Case Report

Severe central nervous system depression in a patient with acute imidacloprid poisoning

Abstract

Imidacloprid belongs to a relatively new class of insecticidal chemistry, the chloronicotinyl neonicotinoid compounds. We report a case of acute ingestion of an insecticide formulation containing imidacloprid. Clinical manifestations included respiratory failure and coma. A previously healthy 67-year-old male patient ingested an unknown quantity of imidacloprid for suicidal purpose. Disorientation, drowsiness, and increased salivation had developed by the time of arrival to a local hospital. On admission, his mental status was decreased (Glasgow Coma Scale score, 3/15). He was intubated and mechanically ventilated. Symptomatic and supportive treatments were given. At the fourth day, the patient was discharged from the hospital. None of the symptoms can be considered characteristic and specific for imidacloprid poisoning as a neonicotinoid com- pound. Although the symptoms can be resolved with supportive measures, none of them can be considered characteristic and specific for imidacloprid poisoning as a neonicotinoid compound.

The nicotinoids are a new class of insecticides with a new mode of action. They have been previously referred to as nitro-quanidines, neonicotinyls, neonicotinoids, chloronicotines, and, more recently, as the chloronicoti- nyls. In 1972, the first lead neonicotinoid, nithiazine, was developed but never commercialized. The next neonico- tinoid, imidacloprid, was developed in 1985 by introdu- cing a 6-chloropyridin-3-pyridylmethyl group as a substituent of the nitromethylene heterocycle. The 6- chloropyridin-3-pyridylmethyl moiety as a heterocyclic group is a common characteristic of the first-generation neonicotinoids [1].

Imidacloprid is a member of a relatively new class of insecticides, the chloronicotinyl neonicotinoid compounds [2,3]. It was introduced into commercial use only in the last decade, and its worldwide use increases. It is currently marketed as several proprietary products worldwide, for example, Admire, Confidor, Gaucho, Merit, Premier, Pre-

mise, and Provado. Very possibly, it is used in the greatest volume globally of all insecticides [4].

Imidacloprid is rapidly and almost completely absorbed after ingestion. It is subsequently metabolized to 6- chloronicotinic acid, which is conjugated with glycine and then eliminated or reduced to guanidine. About 70% to 80% of an administered dose is excreted unchanged in the urine and 20% to 30% in feces [5].

Imidacloprid acts on the central nervous system (CNS) as an agonist at the nicotinic acetylcholine receptor (nAChR). It causes initial stimulation followed by fatigue of the agonized neurons and ultimately interferes with the transmission of neuronal impulses [6-8].

Imidacloprid has selective toxicity to insects and relative sparing of mammals and other vertebrates. Animal studies confirm the relatively low toxicity in animals compared with insects; however, information regarding human exposure and toxicity is quite rare despite its widespread use [3]. We report a case of acute human ingestion of an insecticide containing imidacloprid.

A previously healthy 67-year-old male patient was admitted to our emergency department with poisoning by imidacloprid (Confidor SC-350). He ingested an unknown quantity of imidacloprid (Confidor SC-350) for suicidal purpose. On admission to a local hospital, after 1 hour of ingestion, disorientation, drowsiness, and increased saliva- tion had developed. Disorientation, drowsiness, and increased salivation had developed by the time of arrival. Nasogastric lavage and instillation of activated charcoal were performed. Pralidoxime (250 mg, intramuscular) and atropine sulfate (1 mg, intramuscular) were applied because of the suspicion of organophosphate poisoning. He was transferred to our hospital at the fourth hour of the ingestion.

On admission, his mental status was decreased (Glasgow Coma Scale score [GCS], 3/15), and blood pressure was 80/60 mm Hg, pulse rate was 116 beats/min, and respiratory rate was 10/min. His salivation was dried by atropine. His pupils were dilated and light reflex was weakened. He was intubated and mechanically ventilated for inability in inspiration.

Results of initial laboratory studies were in reference ranges, except for leukocytes (18 500/uL) and glucose (208 mg/dL). Analysis for cholinesterase inhibition was

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negative. Plasma pseudocholinesterase level was 9680 IU/L (reference range, 3600-12 900 IU/L).

The patient was admitted in the intensive care unit for mechanical ventilation and Close monitoring. Symptomatic and supportive treatments, including H₂ receptor blocker and fluid resuscitation, were given. Mechanic ventilation with synchronized intermittent mandatory ventilation mode was applied. At the second day, respiratory disturbance was improved and he was separated from the mechanic ventilation. He was extubated successfully at the same day. The patient’s GCS was 11/15, and other clinical signs and symptoms like lung examination, pupil size, motor tone, and reflexes, were normal. At the third day, the patient’s GCS increased to 15/15 and all findings of the patient became normal. At the fourth day, the patient was discharged from the hospital.

The nicotinoid insecticides are partial agonists on the nAChR. The primary mode of action after ingestion of the insecticide is interference with the nAChR of central and Peripheral nervous system, causing irreversible blockage of postsynaptic nAChR [9,10]. Despite its wide usage, human exposure resulting in toxicity is limited [11]. neonicotinoid insecticides are of relatively low toxicity to humans because they react less with human nAChR subtypes compared with insects, and they do not readily penetrate the human blood brain barrier. With poor penetration through the blood brain barrier, centrally mediated effects would not be expected at low levels of exposure. There has been little in the way of acute overdose or adverse effects reported after human exposure despite wide usage [12].

In rats, imidacloprid is well absorbed orally and widely distributed within 1 hour of administration. However, radiolabeled studies show that imidacloprid is not distributed to fat, CNS tissues, or bone [3]. In our case, the toxicity begun approximately 1 hour after ingestion too.

Imidacloprid would be expected to cause central stimulation before depression, similar to those caused by nicotine poisoning. The clinical manifestation of acute poisoning with imidacloprid consisted of apathetic state, depressed muscular tone, respiratory disturbance, trem- bling, and muscular cramps in severe cases of poisoning. Symptoms occurred within 15 to 40 minutes and were reversible within 8 to 24 hours after treatment [3,12]. After an Intentional ingestion of about 9 g of imidaclo- prid, mild CNS depression was noted. It is likely that the solvent (N-methyl pyrrolidone) was a contributing factor in the CNS depression [3]. Mild CNS depression was noted in one case of human poisoning. In the case of acute ingestion (about 100 mL) of an insecticide formulation containing 9.6% imidacloprid, less than 2% surfactant, and the balance as solvent (N-methyl pyrro- lidone), a 64-year-old man was reported to be disoriented, drowsy, and dizzy. His mild CNS depression is more likely a result of the solvent than the imidacloprid [4]. Our patient manifested disorientation, drowsiness, and increased salivation, but his mental status progressed to

coma. His respiratory effort was poor, deteriorating to apnea, for which he was intubated. He was treated wrongly like organophosphate poisoning on local hospital because of increased salivation.

In comparative acute animal toxicity studies of imida- cloprid, the most consistent finding at a lower dose was decreased activity. At higher doses, the most common effects were tremor, impaired pupillary function, gait incoordination, and hypothermia. After a lethal dose, deaths occurred within 4 to 24 hours [3]. In male and female rats orally gavaged with a single dose of 42 mg/kg imidacloprid suspension in water, the only effect noted was a slight decrease in activity in female rats. At a dose of 150 mg/kg, the only additional effect seen was tremor (1/12 females) and a slight decrease in body temperature and red nasal stain. The dose response is steep at higher doses. Doses of 307 mg/kg caused mortality within 4 to 24 hours in 2 of 12 males and 8 of 12 females. The survivors at 4 hours exhibited severe tremor, profound reduction in body temperature, motor incoordination, and CNS depression [3,12]. There are no Blood concentrations of the agent so it is hard to know how much imidacloprid our patient took, but we think that he ingested large amounts of imidacloprid, as he was in coma status with depressed muscular tone and respiratory disturbance.

Severe cardiac toxicity after massive ingestion of imidacloprid was noted in one case of human poisoning. In the case of acute ingestion of 200 mL of an insecticide formulation containing 9.6% imidacloprid, a 69-year-old woman was reported to have developed ventricular fibrilla- tion and ventricular tachycardia and to be pulseless with undetectable blood pressure approximately 1 hour after arrival. In our case, his mental status was coma but he did not develop fatal arrhythmias [13].

After acute overdose, treatment is primarily supportive. There is no specific antidote for neonicotinoid Insecticide poisoning. Although all symptoms of imidacloprid poisoning can be resolved with supportive measures, none of the symptoms can be considered characteristic and specific [12]. Prognosis may be good after sympto- matic therapy.

In conclusion, we report a severe case of ingestion of a formulated insecticide containing a neonicotinoid, imida- cloprid. Clinical manifestations can be categorized as mild to severe CNS depression. Although none of the symptoms can be considered characteristic and specific for imidaclo- prid poisoning, all symptoms can be resolved with supportive measures.

Aydin Deniz Karatas MD

Kiymet Y. azici Emergency Service Hatay Is. kenderun State Hospital Iskenderun Hatay, Turkey

E-mail address: [email protected] doi:10.1016/j.ajem.2009.01.006

Case Report

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