Download Propofol Treatment of 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
• 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)
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%
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.
• NON CONVULSIVE – absence of overt muscle activity
• has continuous 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.
• 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
THE FINER POINTS OF ANAESTHETIC INFUSIONS
USED IN REFRACTORY STATUS EPILEPTICUS
AGENTS USED…
• MIDAZOLAM
• THIOPENTONE
• PROPOFOL
• KETAMINE
• INHALATIONAL AGENTS
• MAGNESIUM
• LIGNOCAINE
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.
• 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.
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
PROPOFOL
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.
• 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
PROPOFOL INFUSION SYNDROME
• TRIAD - of profound hypotension, lipidemia, and metabolic
acidosis
• MECHANISM:
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.
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.
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
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.
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.
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.
WHAT IS THE “HOLY GRAIL” FOR TREATMENT OF
REFRACTORY STATUS EPILEPTICUS??
• NO CLEAR CONSENSUS
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%).
•
Propofol and Midazolam in the Treatment of Refractory Status Epilepticus Prasad
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 31 Episodes,
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.
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.
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.
• 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
QUESTIONS/COMMENTS
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.
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