What is the treatment for Agitated Delirium and Status Epilepticus?

From the Guidelines

Agitated delirium and status epilepticus require immediate attention, and the most effective approach for status epilepticus involves administering benzodiazepines, followed by second-line agents such as valproate, as it has been shown to be at least as effective as phenytoin with potentially fewer adverse effects 1. For agitated delirium, initial management includes benzodiazepines such as midazolam 5-10mg IM or lorazepam 2-4mg IV/IM, followed by antipsychotics like haloperidol 5-10mg if needed, as recommended by Level B recommendations 1. Key considerations for both conditions include:

• Ensuring patient safety
• Addressing underlying causes (drugs, infection, metabolic disorders)
• Monitoring vital signs
• Providing supportive care including IV fluids For status epilepticus, the treatment protocol involves:
• Benzodiazepines: lorazepam 4mg IV (may repeat once after 5-10 minutes) or midazolam 10mg IM
• Second-line agents: fosphenytoin (20mg PE/kg IV), valproate (40mg/kg IV), or levetiracetam (60mg/kg IV, max 4500mg)
• Refractory cases: propofol, midazolam, or ketamine infusions with EEG monitoring in an ICU setting Both conditions necessitate airway management, continuous cardiac monitoring, and treatment of underlying causes, highlighting the importance of prompt and effective intervention to prevent morbidity, mortality, and improve quality of life 1.

From the FDA Drug Label

The treatment of status, however, requires far more than the administration of an anticonvulsant agent. It involves observation and management of all parameters critical to maintaining vital function and the capacity to provide support of those functions as required. For the treatment of status epilepticus, the usual recommended dose of lorazepam injection is 4 mg given slowly (2 mg/min) for patients 18 years and older. If seizures cease, no additional lorazepam injection is required. If seizures continue or recur after a 10- to 15-minute observation period, an additional 4 mg intravenous dose may be slowly administered

Lorazepam for Status Epilepticus:

• The recommended dose for status epilepticus is 4 mg IV, given slowly (2 mg/min) for patients 18 years and older.
• If seizures continue or recur after a 10- to 15-minute observation period, an additional 4 mg IV dose may be given.
• Key considerations:
  • Airway patency must be assured and respiration monitored closely.
  • Ventilatory support should be given as required.
  • The sedative effects of lorazepam may add to the impairment of consciousness seen in the post-ictal state.
  • Equipment necessary to maintain a patent airway and to support respiration/ventilation should be available 2 2

From the Research

Agitated Delirium and Status Epilepticus

• Agitated delirium and status epilepticus are two distinct medical conditions that require prompt diagnosis and treatment 3, 4.
• Status epilepticus is a neurological emergency characterized by prolonged or repetitive seizures, which can lead to neuronal injury, severe disability, coma, and death if left untreated 5.
• Agitated delirium, on the other hand, is a condition marked by acute mental status change, which can clinically mimic status epilepticus, especially when clinically relevant seizure activity is not appreciated on physical examination 4.

Treatment of Status Epilepticus

• Lorazepam has been well established as a first-line therapy for the treatment of status epilepticus, due to its effectiveness in stopping seizures and its relatively long duration of action compared to other benzodiazepines 3, 6, 7.
• Other treatment options for status epilepticus include intravenous fosphenytoin, valproate, midazolam, propofol, and phenobarbital, which can be used as subsequent steps or in combination with lorazepam 3.
• For refractory status epilepticus, continuous intravenous midazolam and propofol, separately or in combination, are rapidly effective, with pentobarbital remaining the gold standard for prolonged cases 3.

Comparison of Diazepam and Lorazepam

• A meta-analysis of randomized controlled trials comparing the effectiveness of diazepam and lorazepam for the emergency treatment of adult status epilepticus found that intravenous lorazepam was better than intravenous diazepam for the cessation of adult status epilepticus 7.
• The study found that lorazepam had a significantly superior effect on seizure cessation, but no statistically significant relationship was found for mortality, poor neurological outcome, hypotension, or respiratory depression 7.

Management of Status Epilepticus

• Early seizure control remains key in preventing the complications of status epilepticus, and prompt recognition and treatment are essential to stop the seizure and improve patient outcomes 5.
• Seizure monitoring with electroencephalogram (EEG) is often needed when patients do not return to baseline or during anaesthetic wean, but it is resource-intensive, costly, and has not been shown to improve functional outcomes 5, 4.