a) Adequate decontamination of dermal exposure and supportive care are the mainstays of treatment for mild to moderate exposure. Treat hypotension with IV fluids.

a) Preform endotracheal intubation and mechanical ventilation in patients with coma or respiratory depression or recurrent seizures. Treat symptomatic methemoglobinemia with methylene blue Severe metabolic acidosis can be treated with sodium bicarbonate. Treat hypotension with IV fluids, add pressors if necessary.

a) PREHOSPITAL: Because of the risk of seizures and aspiration, prehospital gastrointestinal decontamination should be avoid. If the exposure is dermal, remove the patient's clothes and thoroughly wash the skin.
b) HOSPITAL: Activated charcoal should be used with caution because of the risk of CNS depression and subsequent risk of pulmonary aspiration. Activated charcoal should only be used in a patient who presents soon after an ingestion and who is awake and alert . If the ingestion was recent and involved a liquid formulation, nasogastric suction of gastric contents can be considered. If the exposure is dermal, remove the patient's clothes and thoroughly was the skin.

a) Patients with altered mental status or who are comatose may need endotracheal intubation and mechanical ventilation.

a) None.

a) Initiate oxygen therapy. Treat with methylene blue if patient is symptomatic (usually at methemoglobin concentrations greater than 20% to 30% or at lower concentrations in patients with anemia, underlying pulmonary or cardiovascular disease). METHYLENE BLUE: INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules and 10 mg/1 mL (1% solution) vials. Additional doses may sometimes be required. Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection. NEONATES: DOSE: 0.3 to 1 mg/kg.

a) Dialysis is unlikely to be of benefit due to the large volume of distribution.

a) HOME CRITERIA: Patients with minor dermal exposure can be monitored at home. Patients with prolonged or repeated dermal application or inhalation exposures should be referred to a healthcare facility if they become symptomatic.
b) OBSERVATIONAL CRITERIA: Adults who intentionally ingest indoxacarb or any child with an ingestion should be referred to a healthcare facility. Patients with significant exposures should be observed for 8 hours and may be discharged if asymptomatic and without methemoglobinemia during this time.
c) ADMISSION CRITERIA: Patients with methemoglobinemia, hypotension, mental status changes, seizures, respiratory failure, or persistent metabolic acidosis should be admitted. Patients with respiratory, CNS, or cardiac toxicity should be admitted to an ICU.
d) CONSULT CRITERIA: A medical toxicologist or poison control center should be consulted in cases that involve cardiac or CNS toxicity or clinically significant methemoglobinemia.

a) Failure to identify indoxacarb as the ingested insecticide. Toxicity from coingestants, either formulated with indoxacarb (ie, prophylene glycol) or ingested with to indoxacarb, should be considered.

a) Indoxacarb and it's bioactive metabolite block sodium-dependant action potentials in nerve preparations and isolated neurons of insects, and acts with a higher affinity for inactive channels. The exact mechanism for toxicity is unknown. Neurotoxicity and hemopoietic effects have been documented in studies involving dogs, rats and mice. Intentional ingestion of indoxacarb suggests this compound has deleterious effects in humans, leading to methemoglobinemia.

a) Differential diagnosis is broad and includes other agents that cause may methemoglobinemia.

a) Hypotension has been reported in patients who developed methemoglobinemia after indoxacarb ingestion.
b) CASE REPORT: A 52-year-old man presented with coma (Glasgow Coma Score 8 of 15), hypotension (80/50 mmHg), and methemoglobinemia (cyanosis that persisted despite intubation and 100% oxygen, chocolate brown blood and saturation gap, methemoglobin concentration not determined) after ingesting indoxacarb. He improved with methylene blue therapy (Chhabra et al, 2010).
c) CASE REPORT: A 71-year-old woman presented with coma (Glasgow Coma Score 7 of 15), hypotension (70/60 mmHg), tachypnea (30 breaths/min), metabolic acidosis, and methemoglobinemia (initial methemoglobin concentration 5.4% increased to 29.2% 2 hours later) after ingesting indoxacarb. She developed worsening acidosis and renal failure, was treated with methylene blue and CVVH and recovered (Park et al, 2011).

a) CNS depression and coma have been reported in patients with methemoglobinemia after indoxacarb ingestion.
b) CASE REPORT: A 52-year-old man presented with coma (Glasgow Coma Score 8 of 15), hypotension (80/60 mmHg), and methemoglobinemia (cyanosis that persisted despite intubation and 100% oxygen, chocolate brown blood and saturation gap, methemoglobin concentration not determined) after ingesting indoxacarb. He improved with methylene blue therapy (Chhabra et al, 2010).
c) CASE REPORT: A 71-year-old woman presented with coma (Glasgow Coma Score 7 of 15), hypotension (70/60 mmHg), tachypnea (30 breaths/min), metabolic acidosis, and methemoglobinemia (initial methemoglobin concentration 5.4% increased to 29.2% 2 hours later) after ingesting indoxacarb. She developed worsening acidosis and renal failure, was treated with methylene blue and CVVH and recovered (Park et al, 2011).
d) CASE REPORT: A 48-year-old man presented to the hospital after acute ingestion of an unknown insecticide. Upon presentation, the patient was vomiting with CNS depression (Glasgow coma score 13 of 15). He was treated for organophosphate poisoning with atropine and PAM-200 infusion; however, his status deteriorated and he developed muddy, brown-colored blood and peripheral cyanosis with a methemoglobin concentration of 33%. Upon further investigation with the family, it was found the man had ingested indoxacarb. Treatment for organophosphate ingestion was stopped. The patient was then treated with methylene blue, vitamin C, and other supportive care, and his methemoglobinemia resolved. The patient was discharged from the ICU 7 days after the event without further sequelae (Prasanna et al, 2008).

a) CASE REPORT: A 68-year-old man presented with cyanotic lips and nails and dyspnea after ingesting 50 mL of an insecticide containing 5 g of indoxacarb in 85% of propylene glycol. Laboratory results revealed a blood methemoglobin of 52.7%, fractional oxyhemoglobin of 46% and creatinine 2.44 mg/dL. Following supportive therapy for 26 hours, including methylene blue and vitamin C, his vital signs improved and laboratory results showed methemoglobin and fractional oxyhemoglobin concentrations of 0.3% and 96.7%, respectively. At this time, his CPK and LDH concentrations were 8970 IU/L and 582 IU/L, respectively, and he developed oliguria. Following further supportive care, his condition continued to improve and he was discharged on day 8 with a creatinine of 0.87 mg/dL (Jin, 2012).
b) CASE REPORT: A 71-year-old woman with diabetes mellitus and hypertension ingested approximately 100 mL of an insecticide containing 5 grams of indoxacarb in a suicide attempt. Her total ingestion was reported to be approximately 84.3 mg/kg. She presented to the hospital with methemoglobinemia and acute renal failure. She was treated with methylene blue. However, her acute renal failure persisted despite treatment and she developed metabolic acidosis. After receiving continuous veno-venous hemofiltration and sodium bicarbonate, the patient regained normal renal function and was discharged 14 days after the event (Park et al, 2011).

a) CASE REPORT: A 71-year-old woman with diabetes mellitus and hypertension ingested approximately 100 mL of an insecticide containing 5 grams of indoxacarb in a suicide attempt. Her total ingestion was reported to be approximately 84.3 mg/kg. She presented to the hospital with methemoglobinemia and acute renal failure. She was treated with methylene blue. However, her acute renal failure persisted despite treatment and she developed metabolic acidosis. After receiving continuous veno-venous hemofiltration and sodium bicarbonate, the patient regained normal renal function and was discharged 14 days after the event (Park et al, 2011).

a) Methemoglobinemia has been reported with acute ingestion of indoxacarb.
b) CASE REPORT: A 68-year-old man presented with cyanotic lips and nails and dyspnea after ingesting 50 mL of an insecticide containing 5 g of indoxacarb in 85% of propylene glycol. Laboratory results revealed a blood methemoglobin of 52.7% and fractional oxyhemoglobin of 46%. Following supportive therapy for 26 hours, including methylene blue and vitamin C, his vital signs improved and laboratory results showed methemoglobin and fractional oxyhemoglobin concentrations of 0.3% and 96.7%, respectively. At this time, his CPK and LDH concentrations were 8970 IU/L and 582 IU/L, respectively, and he developed oliguria. Following further supportive care, his condition continued to improve and he was discharged on day 8 (Jin, 2012).
c) CASE REPORT: A 48-year-old man presented to the hospital after acute ingestion of an unknown insecticide. Upon presentation, the patient was vomiting but conscious. He was treated for organophosphate poisoning with atropine and PAM-200 infusion; however, his status deteriorated and he developed muddy, brown-colored blood and peripheral cyanosis with a methemoglobin concentration of 33%. Upon further investigation with the family, it was found the man had ingested indoxacarb. Treatment for organophosphate ingestion was stopped. The patient was then treated with methylene blue, vitamin C, and other supportive care, and his methemoglobinemia resolved. The patient was discharged from the ICU 7 days after the event without further sequelae (Prasanna et al, 2008).
d) CASE REPORT: A 52-year-old man presented to the hospital unconscious and cyanotic after ingesting an unknown insecticide. The patient was initially treated for organophosphate poisoning; however, his condition did not improve. The patient developed chocolate-colored blood, and his SpO2 remained at 83% to 84%, despite treatment with 100% oxygen. Upon further investigation with the family, it was discovered the man had ingested indoxacarb. Treatment for methemoglobinemia was initiated. The patient received methylene blue and ascorbic acid, and his condition quickly improved. He was discharged from intensive care 5 days after the event without further sequelae (Chhabra et al, 2010).
e) CASE REPORT: A 68-year-old man presented to the hospital 2 hours after ingesting 50 mL of 14.5% indoxacarb (145 mg/mL) in a suicide attempt. Upon presentation, he was conscious but had dizziness, headache, and fatigue. Labs revealed a methemoglobin level of 63.5%. The patient recovered after treatment with methylene blue and standard care and was discharged 3 days after the event (Wu et al, 2010).
f) CASE REPORT: A 71-year-old woman with diabetes mellitus and hypertension ingested approximately 100 mL of an insecticide containing 5 grams of indoxacarb in a suicide attempt. Her total ingestion was reported to be approximately 84.3 mg/kg. She presented to the hospital with methemoglobinemia and acute renal failure. She was treated with methylene blue; however, her acute renal failure persisted despite treatment and she developed metabolic acidosis. After receiving continuous veno-venous hemofiltration and sodium bicarbonate, the patient regained normal renal function and was discharged 14 days after the event (Park et al, 2011).

a) CASE REPORT: A 68-year-old man presented with cyanotic lips and nails and dyspnea after ingesting 50 mL of an insecticide containing 5 g of indoxacarb in 85% of propylene glycol. Laboratory results revealed a blood methemoglobin of 52.7%, fractional oxyhemoglobin of 46% and serum creatinine 2.44 mg/dL. Following supportive therapy for 26 hours, including methylene blue and vitamin C, his vital signs improved and laboratory results showed methemoglobin and fractional oxyhemoglobin concentrations of 0.3% and 96.7%, respectively. At this time, his CPK and LDH concentrations were 8970 IU/L and 582 IU/L, respectively, and he developed oliguria. Following further supportive care, his condition continued to improve and he was discharged on day 8 with a creatinine of 0.87 mg/dL (Jin, 2012).

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Determine the methemoglobin concentration and evaluate the patient for clinical effects of methemoglobinemia (ie, dyspnea, headache, fatigue, CNS depression, tachycardia, metabolic acidosis). Treat patients with symptomatic methemoglobinemia with methylene blue (this usually occurs at methemoglobin concentrations above 20% to 30%, but may occur at lower methemoglobin concentrations in patients with anemia, or underlying pulmonary or cardiovascular disorders). Administer oxygen while preparing for methylene blue therapy.

a) INITIAL DOSE/ADULT OR CHILD: 1 mg/kg IV over 5 to 30 minutes; a repeat dose of up to 1 mg/kg may be given 1 hour after the first dose if methemoglobin levels remain greater than 30% or if signs and symptoms persist. NOTE: Methylene blue is available as follows: 50 mg/10 mL (5 mg/mL or 0.5% solution) single-dose ampules (Prod Info PROVAYBLUE(TM) intravenous injection, 2016) and 10 mg/1 mL (1% solution) vials (Prod Info methylene blue 1% intravenous injection, 2011). REPEAT DOSES: Additional doses may be required, especially for substances with prolonged absorption, slow elimination, or those that form metabolites that produce methemoglobin. NOTE: Large doses of methylene blue may cause methemoglobinemia or hemolysis (Howland, 2006). Improvement is usually noted shortly after administration if diagnosis is correct. Consider other diagnoses or treatment options if no improvement has been observed after several doses. If intravenous access cannot be established, methylene blue may also be given by intraosseous infusion. Methylene blue should not be given by subcutaneous or intrathecal injection (Prod Info methylene blue 1% intravenous injection, 2011; Herman et al, 1999). NEONATES: DOSE: 0.3 to 1 mg/kg (Hjelt et al, 1995).
b) CONTRAINDICATIONS: G-6-PD deficiency (methylene blue may cause hemolysis), known hypersensitivity to methylene blue, methemoglobin reductase deficiency (Shepherd & Keyes, 2004)
c) FAILURE: Failure of methylene blue therapy suggests: inadequate dose of methylene blue, inadequate decontamination, NADPH dependent methemoglobin reductase deficiency, hemoglobin M disease, sulfhemoglobinemia, or G-6-PD deficiency. Methylene blue is reduced by methemoglobin reductase and nicotinamide adenosine dinucleotide phosphate (NADPH) to leukomethylene blue. This in turn reduces methemoglobin. Red blood cells of patients with G-6-PD deficiency do not produce enough NADPH to convert methylene blue to leukomethylene blue (do Nascimento et al, 2008).
d) DRUG INTERACTION: Concomitant use of methylene blue with serotonergic drugs, including serotonin reuptake inhibitors (SRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), norepinephrine-dopamine reuptake inhibitors (NDRIs), triptans, and ergot alkaloids may increase the risk of potentially fatal serotonin syndrome (U.S. Food and Drug Administration, 2011; Stanford et al, 2010; Prod Info methylene blue 1% IV injection, 2011).

a) DOSE: 2 to 4 mg/kg intravenously over 5 minutes. Dose may be repeated in 30 minutes (Nemec, 2011; Lindenmann et al, 2006; Kiese et al, 1972).
b) SIDE EFFECTS: Hypotension with rapid intravenous administration. Vomiting, diarrhea, excessive sweating, hypotension, dysrhythmias, hemolysis, agranulocytosis and acute renal insufficiency after overdose (Dunipace et al, 1992; Hix & Wilson, 1987; Winek et al, 1969; Teunis et al, 1970; Marquez & Todd, 1959).
c) CONTRAINDICATIONS: G-6-PD deficiency; may cause hemolysis.