Neurocritical Care Guide 2020-2021, Study notes of Neurobiology

Download Neurocritical Care Guide 2020-2021 and more Study notes Neurobiology in PDF only on Docsity! Neurocritical Care Guide 2020-2021 [PGES Ie SINE MORIBU? University of Pennsylvania 2 Mission Statement The Penn Neurocritical Care Program aims to serve patients with severe acute injury to the nervous system through provision of exceptional, compassionate, cutting-edge care, to make important discoveries through innovative research that lessens the burden of suffering, and to train the next generation of international leaders in Neurocritical Care through a rigorous, multifaceted and comprehensive fellowship program. Editors: Ramani Balu, MD PhD Atul Kalanuria, MD FACP MHCI Contributors: Jonathan Ji, MD Sok Lee, MD Margaret Huynh, DO Jessy Walia, MD Francisco Gomez, MD Kiruba Dharaneeswaran, MD Aleksandra Yakhkind, MD Jason Yoon, MD James Lee, MD James Soh, MD Katherine Kessler, MSN CRNP Advisors: Joshua Levine, MD Monisha Kumar, MD John Chandler, MD 5 THE NEUROLOGIC EXAMINATION MENTAL STATUS: • Attention: Alert, Sleepy, Lethargic, Stuporous, Coma o Does patient open eyes to voice vs sternal rub vs deep pain o Can pt. spell WORLD backwards, count from 20 to 1, perform serial 7s • Language: Fluent/nonfluent, repetition, naming, comprehension o Can p. repeat a phrase (e.g., no ifs ands or buts) o Can pt. name high frequency objects (e.g., watch, pen) and low frequency objects o Can pt. follow 1-step and 2-step commands, midline and appendicular commands? • Memory: can pt. recall 3-5 objects at 1 minute, forward digit span (avg 7), story details • Visuospatial: Organization of space (i.e., ability to draw clock, complex figure), Neglect • Executive: organization of knowledge o Ask pt. to name as many animals as possible in 1 minute (>20 is normal) o Ask pt. to complete oral trails (A1, B2, 3C. .. ) o Ask pt. to perform go/no go tasks CRANIAL NERVES: • Pupils OD/OS, size, reactivity, ptosis • Visual acuity: Snellan eye chart (can use pinhole to correct refraction), color testing • Visual fields: Test all four quadrants, central vision, neglect • Fundus: Assess disc/vasculature/venous pulsations/retina • Extraocular movements: Ab/adductions-both eyes, versions-one eye, alignment • CN V / Face sensation: LT/PP/temp, V1-V3 dist, corneal reflex • CN VII / Face strength— assess upper and lower facial symmetry, hyperacusis, dysgusia, corneal dehydration • CN VIII: Hearing— hi/lo pitch, VOR, vestibular testing (past pointing, Fukuda step test—march in place with eyes closed, Dix-Hallpike, Frenzel lenses—nystagmus) • Palate elevation—Aaaah, gag, uvula position, myoclonus • CN XI: Sternocleidomastoid strength/bulk, trapezius strength/bulk • CN XII -Tongue: position, bulk, fasciculations, strength (tongue against cheek) MOTOR: • Bulk: atrophy, fasciculations • Tone: flaccid, spastic/clasp knife, rigid/lead pipe, cogwheeling, etc. • Abnormal movement -- tremor, dystonia, chorea, athetosis, etc. Note frequency, amplitude and triggers (i.e., rest, postural, action) for tremors • Strength: Pronator drift, 0-5 isolated muscles (3=antigravity), gait testing SENSORY: • Extremities/trunk/back/perineum, Romberg • Anterolateral system/Spinothalamic tract (pain, temperature, some fine touch) • Dorsal Columns (light touch/vibration/2 point discrimination/proprioception) CEREBELLAR: • Distal coordination: Finger-nose-finger, heel-knee-shin, titubation, optic ataxia, nystagmus, rhythm testing / rapid alternating movements • Midline/vermis: Appendicular coordination REFLEXES: • DTRs: 0 to 4+ - note that 3 indicates spread of reflex, not amplitude of response • Jaw jerk (can be used to distinguish between cord & brain lesions) • Frontal release signs: glabellar, rooting, snouting, palmomental, grasp, perseveration • Hoffman and Babinski GAIT: • Ability to arise and sit (proximal movements), base of stance, stability of stance • Also assess posture, initiation of gait, stepping, base of gait, arm swing, turning strength and balance (i.e., with tandem walk, heel/toe, deep knee bend) 6 EXAMINATION OF MENTAL STATUS 1. General Observations o Arousal Affect Communication 2. Attention o Count backwards:20 19 18 17 16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 o Digit span: 539 9703 59128 7681302 52081643 o Vigilance: GFALTRNAJRPOANAGKILOPAWERZMALAKWOPTHAKFLA 3. Orientation: o Date , Time , Place 4. Speech/Language o Speech: dysarthric/hypophonic/spastic/scanning o Fluency: fluent/non fluent//paraphasias//circumlocutions o Repetition: ▪ No ifs ands or buts ▪ Methodist Episcopal o Comprehension: ▪ one step ▪ two-step ▪ imbedded o Naming: ▪ high frequency ▪ low frequency o Reading/Writing: ▪ irregular words ▪ non-words 5. Memory: o Short term: Ball/flag/tree repeat: remember: o Long term: Presidents, historic events, current events 6. Praxis: o Oro buccal o Limb o Tool use 7. Visual spatial/Perceptual o Line bisection o Extinction: visual/auditory/tactile o Object recognition: Visually guided reaching 8. Emotion o Prosody o Expression o Comprehension o Executive/frontal function ▪ Verbal fluency: Category (animals): Letter (F): ▪ Oral trails:Al B2 C3 D4 E5 F6 G7 H8 19 JIO KI I LI2 Ml3 NI4 ▪ Go no go or contrasting programs ▪ Crossed motor inhibition 7 MANAGING ELEVATED ICP Elevated ICP is bad because: • increased intracranial pressure reduces cerebral perfusion pressure (remember: CPP = MAP-ICP) • increased intracranial pressure can lead to herniation. The Monro-Kellie doctrine states that the skull has a fixed volume, so that any increase in volume of one intracranial compartment (e.g. blood, mass, etc.) will result in an increase in ICP. The increase in volume of one intracranial compartment can initially be offset by reductions in volume of other compartments, but after a certain point the brain’s volume buffering capacity is exceeded and disastrous increases in ICP can occur. The absolute ICP number is less important than the rate of rise and the pressure gradient between compartments. Patients can have a normal ICP and still herniate if their baseline is low, and patients with slow, longstanding increases in ICP may be asymptomatic such as patients with slow-growing tumors or idiopathic intracranial hypertension (IIH). All measures used to reduce ICP either reduce the volume of one of the intracranial compartments or change the total volume of the cranium • CSF drainage → reduces CSF volume • Hyperosmolar therapy → reduces brain tissue edema and brain tissue volume • Hyperventilation → reduces cerebral blood flow (CBF), in turn reducing cerebral blood volume (CBV) - transient effect, can lead to rebound increase in CBF • Metabolic therapy (e.g. barbiturate coma or hypothermia) → primary reduction in cerebral metabolic rate (CMRO2), secondary reduction in CBF and CBV • Removal of mass lesion/blood → reduces volume of mass/blood compartment • Craniectomy → increases fixed volume of cranium Symptoms of elevated ICP include: • Headache • Diminished level of consciousness • VI nerve palsies • Impaired upgaze • Cushing’s response (bradycardia, elevated BP, respiratory depression) Herniation Syndromes • Uncal herniation: ipsilateral pupilary dilation--> IIIrd nerve palsy --> contralateral or ipsilateral hemiparesis (Kernohan's notch phenomenon) • Subfalcine herniation: weakness/increased tone in ipsilateral leg (due to contralateral ACA compression) • Tonsillar herniation: respiratory arrest, downbeat nystagmus 10 HTS Infusion Sliding Scale Serum Na+ ICP 3% NaCl Rate <140 >20 Increase rate by 20ml/hr not to exceed 100ml/hr. <20 Continue current rate 141-150 >20 Increase rate by 10ml/hr not to exceed 100ml/hr. <20 Continue current rate 151-160 >20 Increase rate by 5ml/hr not to exceed 100ml/hr. <20 Continue current rate > 160 Stop infusion; recheck serum Na+ in 2 hrs. Call MD. C. Other measures CSF Drainage: Consider ventriculostomy for monitoring and controlling ICP when appropriate. Hyperventilation: Short-lived effects <24hrs; works by increasing vasoconstriction and decreasing cerebral blood volume. Effects achieved at the expense of CBF; therefore should be used only as bridge to definitive therapy (generally urgent surgery). Goal pCO2 25-35 Decompressive Craniectomy: definitive therapy for severe intracranial hypertension (especially consider for acute ischemic stroke with malignant brain swelling, see Acute Ischemic Stroke section below) Hypothermia: a last tier treatment, not likely to improve outcome but does reduce ICP. Use the “Hypothermia in the Neurocritical Care Patient” order set Barbiturate coma: Has been used for medically refractory increased ICP usually in the setting of SAH or head injury. Recent evidence suggests worse outcomes in head injury. 11 Combined ICP and brain tissue oxygen monitoring in TBI Patients ICP < 20 ICP > 20 PbtO2 > 20 A B PbtO2 < 20 C D Treatment is triggered by ICP > 20mmHg and/or PbtO2 < 20 mmHg for > 5 min: Choose at least 1 intervention from a tier before progressing toward the subsequent tier. Scenario B (good PbtO2, high ICP) • Tier 1 (begin within 15 minutes of episode) o Increase angle of HOB, straighten neck, loosen ETT tape, C-collar o Ensure core temp < 38°C o Treat agitation and pain with lowest necessary dose of sedative and analgesic o Adjust minute ventilation for target PaCO2 35 – 45 torr o CSF drainage o Mannitol per protocol o Hypertonic saline per protocol Tier 2 (begin within 60 minutes of episode) o Adjust minute ventilation for target PaCo2 30 – 35 torr o Higher dose of mannitol or administer more frequently o Repeat HCT – look for increased size of intracranial mass lesions o Treat surgically remediable lesions - craniotomy o Lower core temp to 35 – 37°C while treating rigors Tier 3 o Decompressive craniectomy o Therapeutic hypothermia (32 – 34°C) per protocol o Barbiturate (pentobarbital) coma (if possible try test dose of thiopental) o Trial of neuromuscular blockade Scenario C (good ICP, low PbtO2) • Tier 1 (begin within 15 minutes of episode) o Increase angle of HOB, straighten neck, loosen ETT tape, C-collar o Ensure core temp < 38°C o Increase CPP to maximum of 70 mmHg with fluid boluses (goal euvolemia) o Increase PaO2 by increasing FiO2 to maximum of 60 torr o Increase PaO2 by increasing PEEP o Add EEG monitoring and treat seizures if present Tier 2 (begin within 60 minutes of episode) o Increase CPP to maximum of 70 mmHg with pressor o Transfuse PRBC for goal hgb > 10 o Decrease ICP to < 10 mmHg through CSF drainage and/or increased sedation o If significant hypoxemia then increase PaO2 further by increasing FiO2 to 100% and/or increasing PEEP o Adjust minute ventilation for goal PaCO2 45 – 50 torr 12 Scenario D (low PbtO2, high ICP) • Tier 1 (begin within 15 minutes of episode) o Increase angle of HOB, straighten neck, loosen ETT tape, C-collar o Ensure core temp < 38°C o Treat agitation and pain with lowest necessary dose of sedative and analgesic o Mannitol per protocol o Hypertonic saline per protocol o Increase PaO2 by increasing FiO2 to maximum of 60 torr o Add EEG monitoring and treat seizures if present Tier 2 (begin within 60 minutes of episode) o Higher dose of mannitol or administer more frequently o Increase CPP to maximum of 70 mmHg with pressor – however, consider evaluating for hyperemia as cause o If significant hypoxemia then increase PaO2 further by increasing FiO2 to 100% and/or increasing PEEP o Transfuse PRBC for goal hgb > 10 o Repeat HCT – look for increased size of intracranial mass lesions o Treat surgically remediable lesions - craniotomy o Lower core temp to 35 – 37°C while treating rigors Tier 3 o Barbiturate (pentobarbital) coma (if possible try test dose of thiopental to see if ICP and PbtO2 respond appropriately) o Decompressive craniectomy o Lower core temp to 32 – 34.5°C while treating rigors o Trial of neuromuscular blockade 15 Guidelines for recombinant tPA administration CALL THE STROKE TEAM AT 215-452-2793 FOR ANY rt-PA QUESTIONS and do NIH stroke scale on all tPA patients! Indication/ eligibility: Age >/= 18; clinical diagnosis of ischemic stroke with measurable neurological deficit; onset of symptoms less than 4.5 hours ago Strong Contraindications: Symptoms minor or rapidly improving Other stroke or serious head trauma within past 3 months Major surgery within last 14 days Known history of intracranial hemorrhage Uncontrolled hypertension at the time of treatment (>185 mm Hg systolic or >110 mm Hg diastolic) Aggressive treatment needed to lower BP Suspicion of subarachnoid hemorrhage Gastrointestinal or urinary tract hemorrhage within 21 days Arterial puncture at noncompressible site within 7 days Administration of heparin within 48 hours preceding the onset of stroke and an elevated aPTT at presentation Platelet count < 100,000 INR > 1.7 Relative Contraindications: Seizure at the onset of stroke Serum glucose <50 mg/dL or >400 mg/dL Hemorrhagic eye disorder Myocardial infarction in the prior six weeks Suspected septic embolism Infective endocarditis Pretreatment: Additional indications for extended window tPA • Age < 80 years • No history of prior stroke or diabetes • No active anticoagulation • NIHSS <25 • CT hypodensity <1/3 cerebral hemisphere Clearly establish time of onset of symptoms Obtain two IV accesses Monitor BP every 15 min. If over 185/110, BP may be treated with nitroglycerin paste and/or one or two 10-20 mg doses of labetalol given IV within one hour. If these measures do not keep BP below 185/110, do not give t-PA STAT platelet count, CBC, panel-7, PT/PTT, type and screen, t/c pregnancy test in young women Dosing and Administration: 0.9 mg/kg; maximum dose not to exceed 90 mg 10% of the total dose administered as an IV bolus over 1 minute Remaining 90% infused over 60 minutes 16 After t-PA Treatment: *Use EPIC orderset "Acute Ischemic Stroke Post Thrombolysis and Endovascular Thrombectomy Order Protocol" Monitor BP (maintain <180/105) and neuro exam: o -q 15 min for 2 hours after starting the infusion, then o -q 30 min for 6 hours, then o -q hour for 18 hours Head of bed flat No heparin, warfarin, aspirin, or other antiplatelet therapy for 24 hours. Repeat CT scan 24 hours post infusion to exclude intracerebral hemorrhage before initiating any anticoagulants or sooner if any neurologic changes occur. NO invasive procedures (i.e. no central lines, no blood draws, no NG tubes, no foley insertion) for 24 hours after tPA Bleeding precautions: check puncture sites for hematomas. Apply digital pressure or pressure dressing to active compressible bleeding sites. Evaluate urine, stool and emesis for blood. Monitor patient for evidence of gingival bleeding. Unexplained hypotension should prompt a thorough workup: GI bleed, tamponade from pericardial bleed etc. Order repeat CT scan (should be done 24 hrs after tPA was given) If post-24 hour CT scan is negative for bleed, can give ASA, start sub-Q heparin, do invasive procedures, get blood tests, etc; refer to section on acute stroke for relevant studies. (See below for management of positive CT scans) Blood Pressure management post initiation of rt-PA: If diastolic BP >140 mm Hg: o Start an IV infusion of sodium nitroprusside; begin at 0.25-0.5 mcg/kg/min and titrate until diastolic decreases by 20% If systolic BP>230 mm Hg and/or diastolic BP 121-140 mm Hg: o Give labetalol 20 mg IV over 1-2 min. The dose may be repeated and/or doubled every 10 minutes up to 150 mg. Alternatively, after the first bolus of labetalol, an IV infusion of 2-8 mg/min of labetalol may be initiated and continued until the desired BP is reached. If satisfactory response is not achieved, use nitroprusside If systolic BP 180-230 m Hg and/or diastolic BP 105-20 mm Hg on two readings 5 minutes apart: o Give labetalol 10 mg IV over 1-2 min. The dose may be repeated or doubled every 10-20 min, up to 150 mg. Alternatively, after the first bolus of labetalol, start an IV infusion of 2-8 mg/min of labetalol and continue until the desired BP is reached. Monitor BP every 15 min during the antihypertensive therapy. Observe for hypotension. Management of suspected intracranial hemorrhage: (Suspicion of intracranial hemorrhage prompted by neurologic deterioration, new headache, acute hypertension, new onset or increase in nausea/vomiting. If suspect intracranial bleed:) Discontinue rt-PA infusion if still on-going. Obtain a STAT CT scan; take patient down yourself. If CT shows bleed: draw blood: PT, aPTT, platelet count, fibrinogen Prepare to give 6-8 units cryoprecipitate containing Factor VIII and/or 6-8 units platelets. Consult neurosurgery if indicated. 17 Management of tPA associated intracranial hemorrhage (See Pennstroke.org - password = silver9) rimary goal is to give back fibrinogen and clotting factors, which are found in plasma and cryoprecipitate. tPA has a poorly understood antiplatelet effect, so we also give platelets. One unit of cryoprecipitate has the same amount of clotting factors as one unit of FFP. Cryoprecipitate is much more concentrated than FFP and so has a much smaller volume. As a result, cryoprecipitate can be used to deliver a large amount of clotting factors in a short period of time. HOWEVER, cryoprecipitate must be thawed prior to use, which takes time. FFP also has to be thawed and takes longer since the volume is greater. HUP will almost always have several units of thawed plasma ready to be infused, so although it has a lower concentration of clotting factors, plasma can be given much faster than cryoprecipitate. You have to specifically ask for "thawed plasma." Our suggested protocol for reversal of tPA- ssociated ICH is to give: 2 units of thawed plasma (available from blood bank in 5- Can give unmatched if T&S not back 2 bags (5 units per bag) of cryoprecipitate 5 minutes) If the cryo becomes available after the first unit of plasma, stop the plasma and give the cryo 2 doses of platelets One dose is equivalent to 4 units of pooled donor platelets These blood products can be ordered verbally by calling the blood bank at 215-662- and informing them that you need blood for the "tPA Reversal Protocol" 448 You will need the name of the neurology attending, patient name, patient MRN, and patient location to order. f there is a problem, call the transfusion medicine attending on call at 215-838-8449. onsider checking fibrinogen after completion of cryo infusion - if persistently< 100 mg/di, give addit 20 Secondary Stroke Prevention • Antiplatelet agent o ASA 81-325 mg or Plavix 75mg daily as soon as it is safe o ASA and Plavix ONLY if patient has acute coronary syndrome (CURE) or has just been stented. • Statin o Preferably Lipitor 80 mg daily or simvastatin 40 mg daily if total cholesterol > 135 (Heart Protection Study, 2004) • ACE-inhibitor (i.e. ramipril) or ARB o Within 1-2 weeks after D/C (HOPE, PROGRESS, LIFE) • Hypertension: o Patients with flow dependent lesions may need higher BP acutely o Chronically hypertensive patients may have a shifted cerebral autoregulation curve and rapid lowering > 25% may compromise cerebral perfusion • Long-term anticoagulation: o For A fib, EF < 30%, or cardiac thrombus, hypercoagulable state, mechanical valve in the setting of acute ischemic stroke (multiple refs). o No good data exist about when to start--our practice is generally to start ASA within 48 hours, and warfarin in 1-2 weeks. o No benefit to warfarin over aspirin for symptomatic intracranial stenosis (WASID, 2005). • Carotid endarterectomy or stent: o Remember, even lacunes may be due to emboli (20%), so rule out carotid disease. o Consider CEA in >70% stenosis & +/- 50-69% (NASCET, 1997). o Symptomatic patients with poor surgical risk patients benefit from carotid stenting (SAPPHIRE), but more widespread use is not yet established. • Intracranial stenting and interventional neuroradiology: o Limited evidence, but option for patients with multiple events due to symptomatic stenoses > 50% despite medical therapy. • Intracranial hemorrhages: o If ICH, no antiplatelet/anticoagulant therapy x 3 months in general. o If ICH in the face of atrial fibrillation/ cardiac thrombus, can try ASA in 2 weeks, reconsider warfarin in a month after deep ICH if BP controlled, and monitor VERY closely. o Do not resume anticoagulation in amyloid angiopathy or most lobar ICHs. • PFO and IASA o About 25% of people have PFOs. o Ensure there is no other source for a stroke before attributing it to the PFO. Get a complete hypercoag workup. o Recent studies show long term outcomes support PFO closure in cryptogenic stroke in patients < 60 yo (RESPECT, CLOSE, REDUCE studies) o There are no FDA approved PFO closure devices although cardiologists will close them with devices approved for other purposes. The decision is largely a matter of personal preference for the patient. Offer them enrollment in a trial if appropriate. • Atrial flutter vs. fib: o Some cardiac studies suggest that patients in atrial flutter may be going in and out of atrial fibrillation. o Consider outpatient Holter monitor if suspicion of AF. o CHADS2VAS2C scoring system • Glucose: o Screen for diabetes with fasting glucose, HbA1c • Smoking cessation: o Screen and counsel on smoking cessation o Consider nicotine replacement products 21 Stroke Syndromes Eponym/artery Anatomy Signs and symptoms ACA Medial frontal and parietal Contralateral leg > arm weakness Abulia Recurrent artery of Huebner (A branch off A1 segment) Anterioinferior caudate Putamen Anterior limb of internal capsule Contralateral face weakness (Huebner) Contralateral leg weakness (A1 segment) MCA - Superior M2 (anterior) Face and arm > leg weakness / numbness Expressive aphasia (dominant, Broca's) Hemineglect (nondominant) MCA - Inferior M2 (posterior) Homonymous hemi / upper quadrantinopsia Receptive aphasia (dominant Wernicke's) Constructional apraxia (non-dominant) Gerstmann syndrome (Partial MCA) Dominant inferior parietal lobe (angular gyrus) Alexia / agraphia Finger agnosia R-L confusion Acalculia Unilateral PCA Occipital and infero-medial temporal lobes, posterior thalamus Homonymous hemianopsia with macular sparing +/- alexia without agraphia / anomia Balint syndrome (bilateral PCA) Bilateral parieto-occipital lobe Optic ataxia Ocular apraxia Simultanagnosia PCA Callosal branch Dominant occipital lobe with splenium of corpus callosum Alexia without agraphia, or "pure word blindness" Dejerine-Roussy or "thalamic pain syndrome" (PCA branches) Thalamus Contralateral hemisensory loss Contralateral hemibody pain Weber (PCA penetrators) Midbrain, anterior Contralateral weakness, ipsilateral CN III palsy Claude (PCA penetrators) Midbrain, tegmentum Contralateral rubral tremor, ipsilateral CN III palsy +/- contralateral weakness and numbness Benedikt (PCA penetrators) Midbrain, tegmentum Contralateral rubral tremor, ipsilateral CN III palsy, ipsilateral ataxia, contralateral hemisensory loss Raymond (basilar paramedian branches) Pons, ventral-medial Ipsilateral CN VI (spares CN VII) Contralateral weakness Millard-Gruber (basilar short and paramedian branches) Pons, basis pontis and VI and VII fascicles Ipsilateral CN VI and VII palsies Contralateral weakness Foville (basilar shorts and paramedian branches) Pons, tegmentum and caudal third Ipsilateral VI / PPRF (gaze) and VII palsies Contralateral weakness and sensory loss (ML) Marie-Foix (basilar/AICA) Pons / lateral Ipsilateral ataxia, contralateral weakness and numbness Locked-in syndrome (basilar) "de- efferented state" Bilateral ventral pons Bilateral face/arm/leg weakness Bilateral VI palsies Aphonia Wallenberg of lateral medullary syndrome (vertebral artery > PICA) Medulla, lateral Ipsilateral facial sensory loss (CN V) Ipsilateral ataxia, nystagmus, N/V Vertigo, hoarseness, dysphagia Ipsilateral Horner's, contralateral body sensory loss Anterior spinal artery (Dejerine syndrome) Medulla, medial Contralateral weakness Contralateral vibration/proprioceptive loss (ML) Ipsilateral tongue deviation (CN XII nucleus) 22 PRIMARY INTRACEREBRAL HEMORRHAGE Despite aggressive efforts, mortality from ICH is high. Scoring systems have been devised to calculate in-hospital mortality risk and functional outcome based on patient age, initial neurologic examination, hematoma size and site of bleeding (see appendix). It is, however, important to use these scores judiciously when making treatment decisions, since they can provide a “self-fulfilling prophecy”. Most ICHs are secondary to hypertension. These tend to be in deeper structures (thalamus, basal ganglia, brainstem, cerebellum). The (distant) second most common cause in the elderly is secondary to cerebral amyloid angiopathy. Amyloid bleeds tend to be superficial and lobar. Don’t forget other potential causes: • Iatrogenic secondary to systemic anticoagulation • Hemorrhagic conversion of an ischemic infarct • AVM or aneurysm rupture • Trauma • Cerebral Venous Sinus Thrombosis • Vasculitis • Cavernous Malformations • Hemorrhagic Metastases/Primary Tumor • Infection/endocarditis The principles of ICH management involve: • management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) • correction of underlying coagulopathies that may exacerbate bleeding • aggressive blood pressure control to limit hematoma expansion • prevention of other medical complications General Approach to ICH Management • CT scan shows acute blood: is it in a pattern that suggests a hypertensive hemorrhage or amyloid hemorrhage, or something else atypical? • Consider CTA to look for underlying vascular malformation and for “spot sign” o The “spot sign” is a bright spot within the hematoma on contrast enhanced CT angiography o It suggests active bleeding and is strongly associated with hematoma expansion • Are there any correctable coagulopathies? (Also refer to reversal guidelines on page 82) o Aspirin – no clear benefit from platelet transfusion (Sansing et al., Neurology 72:1397, 2009). Do not transfuse platelets. o Plavix – unclear if platelet transfusion beneficial. Do not transfuse platelets. o Warfarin – For ICH or life threatening hemorrhage with elevated INR consider activated Prothrombin Complex Concentrate (PCC). First dose can be given without hematology approval (50 units/kg). Also give intravenous 10 mg vitamin K stat. (Watch for anaphylactoid reaction) FFP is a lot of volume and takes time to thaw. o Heparin – follow PTT and correct with protamine sulfate. Dose for protamine is 1 mg for every 100 units unfractionated heparin given in the last 2 hours. Dose 25 Antithrombotic Reversal agent Vitamin K antagonists for urgent surgery or other invasive procedures If INR >1.5, no signs of bleeding and reversal required in >24h: Vit K 2.5-5 mg PO or, 0.5-1mg IV If INR >1.5, no signs of bleeding and reversal required in <24h: Vit K 2.5-5 PO or 0.5-1 mg IV PLUS FFP and/or 4F-PCC Direct factor Xa inhibitors (andexanet alfa -Andexxa) Activated charcoal (50 g) within 2 h of ingestion, For andexanet alfa: If last dose (<5 mg of apixaban) less than 8 hours or unknown: 400mg, then 4mg/min x120min If last dose (>5 mg/unknown of apixaban) less than 8 hours or unknown: 800mg, then 8mg/min x120min If last dose (<10 mg of rivaroxaban) less than 8 hours or unknown: 400mg, then 4 mg/min x120min If last dose (>10 mg of rivaroxaban) less than 8 hours or unknown: 800mg, then 8mg/min x120min Direct thrombin inhibitors For dabigatran reversal: Activated charcoal (12.5 g x1) if within 2 h of ingestion Idarucizumab 5 g IV (2 infusions of 2.5 g within 15 minutes) Consider hemodialysis for refractory bleeding after repeated infusions For other DTIs: Activated PCC (FEIBA) 50 units/kg IV OR 4 factor PCC 50 units/kg IV Unfractionated heparin Protamine 1 mg IV for every 100 units of heparin administered in the previous 2–3 h (up to 50 mg in a single dose) Low-molecular weight heparins Enoxaparin: Dosed within 8 h: Protamine 1 mg IV per 1 mg enoxaparin (up to 50 mg in a single dose) Dosed within 8–12 h: Protamine 0.5 mg IV per 1 mg enoxaparin (up to 50 mg in a single dose) Minimal utility in reversal >12 h from dosing Dalteparin, Nadroparin and Tinzaparin: Dosed within 3–5 half-lives of LMWH: Protamine 1 mg IV per 100 anti-Xa units of LMWH (up to 50 mg in a single dose) OR rFVIIa 90 mcg/kg IV if protamine is contraindicated Danaparoid rFVIIa 90 mcg/kg IV Pentasaccharides Activated PCC (FEIBA) 20 units/kg IV or rFVIIa 90 mcg/kg IV Thrombolytic agents (plasminogen activators) Cryoprecipitate 10 units IV OR Antifibrinolytics (tranexamic acid 10–15 mg/kg IV over 20 min or e- aminocaproic acid 4–5 g IV) if cryoprecipitate is contraindicated Antiplatelet agents DDAVP 0.4 mcg/kg IV 9 1 If neurosurgical intervention: Platelet transfusion (one apheresis unit) 26 ANEURYSMAL SUBARACHNOID HEMORRHAGE I. INTRODUCTION: Subarachnoid hemorrhage (SAH) is a disorder where bleeding occurs between the arachnoid membrane (the middle membrane covering the brain) and the brain itself, with bleeding onto the surface of the brain. This is usually caused by a “weak spot” in a blood vessel, also known as an aneurysm. Twenty percent of individuals affected have multiple aneurysms. Subarachnoid hemorrahages can also be non-aneurysmal in cause. Examples of this would be a traumatic SAH, rupture of an AVM, or other unidentified causes. The following guidelines address management of aneurysmal subarachnoid hemorrhage II. RISK FACTORS FOR ANEURYSMAL SAH • Hypertension • Cigarette Smoking (greatest risk occurring 3 hours after smoking) • Binge alcohol drinking • Drug abuse • Use of stimulants • Gender: Incidence is greater in females than in males • Age (range 20-65; mean age 50; most common between 35-60) • Disorders associated with weakened blood vessels: 55 ▪ Fibromuscular dysplasia (FMD) ▪ Aneurysms in other blood vessels ▪ Polycystic kidney disease ▪ Ehler-Danlos syndrome ▪ Marfan’s syndrome ▪ Alfa-one antitrypsin deficiency III. PRIOR TO SECURING THE ANEURYSM (Surgical Clip/Neurovascular Coil): Admission labs, tests and procedures • Admit to the NeuroICU • Assess Hunt and Hess Scale57 (Clinical Grade) and Fisher Grade55 (CT Grade) (See Appendix A) • Obtain routine labs, including: • BMP, Ca2+, Mg2+, PO4 -2, CBC, PT, INR, PTT, serial troponins, type and screen • Obtain the following studies: o 12-lead EKG, portable chest X-ray, non-contrast head CT, CT angiogram (CTA; unless contraindicated due to allergy or renal dysfunction) • Alert research coordinator to determine eligibility for clinical studies Neurologic • Place EVD immediately in all patients with hydrocephalus that is symptomatic or have GCS <8. • EVD is left open, at 20 cm above the tragus (EAM) as a start and then adjusted as dictated by ventricular size on HCT or clinical status. The level of 27 the EVD should generally not be lowered prior to securing of the aneurysm as this may predispose to rebleeding. • Start seizure prophylaxis • Leviteracitam load: 1000mg PO/IV on admission • Leviteracitam 500 mg PO/IV q12 hrs x 7 days for seizure prophylaxis ▪ If evidence of renal dysfunction, dose accordingly ▪ It is preferable to administer leviteracitam orally or enterally when able ▪ Discontinue AED POD #7 if there have been no clinical or electrographic seizures • Anti-Fibrinolytics • Consider in patients who cannot be secured in < 24 hours Cardiovascular • Place Arterial line in all patients • Maintain SBP within 10% of baseline SBP if known. If baseline SBP cannot be determined, then maintain SBP < 160 mm Hg. o If SBP > 160 mmHg, optimize analgesia and treat with IV anti- hypertensives o Titratable anti-hypertensives (drips) are favored to control blood pressure to avoid large blood pressure fluctuations. • Start nimodipine 60 mg PO/NGT q4hrs. If BP drops after administration, then decrease nimodipine dose to 30 mg q2hrs. • Statins o Statins taken as home medications should be continued upon admission for SAH. • Vascular access • Place a triple lumen subclavian or IJ venous catheter in selected patients. • Avoid IJ if evidence of severe intracranial hypertension exists or patient is felt to be at high risk for developing intracranial hypertension. • Indications for central line placement: • High grade patient (HH≥3) • Hemodynamic instability • Need for vesicant medications (sedation or vasopressors) • Venous access difficulty • Obtain a transthoracic echocardiogram when: • Unexplained hypotension • Ischemia or ST changes are present on EKG • Response to vasopressor medications is suboptimal • Initial cardiac enzymes are abnormal Renal (Fluids and Electrolytes) 30 • Vascular imaging with a CTA should be performed when clinically feasible. • CTA should be obtained in all patients with suspected vasospasm who do not have contraindications to the procedure. • If CTA is indeterminate or shows evidence of vasospasm, proceed to cerebral angiography. • Perfusion imaging may be considered in appropriate patients. • Advanced cerebral monitors (Licox, microdialysis, etc…) may be considered on a case-by-case basis. Cardiovascular • For patients undergoing craniotomy for aneurysm coiling, SBP should be maintained < 160 mmHg for 24 hours after surgery to minimize risk of postoperative bleeding. Thereafter, SBP parameters should be liberalized to 100 – 200 mmHg. • In aneurysms that are endovascularly coiled, blood pressures can be liberalized to 100-200 mmHg immediately post-procedure. • A higher blood pressure may be needed to achieve adequate regional brain perfusion and these parameters may be adjusted in individual patients (refer to treatment of vasospasm/DCI above). • The presence of other, unruptured aneurysms should not influence hemodynamic management. • Target euvolemia with administration of isotonic or hypertonic IVF as needed. Fluid and Electrolyte Management • Maintain Na+ > 135 mmol/L (see CSW Protocol). • Treat hyponatremia with IV normal saline and oral salt tabs. • For refractory cases, consider the use of fludrocortisone 0.3mg/day or hypertonic saline bolus/infusion to raise serum Na to the target range. • Maintain Mg+2 within normal range Endocrine (Glycemic Control) • Blood glucose monitoring and sliding scale insulin q4 hrs in all patients • Target glycemic threshold <200mg/dL. • Start insulin infusion per HUP Insulin Infusion protocol in patients with serum glucose >200mg/dL x 2 on SSI coverage Temperature Control • Maintain strict normothermia (see Normothermia Protocol). Nutrition Early enteral nutrition benefits critically-ill patients.53 In the neurologically injured patients, continuous enteral feeding via small bore tube or NGT/OGT is safe.54 • Continuous enteral feeding should begin on POD #1 (see NeuroICU Feeding Protocol). • TPN should only be considered in patients who have contraindications or intolerance to enteral feedings. 31 Prophylaxis • See above recommendations for GI and DVT prophylaxis. • Subcutaneous heparin 5000U TID should be added on POD #1. VII. TRANSFER/DISCHARGE PLAN: • Low grade (I-II) patient criteria to transfer out of NeuroICU ▪ Day 10 if no evidence of vasospasm for 48hrs • High grade (III-V) patient criteria to transfer out of NeuroICU ▪ Day 14 and no evidence of vasospasm for 48hrs. • Nimodipine stop after 21 days, not discharged on nimodipine. • Acute brain injury rehab Approach to TCD and clinical examination data EXAM TCD ACTION Normal Normal None Normal Abnormal CTA, Perfusion scan Deteriorating Normal Hypertensive rx, CTA, Perfusion scan Deteriorating Abnormal Hypertensive rx, Angiogram Comatose Normal Consider surveillance CTA, cEEG Comatose Abnormal Non-contrast CT, Angiogram Consider cEEG Risk factors associated with or predictive of vasospasm55 Younger age IVH on admission CT Dehydration Cigarette smoking Poor admission clinical grade Admission systolic blood pressure Thick or diffuse SAH on admission CT Hydrocephalus Hyponatremia Anti-fibrinolytic agents Increased ICP Hypotension Hypoxia Fever 32 Intraventricular Nicardipine for SAH associated vasospasm Cerebral vasospasm remains a major cause of morbidity and mortality after SAH. Several reports suggest that administration of nicardipine intrathecally is both safe and efficacious for this condition. Indications • Aneurysmal subarachnoid hemorrhage • Documented morphologic evidence of severe cerebral vasospasm o Computed tomographic angiogram o Conventional angiogram • Patient already undergoing standard vasospasm treatment including nimodipine, seizure prophylaxis, statins, ventriculostomy, and HHH (hypertension, hypervolemia, hemodilution) therapy. Patients may or may not have already undergone intra arterial nimodipine or angioplasty prior to this therapy. • Agreement by both neurocritical care and neurosurgery attendings that the vasospasm is severe with no disqualifying contraindications with agreement to proceed. Suggested additional functional criteria for “severe” spasm: o Cerebral blood flow decrements on computed tomographic perfusion study or stable xenon computed tomographic cerebral blood flow evaluation , OR o Bedside signs or symptoms such as altered exam, brain hypoxia Contraindications • Absolute o Allergy to nicardipine o No ventriculostomy • Relative, ie, the treating physician must weigh potential benefits vs possible harm o Unsecured aneurysm thought responsible for the subarachnoid hemorrhage o Elevated intracranial pressure o Central nervous system infection o Immunosuppressed o Intraventricular hemorrhage with compromised ventriculostomy function Administration • Dose: Twice daily, 4 mg nicardipine in 2 ml preservative free saline followed by 2 ml preservative free saline flush. Withdraw 4 ml of cerebrospinal fluid before injection (send daily for analysis). • Sterile technique including chlorhexidine skin preparation, mask, hat, sterile gloves. Sterile drape under the chlorhexidine treated stopcock and tubing • Clamp ventriculostomy for 1 hour after injection • Administer for five days. Stop for at least one dose. Reevaluate after therapy cessation for recurrence of original indications. If reevaluation results in need to continue then do so 35 PERIMESENCEPHALIC SUBARACHNOID HEMORRHAGE Introduction Spontaneous, non-traumatic subarachnoid hemorrhage (SAH) most commonly results from rupture of saccular aneurysms (aneurysmal SAH; aSAH). Less commonly, it results from rupture of arteriovenous malformations, arterial dissections, tumors, or other vascular abnormalities. In 10% to 20% of cases, no structural cause for the hemorrhage can be identified on radiographic imaging even after digital subtraction angiography (DSA), the gold standard for the detection of a cerebral aneurysm or other vascular source of the hemorrhage. These non-aneurysmal hemorrhages are termed idiopathic SAH or angiogram-negative SAH. Angiogram-negative SAH have been divided into 2 major groups: Perimesencephalic hemorrhage (PM-SAH), which is strictly defined according to published criteria (see below); and Non-perimesencephalic hemorrhage (nPM-SAH). The category of nPMH includes those SAH not fitting PMH criteria such as diffuse SAH, cortical SAH, CT negative SAH confirmed by lumbar puncture. Definition of PM-SAH The diagnosis of PM-SAH is a diagnosis of exclusion. The bleeding pattern defining PMH is identified on unenhanced CT performed within 24 hours of hemorrhage onset. The PM-SAH pattern is commonly defined using guidelines set out by Rinkel et al. and confirmed by others1,2: 1) center of the hemorrhage located immediately anterior to the midbrain, with or without extension of blood to the anterior part of the ambient cistern or to the basal part of the Sylvian fissures; 2) no complete filling of the anterior interhemispheric fissure and no extension to the lateral Sylvian fissures, except for minute amounts of blood; and 3) absence of frank intraventricular hemorrhage Thirty-eight percent of angiogram-negative SAH (range 21%-77%) have a PM-SAH pattern on their admission CT scan. Management • **Manage as if they have aneurysmal SAH until definitive vascular imaging (DSA) is obtained o Obtain routine labs o EKG, CXR, CT angiogram o EVD – if has hydrocephalus that is symptomatic or GCS < 8 ➢ EVD is left open at 20cm above tragus. Adjust as dictated by ventricular size. Generally not lowered until evaluation for aneurysm has been completed, as it can re-rupture the aneurysm o DSM – obtained within 24 hrs of admission ➢ DSM must rule out aneurysm in order to diagnose as PM-SAH • Neurologic o MRI brain/spine or MRA neck – consider in atypical clinical presentation and younger patients o Vasospasm detection – daily TCD monitoring ➢ CT angiogram if has high concerns o Nimodipine – 60mg q4h or 30mg q2h ➢ Not strong indication as aneurysmal SAH ➢ Stop at discharge or at 14 days (whichever is sooner) o Seizure prophylaxis – discontinue after negative DSA testing • Cardiovascular o SBP < 140 mmHg until negative DSA testing o If meets criteria for PM-SAH, can liberalize SBP goals to maintain normotension 36 • Fluid and electrolyte management o Maintain euvolemia o Goal Na > 135 mmol/L, Mg > 2 • Endocrine o Goal glucose 140 – 180 mg/dL • Prophylaxis o Subcutaneous heparin 5000 unit TID added 24 hrs after presumed bleeding time o GI ppx not required if eating and drinking normally • Patients should be monitored in the ICU until vascular imaging studies are completed and do not show evidence of an aneurysm. • Once vascular studies are negative, patients may be discharged to the floor or INCU based on their nursing and monitoring requirements. • All patients should be considered for evaluation by PT/OT. • Patients require monitoring for hydrocephalus. The risk of hydrocephalus is highest in the first few days after bleeding; generally, most patients are stable for discharge by post-bleed day #7. • When deemed stable by the treating team, patients may be discharged to home or other appropriate facility. 37 40 CONTINUOUS EEG (LTM) GUIDELINES 1. LTM EEG requests only placed by the NICU fellow/attending or Neurology SAR/attending. Non-neurology or NICU services must contact Neurology consult team to request LTM (except for hypothermia hook-ups, which can only be requested from 7 am – 11 pm during the week and 7 am – 7 pm on weekends). 2. LTM reads via email at noon and 5 PM: EEG fellow will contact team with urgent reads, limit calls to EEG fellow 3. Process to obtain LTM: a. Place order in EPIC (type in LTM or EEG, select continuous) b. Send an email to EEGReaders@uphs.upenn.edu, with initials and MRN of the patient, and brief clinical history 4. AFTER HOURS LTM READING: a. New hook up screened by tech (20 min) and fellow will contact team ONLY if there is a concerning finding. b. TECH WILL EMAIL THE EEGREADERS email after every LTM hook-up. c. ALL TECHNICAL ISSUES: should contact tech directly (not fellow) d. Only patients in active STATUS EPILEPTICUS read after 5 pm (once at 9 pm, once 3 am if deemed necessary by the EEG fellow) e. BURST SUPPRESSION: must be monitored by in-house team f. Calls to the fellow: i. Only from Neurology, NICU fellow or an attending (JAR must d/w SAR prior to call) ii. No non-urgent calls (see criteria below regarding when to hook up a patient to LTM) LTM guidelines: g. Criteria for requesting LTM after 5 PM i. Transfer from an OSH for LTM and patient is comatose ii. Convulsions cease but patient has no exam (concerning for nonconvulsive status epilepticus) iii. multiple clinical events highly concerning for seizure (patient obtunded/comatose) h. LTM requests INAPPROPRIATE after 5 PM: i. hypothermia (goal: hook up patient within 12 hours) ii. subarachnoid hemorrhage iii. patients not in coma (e.g. neurological exam able to rule out status epilepticus) GUIDELINE FOR USE OF KETAMINE FOR THE TREATMENT OF REFRACTORY STATUS EPILEPTICUS UNIVERSITY OF PENNSYLVANIA HEALTH SYSTEM BACKGROUND Ketamine is a noncompetitive NMDA receptor antagonist with a unique mechanism of action that has shown to be effective in the treatment of status epilepticus (SE) when traditional GABAergic agents have failed. Models of prolonged status epilepticus demonstrate a downregulation of functional GABAA receptors, with simultaneous upregulated expression of NMDA receptors promoting the excitatory action of glutamate. This suggests that ketamine is a rational antiepileptic agent to be considered for use in later stages of SE, and explains the nature of development of pharmacoresistance to agents targeting the GABA receptor in refractory status epilepticus. DEFINITIONS 1. Status epilepticus (SE) a) Generalized convulsive seizure lasting > 5 minutes or 2 convulsive seizures without interim return to baseline mental status b) For the purposes of this guideline, SE refers to the spectrum of this disease state as a whole, including refractory and super-refractory SE 2. Refractory status epilepticus (RSE) a) Ongoing generalized seizures despite administration of a benzodiazepine (first-line therapy) and an additional IV AED (second-line therapy) at adequate doses 3. Super-refractory status epilepticus (SRSE) a) Failure of one or more first-line continuous anesthetic agents (midazolam, propofol) to achieve seizure- or burst- suppression within 24 hours of initiation of the initial anesthetic agent b) Alternatively, recurrence of seizures upon weaning of first-line anesthetic agents INDICATIONS FOR USE ▪ Adjunctive therapy in patients with super-refractory status epilepticus (SRSE)* ▪ Ketamine may also be considered earlier (adjunctive therapy) in patients with dose-limiting side effects during treatment with midazolam or propofol (e.g., refractory hypotension requiring high dose vasopressor therapy)* *CONCOMITANT USE WITH OTHER CONTINUOUS ANESTHETIC AGENTS ▪ Little data exists on the use of ketamine alone as a first-line or sole agent for the treatment of RSE/SRSE - No prospective data exists for use in adults (case reports/series only) - In most reports, ketamine was added adjunctively to other continuous anesthetic (GABAergic) agents (midazolam, propofol, pentobarbital) ▪ In the context of above indications for use of ketamine, it should be initiated for adjunctive use with other anesthetic agents already in place in order to achieve the goal of seizure- or burst-suppression RESTRICTIONS Use is restricted to patients undergoing continuous EEG monitoring in the Neuro ICU or other ICU with Neurology consultation CONTRAINDICATIONS Absolute: ▪ Absence of an established airway (e.g., mechanically ventilated) ▪ Patients with active or unstable cardiac or coronary disease (i.e., acute atrial or ventricular arrhythmias, STEMI/NSTEMI) Relative: ▪ Severe or uncontrolled hypertension (SBP >200) or tachycardia (HR>120) ▪ History of tachyarrhythmias, distant, well controlled coronary artery disease (CAD, including: stable angina, prior myocardial infarction), or known severe right heart failure - Recommended to omit or use smaller loading doses in these patients ▪ Known or suspected schizophrenia, psychosis, bipolar disorder or generalized anxiety disorder PHARMACOKINETICS 1. Onset of effect: 30-60 seconds after bolus administration 2. Volume of distribution: highly lipophilic with Vd of 2.4 L/kg 42 3. Metabolism: hepatic, to several inactive and active metabolites a) Active metabolite, norketamine – 33% potency of parent compound b) Major substrate of CYP 2B6, 2C9, and 3A4 c) Possible drug interactions: phenytoin and phenobarbital (strong CYP3A4 inducers) i. Concomitant use of either of these agents may lower ketamine concentrations ii. Patients who have been maintained on either of these therapies are likely to require higher doses of ketamine to achieve therapeutic effect 4. Half-life elimination: 2-3 hours 5. Excretion: primarily urine (inactive drug) DOSING AND ADMINISTRATION 1. Loading dose: a) Initial dose: 1-2 mg/kg IV x 1 b) May repeat additional bolus doses of 0.5-2 mg/kg every 5-10 minutes, if continued seizures after initial bolus c) Maximum total loading dose: 5 mg/kg d) NOTE: loading doses are based on actual body weight, capped at a patient weight of 100 kg e) Administer bolus doses at a rate of 0.5 mg/kg/min 2. Continuous infusion: a) Starting dose: 0.5-1 mg/kg/hr (“dosing” (admission) body weight) b) Titrate infusion by 0.5 mg/kg/hr every 5-10 minutes until goal of seizure- or burst-suppression achieved on EEG i. Infusion uptitration may be done in conjunction with administration of supplemental bolus doses, per above, until maximum loading dose of 5 mg/kg is achieved c) Maintain infusion at rate where seizure- or burst- suppression is achieved i. If breakthrough seizures occur, titrate infusion up by 0.5-1 mg/kg/hr every 4-6 hours d) Maximum infusion rate: 10 mg/kg/hr i. Note: Typical continuous infusion rates range from approximately 0.5-5 mg/kg/hr in published studies DURATION OF THERAPY AND WEANING OF INFUSION ▪ Duration of therapy and rate of tapering are at the discretion of the Neuro ICU team or Neurology Consult ▪ Therapeutic doses to achieve seizure- or burst-suppression are typically maintained for 24-48 hours - Consider a longer duration of therapy if recurrence of seizures upon weaning of infusion ▪ The infusion is typically weaned to off over a period of 12-24 hours - As a guide, this may be accomplished by titrating the infusion dose down by 10-20% of the steady-state infusion dose every 2-4 hours ▪ Recurrence of seizures upon tapering may require halting of dose down-titration, and up-titration back to previous step for an additional 24-48 hours while additional AEDs are added/maximized PROCEDURE 1. Provider and RN restrictions/credentialing: a) Ketamine bolus and infusion may be administered by an ACLS-certified nurse if the following conditions are met: i. Provider places the order for ketamine in PennChart ii. Loading and subsequent bolus doses must be administered via Alaris pump as “bolus from bag” iii. ICU provider (including critical care attending, critical care fellow, advanced practice provider (APP), or anesthesiologist) must be physically present for at least 15 minutes if bolus doses are administered iv. A new order must be placed for all bolus doses and infusion rate changes (non-nursing-titratable infusion) b) Subsequent monitoring and assessment, including for infusion titrations, may be done by the critical care nurse 2. Check expiration dates for the infusion - ketamine bag expires 24 hours after being hung ADVERSE EFFECTS ▪ Hypertension ▪ Tachycardia; new or worsening tachyarrhythmias ▪ Hypersalivation (increased production of oral secretions) 45 MYASTHENIA GRAVIS EXACERBATION (or “myasthenic crisis”) • Pathophysiology / Epidemiology: o Autoimmune condition caused by production of autoantibodies targeting post-synaptic AchR or receptor associated proteins of the neuromuscular junction o 2:3 M:F, bimodal peaks – female 20s, males 50s, 20% bulbar only, 2/100,000 annual • Presentation: o Fatigable weakness improving with rest, facial diparesis, ptosis, neck extensor weak, nasal voice, hypotonic/weak, neuromuscular respiratory failure (restlessness, diaphoresis, accessory muscle use, tachypnea, tachycardia, weak neck flexor/extensor, nasal/staccato speech, paradoxical breathing) o * classically need to differentiate from “cholinergic crisis” from overdose of mestinon – weakness, fasciculations, inc sweating/salivation, and miosis • Risk factors / triggers: med non-compliance, excessive activity, infection, stress, or drugs • Workup o Assess respiratory status ➢ vital capacity (VC) and negative inspiratory force (NIF), follow q2 hour ➢ can be misleading due to poor seal and effort ➢ Intubate or consider BiPAP if VC < 15cc/kg, NIF < -30 cm H2O & trending downward. ➢ Avoid succinylcholine (risk of hyperkalemia) ➢ Pulse ox and ABG changes will lag hypoventilation! ➢ Estimated VC = counting aloud in one breath x 100 cc (ex. counts to 25 = 2.5 liters). If facial weakness, VC may be lower due to poor seal on apparatus. ➢ If patient vented for >7 days, consider trach and PEG o Check CXR and cultures o Eliminate any medications that can exacerbate myasthenic symptoms ➢ Vincent et. al. Myasthenia gravis. The Lancet, 2001; 357: 2122:28. o If new diagnosis: ➢ check acetylcholine receptor antibodies ➢ order EMG/NCV with repetitive stim, consider single fiber ➢ check thyroid function tests, infection, other causes of respiratory failure ➢ consider chest CT to rule out thymoma • Acute treatment o Mestinon ➢ 30 PO TID, increase to 60-120 mg q4-6 hrs (maintenance), can increase to 120 mg q3 hrs (maximum) ➢ Long acting Mestinon (timespan) can be given qhs for pts with nocturnal or early morning weakness. ➢ IV mestinon dose is 1/30th of oral dose ➢ Use robinul for excessive GI cholinergic effects but watch for ileus ➢ existing anticholinesterase medications should be stopped while patient’s on vent, due to increased secretions affecting weaning. Restart at ½ dose 1 day prior to extubation. o PLEX/IVIg – similar efficacy ➢ If initial therapy has minimal response, it is reasonable to administer the other therapy ➢ PLEX: administer every other day for total 5 treatment (need HD catheter) ➢ IVIg: 0.4g/kg daily x 5 days (need consent) • Premeds: Tylenol 650mg, Benadryl 25 – 50 mg ➢ High dose steroids (> prednisone 1mg/kg IBW) • Benefits seen in 2-6 weeks, but can acutely worsen symptoms • Long-term treatment o Prednisone, Imuran, other immune suppressants o thymectomy (less effective for late-onset patients or ocular myasthenia). • GI and DVT prophylaxis • Order PT/OT/Rehab consults – may need SNF 46 ACUTE SPINAL CORD COMPRESSION Unlike the brain, the cord rarely recovers function. Initiate treatment as soon as possible. Presentation: 1) Assume cord compression in any cancer patient with back pain 2) Consider if the patient has progressive neurological symptoms, including weakness/numbness (especially symmetric and without facial involvement) and bladder/bowel symptoms. 3) Note general condition, vitals (ie, respiratory distress), back pain, history of trauma, known cancer or infection, duration of symptoms, recreational drug use, history of chronic steroid use (which can mimic cord compression). Exam points: ❖ Note vital signs (especially for respiratory distress, autonomic instability). ❖ Check for a sensory level. ❖ Check rectal exam (for saddle anesthesia, diminished rectal tone). ❖ DTRs may be diminished (ie. spinal shock) or hyperreflexic. ❖ Percuss the spine for tenderness. ❖ Note signs of rheumatoid arthritis which is associated with atlanto-occipital dislocation. Workup + Treatment 1) If trauma suspected, immobilize the neck (usually already done in the ED) 2) STAT MRI spine. Consider starting with plain films if there is a delay in getting an MRI, but the on-call Neuorads fellow should be made aware of the emergent need. 4) Possibly hematology-oncology consult and XRT within 12 hrs if appropriate SPINAL CORD LESIONS Localization Symptoms and signs Craniocervical Junction Neck pain, head tilt, down-beat nystagmus, UMN weakness x 4 Cervical Spinal Cord Neck pain, LMN in UE at level of lesion & b/l UMN below, sensory level, bowel/bladder Thoracic Spinal Cord Back pain, radicular signs, spastic paraparesis, sensory level, bowel/bladder Cauda Equina Syndrome Low back & perineal pain, flaccid paraparesis, areflexic bowel/bladder Conus Medullaris Areflexic bowel/bladder, minimal LE weakness, perineal sense loss Anterior Cord Syndrome Motor & spinothalamic tract (pain/temp) with spared position sense, bowel/bladder Central Cord Syndrome Suspended sensory level (pain/temp), UMN weakness below, intact position sense Brown – Sequard Syndrome Ipsilateral UMN weakness and position sense below lesion, contralateral pain/sense loss below lesion 47 Acute Traumatic Spinal Cord Injury • The pathophysiology of acute spinal cord injury is complex and multifaceted. It involves a primary mechanical injury • The primary injury appears to initiate a host of secondary injury mechanisms including; i. vascular compromise leading to reduced blood flow, ii. electrolyte shifts, permeability changes, loss of cellular membrane integrity, edema, and loss of energy metabolism, iii. biochemical changes including neurotransmitter accumulation, arachidonic acid release, free- radical and prostaglandin production and lipid peroxidation • Ischemia of the spinal cord underlies much of the mechanism of posttraumatic SCI • Ischemia appears to be related to both local and systemic vascular alterations • Local vascular alterations are due to the direct spinal cord injury and focal, post-injury vasospasm • Systemic vascular alterations include reduced heart rate, cardiac arrhythmia, reduced mean arterial blood pressure, reduced peripheral vascular resistance and compromised cardiac output • Respiratory insufficiency and pulmonary dysfunction is common after traumatic spinal cord injury, particularly when the injury occurs at cervical spinal cord level • Spinal immobilization of all trauma patients with SCI is recommended except; i. when patient is awake, alert, and not intoxicated ii. without neck pain or tenderness iii. who do not have an abnormal motor or sensory examination iv. who do not have any significant associated injury • The ASIA international standards are recommended as the preferred neurological examination tool. • Maintaining a mean arterial blood pressure of 85-90 mm Hg after SCI is recommended. • Administration of methylprednisolone for the treatment of acute SCI is not recommended. • Early administration of venous thromboembolism prophylaxis (within 48-72 h) is recommended 50 NEURORADIOLOGY Relative Imaging Densities Tissue MRI CT T1 T2 Gad/other Bone Dark Dark Bright Air Dark Dark Dark Fat Bright Bright Light Gray Water Dark Bright +flair except CSF Brain Anatomic Reverse Anatomic Reverse Anatomic Infarct Dark Bright Subacute +gad Darker w/time Tumor Dark Bright + gad Dark Demyelinating Dark Bright + flair, acute + gad Dark Blood 0-24h Isodense Bright + susceptibility Bright Blood 24h to 3-5d Isodense Dark + susceptibility Bright Blood 3-7d Bright Dark + susceptibility Less bright Blood 1wk –month Bright Bright + susceptibility Darker Blood 2wk-yr Dark Dark + susceptibility Dark ❖ Blood volume on CT scan (in cc) = 0.5 x max length x max width x number of slices x thickness of cuts ❖ Houndsfield units for CT scans ➢ Bone 1000 Gray matter 35-40 ➢ Calcium 100 White matter 25-30 ➢ Acute Blood 85 CSF 0 ➢ Tumor 30-60 Adipose -100 ➢ Air -1000 ❖ An approach to reading head CTs ➢ Collections (extraaxial, intraaxial, cisternal, epidural, subdural, parenchymal, intraventricular etc) ➢ Midline shift (look at pineal gland and septum) & patency of cisterns ➢ Degree & pattern of hypoattenuation, sulcal effacement, hyerdense vessels, lentiform nucleus obscuration, insular ribbon obsuration (signs of stroke) ➢ Fractures, pneumocephalus, hydrocephalus, edema pattern ❖ TCD criteria for > 50% intracranial stenosis (speeds are mean velocities) ➢ MCA >100 cm/s, or >1:2 comparing L vs. R ➢ ACA/ICA (siphon) >90cm/s ➢ PCA >60cm/s ➢ Verts, basilar >80cm/s 51 Criteria for Portable CT Scans It is crucial that Portable CT scanning orders outline the rational for scan in the comment section. When a patient requires a portable HCT, the comment section should clearly define the rational and everyone should be aware (bedside nurse, NCC-NSG team) IE: Leaking ventric with risk of infection in neuro compromised non- intubated patient. We continue our efforts to secure 24/7 availability for CT scanning for our ICU patients. There is an on-call system for CT tech response within an hour’s timeline of a portable HCT request. For portable CT, 2 techs are now in house Monday thru Friday from 0700-2300, on-call after those hours and 1500-0700 on weekends. Any portable need after hours should be requested STAT with comment section highlighting details and a phone call to CT to call in the tech. Appropriate patient populations for Portable CT Scan: Scan Criteria - Post-operative Craniotomy - Acute TBI - Acute Neurological change in any ICU patient – NeuroICU/CT/Rhoads 5 - Gravely ill with high transport risk For best project cooperative and results please note the following: - NP/Resident/MD ordering Portable CT: Use comments section to direct request: 1. Portable CT 2. Specify time if time is a factor (ventric clamp trial, etc) 3. Reason for portable CT: acute change in MS, new CN deficit, motor decline etc. Steroid Preperation of Patients with Contrast Dye Allergy Slow steroid prep: 50 mg prednisone 12 h before CT followed by 50 mg prednisone 2 h before CT followed by 25-50 mg IV Benadryl 1 h before CT scan Rapid steroid prep: 40 mg IV solumedrol 4 h before CT followed by 50 mg IV Benadryl 1 H before CT scan Emergent steroid prep: 200 mg IV hydrocortisone and 50 mg IV Benadryl 1 h before CT scan 52 SCALES AND FORMULAE Glasgow Coma Scale (add up all components to get score, if patient intubated give 1 for verbal score) ASPECTS Score 10 = normal; subtract one point for hypodensity in each of the 10 regions noted below. See also- www.aspectsinstroke.com 55 SUBARACHNOID HEMORRHAGE GRADING SCALES Hunt and Hess Scale Grade Clinical findings 0 No SAH 1 Asymptomatic or mild headache, mild nuchal rigidity 2 Moderate to severe headache, nuchal rigidity, no neurologic deficit, except cranial nerve palsy 3 Drowsiness, confusion, or mild focal deficit 4 Stupor or mild to moderate hemiparesis; possible early decerebrate rigidity 5 Deep coma, decerebrate posturing, moribund WFNS Grade Clinical findings I GCS=15, no motor deficit II GCS 13-14, no motor deficit III GCS 13-14, yes motor deficit IV GCS 7-12, yes or no – motor deficit V GCS 3-6, yes or no – motor deficit Fisher Scale (risk of vasospasm increases with grade until grade 4 which has lower risk) Grade CT scan findings 1 No blood detected 2 Diffuse, thin layer of subarachnoid blood (vertical layers < 1 mm thickness) 3 Localized clot or thick layer of subarachnoid clot (vertical layers > 1mm thickness) 4 Intracerebral or intravintricular blood with diffuse or no subarachnoid blood Modified Fisher Scale (risk of vasospasm increases linearly with grade) Grade CT scan findings 0 No blood detected 1 Diffuse or focal thin subarachnoid blood 56 (no intraventricular blood) 2 Diffuse or focal thin subarachnoid blood (with intraventricular blood) 3 Diffuse or focal thick subarachnoid blood (no intraventricular blood) 4 Diffuse or focal thick subarachnoid blood (with intraventricular blood) Transcranial Doppler (TCD) Normal Values Vessel Mean Velocity (cm/sec) MCA (M1) 40 – 80 ACA (A1) 35 – 60 PCA (P1) 30 – 55 ICA 61 + 16 OA 21 + 5 Carotid Siphon 55 + 15 VA 25 – 50 BA 25 – 60 Transcranial Doppler (TCD) interpretation Mean MCA velocity (cm/sec) Lindegaard ratio (MCA velocity/ICA velocity) Interpretation < 120 <3 Normal 120-150 3 – 4 Mild Vasospasm 150 – 200 5 – 6 Moderate Vasospasm >200 >6 Severe Vasospasm