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convulsive status epilepticus

Prolonged generalized convulsions or recurrent generalized convulsions without recovery of consciousness. Convulsive status epilepticus is a medical emergency, requiring immediate & aggressive therapy. Etiology: 1) structural anomalies a) primary or metastatic CNS tumors b) post-traumatic injury c) CNS infection d) CNS inflammatory process (i.e. Lupus) e) cerebral infarction (embolic most common) 2) non-structural factors a) hypoglycemia b) electrolyte abnormalities: - hyponatremia - hypocalcemia c) uremia d) anoxia e) alcohol & sedative withdrawal f) drug toxicity - theophylline - amphetamines - cocaine - isoniazid 3) in patients with epilepsy, most common causes are: a) subtherapeutic anticonvulsant levels - non-compliance - drug interaction b) acute febrile illness 4) paraneoplastic limbic encephalitis Clinical manifestations: - generalized tonic-clonic seizure - continuous for > 5 minutes or - 2 seizures within 5 minutes without return to baseline between seizures Laboratory: 1) serum chemistries a) serum glucose b) serum electrolytes c) serum Ca+2 & serum Mg+2 d) serum urea nitrogen e) therapeutic drug monitoring: anti-convulsant levels f) serum toxicologies 2) complete blood count (CBC) 3) urine toxicology screen Special laboratory: - continuous EEG monitoring* for patients who are unresponsive or somnolent after status epilepticus to distinguish between nonconvulsive status epilepticus & post-ictal state [4] * 48% of patients treated for convulsive status epilepticus will have subclinical seizures on EEG Radiology: - neuroimaging - computed tomography of head after seizures stop [4] Complications: - longer duration of convulsive status epilepticus associated with worse outcomes [4] - aspiration - rhabdomyolysis - myoglobinuria - hyperthermia - complications of treatment (see Management section) - mortality 20% [4] Management: 1) support vital functions a) monitor vital signs b) soft plastic oral or nasal airway c) supplemental oxygen by face mask d) endotracheal intubation if indicated e) 2 large bore peripheral intravenous (IV) lines f) nasogastric tube g) padding to reduce injury 2) correct hypoglycemia - 50 mL of 50% dextrose with 100 mg of thiamine IV 3) stop seizure activity (5-10 minutes) a) initiate status epilepticus protocol when seizure has lasted > 5 minutes [4] b) intravenous benzodiazepines - lorazepam (Ativan) 2-4 mg @ 1-2 mg/min (preferred agent) - diazepam (Valium) 5-10 mg @ 1-2 mg/min - administer directly into vein to avoid adherence to IV tubing - concomitant bolus administration of patient's maintenance therapy if subtherapeutic [4] c) options if IV access not available: - buccal or intranasal midazolam [5] - diazepam 20 mg per rectum [3,4] - lorazepam 1-4 mg IM, maximum 10 mg [4] - as good as IV for prehospital status epilepticus [6] - IM midazolam [4] d) delays in initiation of benzodiazepine > 10 minutes associated with higher risk of death [10] 4) after administration of benzodiazepine (10-20 minutes) a) fosphenytoin* - load 18-20 mg/kg up to 1000 mg IV - infusion rate at 150 mg/min b) phenytoin (Dilantin)* is alternative - administer through glucose-free IV line to avoid precipitation in tubing - loading dose 20 mg/kg @ <50 mg/min - monitor blood pressure & cardiac rhythm - anticonvulsant effects seen within 20 min - a total dose of 30 mg/kg may be required c) valproic acid if patient allergic to phenytoin [4] 5) continued convulsions (20-60 minutes) a) phenobarbital - IV administration if phenytoin fails to stop seizures - 2nd or 3rd degree heart block - 5-10 mg/kg increments @ <50 mg/min until seizures are controlled - 20 mg/kg achieves serum level of 20 ug/mL - monitor blood pressure & cardiac rhythm - respiratory depression may require intubation b) barbiturate coma or general anesthesia - neuromuscular block - endotracheal intubation - failure of less aggressive measures c) infusion of propofol, midazolam, pentobarbital or thiopental in an ICU setting 6) identify & treat precipitating causes - consider herpes simplex encephalitis - consider paraneoplastic limbic encephalitis - anti-leucine-rich glioma inactivated 1 encephalitis - anti-NMDA receptor encephalitis 7) anticipate & treat complications a) respiratory depression may require intubation b) arrhythmias - phenytoin loading - transient heart block - phenobarbital c) hypotension - phenytoin - phenobarbital d) aspiration e) rhabdomyolysis f) myoglobinuria g) hyperthermia h) nonconvulsive status epilepticus [4] - persistently altered mental status, waxing & waning course, focal neurologic deficits (aphasia, dysarthria ...) 8) prophylaxis against further seizure activity * fosphenytoin & phenytoin are anticonvulsants of choice used as adjunct therapy after administration of benzodiazepine [4]

General

status epilepticus

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 541-42
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 645-46
  3. McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, Martland T, Berry K, Collier J, Smith S, Choonara I. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet. 2005 Jul 16-22;366(9481):205-10. PMID: 16023510
  4. Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  5. Holsti M et al. Intranasal midazolam vs rectal diazepam for the home treatment of acute seizures in pediatric patients with epilepsy. Arch Pediatr Adolesc Med 2010 Aug; 164:747. PMID: 20679166
  6. Silbergleit R et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med 2012 Feb 16; 366:591. PMID: 22335736 http://www.nejm.org/doi/full/10.1056/NEJMoa1107494 - Hirsch LJ Intramuscular versus Intravenous Benzodiazepines for Prehospital Treatment of Status Epilepticus N Engl J Med 2012; 366:659-660February 16, 2012 PMID: 22335744 http://www.nejm.org/doi/full/10.1056/NEJMe1114206
  7. Treiman DM, Meyers PD, Walton NY et al A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998 Sep 17;339(12):792-8. PMID: 9738086
  8. Brophy GM, Bell R, Claassen J et al Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012 Aug;17(1):3-23 PMID: 22528274 (corresponding NGC guideline withdrawn Feb 2018)
  9. Physician's First Watch Editors Guidelines Issued on Managing Convulsive Status Epilepticus Physician's First Watch, Feb 11, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Glauser T, Shinnar S, Gloss D et al Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Currents, Vol. 16, No. 1 (January/February) 2016 pp. 48-61 PMID: 26900382 Free PMC Article http://www.epilepsycurrents.org/doi/pdf/10.5698/1535-7597-16.1.48
  10. George J Delays Raise Death Risk in Kids with Status Epilepticus. 'Untimely' first-line treatment more common when seizures start outside hospital. MedPage Today. January 23, 2018 https://www.medpagetoday.com/neurology/seizures/70695 - Gainza-Lein M, Sanchez Fernandez I, Jackson M et al Association of time to treatment with short-term outcomes for pediatric patients with refractory convulsive status epilepticus. JAMA Neurol; 2018. Jan 22 PMID: 29356811 - Patel AD Time may be of the essence in the treatment of pediatric patients with refractory convulsive status epilepticus. JAMA Neurol; 2018. Jan 22 PMID: 29356824