ANTI EPILEPTIC DRUG (AED) THERAPY IN NEURO INTENSIVE CARE

▪️Mechanisms, that can contribute to the development of seizures after craniotomy: (1) Free radical generation, due to iron and thrombin from blood components that have leaked in the tissue during surgery. (2) Disturbance of ion balance across the cell membranes due to local ischemia or hypoxia.

▪️Investigations which should be considered, in the event of an episode of postoperative seizures : Serum electrolytes, glucose, AED concentrations, ammonia and liver enzymes, toxicology screen, ABG, CT Brain & EEG (to exclude ongoing nonconvulsive seizures or SE). Derangements such as hypoglycemia, hyponatremia, hypocalcemia, hypomagnesemia, hypoxia or hyper-or hypocarbia should be corrected.

▪️ 5-20 Minutes Initial Therapy Phase^

A benzodiazepine is the initial therapy of choice (Level A): Can use either among the three

▶️Intramuscular midazolam (10 mg for > 40 kg, 5 mg for 13-40 kg, single dose, Level A) OR ▶️Intravenous lorazepam (0.1 mg/kg/dose, max: 4 mg/dose, may repeat dose once, Level A) OR ▶️Intravenous diazepam (0.15-0.2 mg/kg/dose, max: 10 mg/dose, may repeat dose once, Level A) 

🔻If none of the 3 options above are available, choose one of the following: 

▶️Intravenous phenobarbital (15 mg/kg/dose, single dose, Level A) OR 

▶️Rectal diazepam (0.2-0.5 mg/kg, max: 20 mg/dose, single dose, Level B) OR 

▶️Intranasal midazolam (Level B), buccal midazolam (Level B)

 🔻If seizures continue:

▪️ 20-40 Minutes Second Therapy Phase^: 

Choose one of the following second line options and give as a single dose 

▶️Intravenous fosphenytoin (20 mg PE/kg, max: 1500 mg PE/dose, single dose, Level U; PE is Phenytoin Equivalent ) OR 

▶️Intravenous valproic acid (40 mg/kg, max: 3000 mg/dose, single dose, Level B) OR 

▶️Intravenous levetiracetam (60 mg/kg, max: 4500 mg/dose, single dose, Level U) 

🔻If none of the options above are available, choose one of the following (if not given already) 

▶️Intravenous phenobarbital (15 mg/kg, single dose, Level B)

🔻If seizures continue^:

▪️40-60 Minutes Third Therapy Phase:

Choices include: 

▶️repeat second line therapy or 

▶️anesthetic doses of either thiopental, midazolam, pentobarbital, or propofol (all with continuous EEG monitoring)

➖Ketamine is also described 

🏮SPECIFIC POINTS:

▪️Phenytoin :  The dose of phenytoin is 18-20 mg/kg, at a rate not to exceed 50 mg/min; slower rates when under general anesthesia). Never mix phenytoin with a 5% dextrose solution; put it in a normal saline solution to minimize the risk of crystal precipitation. Therapeutic range is 10-20 µg/mL

▪️ Fosphenytoin is preferable, as it provides the advantage of a potentially rapid rate of administration with less risk of venous irritation (eg, to avoid the risk of purple-glove syndrome with phenytoin). Fosphenytoin is given at a rate not to exceed 150 mg PE/min). 

▪️ Sometimes, supplementation of the patient's routine medication (guided by stat AED levels) may help suppress their seizures.

▪️Phenobarbital’s sedative effect is minimized after a few weeks and, therefore, in chronic users may not be a problem in the postoperative period.

▪️Valproic acid generally described IV loading dose: 15–20 mg/kg, maintenance 400–600 mg q6h. Take caution while using it in patients with hepatic failure, thrombocytopenia and pancreatitis. The drug should never be given intramuscularly.

▪️ Absent seizures -Drugs used :  Ethosuximide also can be useful, but is not available in parenteral form.

▪️Levetiracetam and lacosamide are available in an IV formulation. These agents are renally eliminated, have minimal interactions with other common medications, and offer advantages in the ease of their use. However, patients with renal impairment will require dosage adjustment. Both agents have complete bioequivalence to the oral dose. Lacosamide is a novel antiepileptic drug, but its effectiveness in treatment of refractory SE is unknown.

▪️ Benzodiazepines are the preferred first-line agents. Lorazepam is preferable to diazepam, because of lack of active metabolites and redistribution to extracerebral tissues. 

▪️ Pentobarbital is preferable to phenobarbital because of shorter elimination ( T 1/2 around 24 h vs. 96 h) and in a meta-analysis was more efficacious than midazolam or propofol

▪️ Some clinicians even consider rapid oral loading of one of the newer AEDs like topiramate, depending on the ongoing clinical urgency. 

▪️ Correct any metabolic imbalances. Control hyperthermia.

Reference: ^Treatment of Convulsive Status Epilepticus in Children and Adults,Epilepsy Currents 16.1 - Jan/Feb 2016 , 2016 American Epilepsy Society Guidelines , 

Status Epilepticus Treatment & Management, 

Julie L Roth, Stephen A Berman, Medscape , Antiepileptic Drug Therapy in Neurosurgical Critical Care, Panayiotis N. Varelas and Denise H. Rhoney, Essentials of Neurosurgical Anesthesia & Critical Care 2012 Strategies for Prevention, Early Detection, and Successful Management of Perioperative Complications