Childhood Convulsive Status Epilepticus - In Search Of Optimal Drug Management In A Resource Limited Setting

This prospective study was conducted at the Red Cross War Memorial Children's Hospital (RCWMCH) and recruitment ran from between March 2015 to March 2018. All patients presenting with convulsive status epilepticus (CSE) who presented to the medical emergency unit at RCWMCH and needed therapeutic intervention were entered into the study by the attending medical staff. Study data was collected using REDCap hosted by the University of Cape Town's eResearch Centre and the study was approved by the UCT Human Research Ethics Council (UCT HREC 297/2005).

Definitions The definition of CSE was defined as any convulsive seizure that lasted longer than five minutes or multiple discrete seizures between which there is no extended period of recovery between events (Trinka et al., 2015). The onset of CSE was defined as the time provided by the caregiver who accompanied the child. The time to admission and to treatment were recorded by the staff in the unit. If children were admitted multiple times, each admission was captured independently, but only data from the first admission was included in this report . The full diagnosis of CSE was described using the multiaxial classification system. However, as it was not possible to perform EEG on all patients, this axes was excluded. Febrile status epilepticus was defined .

Treatment protocols Upon entry into the study, children were randomly allocated to one of two protocols . Both these protocols are well-established treatment protocols used in the sub-Saharan African setting for the management of SE . Randomization of protocols was performed using a free online platform (Research Randomizer ©). Both protocols began with children receiving first-line benzodiazepines (either midazolam, lorazepam or diazepam) which were either administered intravenously (IV), per rectally, intranasally or sublingually. If the children did not respond to single dose of benzodiazepines, they were given a second dose 5-10 minutes after the first dose. Pre-hospital administration of benzodiazepines by emergency services were counted if administered intravenously. However, all other routes of administration were not counted due to the lack of consistency in their administration.

If CSE continued after two doses of benzodiazepines, children were then randomized to second-line agents according to the protocol allocated to them. The one protocol, termed 'Phenobarbital' (PHB), instructed the clinician to give giving an IV bolus of phenobarbital (20mg/kg ). If CSE did not terminate after 5 - 10 minutes, a second dose was given at half the dosage (10mg/kg) and a third dose (10mg/kg) was given if CSE persisted 5-10 minutes after that.

In the second protocol, termed 'Phenytoin / Midazolam infusion' (PHY/MDZ), children were given a dose (20mg/kg) of IV phenytoin mixed with 50mL of normal saline solution and administered over 30 minutes . If the patient was still in CSE 5-10 minutes after the phenytoin was given, they were then started on a midazolam infusion. This included a loading dose of IV midazolam (0.2mg/kg) followed by an infusion set at 3mg/kg into 50mL 5% dextrose water given at a rate of 1-4 mL/hour (equivalent to 1-4 mcg/kg/min ).