Dr. Weingart, EmCrit, interviews Dr. Thomas Bleck, Neuro Critical Care Specialist on Podcast 155 (this link plays the podcast in a new window) and here are the Show Notes for the podcast. Both are outstanding.
And see Resources at the end of the post for eleven references.
I’m guessing every physician will want to listen to this podcast and review (read and listen to) all of the additional outstanding resources that are in the Show Notes (And don’t miss the thoughtful reader questions and comments after the resources).
I went ahead and wrote out a more detailed set of notes for my benefit–so I could quickly review them when needed and also to help fix this great talk interview in my mind.
So here goes:
IM midazolam versus IV lorazepam for status epilepticus: A recent study, RAMPART (1), showed that IM midazolam was as effective as IV lorazepam according to Dr. Bleck.
Therefore if you can’t get an IV in you should just go ahead and give IM midazolam because the longer you wait to give a seizure medicine the worse it’s going to work. So, if you can’t get an IV in right away, go ahead and give the IM midazolam.
Dr. Weingart then asks Dr. Black well then should we maybe be using IV midazolam instead of IV lorazepam because maybe it’ll be more effective than IV lorazepam, given that it works so well IM.
Dr. Bleck says, well, there’s no evidence to support doing that. And there is some real reason that it might be a bad idea. And the reason is that you get a lot of respiratory suppression when you use IV midazolam.
And the whole point is you’d like to stop the seizure right away without having to intubate the patient. And if you get severe respiratory depression then you have to intubate the patient even if the seizures have stopped. So that’s why IV midazolam might not be the way to go if you have an IV. Just go with IV lorazepam.
Dr. Bleck says that the dose of IV lorazepam is 0.1 mg per kilogram [as your first AED]. And Dr. Bleck says if this doesn’t work, don’t fiddle around with another AED. Instead just go to general anesthesia.
From Dr. Weingart’s Show Notes: Which agent is best for General Anesthesia?
High Dose Midazolam (Neurology 2014;82:359) (3)
– loading dose: 0.2 mg/kg
– maintenance: 0.1 - 2.0 mg/kg/hr
may be bad (Prasad A et al Epilepsia 2001;?42:380-386)
For general anesthesia you will use high-dose midazolam or propofol or maybe ketamine as your general anesthetic, Dr. Bleck states [However, later in the interview, Dr. Bleck strongly recommends not using propofol for you general anesthestic because the mortality rate with with propofol has proven much higher than with midazolam]
So what if you do end up having to intubate the seizing patient? Dr. Bleck says, you can give propofol* for induction and succinylcholine if the patient is healthy or rocuronium if the patient is a person with possible chronic neurologic disease.
*Dr. Weingart suggests using Ketamine as your induction agent. [That is what I will use in this situation].
In another talk on Medscape [put in link] Dr. Bleck talks about other circumstances [like unknown seizure duration] when maybe rocuronium would be a better choice.
Patients with chronic neurologic diseases are at risk for fatal hyperkalemia when given succinylcholine. Dr. Bleck points out that a lot of nursing home patients who are bed fast might have unknown neurologic diseases.
There is, then, a discussion by Dr. Bleck about intubating the patient without using a paralytic agent. Using a paralytic will make it impossible to tell if the patient is seizing without EEG monitoring (which may not be immediately available).
However, I would worry that not using a paralytic would increase the operator’s risk of a failed intubation.
The reason Dr. Bleck says that you should go straight to general anesthesia if lorazepam fails is that in the VA study (7) that he mentions the second agent didn’t work very well at all.
Now you say that it is possible that if you don’t wait when the lorazepam fails and immediately go to the next agent it might work better than in the VA study (7).
But Dr. Bleck states that the best option is simply to go to general anesthesia for the patient who continues disease.
[I personally always want to use rocuronium when appropriate because I worry that, for example the child who has to be intubated, might have an unknown chronic neurologic disease and hence be at risk for fatal hyperkalemia. Another example would be an adult in whom you don’t realize they have chronic neurologic disease for one reason or another. And of course burn patients can have fatal hyperkalemia from succinylcholine. See Neuromuscular disease: Succinylcholine hyperkalemia (9)]
But rocuronium will leave the patient paralyzed for 40 minutes and that means we can’t monitor the patient for seizures unless we have EEG monitoring which may not be immediately available.
So that’s why Dr. Black says that succinylcholine in a patient was up walking and talking before the seizure is probably the way to go.
So again Dr. Bleck recommends going straight to high-dose midazolam general anesthesia (3) if IV lorazepam fails . And he recommends that we use midazolam instead of propofol because of propofol mortality is substantially higher than mortality with midazolam.
So what if you decide instead of using general anesthesia when lorazepam fails, to go to a second AED. Which should you choose.
And your choices for the second AED, Dr. Bleck says, are fosphenytion, valproic acid, levetiracetam (Keppra), or lacosamide.
So if you decide to go with a second AED when the first fails rather than general anesthesia which of the four would you use as your second AED, Dr. Weingart asks, in an ER patient for undifferentiated generalized status.
Well, Dr. Bleck has already said that we are not going to use fosphenytoin because of its severe cardiovascular toxicity. And we’re not going to use valproic acid for reasons Dr. Bleck discusses in the interview.
Dr. Bleck recommends either a levetiracetam load at a dose of 1 g and may repeat 1 to 2 times or lacosamide, 200 to 300 mg loading dose (depending on size).
Dr. Bleck states that they have been using a lot of lacosamide and that their success rate with lacosamide has been very good.
So Dr. Weingart then asks: what do you do if the patient is still seizing after IV lorazepam general anesthesia and conventional AED [which would be levetiracetam or lacosamide]. What do you brand that patient at this point?
Dr. Bleck replies: there I would say that the dose of general anesthesia isn’t high enough. There shouldn’t be any seizure that can persist with a high enough dose of general anesthesia. The problem of course is that maybe the blood pressure won’t tolerate a high enough dose of general anesthetic.
In that circumstance Dr. Bleck states, we’ve been going much more quickly to ketamine. The dose is really uncertain but most people even if they got a lot of other meds tolerate a 3 to 5 mg per kilogram loading dose. Then you can either start and infusion or give another loading dose every 20 to 30 min. (2)
Dr. Weingart then asks about the Anaconda inhaled anesthetic device to control status. Dr. Bleck says that he is read about it but has not used it personally.
Dr. Weingart then asks: but you have used induced hypothermia in these patients. Dr. Bleck says yes we have, but we haven’t published on it but another group has.
Dr. Bleck states that electroconvulsive therapy doesn’t work.
Dr. Bleck also states that you have to be able to monitor the EEG continuously. If you can’t then you need to transfer the patient to a hospital where continuous EEG monitoring is possible.
Dr. Bleck states that we are increasingly recognizing inflammatory causes of status epilepticus (autoimmune encephalitis) which suggests that we need to pay attention to treating the etiology of status epilepticus. (6), (10), and (111).
And Dr. Bleck says that the treatment of immunologic causes of status should begin early “with or without a definitive diagnosis of an immunologic cause of status.” And our “Choices [are]: Steroids, IVIG, Plasma exchange, Calcineurin antagonists and other antirejection drugs, Rituximab, Cytotoxic agents.” (6)
Resources [all except (8), (9), (10), and (11) are from Dr. Weingart’s Podcast 155 Show Notes]:
(1) RAMPART (Rapid Anticonvulsant Medication Prior to Arrival Trial): a double-blind randomized clinical trial of the efficacy of intramuscular midazolam versus intravenous lorazepam in the prehospital treatment of [status epilepticus by paramedics. [PubMed Abstract] [Full Text HTML] [Full Text PubReader] [Full Text PDF]. Epilepsia. 2011 Oct;52 Suppl 8:45-7. doi: 10.1111/j.1528-1167.2011.03235.x.
(2) Intravenous ketamine for the treatment of refractory status epilepticus: a retrospective multicenter study. [PubMed Abstract] [Full Text HTML] [Full Text PubReader] [Full Text PDF]. Epilepsia. 2013 Aug;54(8):1498-503. doi: 10.1111/epi.12247. Epub 2013 Jun 12.
(3) High-dose midazolam infusion for refractory status epilepticus. [PubMed Abstract] [Full Text HTML] [Full Text PubReader] [Full Text PDF]. Neurology. 2014 Jan 28;82(4):359-65. doi: 10.1212/WNL.0000000000000054. Epub 2013 Dec 20.
(4) Guidelines for the evaluation and management of status epilepticus. [PubMed Abstract] [Full Text PDF] Neurocrit Care. 2012 Aug;17(1):3-23. doi: 10.1007/s12028-012-9695-z. (The article itself is an outstanding clear guideline and should be read also)
(6) SMACC 2015: Controversies in the acute management of status epilepticus. [Slides of the Talk]. Dr. Thomas Bleck.
(7) The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. [PubMed Abstract] [Full Text PDF]. Brain. 2011 Oct;134(Pt 10):2802-18. doi: 10.1093/brain/awr215. Epub 2011 Sep 13.
(9) Neuromuscular disease: Succinylcholine hyperkalemia [from Open Anesthesia]:
Succinylcholine (SCh) is a depolarizing neuromuscular-blocking agent, which produce sustained opening of the nicotinic cholinergic receptor channel. Under normal conditions, post-junctional membrane depolarization results in leakage of potassium that produces an increase of 0.5 – 1.0 mEq/L in serum K+ concentration. When SCh depolarizes muscle that has been traumatized (crush injury) or denervated (upper motor neuron lesion) enough K+ may leak from cells to produce systemic hyperkalemia and cardiac arrest. This susceptibility to hyperkalemia is thought to be caused by proliferation of junctional and extrajunctional cholinergic receptors.
Patient population at risk for SCh-induced hyperkalemia include patients with upper motor neuron lesions resulting from stroke, brain or spinal cord tumors, other intracerebral or spinal cord masses, closed head injury, or encephalitis and also other disease processes like unhealed third-degree burns, severe intra-abdominal infections, severe metabolic acidosis with hypovolemia, crush injuries, and prolonged nondepolarizing muscle blockade or immobility. Life-threatening potassium release is not reliably prevented by pretreatment with a nondepolarizing agent. The subsequent cardiac arrest can prove to be refractory to routine cardiopulmonary resuscitation, requiring Calcium,, insulin, glucose, bicarbonate, epinephrine, cation-exchange resin, dantrolene, and even cardiopulmonary bypass to reduce metabolic acidosis and serum potassium levels. The risk of hyperkalemia appears to peak 7-10 days after the injury, but the exact time of onset and the duration of the risk period vary.
(10) The Frequency of Autoimmune N-Methyl-D-Aspartate Receptor Encephalitis Surpasses That of Individual Viral Etiologies in Young Individuals Enrolled in the California Encephalitis Project. [PubMed Abstract] [Full Text HTML] [Full Text PDF] Clin Infect Dis. 2012 Apr;54(7):899-904. doi: 10.1093/cid/cir1038. Epub 2012 Jan 26.
(11) Encephalitis with refractory seizures, status epilepticus, and antibodies to the GABAA receptor: a case series, characterisation of the antigen, and analysis of the effects of antibodies. [PubMed Abstract] [View Full Text PDF at ResearchGate] [Download Full Text PDF from ResearchGate]. Lancet Neurol. 2014 Mar;13(3):276-86. doi: 10.1016/S1474-4422(13)70299-0. Epub 2014 Jan 22.