Treatment of refractory Status Ep
EEG evidence of seizures was associated with worse outcome and mortality in children (CCM 2013;41:215)
10 mg IM midazolam was not inferior to 4 mg IV lorazepam (N Engl J Med 2012; 366:591-600)
Poor man’s EEG is pupillary response to light.
Check thyroid, ask about trauma
Syncope can present c twitching
Ictal-retrograde amnesia, incontinence, tongue biting
Postictal (Todds) paralysis-as long as 24 hrs
Neurogenic Pulmonary Edema-from sympathetic discharge-often confused c aspiration
Posterior Shoulder Dislocation
CT Scan for 1st time seizure
Prolactin levels will peak at 20 minutes after seizure and return to baseline in60 minutes.
Loading of Meds
Trick of the Trade from Bryan Hayes:
Give the oral phenytoin load as a single dose.
Supporting Data for Single Dose
- Osborn HH, et al. Single-dose oral phenytoin loading. Ann Emerg Med 1987;16(4):407-12. PMID 3826809
- Evens RP, et al. Pheyntoin toxicity and blood levels after a large oral dose. Am J Hosp Pharm 1980;37(2):232-5. PMID 7361796
- A single 900 mg dose of oral phenytoin sodium was given to 6 healthy men. Total (bound and free) plasma phenytoin levels were within the therapeutic range (10-20 mcg/mL) for two subjects and close (not less than 8.39 mcg/mL) for the remaining four.
- Peak free drug levels were 1.01-1.60 mcg/mL.
- Time to reach total and free peak plasma levels was 6-14 hours and 2-10 hours, respectively.
- Ratanakorn D, et al. Single oral loading dose of phenytoin: a pharmacokinetic study. J Neurol Sci 1997;147(1):89-92. PMID 9094065
- A single oral phenytoin dose of 18.7 mg/kg in males and 24.8 mg/kg in females rapidly produced therapeutic concentration (10 mcg/mL) within an average of 2 hours in males and 2.4 hours in females with minimal side-effects.
If you’re still uncomfortable giving a large single dose, there is also support for two-dose oral loading (which still cuts 2 hours off the ED stay compared to 3 doses).
- Record KE, et al. Oral phenytoin loading in adults: rapid achievement of therapeutic plasma levels. Ann Neurol 1979;5(3):268-70. PMID 443759
- 20 patients were administered an average dose of 19 mg/kg of phenytoin divided into 2-4 increments.
- The authors found that this regimen (in which no increment of the loading dose exceeded 600 mg) is sufficient to achieve and maintain therapeutic plasma concentrations 18-24 hours after initiation of the loading dose.
rapid oral loading of carbamazepine (Ann emerg med 2007;50:121)
Status-serial seizures without consciousness or >30 min of continuous activity
Benzodiazepines are first line therapy
Lorazepam .1 mg/kg given ~2 mg/min will have onset in 3-5 minutes and last hours
Diazepam .2mg/kg given ~ 5mg/min will have onset in ~1 minute but lasts only about ~20 min for antiseizure activity
Valproic acid has recently been made available in an intravenous preparation. The average dose is 10-15 mg/kg but a 20 mg/kg load has been safely used. Although not yet approved for this use in the United States, intravenous valproic acid can successfully treat convulsive status epilepticus.
Benzos- Fosphenytoin- Phenobarb- Pentobarb- Isoflurane
Phenobarb 100 mg boluses until seizure stops
Non-convulsive Status is cause of AMS and can continue post seizure, get EEG
Gelastic Seizures from lesions in temporal or hypothalamus. Differential diagnosis of pathological laughter is also stroke and tumor
Seizures can present with peri-ictal (non-convulsive status) and postictal psychosis or behavior change
B6 for Isonazid Overdoses 5 grams or more
Patients with strychnine poisoning may develop seizure-like activity yet demonstrate normal mental status
get drugs of abuse screen for cocaine and serum for TCA
that old lady twitching their finger may still be having tonic/clonic seizure, but they have just fatigued their twitching to the point that only small movement is left.
Ativan 4mg x2 Q5 minutes
Fosphenytoin 20 mg/kg IV at 150 mg/min
May give additional 10 mg/kg of Fosphenytoin
or IV Valproate 40 mg/kg over 10 minutes may give additional 20 mg/kg
or IV Midazolam 0.2 mg/kg then repeat 0.2-0.4 mg/kg boluses Q 5 minutes. Max load 2 mg/kg. Then start 0.1 mg/kg/hr; dose range 0.05-2 mg/kg/hr
or IV propofol load 1 mg/kg repeat 1-2 mg/kg Q 3min until seizures stop max load 10 mg/kg. Start at 2 mg/kg/hour dose range 1-15 mg/kg/hr
or Phenobarb 20 mg/kg at 50-100 mg/min
then IV pentobarb 5-10 mg/kg at 50 mg/min repeat 5 mg/kg until seizures stop. rate 1 mg/kg/hr range 0.5-10 mg/kg/hr.
Fosphenytoin is a phosphate ester of phenytoin that became available in 1995. It has a safety profile that makes it preferable to phenytoin in certain situations
Fosphenytoin has a peak serum level within approximately one of hour of intramuscular administration and at six minutes after intravenous loading. When ordering fosphenytoin, the physician should use the terminology of “phenytoin equivalents” (PE) to avoid confusion. Thus, the routine loading dose is 18 phenytoin-equivalent units/kg. In emergencies, the recommended infusion rate is 150 PE/minthree times that of phenytoin.
Fosphenytoin is water-soluble, obviating the need for the propylene glycol vehicle. It can be given intramuscularly or intravenously with 100% bioavailability. Fosphenytoin is less of a tissue irritant than the phenytoin/propylene glycol preparation, with pruritus and paresthesias the most common side effects. Patients can receive up to 30 cc IM (yes, thats 30 cc) in either single or multiple sites with minimal local irritation.70 There are minimal cardiotoxic effects though hypotension has been reported with rapid infusions.71 Blood pressure should be carefully monitored, especially in patients with underlying cardiovascular disease. The package insert recommends the use of cardiac monitoring during infusion.
One study showed no cost benefit with fosphenytoin assuming a low complication rate with phenytoin (Pharmacotherapy 20(8):910 August 2000)
In one study, there was no time benefit to the use of fosphentoin loading, nor were there any adverse effects with phenytoin load. (Neuro Res 24:842, Dec 2002) and another (Annals 2004 43:3, p.399)
No adverse drug effects with phenytoin in this study (Academic Emergency Medicine Volume 11, Number 3 244-252)
Consider PO loading of phenytoin in patients who seize secondary to non-compliance.
An oral dose of 19 mg/kg in men and 23 mg/kg in women will produce a therapeutic level in the majority of patients by 3-4 hours.146 However, assess these patients carefully for ataxia and dizziness prior to discharge. Can give whole dose at once, but probably does not load any quicker and higher risk od adverse effects. Better to load 400 mg/hour to 20 mg/kg. Should raise levels by 10.
Ann Emerg Med. 1987 Apr;16(4):407-12. Related Articles, Links Single-dose oral phenytoin loading. Osborn HH, Zisfein J, Sparano R. A single 18 mg/kg dose of oral phenytoin capsules or suspension (mean dose, 1.3 g) was given to 44 patients with recent seizures and no detectable serum phenytoin level. Mean serum phenytoin levels after loading for patients receiving capsules were 6.8 micrograms/mL at two hours, 9.7 micrograms/mL at three to five hours, 12.3 micrograms/mL at six to ten hours, and 15.1 micrograms/mL at 16 to 24 hours. Mean levels for patients receiving suspension were slightly, but not significantly, lower than for patients receiving capsules. No seizures occurred during an eight-hour observation period after loading. Drug toxicity was minimal. Single-dose, 18 mg/kg oral phenytoin loading provides rapid therapeutic levels and is well tolerated.
IV Phenytoin, though it can be given at 50 mg/minute to dose of 20 mg/kg, should actually me 20 mg/minute. Give above forearm in at least 20G IV.
Calculating phenytoin level correction in hypoalbuminemia:
Corrected level= Measured phenytoin level /[(albumin x 0.2) + 0.1]
In renal failure: CrCL < 20
Corrected level= Measured phenytoin level /[(albumin x 0.1) + 0.1]
The recent availability of a parenteral formulation of sodium valproate
(15-20 mg kg−1 loading dose and then 3-6 mg kg−1 min−1 thereafter)
has renewed interest in this agent for the control of SE.
Seizure (2007) 16, 527—532
Modulates GABA-α receptors at a site different from that targeted by benzodiazepines (BZDs) and barbiturates (Epilepsia 2004;45(7):757) Start with 1 mg/kg slow bolus, may repeat in 5 minutes once. Maintenance 2-4/mg/hr titrated between 1 and 15 mg/kg/hr. Worked in ~2 minutes average in incredibly tiny study (Epilepsia 1998;39(10:18)
Can go up to 2.9 mg/kg/hr
Valproate and tegratol can both cause thrombocytopenia
To load depakote, give twice normal dose or 500 mg of depakene
To boost phenobarb, give 100 mg PO
IV Keppra (Levetiracetam)
LEV 20 mg/kg IV over 15 min or LOR 0.1 mg/kg over 2-4 min had similar efficacy to terminate status (J Neurol. 2011 Sep 6) and a 2nd study in the elderly (Acta Neurol Scand 2010: 121: 418–421)
Excellent Review (Epilepsia, 52(Suppl. 8):35–38, 2011)
Non-Convulsive Status Epilepticus
Dementia, meningitis, tumor, history of brain disease might be predictors of non-convulsive status (J Neurol Neurosurg Psych 74:189 February 2003)
The geotrophic eye test is performed by turning the patients head from side to side and observing the eyes. It seems that in psychogenic seizures, the patient will always look away from the examiner, regardless of which way the head is turned.
EEG reading rules for non-neurologists: (Crippen) 1) don’t even try to read neonatal EEGs, especially in premature babies. 2) for other EEGs, remember that the EEG should be the opposite of the ECG: a) the more the EEG looks like VF, the better it is b) the more the EEG looks like sinus rhythm, the worse it is. c) the more the EEG varies in frequency and amplitude over time, the better it is d) focal areas that differ from the rest of the EEG are bad (too slow, or too high or too low in amplitude) e) sharp stuff is almost always bad except at the vertex when falling asleep f) whatever you think looks really bad is probably an artifact 3) all the rest is mere commentary (cf. Hillel)
Review Article on cEEG (Neurocrit. Care 2005;2:330341 and in my desktop box)
Might try levetricatam as piracetam is used in countries that have it. Other thoughts: Pappert EJ, Goetz CG, Vu TQ, Ling ZD, Leurgans S, Raman R, Carvey PM. Animal model of posthypoxic myoclonus: effects of serotonergic antagonists. Neurology. 1999 Jan 1;52(1):16-21 Wicklein EM, Schwendemann G. Use of clonazepam and valproate in patients with Lance Adams syndrome. J R Soc Med. 1993 Oct;86(10):618 Tom ============================== Tom Bleck (email@example.com) Thomas P. Bleck MD FCCM
Dilantin levels are inaccurate 2 hours after IV and 4 hours after IM fosphenytoin
Mount Sinai Protocol
ictal deliberate eye closure is reliable indicator of pseudoseizure
(1) Chung SS, Gerber P, Kirlin KA. Ictal eye closure is a reliable indicator for psychogenic nonepileptic seizures Neurology 2006;66:1730-1.
Ketamine for Status
NMDA receptor antagonist; Barbits/benzos work well early in SE,
not late; Ketamine is opposite
Loading dose: 1-2 mg/kg IV/1 min
Maintenance dose: 0.01-0.03 mg/kg/min cIV (adjust with liver
Principle: use only together with benzos
Advantage: neuroprotective, hemodynamic stability
Disadvantage: prolonged use anecdotally linked to brain atrophy
consistent with animal models of NMDA antagonist-mediated
neurotoxicity, may cause hypertension
intracranial mass, TBI, globe injuries, hydrocephalus, elevated ICP
hypertension, chronic CHF, tachyarrhythmias, MI
Borris 2000; Mazarati 1998, 1999; Mewasingh 2003
temporal lobe seziures can do it (Epileptic Disord 2008; 10 (2): 165-9)