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.
