Efficacy of Phenobarbital for the Treatment of Organophosphate-Induced Refractory Status Epilepticus and Neuronal Injury
Abstract number :
2.024
Submission category :
1. Translational Research: 1A. Mechanisms / 1A4. Mechanisms of Therapeutic Interventions
Year :
2017
Submission ID :
349363
Source :
www.aesnet.org
Presentation date :
12/3/2017 3:07:12 PM
Published date :
Nov 20, 2017, 11:02 AM
Authors :
Doodipala Samba. Reddy, Texas A&M University Health Science Center; A Habib, Texas A&M University Health Science Center; V Golub, Texas A&M University Health Science Center; R Kuruba, Texas A&M University Health Science Center; and X Wu, Texas A&M Univers
Rationale: Organophosphates (OP) such as DFP and soman are lethal chemical agents that can produce seizures, refractory status epilepticus (SE) and brain damage. There are few optimal treatments for late or refractory SE. Phenobarbital is a first-line drug for the treatment of SE. Practically, 40-min or more is often necessary for first responders to arrive and assist in a chemical incident. However, it remains unclear if administration of phenobarbital 40-min after OP intoxication is still effective. Here, we investigated the efficacy of phenobarbital treatment at 40-min post-exposure to OP intoxication. Methods: Acute refractory SE was induced in rats by DFP injection as per a standard paradigm. After 40- minutes, subjects were given phenobarbital (30-100 mg/kg, IM). The progression of seizure activity was monitored by video-EEG recordings. The extent of brain damage was assessed 3 days after DFP by neuropathology quantifications of neurodegeneration and neuronal injury by unbiased stereology. Results: Phenobarbital produced a dose-dependent seizure protection. A substantial decrease in SE was evident at 30 and 60 mg/kg, and a complete seizure termination was noted at 100 mg/kg within 70 after treatment. Neuropathology findings showed dose-dependent neuronal protection with significantly strong protection at 60 and 100 mg/kg cohorts. Although higher doses resulted in protection against refractory SE and neuronal damage, they did not positively correlate with improved survival rate. Moreover, phenobarbital caused serious adverse effects including anesthetic or comatose state and even death. Conclusions: Overall, phenobarbital is not an optimal drug therapy for refractive SE following OP intoxication because of negative outcomes on survival and cardio-respiratory function. Thus, the need for sophisticated support to maintain the cardio-respiratory function and limited survival rates may preclude its use in mass casualty situations. **Supported by NIH CounterACT Grant #U01-NS083460** Funding: **Supported by NIH CounterACT Grant #U01-NS083460**
Translational Research