The Nursing Challenges of Caring for Patients with NORSE Syndrome Melissa V Moreda RN BSN CNRN

disclosures Merz

KS is a 28 yo Korean American female Admitted to OSH –flu-like symptoms for 4-5 days. –nausea/vomiting and Fever. She became disoriented and confused & had a witnessed tonic clonic seizure. Recurrent seizures continued. Case #1 K.S.

Transferred to Duke in Status Epilepticus Workup unremarkable NO past hx of childhood epilepsy, febrile seizure, no head trauma, no meningitis NO family hx of sz, no predisposing evidence

Case #1 K.S. ANYSocial hx: ANY exposure--- what do they work with? any unusual circumstances or any family/friends with recent sickness? Habits: drinking/drugs/etc Allergies: none Medications (any herbals/supplements) Extensive negative workup

Case #1 K.S. Initial lines of anticonvulsants started. Quick escalation of medication dosages and additional anticonvulsants added. Seizures continued. Paralytics added, max therapies reached.

Case #1 K.S. - Hospital Course Day 1--Dilantin, Topamax, Pentobarb gtt, Versed Day 10– Dilantin, Topamax, Pentobarb gtt, Keppra, Zonisamide Day 20– Lidocaine/Magnesium gtt Day 30— Dilantin, Topamax, Clonazepam, Keppra,Phenobarb,Valproate, Ketamine

Case #1 K.S. Day 40-- Ativan gtt, MgSo4, Keppra, Topamax, Valproate, Phenobarb Day Ativan,Keppra,Topamax, Phenobarb, Memantine, Ketamine gtt Day Status continuing Uroseptic - death within 1 hour of foley exchange

Electrical activity of the brain What is the difference between Seizures and Status Epilepticus Abnormal electrical signal Neuron

What is seizure? A single (finite) event of abnormal discharge in the brain that results in an abrupt and temporary altered state of cerebral function.

What is Status Epilepticus? Continuous seizures lasting at least 5 minutes. 2 or more discrete seizures between which there is incomplete recovery of consciousness. OR SE=Medical Emergency

Cellular Respiration & Glycolysis Demand ATP 250% CBF to metabolic demand Metabolic activity in skeletal muscles Oxygen and glucose = cellular destruction and death SE=Medica l Emergenc y Morbidity & Mortality

Status Epilepticus Repeated partial seizures manifesting as focal motor convulsions, focal sensory symptoms, or focal impairment of function (ie: aphasia not associated with LOC) Tonic-clonic most common type. Convulsive more easily seen clinically. Partial less obvious and more difficult to identify. Subclinical only identifiable on cEEG. Wittman & Hirsch--Neurocritical Care 2005: increasing awareness of nonconvulsive seizures in critically ill

What is refractory SE? Benzos not stopping the seizures Failure of max doses of dilantin

Safety & Nursing Care: Convulsive vs Anticonvulsive External Safety: padded rails suction present bed in low position pulse ox/ vitals staying with the patient obtaining benzos & AEDS Family needs education and reassurance

Safety & Nursing Care: Convulsive vs Anticonvulsive A seizure represents actual danger to brain tissue Time is BRAIN Internal Safety:

Returning to Case Study #1K.S. KS has the flu, spikes a fever, starts seizing and doesn’t stop despite multiple line anticonvulsants. Full life support. Completely negative workup. Family, Nurses, MD’s, PRM’s, want to know…. What’s going on here???

NORSE New EpilepticusRefractory StatusOnset

What is it????? *2005 Wilder-Smith,Lim, Teoh, Sharma, Tan, Chen, et al documented and claimed this phenomenon in Singapore.

Of the 7 identified: –Shortest stay: 7 days resulting in death -11 days: 1 patient survived, but in persistent vegetative state with frequent seizures. The other one died. Longest stay: 92 days survived but in persistent vegetative state with frequent seizures as well

NORSE-EEG Relationships Initial eeg captured ictal discharges in all. In 3, eeg showed ictal discharges from bilateral fronto-temporal regions with no side preference. In 1, continuous parasagital ictal discharge. In 3, fronto-temporal discharges originating from the right on 2 occasions and once on the left

Why use these meds??? Status Epilepticus Clinical Guidelines 2003 –Benzodiazepines –Phenytoin loads + maintenance doses –Barbiturates

Wilder-Smith et al Treatments included: –BenzodiazepinesLevetiracetam –PhenytoinIVIG –Valproate –Propofol –Thiopental –Topiramate

Benzos Lorazepam (Ativan ): –increases action of GABA which inhibits neurotransmission, depressing all levels of CNS Problem: hypotension, caution in renal or hepatic impairment, MG BP ICUadmit*ICUadmit*ICUadmit*ICUadmit*ICUadmit

Benzos Diazepam (Valium): Short acting, ½ life minutes, the later ½ eliminated slower. High does and accumulation of active diazepam metabolites = respiratory depression and hypotension 5-20mg IV slowly at 1-2 mg/min Repeat 5-10 mg every 5-10 minutes to a maximum of 100mg/24 hours

Benzos Midazolam(Versed): –Large number of trials reflecting that this medication works –Rapid absorption into brain –Benign from a hemodynamic standpoint –Peds: success of breaking seizures without intubation –Load:0.2mg/kg, maintenance: up to 2 mcg/kg/min, most effective as a gtt –Problem: tachyphylaxis (wears off), accumulates in critically ill.

Phenytoin / Fosphenytoin –may work in motor cortex, may stop spread of activity –Brain stem centers stop tonic phase of grand mal sz –18-20mg/kg, if refractory – may use 30mg/kg –Problem: hypotension, purple glove syndrome, fever, cardiac death from widened QRS

Refractory Status Epilepticus 30 minutes to 1 hour of seizure activity not broken No interval of time between failed treatment and next therapy Start infusions of Benzodiazepines, Propofol, Barbitruates Keep giving bolus doses

Barbiturates Pentobarbital: –Extremely effective halting seizures on eeg by inducing coma –Load: 5-12 mg/kg, maintenance: 1-10 mg/kg Problem: high doses suppress cardiac function,difficult to monitor levels, poor chemotaxis of wbc, paralysis of resp cilia, poikilothermia Dr.Borel

Barbiturates Phenobarbital: –Introduced 1912 –CNS depressant decreasing postsynaptic excitation – elevates seizure threshold by decreasing postsynaptic excitation, possibly stimulating postsynaptic GABA inhibitor responses. –Sometimes given in combo with dilantin 3-4 weeks –Rapidly absorbed by all routes, 3-4 weeks to reach steady state

Medicinal Management Traditional goal of therapy: achieve burst suppression on EEG hours to control or prevent recurrent seizures. Termination of the seizures should occur rapidly to minimize neural damage, correction of metabolic defects, and resuscitation SE=Medical Emergency

What do you do???

Medicinal Management of Refractory Status Epilepticus 1 st Maximize Phenytoin & Benzodiazepine loads. This usually controls 70% of patients. 2 nd Midazolam boluses infusion, Propofol, Barbiturates 3 rd Topiramate, phenobarbital, midazolam, pentobarbital, valproate, levetiracetam, lidocaine, ketamine, thiopental, or isoflurane

Medicinal Management Other treatments we have tried –Antivirals upon arrival –Magnesium drips –Memantine –Ketamine drips –Prn ativan, phenobarb, pentobarb, versed –Giving “holidays” to reintroduce the medications, hopefully to “break through” the seizures.

Wilder-Smith et al Thiopental: anesthetic that is barbiturate based. IVIG: ?autoimmune, does not cross the BBB l: Propofol: difficult to suppress sz while titrating/ balancing hemodynamics –Rosetti et al 2004 burst suppression 31 patients/ 21 successfully suppressed – 1 interesting side effect: EPILEPTIFORM ACTIVITY!!!!

Alternative Therapies Robakis, Hirch 2006 lit review + expert neurointensivists/ epileptologists Tx included: ketamine, gammaglobulin, plasmapheresis, steroids, adrenocorticotropic hormone, high dose phenobarb, isoflurane, lidocaine, ect, ketogenic diet, hypothermia, mag

Lidocaine CNS depression with cessation of convulsions Biphasic: – Blocks inhibitory CNS pathways resulting in stimulation –Blocks inhibitory/excitatory impulses resulting in CNS inhibition (Peralta 2007) Walker, Slovis 1997 effective in peds not responding to barbs Bolus + maintenance dose Toxicity Rare

Ketamine Good Stops Seizures through anesthesia: NMDA antagonist with intrinsic sympathomimetic properties –1-4.5 mg/kg –Borris et al 2000 Bad Neurotoxicity Diffuse cerebellar atrophy 44yo male, tx for status 3 months later- consistent with animal models N- methyl-D-aspartate antagonist –mediated neurotoxicity Ubogu et al2003 SE: Pyschotic

Using Anesthesia for Treatment of Refractory Status Epilepticus Rosetti in Epilepsia 2007 –Each anesthetic has advantages/risks –Depends on the protocols regarding duration and depth of sedation –The biological background of the patient remains the prognostic determinant of SE

Alternative Therapies Hypothermia (31-35C) Corry, Dhar, Murphy, Diringer 2006

Alternative Therapies ECT: - 1 second seizure is induced while anesthetized, wakes minutes later –3x week for up to 15 treatments, return to baseline, 1-2 more treatments

Alternative Therapies Ketogenic Diet: –High fats, low carbs –Strict diet requiring medical supervision –Body burns fat instead of glucose –Kids usually on for 2 years –Should we consider this in tube feeds?

Nursing Considerations ABAirway/Breathing: vented, full support, possiblity of VAP, need for aggressive pulmonary toileting CCirculation: hemodynamically unstable due to AEDs/coma inducing meds requiring vasoactive agents, increased risk of DVTS DDisability: (Neuro exam): pupils sometimes work. Can’t see more damage due to coma

Nursing Considerations EExpose: what does their skin/lines look like? Usually generally edematous, pressure sores common. Med rashes. FFahrenheit: Poikilothermic, immune system suppressed, may need routine pan cultures Family Finances…Increased anxiety GGadgets: Scds, afo boots, hand splints, various machines for life support, eeg electrodes

Nursing Considerations HHead to Toe: Assessment of physical appearance. Oh, how I wish I could wash their hair. IIV’s: site appearance, correct iv doses, do you have enough access? Do you need to make more pentobarb or levophed? Are you waiting for more depakote or an abx? JJP/Drains: hopefully, not needed.

KKeep Family Informed: This is the tricky part. I usually want to cry at this point. LLabs: Are you therapeutic? Have any of the weirdo labs come back from Mayo or the state? Legal: Have we discussed DNR? Nursing Considerations

MMeds: Besides the AEDs, anticoagulants, GI motility agents, ABX, acid reduction agents, blood products, SSI… Do you have any more room on your Medication Administration Record? Movement: PROM NNutrition: Are they actually getting any with their gut shut down? High residuals? Have they developed an ileus? Are they on a bowel regimen with daily stimulation?

??? NORSE at DUKE In the last 10 years at Duke, we can identify at least 8 patients –All young (<35) –Previous good health –Initially Flu-like symptoms or pyschotic behavior, then status –Negative workup –4 AA female, 1 Asian female, 1 Lebanese male, 1 caucasian male and female 4 Survivors!

Diagnosis: By exclusion only When???

Workup Includes: *Radiographic Imagery (ct,mri) *Continuous eeg *Serum samples: Heavy Metals, Complex Virus, RMSF, Arbovirus, Rabies, Leptospiral Abs, Autoimmune *Brain Biopsy

Workup includes: *CSF(culture,gram stains, cryptococcal antigens, herpes PCR polymerase chain reactions- replicate DNA) *Stool (organisms/parasites) *Infection Disease Consult

does having an actual diagnosis matter? YOU TELL ME Why

Difference b/w TBI &NORSE?

Why does having an actual diagnosis matter? Merle Mishel PhD, FAAN- UNC Chapel Hill Uncertainty in Illness Theory

Status Epilepticus NORSE Refractory Status Epilepticus Seizure

Ladessa

I’m a NORSE SURVIVOR!!!!

Case Study #2 K.C.  19 yo female with URI and fever  Z pack started  2 days later, in car with family, started seizing and turning blue, incontinent of urine.  OSH- tonic clonic sz, intubated  Negative primary workup

2 days later extubated Another sz, meds given, intubated Sz continues, bradycardic and cyanotic Transfer to Duke 3 weeks after initial sz, off pentobarb, and smiling at dad Case Study #2 K.C.

Another Survivor!

Bibliography Jirsch J. Hirsch LJ. Nonconvulsive seizures: developing a rational approach to the diagnosis and management in the critically ill population. Clin Neurophysiol (8): Robakis TK, Hirsch LJ. Literature review, case report, and expert discussion of prolonged refractory status epilepticus. Neurocrit Care (1): Khaled KJ, Hirsch LJ. Advances in the Management of Seizures and Status Epilepticus in Critically Ill Patients. Crit Care Clin (22): Wilder-Smith EPV, Lim ECH, Teoh HL, Sharma VK, Tan JJH, Chan BPL, Ong BKC. The NORSE (New Onset Refractory Status Epilepticus) Syndrome: Defining a Disease Entity. Ann Acad Med Singapore. 2005, 34: Hirsch LJ., Kull L. Continuous EEG Monitoring in the Intensive Care Unit. Am. J. END Technol (44): Hickey JV. The Clinical Practice of Neurological and Neurosurgical Nursing.Philadelphia: Lippincott, Corry JJ, Dhar R, Murphy T, Diringer MN. Hypothermia for Refractory Status Epilepticus. Neurocrit Care 2008: 9(2): Rosetti AO. Anesthesia for Treatment of Refractory Status Epilepticus. Epilepsia (8):52-55

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