New York-Presbyterian
Pending approval by Subcommittee of Critical Care Therapeutics
The University Hospitals of Columbia and Cornell Pending approval by Subcommittee of Formulary & Therapeutics Committee LAST UPDATED 5/5/10 GENERALIZED CONVULSIVE STATUS EPILEPTICUS TREATMENT ALGORITHM IN ADULTS There exists a lack of prospective controlled trials regarding the appropriate doses or targeted therapeutic levels for refractory status epilepticus. Many of the recommended doses or targeted therapeutic levels are higher than referenced in the literature and are based upon expert opinions at NYPH. There is a lack of consensus among neurocritical care clinicians and epileptologists on the pharmacological approach to treatment of generalized convulsive status epilepticus after failure of a benzodiazepine. The suggestions below should not replace clinical judgment.
• Diagnose • Begin continuous physiologic
• Draw blood for: CBC, BMP, Ca, Mg, PO4, LFTS, troponin,
phenytoin, valproate, carbamazepine &/or other AED levels,
toxicology screen (urine and blood), ABG
• 50 mL of D50W IV unless glucose level is known and not low
• Lorazepam 4 mg IV over 2 min; if still seizing, repeat X 1 in 5 minutes
• If no rapid IV access give diazepam (Diastat) 20 mg PR (IV diazepam solution can be given PR if Diastat is
not available) or midazolam 10 mg intranasally, buccally or IM (use IV midazolam solution by any of these routes)
If seizures persist, this step can be skipped, especially if proceeding to midazolam or propofol, or can be
performed simultaneously with Step 4 in which case the administration rate of fosphenytoin/phenytoin should be
• Begin fosphenytoin 20 mg PE/kg IV up to 150 mg/min. If fosphenytoin is not available, give phenytoin 20
mg/kg IV (see table for administration and comments) up to 50 mg/min
• Using IV valproate instead of phenytoin/fosphenytoin is a justifiable option as well, particularly in those allergic
If seizures persist, give one of the following 4 options: (refer to Dosing Table below; intubation and/or IV
fluids/pressors may be necessary)
• Continuous IV midazolam (repeat bolus every 5 minutes until seizures stop, titrate to seizure control)
• Continuous IV propofol (repeat bolus every 3-5 minutes until seizures stop, titrate to seizure control)
• IV valproate
• IV phenobarbital If seizing >30 minutes, patient should be on at least one continuous IV drip with boluses
If seizures persist, give continuous IV pentobarbital (refer to dosing table) > 60 minutes
Begin continuous EEG monitoring as soon as possible if the patient does not awaken rapidly or if any continuous IV treatment is used Preferred Order of Medication Use
(For non-convulsive status epilepticus, intermittent seizures or later stages of refractory status epilepticus)
Continuous Infusions Non-continuous Infusions
(Usually do not cause respiratory depression, except phenobarbital)
1. Midazolam 1. Fosphenytoin/phenytoin or valproate 2. Propofol or pentobarbital 2. Levetiracetam 3. Ketamine: only if failure of or 3. Lacosamide: only if failure of or contraindications to phenytoin, valproate 4. Phenobarbital 4. Hypothermia
*Stable in 5% dextrose in water (D5W) as well. Normal Saline is the standard diluent in the NeuroICUs for medicated drips where stability in normal saline has been established, ABC= airway, breathing, circulation, AED= antiepileptic drugs, BMP= basic metabolic panel, Ca= calcium, CBC= complete blood count, DPH= phenytoin, Mg= magnesium, ICP= intracerebral pressure, PE= phenytoin equivalents, PO4= phosphate, UGT= glucoronidation, VPA= valproate
New York-Presbyterian
Pending approval by Subcommittee of Critical Care Therapeutics
The University Hospitals of Columbia and Cornell Pending approval by Subcommittee of Formulary & Therapeutics Committee LAST UPDATED 5/5/10 Acute/Serious Side Effects (SE) Targeted trough drug Special Monitoring/Comments Medication levels for Adjustment in Interactions Dialysis Continuous cardiac monitoring epilepticus recommended for all agents in this setting FOSPHENYTOIN (Cerebyx)
Conversion half-life to phenytoin ~ 15 minutes
Dilute in NS* 2-25
Load: 20 mg/kg IV up to 50 mg/min, 25
mg/min in elderly, patients with pre-existing
PHENYTOIN
Maintenance: 5- 7 mg/kg/day in 2-3 divided
Administer through
• Infuse through dedicated line with 0.22 -5
large vein
• Flush with NS following administration
• Tube feeding inhibits absorption; hold
feeds for administration, flush with NS pre
and post administration, may require higher
KETAMINE LACOSAMIDE (Vimpat)
Maintenance: 200 – 300 mg mg IV/PO over
LEVETIRACETAM
Load: 2.5 g IV over 5 min (1-4 g over 15
Initial: 3-6 g/day divided in 3-4 divided
*Stable in 5% dextrose in water (D5W) as well. Normal Saline is the standard diluent in the NeuroICUs for medicated drips where stability in normal saline has been established, ABC= airway, breathing, circulation, AED= antiepileptic drugs, BMP= basic metabolic panel, Ca= calcium, CBC= complete blood count, DPH= phenytoin, Mg= magnesium, ICP= intracerebral pressure, PE= phenytoin equivalents, PO4= phosphate, UGT= glucoronidation, VPA= valproate
New York-Presbyterian
Pending approval by Subcommittee of Critical Care Therapeutics
The University Hospitals of Columbia and Cornell Pending approval by Subcommittee of Formulary & Therapeutics Committee LAST UPDATED 5/5/10 MIDAZOLAM
0.2-0.4 mg/kg boluses every 5 minutes until
Initial rate: 0.1 mg/kg/h. Bolus and increase
PENTObarbital (Nembutal) Dilute up to 50 mg/mL
Load: 5 mg/kg IV up to 50 mg/min; repeat
traditionally titrated to suppression-burst on
EEG but titrating to seizure suppression is
mg/mL) 50 mg/mL inj (2mL, 20 mL) PHENObarbital (Luminal)
Doses < 300 mg IV over 3-5 min (up to 60
mg/mL (1 mL), 130 mg/mL (1 mL) PROPOFOL
boluses every 3-5 minutes until seizures
pancreatitis, Propofol Infusion Syndrome
stop, up to maximum total loading dose of
(metabolic acidosis, bradycardia, cardiac
mg/kg/hr). Bolus and increase rate until
Maintenance: 17 – 250 microgram/kg/min
• Contraindications: allergy to soy, egg
• Avoid doses > 80 microgram/kg/min (5
VALPROATE
Load: 40 mg/kg ~IV over 10 min; if still
seizing, additional 20 mg/kg over ~5 min
Avoid pancreatitis, low fibrinogen levels,
500 mg/5 mL inj Medication Treatment Pearls:
When checking post-load drug levels, wait at least 2 hours post infusion for fosphenytoin and phenytoin.
Continuous IV infusion duration of treatment: Once seizures are controlled, continue dose for at least 24 hours prior to consideration of wean. Wean over 24 hours.
Loading doses do not require adjustment for renal or hepatic insufficiency.
Consider Hypothermia (31-35 ° C) as a last line treatment for refractory status epilepticus.
*Stable in 5% dextrose in water (D5W) as well. Normal Saline is the standard diluent in the NeuroICUs for medicated drips where stability in normal saline has been established, ABC= airway, breathing, circulation, AED= antiepileptic drugs, BMP= basic metabolic panel, Ca= calcium, CBC= complete blood count, DPH= phenytoin, Mg= magnesium, ICP= intracerebral pressure, PE= phenytoin equivalents, PO4= phosphate, UGT= glucoronidation, VPA= valproate
Neuron cell structure • Dendrites: Contain neuroreceptors that respond when exposed to neurotransmitters. • Soma: Body of neuron cell. DNA in the nucleus in the soma code for all the proteins of the neuron. • Axon hillock: Contains a high concentration of voltage dependent sodium channels and considered the spike initiation zone for action potentials. • Axon: Electrical pathway
Tropical Journal of Pharmaceutical Research August 2011; 10 (4): 365-373 Faculty of Pharmacy, University of Benin, http://dx.doi.org/10.4314/tjpr.v10i4.1 Research Article Formulation and Evaluation of Bioadhesive Cyproheptadine Tablets V Chandrakala V2*, MS Srinath1, Saral A Mary2 and Kumar S Utpal2 1Department of Pharmaceutics, Government College of Pharmacy, Bangalore, Pharmace