We have shown that briefly inhaled isoflurane rapidly halts convulsions and protects the central nervous system (CNS) from organophosphate-induced neuronal loss when administered at 5% for 5 min, even as late as 1 h after organophosphate exposure. In the current study we investigated if an injectable form of isoflurane was as effective as inhaled isoflurane. We used a mixture of 10% isoflurane dissolved in an IV-compatible lipid-water emulsion for intravenous administration. Rats with an implanted jugular vein cannula were infused with 1,000 μL of the 10% isoflurane-lipid emulsion (ILE) mixture at a rate of 200 μL per minute, which achieved full anesthesia lasting approximately 10 min. When administered 30 min after a highly lethal dose of the organophosphate insecticide paraoxon (POX), the short-duration administration halted convulsions over the course of the study and prevented the great majority of neuronal loss as shown by Fluoro-Jade B staining (FJB). Our results indicate that injectable isoflurane is very effective for treating organophosphate poisoning, negating the need for vaporizer equipment and enabling intravenous therapy.

Organophosphate (OP) insecticide poisoning remains a significant world health issue. Despite attempts to reduce OP insecticide use in some countries, they continue to be used extensively in many regions, putting agricultural workers at risk of excess exposure. Furthermore, the high toxicity and ready availability of OP insecticides in agricultural settings have created an additional public health issue due to their use in attempted suicides. Tens of thousands of people are admitted to hospitals every year after intentional ingestion of OP insecticides. The standard treatment regimen for OP poisoning can prevent mortality, even in some severe cases, but these treatments do not protect the central nervous system (CNS) from excitotoxic damage, and therefore, additional neuroprotective treatments are needed. One promising treatment is the use of halogenated ether anesthetics, including isoflurane, a common anesthetic available in hospitals throughout the world. Isoflurane can be administered by inhalation using vaporizer equipment, or it can be injected intravenously as a lipid–water emulsion. In both cases, excellent neuroprotection has been observed in preclinical models, even when administered up to 1 h after the onset of OP insecticide poisoning. Prolonged administration was not necessary for neuroprotective efficacy, with administration times of only 5 min being sufficient. Including inhalational anesthetics as an adjunct to the standard treatment for OP poisoning could significantly reduce chronic morbidities, especially long-term CNS damage. Research is ongoing to bring this promising treatment to human trials.

Organophosphate (OP) insecticide poisoning remains a significant world health issue. Despite attempts to reduce OP insecticide use in some countries, they continue to be used extensively in many regions, putting agriculture workers at risk of excess exposure. Further, the high toxicity and ready availability of OP insecticides in agricultural settings has created an additional public health issue due to their use in attempted suicides. Tens of thousands of people are admitted to hospitals every year after intentional ingestion of OP insecticides. The standard treatment regimen for OP poisoning can prevent mortality, even in some severe cases, but these treatments do not protect the central nervous system (CNS) from excitotoxic damage, and therefore additional neuroprotective treatments are needed. One promising treatment is the use of halogenated ether anesthetics including isoflurane, a common anesthetic available in hospitals throughout the world. Isoflurane can be administered by inhalation using vaporizer equipment, and can be injected intravenously as a lipid-water emulsion. In both cases, excellent neuroprotection has been observed in pre-clinical models, even when administered up to 1 hour after the onset of OP insecticide poisoning. Prolonged administration was not necessary for the neuroprotective efficacy, with administration times of only 5 minutes being sufficient. Research is ongoing to bring this promising treatment to human trials.