EMS arrives with a 39 year old woman who was found down in a generalized tonic clonic seizure. The seizure has been ongoing for at least 12 minutes now. No information is available about her past history. The paramedics were unable to start an IV, but did administer a dose of IM midazolam…
Unlike simple seizures, which will generally resolve without any intervention and require clinical constraint to avoid overtreatment, status epilepticus (with generalized tonic clonic seizures) is a medical emergency that requires immediate management.
The first words out of your mouth should probably be, “what’s the sugar?” Not only is it embarrassing to miss hypoglycemia, it is an easily identifiable and easily treatable etiology of status epilepticus. If for some reason you are unable to get a level, just go ahead and treat empirically with D50W.
What do I do about the airway and breathing?
The first priority should be terminating seizure activity, because that will generally solve any airway and breathing issues. You don’t need to ventilate the patient immediately, but oxygen is important because the patient is burning through it very quickly. I place nasal trumpets bilaterally and apply a non-rebreather facemask in an attempt to provide some apneic oxygenation.
The management of status epilepticus will require venous access. If an IV is not rapidly available, I place an IO. (Initial doses of antiepileptics can be given without an IV, for example IM or IN midazolam, but further treatment will require vascular access.)
Start a benzodiazepine
It really doesn’t matter which one you pick – they all work. Usually this first dose will have already been given before the patient arrives. If an IV has not been started, I will also often use either an IM or intranasal dose before placing an IO.
|Benzo||Pediatric Dose||Usual dose|
If there is no response 4 minutes after the first benzo, I repeat the dose.
Special Case: Eclampsia
Eclampsia must be considered in any female of childbearing age before moving on to second-line medications. Women in their third trimester should be relatively obvious, but eclampsia can occur up to 8 weeks postpartum, so you may need to be treated empirically. Give magnesium 4 grams IV.
Most published algorithms will have with phenytoin or fosphenytoin as the second-line agent. I don’t like this option in the actively seizing patient because it just takes too long (at least 20 minutes). Also, phenytoin is generally contraindicated for toxicologic seizures and I rarely have enough information in the first 15 minutes to exclude overdose. If a patient doesn’t respond to a few good doses of a benzo, I am going to be intubating, and therefore I will be starting a general anesthetic. I will get the phenytoin started as soon as I can after the first dose of benzo doesn’t work, but I understand that it isn’t going to work for 20-30 minutes, so it is really my third line agent. My second line drug is propofol 1.5-2mg/kg IV then 20-200mcg/kg/min. If there are contraindications, primarily any concern about cardiac reserve or hemodynamic stability, ketamine 2 mg/kg IV is a good alternative.
After 2 doses of benzodiazepine don’t work, I am going to intubate. My second line anti-epileptic (propofol) is also my induction agent. First pass success is always important, but especially so after prolonged seizures, with high oxygen demand and very limited ability to pre-oxygenate. My go to will be standard RSI, with apneic oxygenation, but I anticipate I may need to gently bag the patient during the apneic period.
Choice of paralytic
Succinylcholine could cause hyperkalemia if seizures have been extremely prolonged and rhabdomyolysis has already developed or if there is an underlying neurologic disorder. However, the prolonged paralysis of rocuronium increases the risk of developing nonconvulsive status epilepticus. In the ideal situation, nonconvulsive status is quickly and easily diagnosed by EEG, but unfortunately that is just not feasible for many of us. I will generally stick with succinylcholine, unless their is a clear contraindication.
Searching for reversible causes
The search for a reversible cause of seizures is the most important task between doses of benzos and after intubation.
- Almost all patients in status are going to be hot, so infectious causes will come to mind. Empiric antibiotics and acyclovir should probably be given early to everyone.
- In case it was overlooked in the initial few minutes, all women of childbearing age must be considered for the diagnosis of eclampsia.
- Isoniazid toxicity
- Depending on your population (urban hospitals or many countries that aren’t Canada), you might want to treat empirically for isoniazid toxicity. The antidote is pyridoxine (1 gram of pyridoxine for every gram of isoniazid (to a max of 5 grams) in a known overdose, or just 5 grams empirically)
- NaCl 3% 2ml/kg (150 in 70 kg pt); may repeat in 10 minutes if needed
- Sodium channel blocker toxicity
- Sodium bicarbonate IV (100mEq or 2mEq/kg)
- Alcohol withdrawal
- You are already treating this, but will need a lot more benzos
- Hydroxocobalamin 70mg/kg (5 gram standard dose)
- Or the cyanide antidote kit (amyl nitrate, sodium nitrite, and sodium htoisulfate)
- Barbituates: Some people might use these in place of propofol higher in this algorithm. That is reasonable. I like propofol because its a drug I use every single shift. (Phenobarbital 20mg/kg loading dose over 15 min)
- Levetiracetam: If the first anti-epileptic doesn’t work, you are unlikely to get any benefit from adding a second. However, I don’t know any neurologists who can walk by a seizure patient without starting them on levetiracetam these days. A loading dose of 1 gram IV is reasonable
- Ketamine: Although not backed by any evidence in status epilpticus, the use of ketamine (an NMDA receptor antagonist) makes sense in conjunction with the flood of the GABA agonists you have already tried
- Inhalational anesthetics: As a final effort, inhalational anesthetics have been described in cases of status epilepticus
Although older definitions of status epilepticus focused on seizures lasting more than 30 minutes, a more practical definition is any individual seizure lasting more than 5 minutes or 2 seizures without full recovery of consciousness. From an emergency department standpoint, it a patient is still seizing by the time EMA arrives, it is status.
There are many theoretical reasons that one benzo might be chosen over another, but in head to head trials they have always come up identical. The only note I would make about specific agents is that diazepam seems to have a higher rate of recurrent seizures (up to 50% in the first 2 hours) if another antiepileptic is not given. If diazepam was successfully used to stop the seizure, I would probably start phenytoin.
Controversial airway aside
Might a sedative only attempt at intubation make sense in status? In hospitals like mine with no access to EEG, non-convulsive status after paralytics will be very challenging to manage. In a seizing patient, the combination of convulsions and trismus will probably make paralytics necessary for a safe intubation attempt. However, the induction agents that we use are also anti-epileptics that might terminate the seizure, potentially obviating the need for paralysis.
I have no science or even experience to support this approach, but I wonder if it makes sense:
- Give a generous dose of a sedation agent, such as propofol 2mg/kg
- A paralytic is drawn up, but it is not given with the sedative
- At 60 seconds, make a single attempt at intubation without paralysis
- If the tube cannot be easily passed, or there are ongoing convulsions or trismus that prevent laryngoscopy, the paralytic is pushed, the patient is briefly bagged as needed, and the usual intubation algorithm is resumed
Other FOAMed Resources
Shearer P, Riviello J. Generalized convulsive status epilepticus in adults and children: treatment guidelines and protocols. Emergency medicine clinics of North America. 29(1):51-64. 2011. PMID: 21109102
Sharma AN, Hoffman RJ. Toxin-related seizures. Emergency medicine clinics of North America. 29(1):125-39. 2011. PMID: 21109109
Lung DD, Catlett CL, Tintinalli JE. Chapter 165. Seizures and Status Epilepticus in Adults. In: Tintinalli JE et al. eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7e. New York, NY: McGraw-Hill; 2011. http://accessmedicine.mhmedical.com/content.aspx?bookid=348&Sectionid=40381644
Millikan D, Rice B, Silbergleit R. Emergency treatment of status epilepticus: current thinking. Emergency medicine clinics of North America. 27(1):101-13, ix. 2009. PMID: 19218022
McMullan J, Duvivier E and Pollack C. Chapter 102. Seizure Disorders. In: Marx JA et al. eds. Rosen’s Emergency Medicine, 8e. Philadelphia: Elsevier Saunders; 2014.