American Journal of Emergency Medicine 33 (2015) 310.e5–310.e6
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
A fatal case of thiacloprid poisoning Abstract Neonicotinoid insecticides are considered to be less toxic to humans compared to older insecticides such as organophosphates, carbamates, pyrethroids, and organochlorine compounds. However, reports of severe human toxicity with neonicotinoids are emerging. Acute human thiacloprid poisoning and death as a result have not been reported in the literature so far. Here we report a case of thiacloprid poisoning resulting from deliberate ingestion in a 23-yearold man, manifesting with status epilepticus, respiratory paralysis, rhabdomyolysis, metabolic acidosis, and acute kidney injury (AKI), and ultimately giving rise to refractory shock and death. Thiacloprid can cause fatal human toxicity when ingested heavily, and absence of an effective antidote raises concern in this regard. Neonicotinoids belong to a new class of potent insecticides that includes imidacloprid, thiacloprid, thiamethoxam, dinetofuran, clothianidin, and acetamiprid. They are considered to be much less toxic to humans, other mammals, birds, and the environment compared to older insecticides such as organophosphates, carbamates, pyrethroids, and organochlorine compounds [1]. Substitution of the latter with neonicotinoids may potentially reduce the high rates of human morbidity and mortality associated with intentional poisoning from the former agents in developing countries [1]. However, in the recent past, there have been reports of severe human toxicity with imidacloprid, with its widespread availability and use. Thiacloprid, a chloronicotinyl neonicotinoid and a likely carcinogen, is classified by the World Health Organization as a “moderately hazardous” (class II) pesticide based on animal studies. Few reports of poisoning with acetamiprid and clothianidin have been reported [2]. However, to the best of our knowledge, acute severe human toxicity from thiacloprid ingestion and death as a result have not been reported so far. A 23-year-old man was admitted to emergency department 2 hours after deliberate ingestion of about 100 mL of thiacloprid suspension (ALANTO 240SC, containing 21.7% thiacloprid w/w, manufactured by Bayer CropScience, Ankleshwar, Gujarat State, India) mixed with ethanol. The pesticide bottle brought with him is shown in Figure He initially had nausea, vomiting, and agitation and developed multiple episodes of generalized tonic-clonic seizures 2 hours after ingestion. He remained unconscious and required intubation and mechanical ventilation for poor respiratory efforts. Following intubation, gastric lavage was performed. Examination revealed a young man deeply unconscious and not responding to painful stimuli. He was noted to have tachycardia (heart rate between 130 and 150/min), blood pressure between 140/90 and 160/100 mm of Hg, an artificial prosthetic eye on the right side, and dilated and nonreactive left pupil. He was given intravenous thiamine, lorazepam, phenytoin, and valproate, followed by continuous midazolam infusion. Laboratory evaluation at admission revealed the follow-
0735-6757/© 2014 Elsevier Inc. All rights reserved.
ing: serum sodium, 136 mmol/L; potassium, 4.4 mmol/L; glucose, 7.5 mmol/L; calcium, 2.15 mmol/L; phosphate, 1.36 mmol/L; blood urea nitrogen, 15 mmol/L; serum creatinine, 230 μmol/L; bilirubin, 27.4 μmol/L; aspartate transaminase, 63 IU/L; alanine transaminase, 88 IU/L; alkaline phosphatase, 172 IU/L; hemoglobin, 146 g/L; leukocytes, 20.6 × 109/L (93% neutrophils); and platelets, 208 × 10 9/L. Serum cholinesterase level was normal. Electrocardiogram was unremarkable, except for sinus tachycardia. Chest radiograph was normal. Seizures were controlled 8 hours after ingestion. Despite fluid challenge, he developed progressive hypotension and oliguria 30 hours after ingestion; and serum creatinine increased to 371 μmol/L. Serum creatinine kinase level was 6951 U/L, suggesting rhabdomyolysis. Cardiac troponins were negative. Repeat electrocardiogram showed sinus tachycardia. Arterial blood gases showed metabolic acidosis with a pH of 7.20, plasma bicarbonate of 12 mmol/L, and potassium: 4.7 mmol/L. He remained comatose, and right internal jugular double lumen central venous catheter was placed for monitoring of volume status and hemodialysis. However, before hemofiltration could be initiated, he developed shock refractory to vasopressors. He had bradycardia, sustained cardiac arrest, and expired 36 hours after ingestion. Neonicotinoids are potent agonists at the nicotinic acetylcholine receptors, particularly of the α2β4 subtype, and cause neuromuscular paralysis and death of insects by causing excessive depolarization. Neonicotinoid pesticides have low affinity to mammalian nicotinic receptors and poor penetration through the mammalian blood-brain barrier [3]. Human safety data are mainly extrapolated from animal studies. A Sri Lankan study [1] involving 56 imidacloprid poisoning cases found low lethality even with heavy ingestions. However, fatalities from imidacloprid poisoning have been reported [4–8]. Inhalation and dermal contact can also lead to poisoning [2]. The index patient had nausea, vomiting, tachycardia, hypertension, mydriasis with loss of light reflex, and respiratory paralysis, suggesting human nicotinic acetylcholine receptor stimulation by thiacloprid at toxic doses. Similar manifestations have been reported in imdacloprid poisoning [1,4–6]. Neurological toxicity manifesting with recurrent seizures, deep unconsciousness, and rhabdomyolysis has been reported in imidacloprid poisoning as well [4,9]. Ingestion of ethanol along with thiacloprid might have partly contributed to prolonged unconsciousness and respiratory depression, as reported in imidacloprid poisoning [1]. The index patient developed manifestations of multiorgan dysfunction such as AKI, metabolic acidosis, and hypotension before death, similar to that reported in imidacloprid poisoning [1,5]. In the index patient, recurrent seizures might have partly contributed to rhabdomyolysis, AKI, and metabolic acidosis. The refractory hypotension in the index case is less likely to have resulted from myocardial toxicity because cardiac troponins were negative. He developed bradycardia before death. Cardiovascular
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K.V. Vinod et al. / American Journal of Emergency Medicine 33 (2015) 310.e5–310.e6
antidote for neonicotinoid poisoning [3]. Management is mainly symptomatic and supportive. To conclude, thiacloprid, when ingested heavily, can cause severe toxicity similar to imidacloprid and death. In the absence of a specific antidote, the management is mainly symptomatic and supportive. Kolar Vishwanath Vinod, MD⁎ Sadashivan Srikant, MBBS Gnanavel Thiruvikramaprakash, MBBS Tarun Kumar Dutta, MD Dept. of General Medicine Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Dhanvantri Nagar, Puducherry Pondicherry 605006, India ⁎Corresponding author. Tel.:+91 9442604554. fax:+91 413 2272735 E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.08.013
References
Figure. The pesticide bottle brought with the patient containing 21.7% w/w thiacloprid suspension concentrate.
manifestations such as unexplained tachycardia [1] and bradycardia [4–6], ventricular arrhythmias [6,8], and hypotension [1,2,5,6] have been reported in imidacloprid poisoning as well. We could not assay the plasma of the patient for thiacloprid because the facility is unavailable. However, the pesticide bottle brought with the patient and the clinical manifestations make the diagnosis of thiacloprid poisoning highly likely. There is no specific
[1] Mohamed F, Gawarammana I, Robertson TA, Roberts MS, Palangasinghe C, Zawahir S, et al. Acute human self-poisoning with imidacloprid compound: a neonicotinoid insecticide. PLoS One 2009;4:e5127 [Epub]. [2] Lin PC, Lin HJ, Liao YY, Guo HR, Chen KT. Acute poisoning with neonicotinoid insecticides: a case report and literature review. Basic Clin Pharmacol Toxicol 2013; 112:282–6. [3] Tomizawa M, Casida JE. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu Rev Pharmacol Toxicol 2005;45:247–68. [4] Iyyadurai R, George IA, Peter JV. Imidacloprid poisoning—newer insecticide and fatal toxicity. J Med Toxicol 2010;6:77–8. [5] Shadnia S, Moghaddam HH. Fatal intoxication with imidacloprid insecticide. Am J Emerg Med 2008;26:634.e1–4. [6] Yeh IJ, Lin TJ, Hwang DY. Acute multiple organ failure with imidacloprid and alcohol ingestion. Am J Emerg Med 2010;28:255.e1–3. [7] Proenca P, Teixeira H, Castanheira F, Pinheiro J, Monsanto PV, et al. Two fatal intoxication cases with imidacloprid: LC/MS analysis. Forensic Sci Int 2005;153: 75–80. [8] Huang NC, Lin SL, Chou CH, Hung YM, Chung HM, et al. Fatal ventricular fibrillation in a patient with acute imidacloprid poisoning. Am J Emerg Med 2006;24:883–5. [9] Agarwal R, Srinivas R. Severe neuropsychiatric manifestations and rhabdomyolysis in a patient with imidacloprid poisoning. Am J Emerg Med 2007;25:844–5.
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Case Report
A fatal case of thiacloprid poisoning Abstract Neonicotinoid insecticides are considered to be less toxic to humans compared to older insecticides such as organophosphates, carbamates, pyrethroids, and organochlorine compounds. However, reports of severe human toxicity with neonicotinoids are emerging. Acute human thiacloprid poisoning and death as a result have not been reported in the literature so far. Here we report a case of thiacloprid poisoning resulting from deliberate ingestion in a 23-yearold man, manifesting with status epilepticus, respiratory paralysis, rhabdomyolysis, metabolic acidosis, and acute kidney injury (AKI), and ultimately giving rise to refractory shock and death. Thiacloprid can cause fatal human toxicity when ingested heavily, and absence of an effective antidote raises concern in this regard. Neonicotinoids belong to a new class of potent insecticides that includes imidacloprid, thiacloprid, thiamethoxam, dinetofuran, clothianidin, and acetamiprid. They are considered to be much less toxic to humans, other mammals, birds, and the environment compared to older insecticides such as organophosphates, carbamates, pyrethroids, and organochlorine compounds [1]. Substitution of the latter with neonicotinoids may potentially reduce the high rates of human morbidity and mortality associated with intentional poisoning from the former agents in developing countries [1]. However, in the recent past, there have been reports of severe human toxicity with imidacloprid, with its widespread availability and use. Thiacloprid, a chloronicotinyl neonicotinoid and a likely carcinogen, is classified by the World Health Organization as a “moderately hazardous” (class II) pesticide based on animal studies. Few reports of poisoning with acetamiprid and clothianidin have been reported [2]. However, to the best of our knowledge, acute severe human toxicity from thiacloprid ingestion and death as a result have not been reported so far. A 23-year-old man was admitted to emergency department 2 hours after deliberate ingestion of about 100 mL of thiacloprid suspension (ALANTO 240SC, containing 21.7% thiacloprid w/w, manufactured by Bayer CropScience, Ankleshwar, Gujarat State, India) mixed with ethanol. The pesticide bottle brought with him is shown in Figure He initially had nausea, vomiting, and agitation and developed multiple episodes of generalized tonic-clonic seizures 2 hours after ingestion. He remained unconscious and required intubation and mechanical ventilation for poor respiratory efforts. Following intubation, gastric lavage was performed. Examination revealed a young man deeply unconscious and not responding to painful stimuli. He was noted to have tachycardia (heart rate between 130 and 150/min), blood pressure between 140/90 and 160/100 mm of Hg, an artificial prosthetic eye on the right side, and dilated and nonreactive left pupil. He was given intravenous thiamine, lorazepam, phenytoin, and valproate, followed by continuous midazolam infusion. Laboratory evaluation at admission revealed the follow-
0735-6757/© 2014 Elsevier Inc. All rights reserved.
ing: serum sodium, 136 mmol/L; potassium, 4.4 mmol/L; glucose, 7.5 mmol/L; calcium, 2.15 mmol/L; phosphate, 1.36 mmol/L; blood urea nitrogen, 15 mmol/L; serum creatinine, 230 μmol/L; bilirubin, 27.4 μmol/L; aspartate transaminase, 63 IU/L; alanine transaminase, 88 IU/L; alkaline phosphatase, 172 IU/L; hemoglobin, 146 g/L; leukocytes, 20.6 × 109/L (93% neutrophils); and platelets, 208 × 10 9/L. Serum cholinesterase level was normal. Electrocardiogram was unremarkable, except for sinus tachycardia. Chest radiograph was normal. Seizures were controlled 8 hours after ingestion. Despite fluid challenge, he developed progressive hypotension and oliguria 30 hours after ingestion; and serum creatinine increased to 371 μmol/L. Serum creatinine kinase level was 6951 U/L, suggesting rhabdomyolysis. Cardiac troponins were negative. Repeat electrocardiogram showed sinus tachycardia. Arterial blood gases showed metabolic acidosis with a pH of 7.20, plasma bicarbonate of 12 mmol/L, and potassium: 4.7 mmol/L. He remained comatose, and right internal jugular double lumen central venous catheter was placed for monitoring of volume status and hemodialysis. However, before hemofiltration could be initiated, he developed shock refractory to vasopressors. He had bradycardia, sustained cardiac arrest, and expired 36 hours after ingestion. Neonicotinoids are potent agonists at the nicotinic acetylcholine receptors, particularly of the α2β4 subtype, and cause neuromuscular paralysis and death of insects by causing excessive depolarization. Neonicotinoid pesticides have low affinity to mammalian nicotinic receptors and poor penetration through the mammalian blood-brain barrier [3]. Human safety data are mainly extrapolated from animal studies. A Sri Lankan study [1] involving 56 imidacloprid poisoning cases found low lethality even with heavy ingestions. However, fatalities from imidacloprid poisoning have been reported [4–8]. Inhalation and dermal contact can also lead to poisoning [2]. The index patient had nausea, vomiting, tachycardia, hypertension, mydriasis with loss of light reflex, and respiratory paralysis, suggesting human nicotinic acetylcholine receptor stimulation by thiacloprid at toxic doses. Similar manifestations have been reported in imdacloprid poisoning [1,4–6]. Neurological toxicity manifesting with recurrent seizures, deep unconsciousness, and rhabdomyolysis has been reported in imidacloprid poisoning as well [4,9]. Ingestion of ethanol along with thiacloprid might have partly contributed to prolonged unconsciousness and respiratory depression, as reported in imidacloprid poisoning [1]. The index patient developed manifestations of multiorgan dysfunction such as AKI, metabolic acidosis, and hypotension before death, similar to that reported in imidacloprid poisoning [1,5]. In the index patient, recurrent seizures might have partly contributed to rhabdomyolysis, AKI, and metabolic acidosis. The refractory hypotension in the index case is less likely to have resulted from myocardial toxicity because cardiac troponins were negative. He developed bradycardia before death. Cardiovascular
310.e6
K.V. Vinod et al. / American Journal of Emergency Medicine 33 (2015) 310.e5–310.e6
antidote for neonicotinoid poisoning [3]. Management is mainly symptomatic and supportive. To conclude, thiacloprid, when ingested heavily, can cause severe toxicity similar to imidacloprid and death. In the absence of a specific antidote, the management is mainly symptomatic and supportive. Kolar Vishwanath Vinod, MD⁎ Sadashivan Srikant, MBBS Gnanavel Thiruvikramaprakash, MBBS Tarun Kumar Dutta, MD Dept. of General Medicine Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Dhanvantri Nagar, Puducherry Pondicherry 605006, India ⁎Corresponding author. Tel.:+91 9442604554. fax:+91 413 2272735 E-mail address: [email protected] http://dx.doi.org/10.1016/j.ajem.2014.08.013
References
Figure. The pesticide bottle brought with the patient containing 21.7% w/w thiacloprid suspension concentrate.
manifestations such as unexplained tachycardia [1] and bradycardia [4–6], ventricular arrhythmias [6,8], and hypotension [1,2,5,6] have been reported in imidacloprid poisoning as well. We could not assay the plasma of the patient for thiacloprid because the facility is unavailable. However, the pesticide bottle brought with the patient and the clinical manifestations make the diagnosis of thiacloprid poisoning highly likely. There is no specific
[1] Mohamed F, Gawarammana I, Robertson TA, Roberts MS, Palangasinghe C, Zawahir S, et al. Acute human self-poisoning with imidacloprid compound: a neonicotinoid insecticide. PLoS One 2009;4:e5127 [Epub]. [2] Lin PC, Lin HJ, Liao YY, Guo HR, Chen KT. Acute poisoning with neonicotinoid insecticides: a case report and literature review. Basic Clin Pharmacol Toxicol 2013; 112:282–6. [3] Tomizawa M, Casida JE. Neonicotinoid insecticide toxicology: mechanisms of selective action. Annu Rev Pharmacol Toxicol 2005;45:247–68. [4] Iyyadurai R, George IA, Peter JV. Imidacloprid poisoning—newer insecticide and fatal toxicity. J Med Toxicol 2010;6:77–8. [5] Shadnia S, Moghaddam HH. Fatal intoxication with imidacloprid insecticide. Am J Emerg Med 2008;26:634.e1–4. [6] Yeh IJ, Lin TJ, Hwang DY. Acute multiple organ failure with imidacloprid and alcohol ingestion. Am J Emerg Med 2010;28:255.e1–3. [7] Proenca P, Teixeira H, Castanheira F, Pinheiro J, Monsanto PV, et al. Two fatal intoxication cases with imidacloprid: LC/MS analysis. Forensic Sci Int 2005;153: 75–80. [8] Huang NC, Lin SL, Chou CH, Hung YM, Chung HM, et al. Fatal ventricular fibrillation in a patient with acute imidacloprid poisoning. Am J Emerg Med 2006;24:883–5. [9] Agarwal R, Srinivas R. Severe neuropsychiatric manifestations and rhabdomyolysis in a patient with imidacloprid poisoning. Am J Emerg Med 2007;25:844–5.
