Changes in neuronal cellular injury and neural inflammation during refractory status epilepticus (RSE) treatment with Isoflurane and Midazolam – a biomarker-based study

After admission to NCCU if patient is not intubated in the emergency department it will be done in the NCCU and patient will be ventilated

Vitals will be monitored every 15 min Patient will continue to receive the prescribed AEDs All patients will undergo complete hematology, biochemistry electrocardiography and neurological work-up in the form of computed tomography or Magnetic resonance Imaging scan cerebrospinal fluid examination if indicated toxicology screening and AED drug levels for patients on AEDs

If the seizures are not controlled with the initial benzodiazepine and two AEDs the patient will be diagnosed to have RSE and becomes eligible for the study Bispectral Index monitoring will be performed and wherever feasible cerebral oxygen saturation monitoring will also be done The patients will receive either midazolam or isoflurane for the treatment of RSE We plan to recruit alternate patient into midazolam and isoflurane group

In the midazolam group midazolam will be administered as a bolus of 0.05 mg per kg followed by initiation of infusion at 0.1mg per kg per hr. If the seizures recur more than three times in 15 min or the seizures are uncontrolled for 15 min then the dose will be escalated by 0.1 mg per kg per hr The dose at which seizures are controlled will be noted This escalation will continue if seizures are not terminated till a maximum dose of 0.4 mg per kg per h after which the RSE will be considered Super RSE and treatment failure of the study drug will be considered Thereafter thiopentone infusion will be initiated with a bolus of 3 mg per kg followed by a continuous infusion at a rate of 3 to 5 mg per kg per hr

In the isoflurane group isoflurane will be administered using anaesthesia machine and a dedicated vaporiser using a low flow technique and carbondioxide absorber circle system Isoflurane will be administrated at 0.6 MAC. If the seizures recur more than three times in 15 min, or the seizures are uncontrolled for 15 min then the dose will be escalated by 0.2 MAC This escalation will continue if seizures are not terminated till a maximum dose of 1.2 MAC The MAC at which seizures are controlled will be noted If seizures are not controlled even at 1.2 MAC RSE will be considered SRSE, and treatment failure of the study drug will be considered Thereafter thiopentone infusion will be initiated with a bolus of 3 mg per kg followed by a continuous infusion at a rate of 3 to 5 mg per kg per hr The dose at which seizures are controlled will be noted

If seizures are controlled with isoflurane or midazolam, the particular dose of the drug will be continued for 48 hours after which the dose will be reduced by 20 percent every 12 hours and eventually stopped.

At any stage of drug tapering if the seizures recur then tapering will be halted and the dose increased to the previous level and continued for another 24 h Tapering will be restarted if there is no seizure during this 24 h period

NSE and IL-10 levels

Blood samples for estimation of NSE and IL10 levels will be collected before starting the respective study drug and immediately after stopping the drug. A 2ml blood sample will be collected at each time point, the serum will be separated and stored

Estimation of NSE and IL10 levels will be done using ELISA technique using commercially available kits as per the manufacturer instructions