Management of the first stage of convulsive status epilepticus in adults: a systematic review of current randomised evidence

Abstract

Background Convulsive status epilepticus is the most severe form of epilepsy and requires urgent treatment. We synthesised the current evidence on first-line treatments for controlling seizures in adults with convulsive status epilepticus before, or at, arrival at hospital. Methods We conducted a systematic review of randomised controlled trials (RCTs) assessing antiepileptic drugs offered to adults as first-line treatments. Major electronic databases were searched. Results Four RCTs (1234 adults) were included. None were conducted in the UK and none assessed the use of buccal or intranasal midazolam. Both intravenous lorazepam and intravenous diazepam administered by paramedics were more effective than placebo and, notably, intramuscular midazolam was non-inferior to intravenous lorazepam. Overall, median time to seizure cessation from drug administration varied from 2 to 15 min. Rates of respiratory depression among participants receiving active treatments ranged from 6.4 to 10.6%. Mortality ranged from 2 to 7.6% in active treatment groups and 6.2 to 15.5% in control groups. Conclusions Intravenous and intramuscular benzodiazepines are safe and effective in this clinical context. Further research is needed to establish the most clinically and cost-effective first-line treatment and preferable mode of administration. Head-to-head trials comparing buccal versus intranasal midazolam versus rectal diazepam would provide useful information to inform the management of the first stage of convulsive status epilepticus in adults, especially when intravenous or intramuscular access is not feasible. Approaches to improve adherence to clinical guidelines on the use of currently available benzodiazepines for the first-line treatment of convulsive status epilepticus should also be considered.

Management of convulsive status epilepticus: recent updates

“…Seizure cessation was approximately 60% with IV lorazepam and 40% with IV diazepam, achieved 2 to 15 minutes after administration. The seizure cessation rate with both BZDs was higher than that of the placebo group, and seizure recurrence was observed in approximately 10% of the patients [ 17 ]. Respiratory depression was seen in 6.4% with IM midazolam and 10.6% with IV lorazepam, which was lower than in the placebo group (15.5%).…”

“…Respiratory depression was seen in 6.4% with IM midazolam and 10.6% with IV lorazepam, which was lower than in the placebo group (15.5%). Mortality was 2% to 7.6% with BZD treatment, which was lower than that of the placebo group (6.2%–15.5%) [ 17 ].…”

Prehospital seizures: Short‐term outcomes and risk stratification based in point‐of‐care testing

“…2 In prehospital care, that is, attention given by the Emergency Medical Services (EMS) outside of hospital, the primary challenge is to stop the seizure as soon as possible, followed by an appropriate handling of systemic complications, that is, advanced airway management, use of second-and third-line anticonvulsants, goal-guided volume replacement, electrolyte restoration and balancing and/or acidosis conditions. 3 To add to this, status epilepticus, defined as prolonged seizure or a series of seizures with incomplete return to baseline, 4 although uncommon (5%), 5 is a life-threatening condition with a mortality rate of 20%. 6 On the other hand, seizures in patients never diagnosed with epilepsy have been proved to hide a potentially underlying organic cause, such as trauma brain injury (TBI), stroke, infections, poisoning, space-occupying brain lesions, hypoglycaemia or hydroelectrolytic alterations.…”

“…What is more, 75% of the patients assisted for having seizures are transferred to the emergency department (ED) 2 . In prehospital care, that is, attention given by the Emergency Medical Services (EMS) outside of hospital, the primary challenge is to stop the seizure as soon as possible, followed by an appropriate handling of systemic complications, that is, advanced airway management, use of second‐ and third‐line anticonvulsants, goal‐guided volume replacement, electrolyte restoration and balancing and/or acidosis conditions 3 . To add to this, status epilepticus, defined as prolonged seizure or a series of seizures with incomplete return to baseline, 4 although uncommon (5%), 5 is a life‐threatening condition with a mortality rate of 20% 6 .…”

Semaphorin 4D induced inhibitory synaptogenesis restores benzodiazepine sensitivity in a mouse model of Status Epilepticus

“…First line treatment for SE is intravenous or intramuscular administration of benzodiazepines (BZD; e.g. diazepam) (Cruickshank et al, 2022). Benzodiazepines enhance the activity of GABA A receptor subunits, thereby affecting existing GABAergic synapses, and increasing inhibitory tone in the brain.…”