What is the preferred agent, etomidate (amidate) or ketamine, for the induction of status epilepticus?

Ketamine vs Etomidate for Induction in Status Epilepticus

Ketamine is the preferred induction agent for intubation in status epilepticus, while etomidate should be avoided due to lack of anticonvulsant properties and concerns about adrenal suppression in critically ill patients. 1

Rationale for Ketamine as Preferred Agent

Mechanism Supporting Use in Status Epilepticus

• Ketamine acts as a noncompetitive NMDA receptor antagonist, which is particularly relevant in status epilepticus where NMDA receptors become upregulated and GABA receptors downregulate during prolonged seizures. 2
• During refractory status epilepticus, traditional GABAergic medications (benzodiazepines, barbiturates) become progressively less effective as GABA receptor numbers and activity decrease, making NMDA antagonism theoretically advantageous. 2
• Ketamine maintains hemodynamic stability through sympathomimetic properties, which is critical in critically ill seizure patients who may be hemodynamically compromised. 3, 1

Clinical Evidence for Ketamine in Status Epilepticus

• In pediatric refractory status epilepticus, ketamine (median dose 40 μg/kg/min) achieved resolution in 67% (6/9) of children with super-refractory cases lasting more than 24 hours, with no serious adverse events reported. 4
• A multicenter retrospective study of 60 episodes of refractory status epilepticus found ketamine contributed to permanent seizure control in 32% of cases, with 12% showing definitive response where ketamine was the last drug added. 5
• Ketamine appears most effective when: infusion rates exceed 0.9 mg/kg/h, introduced within 8 days of SE onset, and used before failure of seven or more drugs. 5
• Case reports demonstrate rapid seizure cessation with ketamine (1 mg/kg IV) in refractory pediatric status epilepticus after failure of multiple benzodiazepines, levetiracetam, and fosphenytoin. 6

Why Etomidate Should Be Avoided

Lack of Anticonvulsant Properties

• Etomidate has been used historically to control refractory status epilepticus through cortical suppression, but this requires continuous infusion (mean 25 μg/kg/min) rather than single induction doses. 7
• Single induction doses of etomidate (0.3 mg/kg) used for intubation do not provide meaningful anticonvulsant effect and offer no therapeutic advantage in status epilepticus. 7

Adrenal Suppression Concerns

• Pediatric critical care guidelines explicitly recommend against etomidate use in critically ill children, particularly those with septic shock, due to adrenal suppression even after a single dose. 8
• The American College of Critical Care Medicine states that even one dose of etomidate for intubation is independently associated with increased mortality in children and adults with septic shock, possibly secondary to inhibition of adrenal corticosteroid biosynthesis. 8
• While adult RSI guidelines suggest no mortality difference between etomidate and other induction agents in general critically ill populations, these studies did not specifically examine status epilepticus patients who may have additional metabolic stress. 8

Pediatric Guidelines Explicitly Favor Ketamine

• The American College of Critical Care Medicine recommends using ketamine with atropine premedication for sedation and intubation in pediatric septic shock, explicitly avoiding etomidate. 8
• Ketamine maintains cardiovascular stability through intact adrenal axis function and reduces systemic inflammatory responses, making it superior in critically ill patients. 8

Practical Administration Protocol

Ketamine Dosing for RSI in Status Epilepticus

• Administer ketamine 1-2 mg/kg IV as the induction agent, followed immediately by a neuromuscular blocking agent (succinylcholine 1-1.5 mg/kg or rocuronium 1.0-1.2 mg/kg). 3, 1
• Consider using the lower end of the ketamine dose range (1 mg/kg) in patients with cardiovascular compromise to minimize hemodynamic effects while maintaining adequate sedation. 1
• Atropine premedication (0.01-0.02 mg/kg) may be considered to prevent increased salivation, particularly in pediatric patients. 8

Post-Intubation Considerations

• Following successful intubation, consider transitioning to continuous ketamine infusion (0.9-2 mg/kg/h or 15-60 μg/kg/min) if seizures remain refractory to standard anticonvulsants. 4, 5
• Administer midazolam concurrently with ketamine infusions to prevent emergence reactions. 4
• Monitor for paradoxical hypotension in patients with depleted catecholamine stores, though this is uncommon. 1

Critical Pitfalls to Avoid

• Never administer the neuromuscular blocking agent before the sedative-hypnotic (ketamine), as this causes awareness during paralysis, which occurs in approximately 2.6% of emergency department intubations. 3
• Do not use etomidate in pediatric status epilepticus patients or those with suspected sepsis/septic shock due to adrenal suppression concerns. 8
• Avoid delaying ketamine administration in refractory status epilepticus—efficacy decreases significantly when introduced more than 8 days after SE onset or after failure of seven or more drugs. 5
• Have vasopressors immediately available, though ketamine's sympathomimetic properties typically maintain hemodynamic stability better than other induction agents. 3, 1