Multimodal therapy successfully treats methemoglobinemia caused by emamectin benzoate and indoxacarb poisoning: a case report

Abstract

Poisoning from emamectin benzoate combined with indoxacarb can cause neurological symptoms and methemoglobinemia, which may present clinically as confusion, cyanosis, dyspnea, and limb convulsions. In such cases, naloxone can be used to alleviate neurological symptoms, while high-dose vitamin C and low-concentration methylene blue can reduce methemoglobin (MetHb) to improve hypoxic symptoms. Hemoperfusion and continuous renal replacement therapy (CRRT) can rapidly remove exogenous and endogenous toxins from the blood, effectively protecting against organ damage to the heart, liver, and kidneys caused by emamectin benzoate poisoning.

Case report

A 63-year-old male patient was admitted to the emergency department after ingesting approximately 100 ml of 9% emamectin benzoate and indoxacarb pesticide following alcohol intoxication. He was found by family members about 3.5 h later and was admitted to Qingdao Eighth People’s Hospital at 03:43 on September 10, 2022. Upon admission, the patient was drowsy with a Glasgow Coma Scale (GCS) score of 11. Physical examination revealed normal complexion, coffee-colored vomitus at the corner of the mouth, temperature of 36.5 °C, pulse rate of 72 beats per minute, respiratory rate of 27 breaths per minute, blood pressure of 120/83 mmHg, normal SpO2, equal and round pupils of about 2.5 mm, sensitive light reflexes, clear lung sounds without dry or wet rales, regular heart rhythm, soft abdomen without tenderness, normal muscle strength and tone in all limbs, and negative pathological reflexes. The patient received gastric lavage with 1000 ml of water, urgent blood gas analysis, liver and kidney function tests, coagulation tests, and a cranial CT scan. Naloxone 0.4 mg was administered intravenously to promote awakening, and pantoprazole 80 mg was given intravenously to protect the gastric mucosa. At 04:31, the emergency test results showed a cholinesterase level of 6660.00 U/L, potassium 3.18 mmol/L (decreased), sodium 139 mmol/L, chloride 98.30 mmol/L, phosphorus 1.68 mmol/L (increased), and CO2 of 21.10 mmol/L. At 05:03, the pH was 7.33 (decreased), PaO2 was 101.00 mmHg (increased), PaCO2 was 43.10 mmHg, SaO2, and oxyhemoglobin (HbO2) were observed (Fig. 1). The actual bicarbonate was 22.70 mmol/L, standard bicarbonate was 21.70 mmol/L, potassium was 3.00 mmol/L (decreased), sodium was 140.00 mmol/L, chloride was 99.00 mmol/L, calcium was 1.10 mmol/L (decreased), anion gap was 18.00 (increased), lactate was 3.60 mmol/L (increased), and glucose was 7.60 mmol/L (increased). The coagulation test and cranial CT scan showed no significant abnormalities. During emergency treatment, the patient gradually developed cyanosis of the face and lips, accompanied by rapid breathing and an increased heart rate to about 95–110 beats per minute, with SaO2 dropping to about 80–85%. For further diagnosis and treatment, the patient was admitted to the ICU at 05:30. Upon admission, the patient had a GCS score of 8. At 06:31, arterial blood gas analysis and related auxiliary examinations showed PaCO2 of 31.9 mmHg (decreased), PaO2 of 69.7 mmHg (decreased), absolute neutrophil count of 6.84 × 10^9/L (increased), and neutrophil percentage of 76.10% (increased).

Fig. 1

Changes of SaO2, HbO2 and MetHb values with time before and after treatment

The patient was drunk and had a clear history of taking toxic substances, with shortness of breath accompanied by cyanosis of the mouth, lip and finger tip. During the blood gas analysis, the arterial blood color was dark brown to the naked eye, and the examination results showed that HbO2 decreased, MetHb increased, and SaO₂ was normal. Hypoxemia and methbemia caused by drug poisoning were considered.The patient was given continuous high-flow oxygen, intravenous methylene blue 120 mg, 5% glucose injection 500 ml + vitamin C injection 3 g + vitamin B6 injection 0.2 g every 12 h for two days, and hemofiltration + hemoperfusion once. Symptomatic treatments included 0.9% sodium chloride injection 100 ml + pantoprazole sodium 10 mg, 5% glucose injection 100 ml + riboflavin phosphate sodium injection 15 ml, compound amino acid injection 500 ml, and 0.9% sodium chloride injection 100 ml + ambroxol hydrochloride 60 mg, all administered once daily for two days. After these treatments, the patient’s consciousness gradually improved, with a GCS score of 10, and symptoms of dyspnea and cyanosis were relatively relieved. Laboratory test results also improved significantly ( Fig. 1). In the afternoon, the patient’s condition continued to improve, with a GCS score of 15, disappearance of cyanosis and dyspnea, and arterial blood gas analysis showing SaO₂, HbO₂, and MetHb close to normal (Fig. 1). The patient was transferred out of the ICU to the general ward for observation for two days and was discharged cured.

Discussion

Emamectin Benzoate, the full name of emamectin, is a new high-efficiency semisynthetic antibiotic insecticide synthesized from avermectin B₁ [1]. The main manifestations of acute poisoning in animals are fatigue, muscle tremor and other nervous system toxic symptoms. The mechanism of action is that as an agonist of Aminobutyricacid (GABA) receptor, it causes the release of GABA from postsynaptic neurons in the brain, and then causes the increase of cell membrane permeability to chloride (CL-). As a result, CL- flows into the nerve cells in large amounts, destroying the normal membrane potential inside and outside the nerve cells, causing the loss of cell function, reducing the excitability of neurons, and disturbing the normal nerve conduction [2]. Emamectin salt poisoning in humans can cause neurotoxic symptoms such as confusion and limb convulsions [3]. Naloxone can relieve the inhibitory effect of poisonings on the central nervous system, excite the sympathetic adrenal medulla, and enhance the catecholamine effect. The patient in this case only showed mild disturbance of consciousness in the early stage of poisoning, and no neurological symptoms such as pupil dilation and limb convulsions occurred, which was considered to be related to the early time of treatment and the early application of naloxone. Indoxacarb is a new type of diazine broad-spectrum insecticide developed by Dupont of the United States [4]. Its mechanism of action is to irreversibly block the sodium channel of insect nerve cells and destroy the transmission of nerve impulses, leading to insect motor dysfunction and eventually paralysis and death [5]. At present, there have been many reports of methbemia caused by indenacarb poisoning at home and abroad [6,7,8,9,10]. The patient in this case had a clear history of taking poison. Combined with its clinical symptoms and previous reports, it was considered that indenacarb poisoning caused the increase of MetHb, which led to the decrease of HbO2 index.

Emamtrel salt poisoning has no specific antidote, and can produce acidic metabolites after entering the human body, which can directly damage the contact site, liver, kidney, lung, brain and other solid organs. Hemoperfusion + CRRT can quickly remove exogenous and endogenous toxins in the blood, which can play an effective protective role in the damage of heart, liver, kidney and other organs caused by emamtrel salt poisoning [11]. Naloxone can relieve the inhibitory effect of emamectin salt poisoning on the central nervous system, and has a good awakening effect on the consciousness disorder caused by it [12]. In normal human body, hemoglobin molecules bound with oxygen contain divalent iron (Fe²⁺). When it is oxidized to trivalent iron (Fe3+), it loses the ability to carry and release oxygen, and methbemia occurs. Clinical manifestations include cyanosis, shortness of breath and a series of symptoms [13]. Methylene blue itself is an oxidant but can have two different effects on hemoglobin, depending on the blood concentration. In the process of glucose 6-phosphate dehydrogenation, under the action of methemoglobin reductase, the electron of reduced coenzyme II(NADPH) was transferred to methylene blue, which was reduced to white methylene blue, and the white methylene blue transferred the electron to Fe³⁺ It is reduced to Fe²⁺ normal hemoglobin, thereby restoring the oxygen-carrying function of Hb. Vitamin C is an effective antioxidant, which can reduce Fe³⁺ to Fe²⁺ with low price and no toxic side effects. It can quickly relieve MeHb symptoms and relieve hypoxia [14]. After the application of low dose of methylene blue and high dose of vitamin C, the hypoxia symptoms such as cyanosis and shortness of breath were rapidly relieved, blood gas analysis showed that MetHb index gradually returned to normal, and methbemia was rapidly corrected.

There are relatively few clinical case reports of emamectin · indenacarb poisoning, which can lead to neurological symptoms and methbemia in patients. The patient in this case ingested approximately 100 ml of 9% Emamectin Benzoate-Indoxacarb. At this toxic dose, the administration of 0.4 mg of Naloxone once, 120 mg of Methylene Blue once, and 3 g of Vitamin C injection twice a day for 2 days was sufficient to alleviate the neurological toxicity symptoms and methemoglobinemia (MetHb).Indenacarb can irreversibly block the sodium channel of nerve cells, leading to organic damage to important organs such as heart, liver, and kidney. Early hemoperfusion + CRRT to remove the absorbed toxin in the body is of great significance to reduce the damage to important organs caused by poisoning. In this case, through the above comprehensive treatment plan, the patient finally recovered and was discharged. In addition to common drugs and chemicals, indenacarb insecticide can also cause toxic methemoglobinemia, which should be vigilant in clinical work. It is hoped that the diagnosis and treatment experience of this case can provide reference for the clinical treatment of emamectin · indacarb poisoning.