Saturday, April 03, 2010

status epilepticus pearls

1,  Among patients with convulsive SE that stops, 14 % have ongoing  subclinical status and 48 % have ongoing intermittent seizures (DeLorenzo et al., Epilepsia 1998)

2.  Risk factors for increased mortality in SE include higher age, intubated, length of time till treated

3.  Fever contributes to cerebellar injury, and neuromuscular blockade prevents (Meldrum 1973 Arch Neurol)

4.  Among eleven patients with SE who died acutely, 8 had contraction band necrosis of cardiac muscle, and died due to initial catechol release Manno et al. Ann Neurol 2005)

5.  Neuron specific enolase (NSE) is unvestigated as a marker for neuronal injury in prolonged SE

6.  The VA cooperative study (Treiman et al, NEJM, 1998) looked at overt status and found the efficacy of each of the following regimens in stopping SE:  lorazepam, 65 %, phenobarbital 58 %, diazepam plus phenytoin, 56 % ,and phenytoin alone 44 %.  Subjects who failed the first drug responded to the second drug (7 %) and the third drug (2.3 %) at a low rate.  The only significant difference statistically was between lorazepam and phenytoin.

7.  Inttravenous valproate may be as good or better than phenytoin or fos-phenytoin ( Aggarwal et al, Seizure, 2007) both as a first line and second line agent (Misra Neurology 2006). If used with phenytoin, it may increase the free level of the drug, paradoxically causing increased seizure.  Antibiotics such as merepenem and amikacin may cause a dramatic fall off in the blood level of valproate, possibly due to increased renal excretion.  Beware of other p450 metabolized medications.  Valproate is a broad spectrum antiepileptic drug, with action against all seizure types including postanoxic myoclonus, and does not sedate or cause hypotension.  Therefore it may be DOC in patients with a DNR order.  Dose is 25

8.  Initial dose of thiopental in ICU setting is 2-4 mg/kg bolus, then 3-5 mg/kg/hour. Pentobarb has slower onset and offset than thiopental and should be dosed initially at 5 mg/kg with repeated boluses of same until seizures stop, with initial maintenance at 25-50 mg/minute, titrated to burst suppression.  Half life is over 34 hours.  Midazolam initial dose is .2 mg/kg, repeated every five minutes up to 2 mg/kg until seizures stop, with a continuous dose range of 0.05 - 2.9 mg/kg/hour. 

9. Propofol has rapid onset and rapid clearing.  Dose is bolus of 1-2 mg/kg,  then a continuous infusion of 1-15 mg/kg/hr with a maximum dose of 5 mg/kg/hr if maintained for days. Beware of "propofol infusion syndrome" of metabolic acidosis, cardiac failure, rhabdomyolysis, hypotension, and death.Risk factors are prolonged doses (> 48 hours), high doses (>5 mg/kg/hr), head injury, lean body mass, and concurrent use of catechols or steroids.  Concurrent clonazepam may also help prevent PIS (Rosetti et al, Epilepsia 2004).

10.  Intravenous levitiracetam is useful in benzo refractory partial seizures, usually stopping it  without causing severe AE's (Knake et al. JNNP 2008).

11.  Ellis looked at patients with grade 3 or 4 hepatic encephalopathy, and found of 42 total patients split between prophylactic AED and controls, subclinical status was common among the control group (45 %) but not in the treated group with    (15 %).  At autopsy the control group had more brain edema (Ellis et al, Hepatology 2000).  This constitutes an argument for continuous EEG monitoring.

12.  In renal patients, AED's are divided into the dialyzable and the nondialyzable.  Highly bound drugs (PTN, VPA, CBZ) are not dialyzed significantly.  Moderate protein binding eg LTG (lamotrigine) may need pre and post dialysis levels.  AED's THAT REQUIRE REPLACEMENT AFTER DIALYSIS ARE GBN, PREGABALIN, ETHOSUXIMIDE, LEVITIRACETAM, PHENOBARBITAL AND TOPIRIMATE. The serum concentrations of these can decrease 50 % after dialysis

13.  Among posttransplant patients, many seizures occur, and many are nonconvulsive. In liver transplant, the incidence may be as high as one third, slightly less in pancreatic, much less with other organs.  Day 4-6 post transplant is highest occurrence.  Most patients do not have prior seizures.  Short term AED's are indicated.

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