Rhabdomyolysis, methemoglobinemia and acute kidney injury after indoxacarb poisoning

To the Editor:

Indoxacarb is an oxadiazine pesticide that has high insecticidal and low mammalian toxicity. There have been several cases of indoxacarb-induced methemoglobinemia and acute kidney injury (AKI), but no case of indoxacarb-induced rhabdomyolysis and AKI has been reported.^1–3 We wish to report a patient presenting with rhabdomyolysis, AKI and methemoglobinemia after ingestion of indoxacarb in propylene glycol.

A 68-year-old male was admitted to the emergency room after ingestion of 250 mL of insecticide containing 5 g of indoxacarb in 85% of propylene glycol (Steward Gold, Korea) in a suicide attempt. He had a past history of hypertension. His mental status was clear with Glasgow Coma Scale score of 15 and blood pressure was 90/50 mmHg, temperature 36.7°C, heart rate 110 per minute, respiratory rate 22. Laboratory data are shown in the table. Because cyanosis of lips and nails was noticed, and he complained of breathing difficulty despite of oxygen therapy, he was intubated. Thereafter, gastric lavage was initiated, and charcoal was administered together with intravenous isotonic saline. At that time, blood methemoglobin and fractional oxyhemoglobin (FO₂Hb) (RapidLab1265, Siemens Healthcare Diagnostics Ltd., Germany) concentrations were 52.7% and 46.0%, respectively (Table 1). He was given 1 mg/kg of methylene blue intravenously at intervals of 8 h with 1 g of vitamin C. After 26 hours of treatment, methemoglobin and FO₂Hb levels were 0.3% and 96.7%, respectively, his vital signs improved, and the endotracheal tube was removed. However, he was given isotonic saline continuously because CPK and LDH levels had continued to increase up to 8970 IU/L and 582 IU/L, and he developed oliguria.

Table 1. Laboratory data during hospitalization.

	Admission	1^st day	3^rd day	8^th day
pH	7.24	7.49	7.48	7.46
PaO2 (mmHg)	249	224	110	133
PaCO2 (mmHg)	28	30	35	37
Base excess (mmol/L)	−14	0.5	2.5	4.1
Bicarbonate (mmol/ L)	14.1	24.9	26.7	28.1
Methemoglobin (%)	52.7	0.3
Fractional oxyhemoglobin (%)	46.0	96.7
Sodium(mEq/L)	140	143	136	139
Potassium (mEq/L)	3.4	4.1	4.2	4.3
Chloride (mEq/L)	107	111	104	103
Blood urea nitrogen (mg/dL)	39.3	35.6	29.5	22.1
Creatinine (mg/dL)	2.44	2.27	1.07	0.87
Creatine phosphokinase (IU/L)	3814	8970	4631	456
Lactate dehydrogenase (IU/L)	256	582	355	266

On day 3 of admission, serum creatinine concentration was 1.07 mg/dL and CPK and LDH levels fell to 4631 IU/L and to 355 IU/L, respectively. He was transferred general ward and discharged in a stable condition at day 8, when CPK and LDH levels were resolving to 456 IU/L and 266 IU/L, respectively.

The symptoms of methemoglobinemia are often nonspecific, but as methemoglobin levels increase, typical symptoms develop. Levels of 20–50% will cause respiratory distress, dizziness, headache, and fatigue as in this case. Lethargy and stupor develop at levels around 50% and death may occur around 70%.^1,2

Indoxacarb is an oxadiazine insecticide and human toxicity includes blurred vision, skin sensitization, and alteration in blood cell count. Several reports suggested that methemoglobinemia occurs after indoxacarb ingestion because its aromatic metabolites can biotransform to active intermediates that produce methemoglobin.^1–3 A toxicity study on rats showed elevated serum creatinine levels and a decreased kidney weight, suggesting indoxacarb induced renal injury. The mechanism of indoxacarb-induced renal injury in humans remains unclear. In our patient, rhabdomyolysis may have been induced by methemoglobinemia.^4,5 AKI may also result from indoxacarb-induced circulatory shock. We report what we believe is the first case of acute toxicity induced by indoxacarb presenting with rhabdomyolysis, methemoglobinemia, and AKI. Clinicians should be aware of this rare, but important complication that may present after ingestion. This patient was treated with methylene blue and hydration and recovered successfully.