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REFRACTORY STATUS EPILEPTICUS

REFRACTORY STATUS EPILEPTICUS. USE OF ANAESTHETIC AGENTS R MAHARAJ. LECTURE OUTLINE. CURRENT CONCEPTS ON DEFINITION AND MANAGEMENT DEFINITIONS ANEASTHETIC AGENTS USED THE IDEAL ANAESTHETIC AGENT SUMMARY. CURRENT THINKING??. More aggressive and early treatment of seizures

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REFRACTORY STATUS EPILEPTICUS

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  1. REFRACTORY STATUS EPILEPTICUS USE OF ANAESTHETIC AGENTS R MAHARAJ

  2. LECTURE OUTLINE • CURRENT CONCEPTS ON DEFINITION AND MANAGEMENT • DEFINITIONS • ANEASTHETIC AGENTS USED • THE IDEAL ANAESTHETIC AGENT • SUMMARY

  3. CURRENT THINKING?? • More aggressive and early treatment of seizures • Hence change in definition of status epilepticus… • Generalized convulsive status epilepticus in adults and older children (greater than 5years old) refers to greater than 5 minutes of a continuous seizure, or two or more discrete seizures between which there is incomplete recovery of consciousness. (Lowenstein et al, EPILEPSIA, 1999)

  4. REFRACTORY STATUS EPILEPTICUS • DEFINED AS: • SEIZURES NOT RESPONDING TO 1ST LINE (BENZODIAZAPINES) OR 2ND LINE ( PHENYTOIN/ VALPROATES/ PHENOBARBITONE) AGENTS. • Occurs in ~ 20% patients in status epilepticus • Mortality rate > 20%

  5. CONVULSIVE VS NONCONVULSIVE STATUS EPILEPTICUS • Based on clinical and electrical(EEG) changes. • CONVULSIVE – characterised by prolonged tonic clonic muscle contractions, associated loss of consciousness. • Prolonged convulsive status epilepticus can degenerate into a non convulsive state  look for subtle mouth twitching, eye movements etc.

  6. NON CONVULSIVE – absence of overt muscle activity • hascontinuous or near-continuous generalized electrical seizure activity for at least 30 minutes without physical convulsions. • Diagnosis can be difficult - physical signs: agitation or confusion, nystagmus, or bizarre behaviors such as lip smacking or picking at items in the air. • NB!! DO NOT LABEL ALL STRANGE BEHAVIOUR AS PSYCHIATRIC.

  7. NCSE is categorized into absence or complex partial SE based on EEG criteria • Absence SE - benign form of SE that does not cause serious brain damage. • Complex partial SE is associated with neuronal injury and high morbidity and mortality ~ 3 times higher. • aggressive treatment advocated

  8. THE FINER POINTS OF ANAESTHETIC INFUSIONS USED IN REFRACTORY STATUS EPILEPTICUS

  9. AGENTS USED… • MIDAZOLAM • THIOPENTONE • PROPOFOL • KETAMINE • INHALATIONAL AGENTS • MAGNESIUM • LIGNOCAINE

  10. MIDAZOLAM • a short-acting benzodiazepine • loading dose of 0.2 mg/kg • maintained at a continuous infusion of 0.05 to 2.0 mg/kg per hour • Induction is rapid and effective. • metabolized via hepatic mechanisms - may require dose adjustment.

  11. Hypotension less frequently ,lesser degree VS propofol or the barbiturates. • usually regain consciousness within an hour of drug withdrawal • may be prolonged with longer duration of treatment. • main limitation- rapid development of tachyphylaxis - often requires the persistent escalation of dosing.

  12. THIOPENTONE • BOLUS - 75- to 125-mg IV boluses. • INFUSION- 1 and 5mg/kg per hour. • redistribute rapidly to body fat, hence rapid brain penetration • prolonged elimination. • Barbiturates are immunosuppressive -> increase in nosocomial infections. - some investigators tend to prescribe barbiturates only after midazolam and propofol fail. • MAJOR S/E: hypotension –requires close BP monitoring

  13. PROPOFOL

  14. PROPOFOL… • short-acting non barbiturate hypnotic • GABA A agonist similar to the benzodiazepines and barbiturates. • loading dose of 3 to 5mg/kg • infusion: 1 to 15mg/kg per hour. • advantage VS Midazolam/Thiopentone - rapid induction and elimination.

  15. avoided in children - severe metabolic acidosis. • seizures have been associated with both the induction and withdrawal of propofol. ? Clinical importance • should be reduced slowly under continuous EEG monitoring. • side effects: hypotension, due to fat emulsion – feeding regimes need to be adjusted in prolonged infusions

  16. PROPOFOL INFUSION SYNDROME • TRIAD - of profound hypotension, lipidemia, and metabolic acidosis • MECHANISM:

  17. KETAMINE • effective in controlling recalcitrant seizures in some animal models • used recently with some clinical success. • neuroprotective - simultaneously controls seizures and blocks glycine-activated NMDA receptors. Sheth RD, Gidal BE. Refractory status epilepticus: response to ketamine. Neurology. 1998;51:1765-1766. Fujikawa DG. Neuroprotective effect of ketamine administered after status epilepticus onset. Epilepsia. 1995;36:186-195. • Caution in raised intracranial pressure.

  18. INHALATIONAL AGENTS • an alternative approach to the treatment of RSE. • ADVANTAGES - rapid onset of action, ability to titrate the dose according to the effects demonstrated on the electroencephalogram (EEG). • isoflurane and desflurane usually used.

  19. INHALATIONAL AGENTS … • mechanism of action of IA - not well understood. • the antiepileptic effects of isoflurane are likely due to potentiation of inhibitory postsynaptic GABAA receptor–mediated currents • effects on thalamocortical pathways have also been implicated Mirsattari SM, Sharpe MD, Young GB. Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane. Arch Neurol 2004;61:1254-9

  20. NEWER AGENTS • Topiramate via nasogastric tube. Effective dosages ranged from 300 to 1,600 mg/d • Levetiracetam (500-3000 mg/day) by nasogastric route. • Well designed studies are needed to assess above.

  21. WHEN IS REFRACTORY STATUS EPILEPTICUS CONTROLLED??? • EEG FEATURES: • BURST SUPPRESSION VS TOTAL EEG SUPPRESSION VS SUPPRESSION OF EPILEPTIFORM ACTIVITY • MOST AUTHORS ADVOCATE BURST SUPPRESSION AS ACCEPTABLE • ALTHOUGH NO STUDIES TO PROVE THAT THIS GIVES MOST FAVOURABLE PATIENT OUTCOMES.

  22. MONITORING IN REFRACTORY STATUS EPILEPTICUS • depth and duration of anesthesia that should be used to treat SE are unknown. • titration to a burst-suppression pattern on the EEG • maintained for 12 to 48 hours • slowly weaned while the patient is observed and the EEG is monitored for seizures. • If seizures recur, the process is repeated at progressively longer intervals.

  23. WHAT IS THE “HOLY GRAIL” FOR TREATMENT OF REFRACTORY STATUS EPILEPTICUS?? • NO CLEAR CONSENSUS

  24. WHAT IS THE “HOLY GRAIL” FOR TREATMENT OF REFRACTORY STATUS… • EFNS guidelines 2006 - No large randomised control trials comparing different agents. • Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002; 43: 146–153 Pentobarbital was more effective than either propofol or midazolam in preventing breakthrough seizures (12 vs. 42%).

  25. Propofol and Midazolam in the Treatment of Refractory StatusEpilepticusPrasad A, Worrall BB, Bertram EH, Bleck TP, Epilepsia 2001;42:380–386 Retrospective review of a small sample size… both infusions have similar efficacy • Propofol Treatment of Refractory Status Epilepticus: A Study of 31Episodes, Rossetti AO, Reichhart MD, Schaller MD, Despland PA Bogousslavsky J, Epilepsia 2004;45:757–763[PubMed] Propofol administered with clonazepam found to be effective in controlling refractory episodes.

  26. ANAESTHETISING AGENT ALONE VS ANAESTHETISING AGENT PLUS CONVENTIAL ANTI-EPILEPTIC • The management of refractory generalised convulsive and complex partial status epilepticus in three European countries: a survey among epileptologists and critical care neurologists,M Holtkamp, F Masuhr, L Harms, K M Einhäupl, H Meierkord, K Buchheim J Neurol Neurosurg Psychiatry 2003;74:1095–1099 • Most respondents- use another non-anaesthetising anticonvulsant for generalised convulsive (65%) and complex partial status epilepticus (64%). • general anaesthetic - generalised convulsive VS in complex partial status epilepticus (35% v 16%) -if first line anticonvulsants failed to terminate the seizures. • The non-anaesthetising drug of choice was phenobarbitone.

  27. Time point of induction of general anaesthesia after failure of first line drugs, and preferred anaesthetic… • All used general aneasthesia as part of their protocol • In generalised CSE, half the respondents proceeded to general anaesthesia within 30 minutes of the onset of the condition. • 61% withheld general anaesthesia complex partial status epilepticus for more than one hour after seizure onset • 21% would wait > 1 hr in patients with generalised seizures.

  28. preferred first choice agents- barbiturates (58%), predominantly thiopentone. • 29% used propofol. • Followed by IV midazolam, as the first anaesthetising drug. • Ketamine and isoflurane were chosen by only a few respondents

  29. QUESTIONS/COMMENTS

  30. TAKE HOME POINTS… • Early administration of first line agents. • Use of an accelerated algorithm – first and second line agents simultaneously. • Look for reversible causes and correct. • Prevent secondary insults. • For refractory status – no consensus as to which drugs are superior, use local guidelines. • Anaesthetic infusions should ideally be started in ICU with haemodynamic and EEG monitoring.

  31. REFERENCES • EFNS guideline on the management of status epilepticus, H. Meierkorda, P. Boonb, B. Engelsenc, K. Go¨cked, S. Shorvone, P. Tinuperf and M. Holtkamp; European Journal of Neurology 2006, 13: 445–450 • EmergencyTreatment of Status Epilepticus:Current Thinking, Dan Millikan, MD, Brian Rice, MD, Robert Silbergleit, MD*; Emerg Med Clin N Am 27 (2009) 101–113 • New Management Strategies in the Treatment of Status Epilepticus, EDWARD M. MANNO, MD; Mayo Clin Proc. 2003;78:508-518 • Treatment of Refractory Status Epilepticus With Inhalational Anesthetic Agents Isoflurane and Desflurane, Seyed M. Mirsattari, MD; Michael D. Sharpe, MD; G. Bryan Young, MD, FRCPC; Arch Neurol. 2004;61:1254-1259

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