting an herbicide. Upon hospital admission, the patient was alert, with a Glasgow Coma Scale score of 15, and the following vital signs: blood pressure of 141/78 mmHg, pulse rate of 125/min, respiratory rate of 18/min, body temperature of 36°C, and oxygen saturation of 97%. The trade name of the herbicide was Basagran, a herbicide comprising bentazone (40%) and a solvent (60%). The 500-mL vessel was empty. Upon the patient’s arrival, 1 L of normal saline was administered intravenously into her right basilic vein, emergency blood sampling was conducted, and gastric lavage with a large bore orogastric tube was performed with 4 L saline solution. The lavage cleared the gastric contents; they were bright red in color. About 10 minutes after the patient’s arrival to the hospital, during the gastric lavage, the patient defecated with loose stools indicative of diarrhea. About 25 minutes after the patient’s arrival at the ED, a 16-Fr nasogastric tube was inserted, through which the emergency physician administered 50 g of activated charcoal. Forty minutes after the patient’s arrival at the ED, the patient’s complete blood count and urine analysis results were reported. They were normal. The emergency physician continuously monitored the patient at the bedside, and nurses prepared to transfer the patient to the intensive care unit and removed the ECG lead and oxygen saturation monitoring probe of the fixed monitor. About 52 minutes after the patient’s arrival at the ED, the emergency physician noticed that her consciousness suddenly deteriorated while her breathing weakened. Immediately, the nurses reattached the ECG lead and oxygen saturation probe, and the emergency physician identified the ECG rhythm as asystolic. The oxygen saturation could not be determined. Immediately, chest compression and bag-mask ventilation were performed, and 1 mg of epinephrine was administered intravenously through the peripheral vein. Since then, 1 mg of epinephrine was injected intravenously every 2 to 3 minutes. Oxygen was administered at a flow rate of 15 L/min through a bag mask. After 2 minutes of CPR, 20 mg of etomidate was injected intravenously for endotracheal intubation. However, the temporomandibular joint remained firmly fixed. The muscles of the body, including those of the extremities, were rigid. After 3 minutes of CPR, a muscle relaxant, succinylcholine (50 mg), was injected intravenously. After succinylcholine injection, the temporomandibular joint did not show any relaxation response. Physical traction of the joint was ineffective. After 7 minutes of CPR, 100 mg of succinylcholine was injected intravenously, but the temporomandibular joint did not relax. While the chest compressions and bag mask ventilation continued, and the ECG remained asystolic, the emergency physician performed needle-cricothyroidotomy. Finally, the emergency physician successfully performed surgical cricothyroidotomy after 12 minutes of CPR. After surgical cricothyroidotomy, the oxygen saturation was 100%, but the ECG continuously showed asystole. The emergency physician declared the victim dead after 63 minutes of CPR. A total of 21 mg of epinephrine had been administered. The body, including the articular jaw, fingers, and toes, was stiff and showed no change at all until death. During CPR, the initial blood biochemical test results were reported as normal, except for the Na+ result, which was 148 (136 to 145) mmol/L. No autopsy or toxicological study was performed.

Bentazone is a herbicide that inhibits carbon dioxide fixation in plants such as rice and corn, thus interfering with photosynthesis [5,6]. In a rat model, bentazone was rapidly absorbed and mostly excreted in the urine [7]. An hour after its oral administration, it was distributed to the stomach, liver, kidneys, and heart of the rat, but not to its brain or spinal cord [7]. The substance was metabolized to 6-OH bentazone and 8-OH bentazone through hydroxylation. The symptoms of acute bentazone overdose in the experimental animal model were shallow accelerated breathing, dyspnea, central nervous system depression, pronounced increase in body temperature, and rapid onset of rigor mortis [8]. The lethal dose (LD 50) was 1,100 mg/kg in rats and 2,918 mg/kg in pheasants [6]. Acute intoxication did not cause any statistically significant changes in the hemoglobin, erythrocyte, or leukocyte counts [6].

Turcant et al. [5] noted that the effects of benzodiazepines or competitive neuromuscular blocking agents and the mechanism of the muscle rigidity caused by bentazone are yet to be evaluated. Direct muscular toxicity was suspected, but central nervous system toxicity was very unlikely because in the experimental animal model, bentazone did not cross the blood-brain barrier.

Bentazone may also have direct toxicity on the kidney and liver [6]. Wu et al. [6] proposed that direct organ toxicity in acute bentazone overdose may be because of the chemical nature of bentazone metabolism. Through bentazone metabolism, OH metabolites, oxidative stress, and oxygen free radicals were produced. These reactive oxygen species can induce oxidative modification of cellular carbohydrates, proteins, lipids, and nucleic acids [9], especially in organs with high metabolic rates and oxygen demand such as muscle, liver, and kidneys [6]. As mentioned before, in the animal model, bentazone was rapidly absorbed in and distributed to the stomach, liver, kidneys, and heart. We thus speculated that bentazone can be rapidly distributed to and accumulate in specific organs such as the muscles, including the heart, gastrointestinal tract, respiratory system, and skeletal muscles, and can directly damage them and eventually cause organ failure. Muller et al. [4] proposed that a dose of 686 to 1,371 mg ingested per kg of body weight is within the predictable lethal ingestion range.

Acute bentazone overdose is uncommon. We searched Medline for cases of acute bentazone overdose from 1966 to 2015, and found only four English papers on human acute bentazone overdose, including three fatal cases in France, Denmark, and China [3-6] (Table 1). The symptoms of acute bentazone overdose were gastrointestinal, such as nausea, vomiting, diarrhea, and abdominal pain, respiratory, such as cough, tachypnea, dyspnea, and apnea, cardiovascular, such as tachycardia and cardiac arrest, and musculoskeletal, such as muscle rigidity. The initial symptoms were gastrointestinal, such as nausea, vomiting, and diarrhea. In the cases of acute bentazone overdose, acute renal failure and acute toxic hepatitis developed. In all the reported cases, the overdose route was oral, the reason for the overdose was a suicide attempt, and the victims were male. In our case, the symptoms were similar to those of the other reported cases: tachycardia, diarrhea, muscle rigidity, and cardiac arrest. The route and the reason for the overdose were the same as those in the previously reported cases. The difference between the previously reported cases and our case is that in the previous reports, the physicians did not attempt any form of surgical airway procedure, while in our case, the emergency physician performed surgical cricothyroidotomy. However, even though surgical airway insertion was performed in our case, the mortality outcome was the same.

Through our case, we found that the depolarizing skeletal muscle relaxant succinylcholine might not be able to reverse the muscle rigidity caused by acute bentazone overdose. Development of muscle rigidity was observed before injection of succinylcholine, and even after three times the normal 1 mg/kg dose of succinylcholine was used, no relaxation of the rigid muscles was observed.

To our knowledge, this is the first reported fatal case of acute bentazone overdose, despite cricothyroidotomy during CPR. The muscular toxicity seen in acute bentazone overdose has already been reported in previous fatal cases [5], but no attempts have been made to perform a surgical airway procedure during CPR. In this case, the emergency physician performed surgical cricothyroidotomy after failure of rapid-sequence intubation. In addition, we found that the muscle relaxant succinylcholine might be ineffective against muscle rigidity in acute bentazone overdose.

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