Complete resolution of acute abamectin toxicity; a deep dive into the pathophysiology leading to appropriate management: A case report

Complete resolution of acute abamectin toxicity; a deep dive into the pathophysiology leading to appropriate management: A case report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Complete resolution of acute abamectin toxicity; a deep dive into the pathophysiology leading to appropriate management: A case report Rizwan Sadiq, Muhammad Mehwar Anjum, Muhammad Umar Mian, Muhammad Rizwan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4829453/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Abamectin toxicity in humans is an uncommon but potentially fatal cause of pesticide poisoning. In this case report, a 14-year-old boy drank almost 50 ml of 1.8% Abamectin pesticide spray. Based on the history given by his brother, the patient initially got irritable with a strong smell of poison and froth coming out of his mouth. At the time of presentation in the Emergency Department (ED), the patient was vomiting and then gradually developed altered mental status with hypotension, tachycardia, hyperaemic conjunctiva, and dermal erythema. He was treated symptomatically with antihistamines, steroids, fluids, and vaso-active agents. His vitals stabilised within 24 hours of the intake and after 3 days of hospital stay including 2 days of observation, he was discharged in good condition with complete recovery. Although abamectin intoxication has a higher threshold for toxicity in humans, there are still an increasing number of cases of it. Consumption of substantial amounts can still prove to be fatal. There is a lack of literature and research on its mechanism of toxicity, pathophysiology, or management guidelines. Yet cases like this are managed based on supportive principles with complete recovery and no sequelae. Abamectin Antihistamine Pesticide Poisoning Supportive INTRODUCTION Avermectins are new pesticides with a wide margin of safety, however, in severe cases of intoxication, they cause coma, hypotension, acidosis and even death. It is of a microbial origin and derived from an actinomycete-named Streptomyces avermectilis. With its gastrointestinal (GI) and contact actions, it affects a broad spectrum of worms, insects, and arachnids. Ivermectin has been applied to humans and animals as an antihelminthic medication (De Sole et al. 1989 ; Starkey and Blagburn 2023 ). Ivermectin also works well in humans to shield against the harmful effects of Onchocerca volvulus, the filarial worm that causes onchocerciasis, or river blindness (Aziz et al. 1982 ). Abamectin is an ivermectin analog that is used to control agriculturally significant insects and mites in fruit trees and vegetables. It contains at least 80% Avermectin-B1a and less than 20% Avermectin-B1b (Starkey & Blagburn, 2023 ; Agarwal, 1998). Currently, agricultural Ivermectin (Ivomec; Merial, London, United Kingdom) and Abamectin (Agri-Mek/Vertimec; Novartis Crop Protection, Basel, Switzerland) are offered for sale in markets around the globe to treat parasite infections in cattle and crop protection, respectively. The toxic effects of abamectin in humans are not clearly defined (Chung et al. 1999 ; Karunatilake et al. 2012 ). Abamectin activates glutamate chloride channels in invertebrate nerve and muscle cells. The affected insect becomes paralyzed, stops feeding, and dies in a few days. In nonhuman subjects, some researchers have found that hypotension induced by abamectin intoxication may be related to nitric oxide. But in humans, the administration of vaso-pressors may maintain the normal range of blood pressure via nitric oxide regulation thus counteracting the effect of Abamectin (Hsu et al. 2003 ). Abamectin has GABA-like action in the central nervous system, but due to the blood brain barrier (BBB) humans are less susceptible to the effects of this toxin (Chung et al. 1999 ). Intoxication manifestations include mydriasis, vomiting, tremors, seizures, partial ptosis, confusion, and coma (Karunatilake et al. 2012 ; Pirasath et al. 2021 ). Mild intoxications manifest symptoms such as nausea, vomiting, diarrhea, and weakness (Wu et al. 2022 ). In severe poisoning hypotension, coma and respiratory failure occur (Rajaratnam et al. 2024 ). In chronic exposure, fertility failure in men with effect on semen is considered (Celik-Ozenci et al. 2012 ). Most patients were poisoned in an attempt to commit suicide by Abamectin (Wu et al. 2022 ). In a study, lethal dose of Abamectin was 10mg/kg body weight for mice (Rajaratnam et al. 2024 ). Based on unknown antidote for poisoning with this pesticide and the fact that human toxicity of this substance is not fully understood, one acute abamectin poisoning case was reported. CASE REPORT A 14-year-old boy presented to the Medical Emergency Department of Sheikh Zayed Hospital, Rahim Yar Khan, Pakistan with a history of intentional drinking of almost 50 ml of 18g/L (1.8% Emulsifiable Concentrate (EC)) Abamectin Pesticide Spray, 45 minutes before presenting to the hospital emergency. Patient history was taken from his brother, according to which, the patient initially got irritable and had a strong smell of poison and froth coming out of his mouth. At the initial emergency presentation, the patient was vomiting, and within 45 minutes, he gradually developed altered mental status along with hypotension, tachycardia, hyperaemic conjunctiva, and dermal erythema. After doing a gastric lavage with activated charcoal, the patient was given 1L Normal Saline, 45.5 mg pheniramine maleate, 250 mg Methylprednisolone, 1g Ceftriaxone, 40 mg Omeprazole, and 10 mg Metoclopramide intravenously, and 5mg of Haloperidol intramuscularly. Oxygen inhalation therapy was also started at 10 L/min along with Dopamine Infusion at 10 drops/min. The patient’s laboratory findings were normal at presentation and are given in Table 1 . Table 1 Labs at the time of admission in the emergency room Laboratory results Parameter Value Normal Value Complete Blood Count Hemoglobin 13.5gm/dL 13-17g/dL TLC 9700/mm 3 4000-11,000/mm 3 Neutrophils 77% 40–75% Lymphocytes 20% 20–45% Monocytes 02% 02–10% Eosinophils 01% 01–06% Platelet Count 253,000/mm 3 150,000-450,000/mm 3 Complete metabolic panel Glucose, Random 78mg/dL 80-140mg/dL Urea 34mg/dL 17-43mg/dL Creatinine 0.6mg/dL 0.9-1.3mg/dL Total Bilirubin 0.4mg/dL 0.3-1.2mg/dL ALT 41U/L < 50U/L Sodium 141mmol/L 136-145mmol/L Potassium 4.1mmol/L 3.5-5.1mmol/L The patient was kept nil per oral (NPO) and he regained consciousness after 16 hours of the initiation of treatment. His blood pressure, temperature, and oxygen saturation normalized, and dopamine and supplemental oxygen were gradually tapered off. He was kept under observation for 2 days on 1L Normal Saline once daily (OD), 100mg Hydrocortisone Sodium Succinate thrice daily (TDS), 45.5mg Pheniramine Maleate OD, 40mg Omeprazole OD and 10mg Metoclopramide intravenously as required (PRN). As he was having no residual signs and symptoms of Abamectin intoxication, he was discharged with a prescription for Cap. Omeprazole 40mg OD and a multivitamin OD for 7 days. A follow-up appointment scheduled 1 week later showed complete recovery with no sequelae of any kind. DISCUSSION Abamectin has three main documented mechanisms: activation of Glutamate-gated Chloride (GluCl) channels causing hyperpolarization, increase of Nitric Oxide (NO), and activation of GABA-ergic neurons in the CNS. Most of the peripheral effects of Abamectin can be explained by the increase of NO in the peripheral blood, like hypotension, tachycardia explained by the reflex baroreceptor activation, diarrhea, and vomiting. Mydriasis is one of the lesser understood manifestations of the Abamectin toxicity. It could be explained by one of the following mechanisms: (i) Reflex central sympathetic activation due to the peripherally acting NO could lead to the mydriasis. The ptosis can be explained by NO causing vascular insufficiency of the oculomotor nerve. The extra-ocular manifestation may have been masked by most of the patients being in an altered state of consciousness (Chung et al. 1999 ). (ii) The GABA-ergic neuronal activation might be the cause of oculomotor nerve depression, causing the mydriasis. The other explanations can include the inactivity of the dilator pupilae muscles due to the GABA-ergic inactivation of the short ciliary nerve fibres that innervate these muscles, since studies suggest a mild level of GABA-ergic involvement in the CNS (Njoo et al. 1995 ). (iii) GluCl channel hyperpolarization in the muscles might inactivate the dilator pupilae muscles causing the mydriasis, as well as the levator palpebrae superioris muscle resulting in the ptosis (Chung et al. 1999 ). But, more high quality, niche studies are required to accurately delineate these mechanisms. According to the manufacturer's brochure as seen in Supplementary Material 1, the effective substance of Abamectin in this pesticide spray is 18gm/L (1.8% EC). The presented case in this study, had consumed almost 50cc (900mg), which is approximately two times of the lethal dose (i.e. 22.5mg/kg). Our patient became unconscious within 2–3 hours. The most common presentation in avermectin poisoning as seen in a retrospective study (Wu et al. 2022 ) was drowsiness (47%), followed by shortness of breath (SOB)/dyspnea (33%), and nausea/vomiting (22%). Pirasath et al. ( 2021 ) reported a case that presented with nausea, vomiting, and altered level of consciousness. In our case, primary symptoms consisted of irritability, vomiting, mydriasis, hypotension, and drowsiness. Skin manifestations have not been reported in Abamectin poisoning previously except in one study by Aminiahidashti et al. ( 2014 ). One commonly overlooked notion regarding pesticide poisoning is the role of adjuvants used with the primary pesticide. For instance, chlorfluazuron is sometimes used as an adjunct with abamectin, and the former in itself has a poisonous nature for humans (Park et al. 2015 ). This highlights a new problem where pesticide companies as in this case, do not mention all the adjuncts used within the spray that could possibly be falsifying the safety profile of Abamectin (Mesnage and Antoniou 2017 ). This is further seen when the same pesticide has varying efficacy on plants against insects with different formulations. Studies on pesticide poisoning like this could pave the way forward for all pesticide companies to mention a comprehensive list of ingredients including adjuncts used in their products to better understand and treat their rare intoxication cases. Nevertheless, the patient’s dermal erythema resolved quickly possibly due to antihistamines, but systemic manifestations persisted. In our patient, hypotension and altered mental status occurred as a progression of drowsiness which can indicate severe intoxication. In one study, seven persons developed mild symptoms including nausea, vertigo, dizziness, weakness, and diarrhea (Pirasath et al. 2021 ). In a study by Soyuncu et al. ( 2007 ), a 25-year-old female presented consuming 108mg/kg Abamectin who developed tremors, altered mental status and respiratory failure, which were treated with supplemental ventilation. In our study, the case exhibited minimal respiratory complications, which were effectively managed with moderate oxygen therapy as compared to the case reported in another study on 18 patients in which 11 showed severe symptoms such as coma, hypotension, and shock (Chung et al. 1999 ). One 72-year-old male died because of aspiration pneumonia after severe intoxication resulting from consumption of 100.7mg/kg Abamectin. Xing ( 2020 ) reported brain dysfunction with abnormal EEG in a 46 years old woman after recovering from abamectin poisoning. In our patient initial lab findings did not suggest liver or kidney damage even though abamectin poisoning is reported to cause hepatotoxicity in rats and nephrotoxicity in carps (Maioli et al. 2013 ; Wu et al. 2023 ). The management protocol in this case follows recommended practices for pesticide poisoning such as gastric lavage and activated charcoal as there are no specific guidelines for abamectin poisoning. In the present case study, the patient developed signs of hypotension and tachycardia that were treated by fluids and vaso-active agents. The patient was given PPIs and antibiotic cover to prevent or treat any damaging effects on the GI tract. A similar case was successfully treated by following conservative care like gastric lavage, charcoal, and vaso-active agents (Aminiahidashti et al. 2014 ). There is no specific antidote for abamectin. However, one patient recovered consciousness after administering just flumazenil and at the same time in at least two patients no such effect of flumazenil as an antidote or empiric treatment for abamectin poisoning in their study was seen (Chung et al. 1999 ; Sun et al. 2015 ). In our case, absence of long term follow up also limits the ability to assess any chronic effect of poisoning. Even though the patient’s lab results upon admission were normal, it is recommended to monitor the hepatic and renal functions. Higher quality and newer studies with more power as well as systematic reviews need to be done on abamectin intoxication to integrate existing literature like establish the role of glutamate gated chloride channels in peripheral nervous system, NO mediated effects, GABA-ergic effects after crossing BBB and the possible rationales behind the use of first generation antihistamines specially in the setting of antimuscarinic like symptoms. Furthermore, the preference of first-generation antihistamines over second generation antihistamines goes against the principles of symptomatic management as it should theoretically worsen all the major symptoms seen in abamectin toxicity across multiple studies; diarrhoea, hypotension, erythema, vomiting, altered mental status. Still, it was seen as efficacious in all the reviewed literature and was the basis of prescription in our case as well. It is possible that the vaso-pressors alone could be enough to mitigate the patients’ symptoms and antihistamines had no direct effect. There is a lack of literature on Abamectin and the mechanism of its toxicity in humans. Despite some studies of its effects on insects, mice or mammalian cells, the exact mechanism of its action or pathophysiology is not established, leading to a spectrum of signs and symptoms across multiple case studies. There is varying evidence on what the typical presentation is and there is a lack of management guidelines. Thus, future research should focus on determining the ideal regimen with rationale and standardising the treatment protocol as well as investigating the short term and long-term effects of abamectin poisoning. STATEMENTS AND DECLARATIONS ACKNOWLEDGEMENTS: None Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Author contributions: All authors contributed to the study conception, literature review and design. Material preparation was done by Muhammad Mehwar Anjum, data collection was done by Rizwan Sadiq and the analysis was done by Muhammad Umar Mian. In the first draft of the manuscript the introduction was written by Aqsa Aamir Butt, the case presentation was written by Muhammad Umar Mian and discussion by Muhammad Rizwan, while the abstract and references list were managed by Muhammad Mehwar Anjum. Rizwan Sadiq reviewed the manuscript and made it coherent with better transitions. Rizwan Sadiq, Muhammad Mehwar Anjum and Muhammad Umar Mian suggested changes and Aqsa Aamir Butt and Muhammad Rizwan reviewed them. All authors collectively worked, read and approved the final manuscript. Ethics approval: The case was managed and supervised by the lead author and under the care of other authors. The consent was taken from the patients. All ethical guidelines were kept in consideration during the formulation and writing of this study. Consent to participate: Informed written consent was obtained from all individual participants like the patient and their attendants for the use of their data with anonymity guaranteed in this study so that this rare toxicity could be better understood and documented. Consent to publish: The authors affirm that the patient and their guardians provided informed consent for publication of their clinically relevant data and lab results in this study. References Aminiahidashti H, Jamali SR, Gorji AMH (2014) Conservative Care in Successful Treatment of Abamectin Poisoning. Toxicol Int 21:322. https://doi.org/10.4103/0971-6580.155386 Aziz MA, Diop IM, Diallo S, et al (1982) Efficacy and tolerance of ivermectin in human onchocerciasis. Lancet 2:171–173. https://doi.org/10.1016/S0140-6736(82)91026-1 Celik-Ozenci C, Tasatargil A, Tekcan M, et al (2012) Effect of abamectin exposure on semen parameters indicative of reduced sperm maturity: a study on farmworkers in Antalya (Turkey). Andrologia 44:388–395. https://doi.org/10.1111/J.1439-0272.2012.01297.X Chung K, Yang CC, Wu ML, et al (1999) Agricultural Avermectins: An Uncommon But Potentially Fatal Cause of Pesticide Poisoning. Ann Emerg Med 34:51–57. https://doi.org/10.1016/S0196-0644(99)70271-4 De Sole G, Remme J, Awadzi K, et al (1989) Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials. Bull World Health Organ 67:707 Hsu DZ, Chiang PJ, Hsu CH, et al (2003) The elucidation of epinephrine as an antihypotensive agent in abamectin intoxication. Hum Exp Toxicol 22:433–437. https://doi.org/10.1191/0960327103HT378OA Karunatilake H, Amarasinghe S, Dassanayake S, et al (2012) Partial ptosis, dilated pupils and ataxia following abamectin poisoning. Ceylon Med J 57:125–126. https://doi.org/10.4038/CMJ.V57I3.4706 Maioli MA, de Medeiros HCD, Guelfi M, et al (2013) The role of mitochondria and biotransformation in abamectin-induced cytotoxicity in isolated rat hepatocytes. Toxicology in Vitro 27:570–579. https://doi.org/10.1016/J.TIV.2012.10.017 Mesnage R, Antoniou MN (2017) Ignoring Adjuvant Toxicity Falsifies the Safety Profile of Commercial Pesticides. Front Public Health 5:1. https://doi.org/10.3389/FPUBH.2017.00361 Njoo FL, Beek WMJ, Keukens HJ, et al (1995) Ivermectin detection in serum of onchocerciasis patients: relationship to adverse reactions. Am J Trop Med Hyg 52:94–97. https://doi.org/10.4269/AJTMH.1995.52.94 Park ES, Kang S, Kim AJ, et al (2015) A Case of Chlorfluazuron Insectisides Poisoning with Mental Change. Journal of the Korean Society of Clinical Toxicology 13:40–42 Pirasath S, Nageswaran B, Vasana Karunasena RP, Gevakaran M (2021) Acute abamectin toxicity: a case report. Toxicol Commun 5:66–68. https://doi.org/10.1080/24734306.2021.1881233 Rajaratnam A, Kularatne WKS, Bowattage S (2024) Abamectin poisoning: a case report and review of literature. Asian Journal of Internal Medicine 3:49–53. https://doi.org/10.4038/AJIM.V3I1.95 Soyuncu S, Oktay C, Berk Y, Eken C (2007) Abamectin intoxication with coma and hypotension. Clin Toxicol (Phila) 45:299–300. https://doi.org/10.1080/15563650601072225 Starkey LA, Blagburn BL (2023) Antiparasitic Drugs. Greene’s Infectious Diseases of the Dog and Cat, Fifth Edition 149–160. https://doi.org/10.1016/B978-0-323-50934-3.00013-6 Sun B, Jia L, Nie S (2015) Administration of flumazenil in a patient with acute abamectin intoxication case report and review of the literature. West Indian Medical Journal 64:162–164. https://doi.org/10.7727/WIMJ.2013.306 Wu X, Ma Y, Li X, et al (2023) Molecular mechanism of kidney damage caused by abamectin in carp: Oxidative stress, inflammation, mitochondrial damage, and apoptosis. Toxicology 494:153599. https://doi.org/10.1016/J.TOX.2023.153599 Wu YK, Chang CH, Yu JH, et al (2022) Intentional avermectin pesticide ingestion: a retrospective multicenter study. Clin Toxicol 60:1099–1105. https://doi.org/10.1080/15563650.2022.2104729 Xing ZY (2020) Abamectin poisoning with severely abnormal electroencephalogram: A case report. https://doi.org/101177/0748233720966506 36:946–950. https://doi.org/10.1177/0748233720966506 Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterial1.jpg Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4829453","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":342494857,"identity":"e0584648-5b11-451e-bcdb-0b20927d4ad9","order_by":0,"name":"Rizwan Sadiq","email":"","orcid":"","institution":"Shaikh Zayed Hospital","correspondingAuthor":false,"prefix":"","firstName":"Rizwan","middleName":"","lastName":"Sadiq","suffix":""},{"id":342494858,"identity":"ed701e77-1d48-4e24-b792-cc57b2b7ff12","order_by":1,"name":"Muhammad Mehwar Anjum","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYFACHhBhA8QHGBg+VABpZuYGYrSkgbUwzjgD0sJIlJbDYCYzbxuIIqBFt733mMTPPYflzRnPmG7mnVcbzd8O1PKjYhtOLWZnzqVJ9jxLN9zZcMbs5txtx3NnHGZsYOw5cxu3lhs5Zjd4DlgzbjhwxuzG223HchuAWpgZ2/Bouf/G7OafA8z2YC28c47lzieo5QaP2W2eA86JIC03eRtqcjcQ1HImx/y3zIG05A0HjpXdnHHsQO5GoJaDeP1y/Iyx4ZsDNrYbbhzeduNDTV3uvPOHDz74UYFbCwJIHACRkAg6QIR6IOBvAJF1xCkeBaNgFIyCEQUAnVpqrIJsUzwAAAAASUVORK5CYII=","orcid":"","institution":"Shaikh Zayed Hospital","correspondingAuthor":true,"prefix":"","firstName":"Muhammad","middleName":"Mehwar","lastName":"Anjum","suffix":""},{"id":342494859,"identity":"8c382588-e571-48b4-93a2-d47e7dbe34d3","order_by":2,"name":"Muhammad Umar Mian","email":"","orcid":"","institution":"Allama Iqbal Medical College","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Umar","lastName":"Mian","suffix":""},{"id":342494860,"identity":"22c08dce-cea0-45a0-8044-475526c29cf7","order_by":3,"name":"Muhammad Rizwan","email":"","orcid":"","institution":"Shaikh Zayed Hospital","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"","lastName":"Rizwan","suffix":""},{"id":342494861,"identity":"8ce6a48b-08fe-43a2-a296-870a514153ce","order_by":4,"name":"Aqsa Aamir Butt","email":"","orcid":"","institution":"Shaikh Zayed Hospital","correspondingAuthor":false,"prefix":"","firstName":"Aqsa","middleName":"Aamir","lastName":"Butt","suffix":""}],"badges":[],"createdAt":"2024-07-30 14:15:10","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-4829453/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4829453/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62922727,"identity":"0a91464f-5eb2-4ee4-8972-033349ef4e80","added_by":"auto","created_at":"2024-08-21 06:03:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":257247,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4829453/v1/72150fef-717b-4847-b40d-19f3c7aac755.pdf"},{"id":62922724,"identity":"2317f1c9-5ce6-4f9e-89cc-91ececd561c0","added_by":"auto","created_at":"2024-08-21 06:03:09","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":220945,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterial1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4829453/v1/63c0e6f4674f7f8601ba7cd6.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Complete resolution of acute abamectin toxicity; a deep dive into the pathophysiology leading to appropriate management: A case report","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAvermectins are new pesticides with a wide margin of safety, however, in severe cases of intoxication, they cause coma, hypotension, acidosis and even death. It is of a microbial origin and derived from an actinomycete-named Streptomyces avermectilis. With its gastrointestinal (GI) and contact actions, it affects a broad spectrum of worms, insects, and arachnids. Ivermectin has been applied to humans and animals as an antihelminthic medication (De Sole et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e1989\u003c/span\u003e; Starkey and Blagburn \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2023\u003c/span\u003e). Ivermectin also works well in humans to shield against the harmful effects of Onchocerca volvulus, the filarial worm that causes onchocerciasis, or river blindness (Aziz et al. \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e1982\u003c/span\u003e). Abamectin is an ivermectin analog that is used to control agriculturally significant insects and mites in fruit trees and vegetables. It contains at least 80% Avermectin-B1a and less than 20% Avermectin-B1b (Starkey \u0026amp; Blagburn, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2023\u003c/span\u003e; Agarwal, 1998). Currently, agricultural Ivermectin (Ivomec; Merial, London, United Kingdom) and Abamectin (Agri-Mek/Vertimec; Novartis Crop Protection, Basel, Switzerland) are offered for sale in markets around the globe to treat parasite infections in cattle and crop protection, respectively.\u003c/p\u003e \u003cp\u003eThe toxic effects of abamectin in humans are not clearly defined (Chung et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1999\u003c/span\u003e; Karunatilake et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Abamectin activates glutamate chloride channels in invertebrate nerve and muscle cells. The affected insect becomes paralyzed, stops feeding, and dies in a few days. In nonhuman subjects, some researchers have found that hypotension induced by abamectin intoxication may be related to nitric oxide. But in humans, the administration of vaso-pressors may maintain the normal range of blood pressure via nitric oxide regulation thus counteracting the effect of Abamectin (Hsu et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). Abamectin has GABA-like action in the central nervous system, but due to the blood brain barrier (BBB) humans are less susceptible to the effects of this toxin (Chung et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1999\u003c/span\u003e). Intoxication manifestations include mydriasis, vomiting, tremors, seizures, partial ptosis, confusion, and coma (Karunatilake et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Pirasath et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Mild intoxications manifest symptoms such as nausea, vomiting, diarrhea, and weakness (Wu et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). In severe poisoning hypotension, coma and respiratory failure occur (Rajaratnam et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). In chronic exposure, fertility failure in men with effect on semen is considered (Celik-Ozenci et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Most patients were poisoned in an attempt to commit suicide by Abamectin (Wu et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). In a study, lethal dose of Abamectin was 10mg/kg body weight for mice (Rajaratnam et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Based on unknown antidote for poisoning with this pesticide and the fact that human toxicity of this substance is not fully understood, one acute abamectin poisoning case was reported.\u003c/p\u003e"},{"header":"CASE REPORT","content":"\u003cp\u003eA 14-year-old boy presented to the Medical Emergency Department of Sheikh Zayed Hospital, Rahim Yar Khan, Pakistan with a history of intentional drinking of almost 50 ml of 18g/L (1.8% Emulsifiable Concentrate (EC)) Abamectin Pesticide Spray, 45 minutes before presenting to the hospital emergency. Patient history was taken from his brother, according to which, the patient initially got irritable and had a strong smell of poison and froth coming out of his mouth. At the initial emergency presentation, the patient was vomiting, and within 45 minutes, he gradually developed altered mental status along with hypotension, tachycardia, hyperaemic conjunctiva, and dermal erythema. After doing a gastric lavage with activated charcoal, the patient was given 1L Normal Saline, 45.5 mg pheniramine maleate, 250 mg Methylprednisolone, 1g Ceftriaxone, 40 mg Omeprazole, and 10 mg Metoclopramide intravenously, and 5mg of Haloperidol intramuscularly. Oxygen inhalation therapy was also started at 10 L/min along with Dopamine Infusion at 10 drops/min. The patient\u0026rsquo;s laboratory findings were normal at presentation and are given in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLabs at the time of admission in the emergency room\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eLaboratory results\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNormal Value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplete Blood Count\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.5gm/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13-17g/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTLC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9700/mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4000-11,000/mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophils\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026ndash;75%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u0026ndash;45%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonocytes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e02%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e02\u0026ndash;10%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEosinophils\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e01%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e01\u0026ndash;06%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet Count\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e253,000/mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e150,000-450,000/mm\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplete metabolic panel\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlucose, Random\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80-140mg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17-43mg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.6mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.9-1.3mg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Bilirubin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.4mg/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3-1.2mg/dL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41U/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;50U/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSodium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e141mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136-145mmol/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePotassium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.1mmol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5-5.1mmol/L\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe patient was kept nil per oral (NPO) and he regained consciousness after 16 hours of the initiation of treatment. His blood pressure, temperature, and oxygen saturation normalized, and dopamine and supplemental oxygen were gradually tapered off.\u003c/p\u003e \u003cp\u003eHe was kept under observation for 2 days on 1L Normal Saline once daily (OD), 100mg Hydrocortisone Sodium Succinate thrice daily (TDS), 45.5mg Pheniramine Maleate OD, 40mg Omeprazole OD and 10mg Metoclopramide intravenously as required (PRN). As he was having no residual signs and symptoms of Abamectin intoxication, he was discharged with a prescription for Cap. Omeprazole 40mg OD and a multivitamin OD for 7 days. A follow-up appointment scheduled 1 week later showed complete recovery with no sequelae of any kind.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eAbamectin has three main documented mechanisms: activation of Glutamate-gated Chloride (GluCl) channels causing hyperpolarization, increase of Nitric Oxide (NO), and activation of GABA-ergic neurons in the CNS. Most of the peripheral effects of Abamectin can be explained by the increase of NO in the peripheral blood, like hypotension, tachycardia explained by the reflex baroreceptor activation, diarrhea, and vomiting. Mydriasis is one of the lesser understood manifestations of the Abamectin toxicity. It could be explained by one of the following mechanisms: (i) Reflex central sympathetic activation due to the peripherally acting NO could lead to the mydriasis. The ptosis can be explained by NO causing vascular insufficiency of the oculomotor nerve. The extra-ocular manifestation may have been masked by most of the patients being in an altered state of consciousness (Chung et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1999\u003c/span\u003e). (ii) The GABA-ergic neuronal activation might be the cause of oculomotor nerve depression, causing the mydriasis. The other explanations can include the inactivity of the dilator pupilae muscles due to the GABA-ergic inactivation of the short ciliary nerve fibres that innervate these muscles, since studies suggest a mild level of GABA-ergic involvement in the CNS (Njoo et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e1995\u003c/span\u003e). (iii) GluCl channel hyperpolarization in the muscles might inactivate the dilator pupilae muscles causing the mydriasis, as well as the levator palpebrae superioris muscle resulting in the ptosis (Chung et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1999\u003c/span\u003e). But, more high quality, niche studies are required to accurately delineate these mechanisms.\u003c/p\u003e \u003cp\u003eAccording to the manufacturer's brochure as seen in Supplementary Material 1, the effective substance of Abamectin in this pesticide spray is 18gm/L (1.8% EC). The presented case in this study, had consumed almost 50cc (900mg), which is approximately two times of the lethal dose (i.e. 22.5mg/kg). Our patient became unconscious within 2\u0026ndash;3 hours. The most common presentation in avermectin poisoning as seen in a retrospective study (Wu et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2022\u003c/span\u003e) was drowsiness (47%), followed by shortness of breath (SOB)/dyspnea (33%), and nausea/vomiting (22%). Pirasath et al. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e) reported a case that presented with nausea, vomiting, and altered level of consciousness. In our case, primary symptoms consisted of irritability, vomiting, mydriasis, hypotension, and drowsiness. Skin manifestations have not been reported in Abamectin poisoning previously except in one study by Aminiahidashti et al. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2014\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOne commonly overlooked notion regarding pesticide poisoning is the role of adjuvants used with the primary pesticide. For instance, chlorfluazuron is sometimes used as an adjunct with abamectin, and the former in itself has a poisonous nature for humans (Park et al. \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). This highlights a new problem where pesticide companies as in this case, do not mention all the adjuncts used within the spray that could possibly be falsifying the safety profile of Abamectin (Mesnage and Antoniou \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). This is further seen when the same pesticide has varying efficacy on plants against insects with different formulations. Studies on pesticide poisoning like this could pave the way forward for all pesticide companies to mention a comprehensive list of ingredients including adjuncts used in their products to better understand and treat their rare intoxication cases. Nevertheless, the patient\u0026rsquo;s dermal erythema resolved quickly possibly due to antihistamines, but systemic manifestations persisted.\u003c/p\u003e \u003cp\u003eIn our patient, hypotension and altered mental status occurred as a progression of drowsiness which can indicate severe intoxication. In one study, seven persons developed mild symptoms including nausea, vertigo, dizziness, weakness, and diarrhea (Pirasath et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). In a study by Soyuncu et al. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2007\u003c/span\u003e), a 25-year-old female presented consuming 108mg/kg Abamectin who developed tremors, altered mental status and respiratory failure, which were treated with supplemental ventilation. In our study, the case exhibited minimal respiratory complications, which were effectively managed with moderate oxygen therapy as compared to the case reported in another study on 18 patients in which 11 showed severe symptoms such as coma, hypotension, and shock (Chung et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1999\u003c/span\u003e). One 72-year-old male died because of aspiration pneumonia after severe intoxication resulting from consumption of 100.7mg/kg Abamectin. Xing (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2020\u003c/span\u003e) reported brain dysfunction with abnormal EEG in a 46 years old woman after recovering from abamectin poisoning. In our patient initial lab findings did not suggest liver or kidney damage even though abamectin poisoning is reported to cause hepatotoxicity in rats and nephrotoxicity in carps (Maioli et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Wu et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2023\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe management protocol in this case follows recommended practices for pesticide poisoning such as gastric lavage and activated charcoal as there are no specific guidelines for abamectin poisoning. In the present case study, the patient developed signs of hypotension and tachycardia that were treated by fluids and vaso-active agents. The patient was given PPIs and antibiotic cover to prevent or treat any damaging effects on the GI tract.\u003c/p\u003e \u003cp\u003eA similar case was successfully treated by following conservative care like gastric lavage, charcoal, and vaso-active agents (Aminiahidashti et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2014\u003c/span\u003e). There is no specific antidote for abamectin. However, one patient recovered consciousness after administering just flumazenil and at the same time in at least two patients no such effect of flumazenil as an antidote or empiric treatment for abamectin poisoning in their study was seen (Chung et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e1999\u003c/span\u003e; Sun et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). In our case, absence of long term follow up also limits the ability to assess any chronic effect of poisoning. Even though the patient\u0026rsquo;s lab results upon admission were normal, it is recommended to monitor the hepatic and renal functions.\u003c/p\u003e \u003cp\u003eHigher quality and newer studies with more power as well as systematic reviews need to be done on abamectin intoxication to integrate existing literature like establish the role of glutamate gated chloride channels in peripheral nervous system, NO mediated effects, GABA-ergic effects after crossing BBB and the possible rationales behind the use of first generation antihistamines specially in the setting of antimuscarinic like symptoms. Furthermore, the preference of first-generation antihistamines over second generation antihistamines goes against the principles of symptomatic management as it should theoretically worsen all the major symptoms seen in abamectin toxicity across multiple studies; diarrhoea, hypotension, erythema, vomiting, altered mental status. Still, it was seen as efficacious in all the reviewed literature and was the basis of prescription in our case as well. It is possible that the vaso-pressors alone could be enough to mitigate the patients\u0026rsquo; symptoms and antihistamines had no direct effect.\u003c/p\u003e \u003cp\u003eThere is a lack of literature on Abamectin and the mechanism of its toxicity in humans. Despite some studies of its effects on insects, mice or mammalian cells, the exact mechanism of its action or pathophysiology is not established, leading to a spectrum of signs and symptoms across multiple case studies. There is varying evidence on what the typical presentation is and there is a lack of management guidelines. Thus, future research should focus on determining the ideal regimen with rationale and standardising the treatment protocol as well as investigating the short term and long-term effects of abamectin poisoning.\u003c/p\u003e"},{"header":"STATEMENTS AND DECLARATIONS","content":"\u003cp\u003eACKNOWLEDGEMENTS: None\u003c/p\u003e\n\u003cp\u003eFunding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript\u003c/p\u003e\n\u003cp\u003eCompeting Interests: The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eAuthor contributions: All authors contributed to the study conception, literature review and design. Material preparation was done by Muhammad Mehwar Anjum, data collection was done by Rizwan Sadiq and the analysis was done by Muhammad Umar Mian. In the first draft of the manuscript the introduction was written by Aqsa Aamir Butt, the case presentation was written by Muhammad Umar Mian and discussion by Muhammad Rizwan, while the abstract and references list were managed by Muhammad Mehwar Anjum. Rizwan Sadiq reviewed the manuscript and made it coherent with better transitions. Rizwan Sadiq, Muhammad Mehwar Anjum and Muhammad Umar Mian suggested changes and Aqsa Aamir Butt and Muhammad Rizwan reviewed them. All authors collectively worked, read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eEthics approval: The case was managed and supervised by the lead author and under the care of other authors. The consent was taken from the patients. All ethical guidelines were kept in consideration during the formulation and writing of this study.\u003c/p\u003e\n\u003cp\u003eConsent to participate: Informed written consent was obtained from all individual participants like the patient and their attendants for the use of their data with anonymity guaranteed in this study so that this rare toxicity could be better understood and documented.\u003c/p\u003e\n\u003cp\u003eConsent to publish: The authors affirm that the patient and their guardians provided informed consent for publication of their clinically relevant data and lab results in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAminiahidashti H, Jamali SR, Gorji AMH (2014) Conservative Care in Successful Treatment of Abamectin Poisoning. Toxicol Int 21:322. https://doi.org/10.4103/0971-6580.155386\u003c/li\u003e\n \u003cli\u003eAziz MA, Diop IM, Diallo S, et al (1982) Efficacy and tolerance of ivermectin in human onchocerciasis. Lancet 2:171\u0026ndash;173. https://doi.org/10.1016/S0140-6736(82)91026-1\u003c/li\u003e\n \u003cli\u003eCelik-Ozenci C, Tasatargil A, Tekcan M, et al (2012) Effect of abamectin exposure on semen parameters indicative of reduced sperm maturity: a study on farmworkers in Antalya (Turkey). Andrologia 44:388\u0026ndash;395. https://doi.org/10.1111/J.1439-0272.2012.01297.X\u003c/li\u003e\n \u003cli\u003eChung K, Yang CC, Wu ML, et al (1999) Agricultural Avermectins: An Uncommon But Potentially Fatal Cause of Pesticide Poisoning. Ann Emerg Med 34:51\u0026ndash;57. https://doi.org/10.1016/S0196-0644(99)70271-4\u003c/li\u003e\n \u003cli\u003eDe Sole G, Remme J, Awadzi K, et al (1989) Adverse reactions after large-scale treatment of onchocerciasis with ivermectin: combined results from eight community trials. Bull World Health Organ 67:707\u003c/li\u003e\n \u003cli\u003eHsu DZ, Chiang PJ, Hsu CH, et al (2003) The elucidation of epinephrine as an antihypotensive agent in abamectin intoxication. Hum Exp Toxicol 22:433\u0026ndash;437. https://doi.org/10.1191/0960327103HT378OA\u003c/li\u003e\n \u003cli\u003eKarunatilake H, Amarasinghe S, Dassanayake S, et al (2012) Partial ptosis, dilated pupils and ataxia following abamectin poisoning. Ceylon Med J 57:125\u0026ndash;126. https://doi.org/10.4038/CMJ.V57I3.4706\u003c/li\u003e\n \u003cli\u003eMaioli MA, de Medeiros HCD, Guelfi M, et al (2013) The role of mitochondria and biotransformation in abamectin-induced cytotoxicity in isolated rat hepatocytes. Toxicology in Vitro 27:570\u0026ndash;579. https://doi.org/10.1016/J.TIV.2012.10.017\u003c/li\u003e\n \u003cli\u003eMesnage R, Antoniou MN (2017) Ignoring Adjuvant Toxicity Falsifies the Safety Profile of Commercial Pesticides. 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Toxicology 494:153599. https://doi.org/10.1016/J.TOX.2023.153599\u003c/li\u003e\n \u003cli\u003eWu YK, Chang CH, Yu JH, et al (2022) Intentional avermectin pesticide ingestion: a retrospective multicenter study. Clin Toxicol 60:1099\u0026ndash;1105. https://doi.org/10.1080/15563650.2022.2104729\u003c/li\u003e\n \u003cli\u003eXing ZY (2020) Abamectin poisoning with severely abnormal electroencephalogram: A case report. https://doi.org/101177/0748233720966506 36:946\u0026ndash;950. https://doi.org/10.1177/0748233720966506\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Abamectin, Antihistamine, Pesticide, Poisoning, Supportive ","lastPublishedDoi":"10.21203/rs.3.rs-4829453/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4829453/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAbamectin toxicity in humans is an uncommon but potentially fatal cause of pesticide poisoning. In this case report, a 14-year-old boy drank almost 50 ml of 1.8% Abamectin pesticide spray. Based on the history given by his brother, the patient initially got irritable with a strong smell of poison and froth coming out of his mouth. At the time of presentation in the Emergency Department (ED), the patient was vomiting and then gradually developed altered mental status with hypotension, tachycardia, hyperaemic conjunctiva, and dermal erythema. He was treated symptomatically with antihistamines, steroids, fluids, and vaso-active agents. His vitals stabilised within 24 hours of the intake and after 3 days of hospital stay including 2 days of observation, he was discharged in good condition with complete recovery. Although abamectin intoxication has a higher threshold for toxicity in humans, there are still an increasing number of cases of it. Consumption of substantial amounts can still prove to be fatal. There is a lack of literature and research on its mechanism of toxicity, pathophysiology, or management guidelines. Yet cases like this are managed based on supportive principles with complete recovery and no sequelae.\u003c/p\u003e","manuscriptTitle":"Complete resolution of acute abamectin toxicity; a deep dive into the pathophysiology leading to appropriate management: A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-21 06:03:04","doi":"10.21203/rs.3.rs-4829453/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7dedad50-d95c-4012-be0a-f22e37fbe38f","owner":[],"postedDate":"August 21st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-21T06:03:04+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-21 06:03:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4829453","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4829453","identity":"rs-4829453","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}