The Nursing Challenges of Caring for Patients with

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

disclosures • Merz

Case #1 K. S. • KS is a 28 yo Korean American female • Admitted to OSH – flu-like symptoms for 4 -5 days. – nausea/vomiting and 105. 0 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. • Social 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, Mg. So 4, Keppra, Topamax, Valproate, Phenobarb • Day 50 -- Ativan, Keppra, Topamax, Phenobarb, Memantine, Ketamine gtt • Day 62 -- Status continuing Uroseptic - death within 1 hour of foley exchange

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

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. OR • 2 or more discrete seizures between which there is incomplete recovery of consciousness. SE=Medical Emergency

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

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 c. EEG. • Wittman & Hirsch--Neurocritical Care 2005: increasing awareness of nonconvulsive seizures in critically ill

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

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 Internal Safety: A seizure represents actual danger to brain tissue Time is BRAIN

Returning to Case Study #1 K. 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 Onset Status Refractory Epilepticus

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

11 7 0 11 15 24 65 50 92 100 • 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

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

Wilder-Smith et al • Treatments included: – Benzodiazepines Levetiracetam – Phenytoin IVIG – 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 ICUadmit*ICUadmit*ICUadmit BP BP BP

Benzos • Diazepam (Valium): • Short acting , ½ life 16 -90 minutes, the later ½ eliminated slower. • High does and accumulation of active diazepam metabolites = respiratory depression and hypotension • 5 -20 mg IV slowly at 1 -2 mg/min Repeat 5 -10 mg every 5 -10 minutes to a maximum of 100 mg/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. 2 mg/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 -20 mg/kg, if refractory – may use 30 mg/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 – elevates seizure threshold by decreasing postsynaptic excitation, possibly excitation stimulating postsynaptic GABA inhibitor responses. – Sometimes given in combo with dilantin – Rapidly absorbed by all routes, 3 -4 weeks to reach steady state

Medicinal Management • Traditional goal of therapy: achieve burst suppression on EEG 12 -24 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

When your clinical guidelines fail in stopping seizures… 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 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 • 44 yo male, tx for status 3 months later- consistent with animal models Nmethyl-D-aspartate antagonist –mediated neurotoxicity • Ubogu et al 2003 • 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 -35 C) • Corry, Dhar, Murphy, Diringer 2006

Alternative Therapies • ECT: -1 second seizure is induced while anesthetized, wakes 10 -15 minutes later – 3 x 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 • Airway/Breathing: vented, full support, possiblity of VAP, need for aggressive pulmonary toileting • Circulation: hemodynamically unstable due to AEDs/coma inducing meds requiring vasoactive agents, increased risk of DVTS • Disability: (Neuro exam): pupils sometimes work. Can’t see more damage due to coma

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

Nursing Considerations • Head to Toe: Assessment of physical appearance. Oh, how I wish I could wash their hair. • IV’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? • JP/Drains: hopefully, not needed.

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

Nursing Considerations • Meds: 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 • Nutrition: 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 Survivors! – 4 AA female, 1 Asian female, 1 Lebanese male, 1 caucasian male and female 4

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

Why does having an actual diagnosis matter? • YOU TELL ME

Difference b/w TBI &NORSE?

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

Status Epilepticus Seizure Refractory Status Epilepticus Seizure NORSE

Ladessa

I’m a NORSE SURVIVOR!!!!

Case Study #2 K. C. § 19 yo female with URI and fever 101. 0 § 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

Case Study #2 K. C. • 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

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. 2007118(8): 1660 -70. Robakis TK, Hirsch LJ. Literature review, case report, and expert discussion of prolonged refractory status epilepticus. Neurocrit Care. 2006. 4(1): 35 -46. Khaled KJ, Hirsch LJ. Advances in the Management of Seizures and Status Epilepticus in Critically Ill Patients. Crit Care Clin. 2007. (22): 637 -659. 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: 417 -20. Hirsch LJ. , Kull L. Continuous EEG Monitoring in the Intensive Care Unit. Am. J. END Technol. 2004 (44): 137 -158. Hickey JV. The Clinical Practice of Neurological and Neurosurgical Nursing. Philadelphia: Lippincott, 1997. Corry JJ, Dhar R, Murphy T, Diringer MN. Hypothermia for Refractory Status Epilepticus. Neurocrit Care 2008: 9(2): 189 -97. Rosetti AO. Anesthesia for Treatment of Refractory Status Epilepticus. Epilepsia 2007. 48 (8): 52 -55

Please contact me with questions or insight… mored 001@mc. duke. edu