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Anoxic Brain Injury / Neuroprognostication

VERSION: 1.1 CREATED: January 30, 2026 REVISED: January 30, 2026 STATUS: Approved


DIAGNOSIS: Anoxic Brain Injury / Neuroprognostication

ICD-10: G93.1 (Anoxic brain damage, not elsewhere classified), G93.82 (Brain death), I46.9 (Cardiac arrest, cause unspecified), I46.2 (Cardiac arrest due to underlying cardiac condition), I46.8 (Cardiac arrest due to other underlying condition), G93.6 (Cerebral edema), G40.901 (Epilepsy with status epilepticus — post-anoxic seizures), G25.3 (Myoclonus — post-anoxic myoclonus)

CPT CODES: 85025 (CBC with differential), 80053 (CMP (BMP + LFTs)), 82803 (Arterial blood gas (ABG)), 83605 (Lactate), 84484 (Troponin (serial)), 85610 (PT/INR), 85384 (Fibrinogen), 82947 (Blood glucose), 83735 (Magnesium), 82330 (Calcium, ionized), 84100 (Phosphorus), 84703 (Pregnancy test (beta-hCG)), 86900 (Blood type and screen), 80307 (Urine drug screen), 80320 (Blood alcohol level), 83519 (Neuron-Specific Enolase (NSE)), 85379 (D-dimer), 84145 (Procalcitonin), 82533 (Cortisol (AM)), 84443 (TSH), 83880 (BNP / NT-proBNP), 82140 (Ammonia), 83930 (Serum osmolality), 83036 (HbA1c), 80061 (Lipid panel), 82375 (Carboxyhemoglobin), 70450 (CT head without contrast), 93000 (ECG (12-lead)), 71046 (Chest X-ray), 93458 (Coronary angiography / cardiac catheterization), 95700 (Continuous EEG (cEEG)), 93306 (Echocardiogram (TTE)), 70553 (MRI brain with DWI/ADC), 95925 (SSEP (somatosensory evoked potentials)), 76390 (MR spectroscopy), 75557 (Cardiac MRI), 75574 (CT angiography coronary), 93620 (Electrophysiology study (EPS)), 78608 (PET brain (FDG))

SYNONYMS: Anoxic brain injury, ABI, hypoxic-ischemic encephalopathy, HIE, post-cardiac arrest syndrome, PCAS, post-cardiac arrest brain injury, anoxic encephalopathy, cerebral anoxia, global cerebral ischemia, post-arrest encephalopathy, cardiac arrest brain injury, neuroprognostication, post-resuscitation care, anoxic brain damage, hypoxic brain injury, cerebral hypoxia, post-cardiac arrest care, return of spontaneous circulation, ROSC, comatose survivor of cardiac arrest, post-anoxic myoclonus, Lance-Adams syndrome

SCOPE: Acute management, targeted temperature management (TTM), neuroprognostication, and rehabilitation pathway for anoxic brain injury following cardiac arrest or other causes of global cerebral hypoxia in adults. Covers post-cardiac arrest care bundle (TTM 32-36C for 24h, hemodynamic optimization, seizure management), multimodal neuroprognostication (clinical exam, EEG, SSEP, MRI, biomarkers, CT), confounder identification and elimination, myoclonus classification, and rehabilitation pathway for survivors. Excludes neonatal HIE, pediatric cardiac arrest, primary respiratory arrest without cardiac arrest, focal stroke, and traumatic brain injury.


DEFINITIONS: - Anoxic Brain Injury (ABI): Diffuse brain injury from global cessation of cerebral blood flow (cardiac arrest) or oxygen delivery (severe hypoxia) - Post-Cardiac Arrest Syndrome (PCAS): Multi-organ dysfunction following ROSC, including anoxic brain injury, myocardial dysfunction, systemic ischemia-reperfusion injury, and persistent precipitating pathology - Targeted Temperature Management (TTM): Controlled cooling to 32-36C for at least 24h to reduce secondary neuronal injury - Neuroprognostication: Multimodal assessment of neurological outcome performed no earlier than 72h after return to normothermia - Lance-Adams Syndrome: Chronic post-hypoxic action myoclonus in cardiac arrest survivors who regain consciousness; distinct from early status myoclonus and compatible with good outcome


PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting


CRITICAL: NEUROPROGNOSTICATION TIMING

Do NOT prognosticate before 72 hours after return to normothermia (rewarming). Earlier assessment is unreliable due to residual effects of sedation, hypothermia, metabolic derangements, and neuromuscular blocking agents. No single test is sufficient for prognostication — a multimodal approach is mandatory (AAN 2023, ERC/ESICM 2021).


═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════

1. LABORATORY WORKUP

1A. Essential/Core Labs

Test Rationale Target Finding ED HOSP OPD ICU
CBC with differential (CPT 85025) Baseline; infection screen; thrombocytopenia from ischemia-reperfusion Normal STAT STAT ROUTINE STAT
CMP (BMP + LFTs) (CPT 80053) Electrolytes; renal function (ischemic ATN common); hepatic injury (shock liver); glucose management Normal; watch Cr, LFTs, K STAT STAT ROUTINE STAT
Arterial blood gas (ABG) (CPT 82803) Oxygenation; ventilation; acid-base status; lactate clearance pH 7.35-7.45; PaCO2 35-45; PaO2 >60; lactate trending down STAT STAT - STAT
Lactate (CPT 83605) Tissue perfusion marker; serial clearance predicts survival <2 mmol/L; clearance >20% at 6h is favorable STAT STAT - STAT
Troponin (serial) (CPT 84484) Myocardial injury is nearly universal post-arrest; ACS as precipitant; myocardial dysfunction severity Trend; peak predicts myocardial dysfunction severity STAT STAT - STAT
PT/INR (CPT 85610), aPTT (CPT 85730) Coagulopathy from ischemia-reperfusion (DIC common); pre-procedural Normal STAT STAT - STAT
Fibrinogen (CPT 85384) DIC screen; consumptive coagulopathy from prolonged arrest >150 mg/dL STAT STAT - STAT
Blood glucose (CPT 82947) Hyperglycemia worsens neurological outcomes; hypoglycemia mimics encephalopathy 140-180 mg/dL target (avoid <70 and >180) STAT STAT ROUTINE STAT
Magnesium (CPT 83735) Hypomagnesemia lowers seizure threshold; arrhythmia risk >2.0 mg/dL STAT STAT ROUTINE STAT
Calcium, ionized (CPT 82330) Cardiac rhythm stability; seizure threshold Normal STAT STAT ROUTINE STAT
Phosphorus (CPT 84100) Refeeding risk; electrolyte management Normal STAT ROUTINE ROUTINE STAT
Pregnancy test (beta-hCG) (CPT 84703) Affects imaging and medication decisions Document result STAT STAT - STAT
Blood type and screen (CPT 86900) Potential need for blood products; DIC management On file STAT STAT - STAT
Urine drug screen (CPT 80307) Toxicologic cause of arrest (cocaine, opioids, amphetamines); affects prognostication timeline Document result STAT - - STAT
Blood alcohol level (CPT 80320) Confounding factor for neurological exam; withdrawal risk Document result STAT - - STAT

1B. Extended Workup (Second-line)

Test Rationale Target Finding ED HOSP OPD ICU
Neuron-Specific Enolase (NSE) (CPT 83519) Prognostic biomarker; draw at 24h, 48h, and 72h post-ROSC. NSE >33 ug/L at 48-72h associated with poor outcome (FPR <5% per ERC/ESICM 2021). Must exclude hemolysis (falsely elevates NSE) <33 ug/L at 48-72h suggests potential for recovery; >60 ug/L highly predictive of poor outcome - URGENT - URGENT
D-dimer (CPT 85379) DIC screening; ischemia-reperfusion coagulopathy Normal URGENT ROUTINE - URGENT
Procalcitonin (CPT 84145) Differentiate post-arrest SIRS from infection; guide antibiotic decisions <0.5 ng/mL (elevated common post-arrest without infection) URGENT ROUTINE - URGENT
Cortisol (AM) (CPT 82533) Adrenal insufficiency from prolonged shock; critical illness-related corticosteroid insufficiency >18 ug/dL - ROUTINE - ROUTINE
TSH (CPT 84443) Hypothyroidism as contributing factor Normal - ROUTINE ROUTINE -
BNP / NT-proBNP (CPT 83880) Post-arrest myocardial dysfunction severity; volume status Elevated (expected post-arrest) URGENT ROUTINE - URGENT
Ammonia (CPT 82140) Hepatic encephalopathy confounding neurologic exam; shock liver Normal URGENT ROUTINE - URGENT
Serum osmolality (CPT 83930) Monitor during osmotherapy if cerebral edema develops 280-320 mOsm/kg - ROUTINE - ROUTINE
HbA1c (CPT 83036) Diabetes management; glucose control optimization <7.0% - ROUTINE ROUTINE -
Lipid panel (CPT 80061) Cardiovascular risk for secondary prevention Document baseline - ROUTINE ROUTINE -

1C. Rare/Specialized (Refractory or Atypical)

Test Rationale Target Finding ED HOSP OPD ICU
S100B protein Additional prognostic biomarker; less studied than NSE; elevated >0.18 ug/L at 24-48h suggests poor outcome Normal - EXT - EXT
Tau protein (serum or CSF) Emerging biomarker for axonal injury severity; research context Lower levels favorable - EXT - EXT
GFAP (glial fibrillary acidic protein) Emerging astrocytic injury biomarker; elevated in severe ABI Lower levels favorable - EXT - EXT
Neurofilament light chain (NfL) serum Emerging biomarker for axonal injury; correlates with outcome at 24-72h post-arrest Lower levels favorable - EXT - EXT
Genetic testing (SCN5A, KCNQ1, etc.) Channelopathy workup if arrest etiology unclear in young patient without structural heart disease Document result - - EXT -
Toxicology (expanded) Cyanide, carbon monoxide, organophosphates if environmental exposure suspected Negative STAT EXT - STAT
Carboxyhemoglobin (CPT 82375) Carbon monoxide poisoning as cause of anoxia; house fire, CO exposure <3% (non-smoker); <10% (smoker) STAT - - STAT

2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study Timing Target Finding Contraindications ED HOSP OPD ICU
CT head without contrast (CPT 70450) Immediately post-ROSC; rule out primary intracranial event as cause of arrest Exclude hemorrhage, stroke, herniation, mass as primary cause. Post-anoxic findings: diffuse sulcal effacement, loss of gray-white differentiation (GWR) — GWR <1.1 at 24-48h predicts poor outcome Pregnancy (benefit outweighs risk) STAT STAT - STAT
ECG (12-lead) (CPT 93000) Immediately post-ROSC; identify STEMI (emergent cath), arrhythmia, QTc, Brugada, channelopathy STEMI -> emergent PCI; arrhythmia identification; QTc assessment None STAT STAT - STAT
Chest X-ray (CPT 71046) ETT position; rib fractures from CPR; aspiration; pulmonary edema Normal; exclude complications None STAT ROUTINE - STAT
Coronary angiography / cardiac catheterization (CPT 93458) Emergent if STEMI; urgent if no obvious non-cardiac etiology and shockable rhythm (VF/VT). AHA/ILCOR: emergent PCI for STEMI; consider early cath for non-STEMI arrests with shockable rhythm Identify and treat coronary occlusion as precipitant of arrest Active bleeding; known anaphylaxis to contrast STAT STAT - STAT
Continuous EEG (cEEG) (CPT 95700) Initiate within 12h of ICU admission; detect nonconvulsive seizures (NCSE in 10-30% of comatose post-arrest); monitor for burst-suppression; assess background reactivity for prognostication at >=72h Background: continuous vs burst-suppression vs suppression; reactivity to stimuli; seizures/NCSE. Highly malignant patterns (suppression, burst-suppression without reactivity) predict poor outcome None - STAT - STAT
Echocardiogram (TTE) (CPT 93306) Within 24h; assess post-arrest myocardial dysfunction (stunned myocardium); EF for hemodynamic management; identify structural cause (HCM, valvular) Post-arrest EF often 25-40% (usually recovers by 72h); wall motion abnormalities; structural abnormality None URGENT URGENT - URGENT

2B. Extended

Study Timing Target Finding Contraindications ED HOSP OPD ICU
MRI brain with DWI/ADC (CPT 70553) Day 2-7 post-ROSC (optimal at day 3-5); critical for neuroprognostication. DWI is most sensitive imaging modality for anoxic injury Extensive cortical and subcortical restricted diffusion (DWI bright, ADC dark) = poor outcome. Diffuse cortical involvement, basal ganglia, thalamic, brainstem involvement all predict poor outcome. Quantitative ADC values may improve accuracy Pacemaker (non-MRI-conditional); hemodynamic instability; active TTM devices (MRI-compatible alternatives exist) - URGENT ROUTINE URGENT
SSEP (somatosensory evoked potentials) (CPT 95925) Perform at >=72h post-ROSC after rewarming and sedation washout. Bilateral absence of N20 cortical responses is one of the most reliable poor prognostic indicators (FPR <1%) Bilateral N20 present = good sign. Bilateral N20 absent = poor prognosis (FPR ~0-1% per AAN). N20 amplitude <0.62 uV also predictive None absolute; requires cooperative technician and reduced electrical interference - URGENT - URGENT
CT head with quantitative GWR measurement At 24-48h post-ROSC; measure gray-white matter ratio at basal ganglia level and centrum semiovale GWR <1.10 at caudate nucleus level at 24-48h predicts poor outcome (FPR <5%). Diffuse sulcal effacement, absent basal cisterns, loss of differentiation Pregnancy (benefit outweighs risk) - URGENT - URGENT
MR spectroscopy (CPT 76390) If available; assess metabolic injury severity Reduced NAA/Cr ratio; elevated lactate peak = poor prognosis Pacemaker (non-MRI-conditional); hemodynamic instability - EXT - EXT
Cardiac MRI (CPT 75557) After stabilization; assess myocardial injury, cardiomyopathy, fibrosis, ARVC Structural/ischemic etiology of arrest; myocardial viability Pacemaker (non-MRI-conditional); hemodynamic instability - ROUTINE ROUTINE -

2C. Rare/Specialized

Study Timing Target Finding Contraindications ED HOSP OPD ICU
CT angiography coronary (CPT 75574) If catheterization deferred or non-STEMI; non-invasive coronary evaluation Coronary disease; anomalous coronary artery Contrast allergy; renal impairment URGENT ROUTINE - URGENT
Electrophysiology study (EPS) (CPT 93620) After recovery; if arrhythmic etiology suspected and ICD consideration Inducible VT/VF; risk stratification for ICD Hemodynamic instability - - ROUTINE -
Brain CT perfusion (CPT 0042T) Research context; assess global cerebral perfusion Absent cortical perfusion predicts poor outcome Contrast allergy - EXT - EXT
PET brain (FDG) (CPT 78608) Research/rare context; cortical metabolic assessment Absent cortical metabolism Pregnancy - - EXT -

3. TREATMENT

CRITICAL: POST-CARDIAC ARREST CARE BUNDLE (First 24-72 Hours)

  1. Airway and ventilation - target normoxia (PaO2 75-100) and normocapnia (PaCO2 35-45)
  2. Targeted temperature management - 32-36C for at least 24h
  3. Hemodynamic optimization - MAP >65, treat post-arrest myocardial dysfunction
  4. Seizure detection and treatment - continuous EEG monitoring; treat electrographic seizures
  5. Glucose management - target 140-180 mg/dL; avoid hypoglycemia
  6. Coronary reperfusion - emergent PCI if STEMI; early angiography for shockable rhythms

3A. Acute/Emergent

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Targeted Temperature Management (TTM) — cooling to 32-36C IV/External ALL comatose cardiac arrest survivors (GCS motor <6 after ROSC). TTM2 trial: no difference between 33C vs 36C; both superior to fever. AHA/ILCOR 2020: target 32-36C for at least 24h 32-36C :: external/IV :: continuous x 24h :: Initiate cooling ASAP post-ROSC; use surface (Arctic Sun) or intravascular (Thermogard) cooling; target temperature within 4h; maintain for at least 24h; rewarm at 0.25C/h (avoid >0.5C/h); prevent fever (<37.7C) for at least 72h after ROSC Active hemorrhage (relative); refractory cardiogenic shock (relative); terminal illness (relative) Core temperature (esophageal or bladder probe) continuously; shivering assessment (BSAS) q1h; electrolytes (K, Mg, Ca, Phos) q4-6h during cooling; coagulation q12h; skin checks q4h for surface cooling STAT STAT - STAT
Meperidine (Demerol) IV Shivering during TTM (counterproductive; increases metabolic demand and defeats cooling); first-line anti-shivering agent 25-50 mg :: IV :: q4h PRN :: 25-50 mg IV q4h PRN shivering; first-line anti-shivering agent MAOIs; seizure disorder (lowers threshold); renal impairment (normeperidine accumulation) Shivering scale (BSAS); sedation; respiratory status - - - STAT
Buspirone PO/NG Adjunctive anti-shivering during TTM; lowers shivering threshold by 0.7C 30 mg :: PO :: q8h :: 30 mg PO/NG q8h; lowers shivering threshold by 0.7C MAOIs Shivering scale - - - ROUTINE
Magnesium sulfate IV Adjunctive anti-shivering; lowers shivering threshold and seizure threshold 2-4 g :: IV :: bolus then infusion :: 2-4 g IV bolus then 1-2 g/h infusion; target Mg 3-4 mg/dL Renal failure (accumulation); severe bradycardia Mg level q4-6h; deep tendon reflexes; HR - - - STAT
Cisatracurium IV Refractory shivering despite first-line measures during TTM; note: obscures clinical exam and must be discontinued well before prognostication 0.15 mg/kg :: IV :: bolus then infusion :: 0.15 mg/kg IV bolus, then 1-3 mcg/kg/min infusion; titrate to train-of-four 1-2/4 Caution in myasthenia gravis Train-of-four (TOF) q4h; cEEG mandatory when paralyzed (seizures undetectable clinically) - - - STAT
Norepinephrine IV Post-arrest myocardial dysfunction with MAP <65 mmHg; first-line vasopressor for post-arrest shock 0.1-0.5 mcg/kg/min :: IV :: infusion :: Start 0.05-0.1 mcg/kg/min; titrate to MAP >65 (or >80 if signs of cerebral hypoperfusion); max 2 mcg/kg/min Peripheral line extravasation (central access preferred) Arterial line BP; MAP; urine output; lactate q4-6h STAT STAT - STAT
Dobutamine IV Post-arrest cardiogenic shock with reduced EF (<30%); augment cardiac output when vasopressors alone insufficient 2.5-20 mcg/kg/min :: IV :: infusion :: Start 2.5 mcg/kg/min; titrate to cardiac output and MAP; consider with echo guidance LVOT obstruction; severe tachyarrhythmia HR; BP; cardiac output (echo or PA catheter); arrhythmia - - - STAT
Vasopressin IV Adjunctive vasopressor for refractory hypotension when norepinephrine dose >0.3 mcg/kg/min 0.01-0.04 units/min :: IV :: infusion :: 0.01-0.04 units/min; does not titrate above 0.04 Digital ischemia (relative); peripheral vascular disease MAP; urine output; peripheral perfusion; serum Na - - - STAT
Levetiracetam IV First-line for post-anoxic seizures and NCSE (common in 10-30% of comatose post-arrest patients); treat all electrographic seizures aggressively 1000-1500 mg :: IV :: BID :: 1000-1500 mg IV load; then 500-1000 mg IV BID; transition to PO when able; no hepatic metabolism; minimal drug interactions Severe renal impairment (dose adjust for CrCl <30) cEEG; renal function; seizure recurrence STAT STAT - STAT
Valproic acid (Depakote) IV Second-line for post-anoxic seizures; add if seizures refractory to levetiracetam 20-40 mg/kg :: IV :: load then BID :: 20-40 mg/kg IV load over 15 min (max 3000 mg); then 500 mg IV q12h; target level 50-100 ug/mL Hepatic failure; mitochondrial disease (Alpers); pregnancy (teratogenic); thrombocytopenia LFTs; ammonia; CBC; drug level; pancreatitis symptoms STAT STAT - STAT
Regular insulin IV Hyperglycemia (>180 mg/dL); target 140-180 mg/dL; avoid hypoglycemia (<70 mg/dL) which worsens neurologic injury per protocol :: IV :: infusion :: Continuous insulin infusion titrated to BG 140-180; transition to sliding scale when hemodynamically stable and tolerating nutrition Hypoglycemia risk BG q1h while on drip; q4-6h on sliding scale; potassium with each BG STAT STAT - STAT
Mechanical ventilation optimization - ALL intubated post-arrest patients; target normoxia and normocapnia per protocol :: - :: continuous :: Target PaO2 75-100 mmHg (avoid hyperoxia PaO2 >300); PaCO2 35-45 mmHg (avoid hypo/hypercapnia); PEEP as needed N/A ABG q4-6h during active TTM; SpO2 continuous; EtCO2 continuous STAT STAT - STAT

3B. Symptomatic Treatments

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Propofol IV Sedation during TTM; additional anti-seizure properties; preferred for shorter-acting effect facilitating neurological assessment 5-80 mcg/kg/min :: IV :: infusion :: 5-50 mcg/kg/min; titrate to RASS -4 to -5 during active TTM; wean after rewarming Propofol infusion syndrome risk (monitor for metabolic acidosis, rhabdomyolysis, hypertriglyceridemia if >48h at high doses >70 mcg/kg/min); egg/soy allergy Triglycerides q24h; CK if prolonged use; RASS; cEEG - - - STAT
Fentanyl IV Analgesia and sedation during TTM; preferred analgesic during hypothermia (hepatic metabolism reduced) 25-200 mcg/h :: IV :: infusion :: 25-100 mcg/h continuous infusion; titrate to RASS target; bolus 25-50 mcg PRN Respiratory depression (ventilated patients); severe hepatic impairment RASS; respiratory rate (if not ventilated); bowel function - - - STAT
Midazolam IV Alternative/adjunctive sedation if propofol contraindicated; anti-seizure properties 0.02-0.1 mg/kg/h :: IV :: infusion :: 0.02-0.1 mg/kg/h continuous; accumulates with prolonged use; prolongs sedation washout (confounder for prognostication) Severe hepatic impairment; prolonged use delays prognostication RASS; cEEG; watch for prolonged effect delaying prognostication - - - STAT
Acetaminophen IV Fever prevention and treatment post-TTM; target normothermia (<37.7C) for at least 72h post-ROSC 1000 mg :: IV :: q6h :: 1000 mg IV q6h scheduled (not PRN); max 4g/day Severe hepatic impairment Temperature q4h; LFTs - STAT - STAT
Pantoprazole IV GI stress ulcer prophylaxis; post-arrest patients at high risk 40 mg :: IV :: daily :: 40 mg IV daily; transition to PO when tolerating C. difficile risk with prolonged use GI symptoms - ROUTINE - ROUTINE
Enoxaparin SC DVT prophylaxis; immobilized comatose patients at high VTE risk; start after active hemorrhage excluded and hemostasis adequate 40 mg :: SC :: daily :: 40 mg SC daily; start 24-48h post-ROSC if no active bleeding Active hemorrhage; platelet count <50,000; DIC Platelet count; signs of bleeding; anti-Xa level if renal impairment - ROUTINE - ROUTINE
Pneumatic compression devices External DVT prophylaxis; start IMMEDIATELY in all post-arrest patients apply bilaterally :: external :: continuous :: Apply bilaterally on admission; maintain continuously when not ambulating Active DVT; skin breakdown Skin checks; compliance STAT STAT - STAT
Clonazepam PO/NG Post-anoxic myoclonus (both early status myoclonus and Lance-Adams syndrome); first-line for myoclonus suppression 0.5 mg :: PO :: BID :: Start 0.5 mg PO BID; titrate by 0.5 mg q3d to effect; max 6 mg/day Severe respiratory depression (non-ventilated); severe hepatic impairment Sedation; respiratory status; swallowing function - ROUTINE ROUTINE ROUTINE
Valproic acid (myoclonus) PO/IV Post-anoxic myoclonus (adjunctive or alternative to clonazepam) 250 mg :: PO :: BID :: Start 250 mg PO BID; titrate to 500-1000 mg TID; target level 50-100 ug/mL Hepatic failure; mitochondrial disease; pregnancy LFTs; ammonia; CBC; drug level - ROUTINE ROUTINE ROUTINE
Levetiracetam (myoclonus) PO/IV Post-anoxic myoclonus (adjunctive; less effective as monotherapy for myoclonus than clonazepam) 500 mg :: PO :: BID :: Start 500 mg PO BID; titrate to 1000-1500 mg BID Severe renal impairment (dose adjust) Behavioral changes; renal function - ROUTINE ROUTINE ROUTINE

3C. Second-line/Refractory

Treatment Route Indication Dosing Contraindications Monitoring ED HOSP OPD ICU
Lacosamide IV Post-anoxic refractory seizures not controlled by levetiracetam and valproic acid 200 mg :: IV :: load then BID :: 200 mg IV load over 15 min; then 100-200 mg IV BID; target level 10-20 ug/mL PR prolongation >200 ms; second/third-degree heart block; severe hepatic impairment ECG (PR interval); cardiac rhythm - URGENT - URGENT
Phenobarbital IV Refractory post-anoxic status epilepticus (third-line ASM) 15-20 mg/kg :: IV :: load then daily :: 15-20 mg/kg IV load at 50-75 mg/min; then 1-3 mg/kg/day maintenance; target level 20-40 ug/mL Severe respiratory depression (intubated patients only); acute intermittent porphyria Drug level; respiratory status; BP (causes hypotension); sedation - - - STAT
Midazolam infusion (RSE) IV Continuous seizure activity despite two ASMs (refractory status epilepticus protocol) 0.2 mg/kg :: IV :: bolus then infusion :: 0.2 mg/kg IV bolus, then start 0.1 mg/kg/h; titrate q15min by 0.1 mg/kg/h to EEG seizure suppression or burst-suppression; max 2 mg/kg/h Hemodynamic instability (may worsen) cEEG mandatory; BP; vasopressor requirements - - - STAT
Pentobarbital IV Super-refractory post-anoxic status epilepticus (when midazolam/propofol infusions fail) 5 mg/kg :: IV :: load then infusion :: 5 mg/kg IV load over 1h (may repeat 5 mg/kg boluses); maintenance 1-5 mg/kg/h; titrate to burst-suppression on cEEG Hemodynamic instability (severe myocardial depression); porphyria cEEG; arterial line; vasopressors (nearly always required); ileus; temperature (poikilothermia) - - - STAT
Ketamine IV Adjunctive for refractory post-anoxic seizures; NMDA antagonism addresses late-stage glutamate excitotoxicity 1-2 mg/kg :: IV :: bolus then infusion :: 1-2 mg/kg IV bolus; then 1-5 mg/kg/h infusion; titrate to cEEG Elevated ICP (relative — disputed); severe hypertension cEEG; BP (may increase); HR; oral secretions - - - STAT
Mannitol 20% IV Elevated ICP with clinical signs of herniation (post-anoxic cerebral edema); acute temporizing measure 1-1.5 g/kg :: IV :: bolus :: 1-1.5 g/kg IV bolus for acute herniation; 0.25-0.5 g/kg q4-6h maintenance Anuria; serum osmolality >320 Serum osmolality q4-6h; Cr; urine output - - - STAT
Hypertonic saline 23.4% IV Acute herniation from post-anoxic cerebral edema; requires central venous access 30 mL :: IV :: bolus :: 30 mL IV via central line over 10-20 min for acute herniation No central access; hypernatremia >160 Na q4-6h; osmolality - - - STAT
Hypertonic saline 3% IV ICP management; less emergent than 23.4%; can give via peripheral line 150-500 mL :: IV :: bolus or infusion :: 150-500 mL bolus or 0.5-1 mL/kg/h continuous infusion; target Na 145-155 Hypernatremia >160 Na q4-6h; osmolality - - - STAT

3D. Chronic/Rehabilitation Therapies (Survivors)

Treatment Route Indication Dosing Pre-Treatment Requirements Contraindications Monitoring ED HOSP OPD ICU
ICD (implantable cardioverter-defibrillator) Procedure Secondary prevention of sudden cardiac death in survivors with cardiac etiology and EF <=35% (or per electrophysiology study); typically implanted before discharge or at 40 days post-MI N/A :: Procedure :: once :: Per cardiology/electrophysiology; ICD vs S-ICD per anatomy Cardiac workup complete; EF assessment; electrophysiology study if indicated; shared decision-making Active infection; terminal illness with <1yr life expectancy Device checks q3-6 months; wound; inappropriate shocks - ROUTINE ROUTINE -
Amantadine PO Arousal promotion in patients with disorders of consciousness (vegetative state/minimally conscious state); accelerates functional recovery 100 mg :: PO :: BID :: 100 mg PO BID (via NG if needed); increase to 200 mg BID; give before noon to avoid insomnia Baseline renal function; seizure history assessment Renal impairment (dose adjust); seizure history (relative — lowers threshold) Renal function; seizure activity; livedo reticularis; hallucinations - ROUTINE ROUTINE ROUTINE
Sertraline PO Depression and emotional lability in ABI survivors; common post-anoxic complication 25 mg :: PO :: daily :: Start 25 mg PO daily; increase by 25 mg q1-2 weeks; max 200 mg daily Baseline ECG if cardiac risk factors MAOIs; QT prolongation Suicidality; serotonin syndrome signs; QTc if risk factors - ROUTINE ROUTINE -
Methylphenidate PO Cognitive impairment and attention deficits in ABI survivors; post-anoxic apathy/abulia 5 mg :: PO :: BID :: Start 5 mg PO BID (morning and noon); titrate by 5 mg q3-5 days; max 60 mg/day; avoid afternoon dosing Baseline HR and BP; cardiac arrhythmia screen Uncontrolled hypertension; severe anxiety; cardiac arrhythmia; psychosis HR; BP; appetite; sleep; behavioral changes - ROUTINE ROUTINE -
Modafinil PO Excessive daytime somnolence and fatigue in ABI survivors 100 mg :: PO :: daily :: Start 100 mg PO daily in morning; increase to 200 mg; max 400 mg/day Baseline hepatic function; cardiac screening Severe hepatic impairment; cardiac arrhythmia BP; HR; sleep quality; mood - - ROUTINE -
Baclofen PO Spasticity in ABI survivors with upper motor neuron signs; post-anoxic posturing or hypertonia 5 mg :: PO :: TID :: Start 5 mg PO TID; titrate by 5 mg/dose q3d; max 80 mg/day; do not stop abruptly Baseline renal function Renal impairment (dose adjust); seizure risk (withdrawal) Sedation; weakness; urinary retention - ROUTINE ROUTINE ROUTINE
Tizanidine PO Spasticity alternative; post-anoxic hypertonia 2 mg :: PO :: TID :: Start 2 mg PO TID; titrate by 2 mg q3-7d; max 36 mg/day Baseline LFTs; avoid concurrent CYP1A2 inhibitors Hepatic impairment; concurrent CYP1A2 inhibitors (fluvoxamine, ciprofloxacin) LFTs at baseline, 1mo, 3mo, 6mo; BP (hypotension); sedation - ROUTINE ROUTINE -
Botulinum toxin type A (Botox) IM Focal spasticity in ABI survivors (upper or lower extremity) not responding to oral agents per muscle group :: IM :: q12 weeks :: Dose per target muscles; typical total 200-400 units; repeat q12 weeks; onset 3-7 days Muscle selection by trained provider; identify target muscles with ultrasound/EMG guidance Infection at injection site; neuromuscular junction disorder Weakness (focal); dysphagia (if cervical muscles); antibody formation - - ROUTINE -

4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation ED HOSP OPD ICU
Neurology/neurocritical care consult for neuroprognostication guidance and seizure management in all comatose post-arrest patients STAT STAT - STAT
Cardiology consult for coronary evaluation, post-arrest myocardial dysfunction management, and arrhythmia workup STAT STAT ROUTINE STAT
Electrophysiology consult for ICD evaluation in cardiac arrest survivors with arrhythmic etiology - ROUTINE ROUTINE -
Palliative care consult for goals of care discussion and family support when neuroprognostication suggests poor outcome - URGENT - URGENT
Physical therapy for early mobilization protocol when neurologically and hemodynamically stable; passive range of motion to prevent contractures in comatose patients - URGENT ROUTINE URGENT
Occupational therapy for ADL assessment, cognitive rehabilitation, and adaptive equipment in ABI survivors - URGENT ROUTINE URGENT
Speech-language pathology for swallow evaluation (high aspiration risk in ABI survivors), communication assessment, and cognitive-linguistic rehabilitation - URGENT ROUTINE URGENT
Neuropsychology for formal cognitive assessment in ABI survivors at 3-6 months post-injury to identify specific deficits and guide rehabilitation - - ROUTINE -
Rehabilitation medicine (physiatry) for comprehensive rehabilitation planning and disposition (acute rehab vs skilled nursing) - ROUTINE ROUTINE -
Social work for family support, advance directive assistance, guardianship if needed, and community resource coordination - ROUTINE ROUTINE ROUTINE
Chaplain/spiritual care for spiritual support for patient family during critical illness and end-of-life discussions - ROUTINE - ROUTINE
Organ procurement organization (OPO) notification when brain death or withdrawal of life-sustaining treatment being discussed; federal requirement in most jurisdictions - ROUTINE - ROUTINE
Psychiatry consult for post-cardiac arrest anxiety, PTSD, depression in survivors who regain consciousness - ROUTINE ROUTINE -

4B. Patient / Family Instructions

Recommendation ED HOSP OPD ICU
Explain that anoxic brain injury occurs because the brain was deprived of oxygen during cardiac arrest and that recovery is unpredictable in the first 72 hours STAT ROUTINE ROUTINE STAT
Reassure family that targeted temperature management (cooling) is a standard evidence-based treatment and that the patient appears deeply sedated because of medications and cooling, not necessarily because of brain injury severity STAT ROUTINE - STAT
Explain that formal neuroprognostication will not occur until at least 72 hours after rewarming because sedation and hypothermia confound the neurological exam - ROUTINE - ROUTINE
Inform family that neuroprognostication uses multiple tests together (exam, EEG, SSEP, MRI, blood tests) and that no single test alone determines outcome - ROUTINE - ROUTINE
If poor prognosis confirmed through multimodal testing, discuss goals of care including comfort care, withdrawal of life-sustaining treatment, and organ donation in a compassionate and unhurried manner - ROUTINE - ROUTINE
For survivors: explain that recovery from anoxic brain injury is a prolonged process (months to years); cognitive, emotional, and physical deficits are common; and rehabilitation is essential - ROUTINE ROUTINE ROUTINE
For survivors: report immediately if new seizures (shaking, staring, confusion), worsening weakness, difficulty swallowing, or significant mood changes occur as these may indicate complications requiring treatment adjustment - ROUTINE ROUTINE ROUTINE
For survivors: do not drive until formally cleared by neurology due to risk of seizures and cognitive impairment following anoxic brain injury - ROUTINE ROUTINE -
Provide written information about cardiac arrest survivors support groups and brain injury advocacy organizations (Brain Injury Association of America, Sudden Cardiac Arrest Foundation) - ROUTINE ROUTINE -

4C. Lifestyle & Prevention

Recommendation ED HOSP OPD ICU
Cardiac rehabilitation program enrollment for all cardiac arrest survivors to improve cardiovascular fitness and reduce recurrence risk - ROUTINE ROUTINE -
Smoking cessation as smoking increases cardiac arrhythmia and recurrent arrest risk - ROUTINE ROUTINE -
Strict medication adherence for cardiac medications (antiarrhythmics, beta-blockers, antiplatelets, statins) to prevent recurrent arrest - ROUTINE ROUTINE -
Alcohol cessation or strict limitation to reduce cardiomyopathy progression and seizure threshold lowering - ROUTINE ROUTINE -
Regular aerobic exercise (30 min moderate intensity 5 days/week) after cardiac rehabilitation clearance to improve cardiovascular outcomes - - ROUTINE -
Mediterranean or DASH diet for cardiovascular risk reduction - ROUTINE ROUTINE -
Blood pressure target <130/80 mmHg for cardiovascular risk reduction - ROUTINE ROUTINE -
HbA1c target <7.0% for diabetic patients to reduce cardiovascular risk - ROUTINE ROUTINE -
CPAP compliance if obstructive sleep apnea present as OSA increases arrhythmia and recurrent arrest risk - ROUTINE ROUTINE -
Home AED (automated external defibrillator) placement for household members trained in BLS if patient at ongoing arrhythmia risk - - ROUTINE -
Fall prevention program for ABI survivors with gait instability, cognitive impairment, or seizure risk - ROUTINE ROUTINE -
Cognitive rehabilitation exercises (memory aids, structured routines, environmental modifications) for daily function optimization - - ROUTINE -

═══════════════════════════════════════════════════════════════ SECTION B: REFERENCE (Expand as Needed) ═══════════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis Key Distinguishing Features Tests to Differentiate
Residual sedation / medication effect History of prolonged sedation; improves with time after washout; normal SSEP and MRI Sedation washout (5 half-lives); pharmacokinetic assessment; drug levels
Non-convulsive status epilepticus (NCSE) May mimic or coexist with anoxic coma; electrographic seizure activity; some patients improve with ASM treatment cEEG (mandatory; seizures in 10-30% of comatose post-arrest patients)
Metabolic encephalopathy Renal failure, hepatic failure, electrolyte disturbances, hypothyroidism; potentially reversible CMP; ammonia; TSH; renal function; blood gas
Traumatic brain injury History of trauma preceding arrest; focal findings on CT; epidural/subdural hematoma CT head; clinical history; mechanism
Primary intracranial hemorrhage (ICH/SAH) Focal deficits; hemorrhage on CT preceding arrest; headache history CT head at admission; CTA
Acute ischemic stroke (large vessel) Focal deficits; vessel occlusion on CTA; asymmetric DWI changes CTA; MRI DWI (focal rather than global restriction)
Basilar artery occlusion Locked-in syndrome mimics coma; preserved vertical eye movements and blinks; posterior circulation stroke CTA (basilar occlusion); MRI brainstem DWI; clinical exam for locked-in
Toxic/metabolic coma Drug overdose, poisoning (CO, cyanide); may respond to specific antidotes; history of exposure Toxicology screen; carboxyhemoglobin; cyanide level; osmolar gap
Hypothermia (primary) Environmental exposure history; core temp <35C preceding arrest; reversibility with rewarming Core temperature; history; rewarm before declaring poor prognosis
Psychogenic unresponsiveness Inconsistent exam findings; may resist eye opening; normal EEG, SSEP, MRI EEG (normal alpha); SSEP normal; MRI normal; caloric testing (nystagmus)
Brain death / death by neurologic criteria Absent all brainstem reflexes; no respiratory drive; irreversible cessation of all brain function Formal brain death evaluation protocol (see separate template)

6. MONITORING PARAMETERS

Parameter Frequency Target/Threshold Action if Abnormal ED HOSP OPD ICU
Core temperature (esophageal or bladder) Continuous during TTM; q4h after rewarming 32-36C during TTM; <37.7C for 72h post-ROSC Adjust cooling device; anti-shivering protocol; investigate fever source STAT STAT - STAT
Arterial blood pressure (arterial line preferred) Continuous (ICU); q15min (ED); q4h (OPD) MAP >65 mmHg (>80 if cerebral hypoperfusion signs); avoid SBP <90 Titrate vasopressors/inotropes; volume resuscitation; echo STAT STAT ROUTINE STAT
GCS / Neurologic exam q1h x 24h during TTM; q2h x 24h after rewarming; q4h thereafter; formal exam at >=72h after rewarming Improvement in motor response; pupillary reactivity; brainstem reflexes If declining: STAT CT; rule out new event; reassess prognostication STAT STAT ROUTINE STAT
Continuous EEG (cEEG) Continuous x 48-72h minimum; longer if seizures detected No seizures; improving background (continuous, reactive); absence of highly malignant patterns Treat seizures aggressively; highly malignant pattern (suppression, burst-suppression without reactivity) is poor prognostic sign - STAT - STAT
Blood glucose q1h during insulin drip; q4-6h on sliding scale 140-180 mg/dL Adjust insulin; avoid hypoglycemia <70 STAT STAT ROUTINE STAT
Serum electrolytes (K, Mg, Ca, Phos) q4-6h during TTM (hypothermia causes intracellular K shift, hypomagnesemia); q12h after rewarming K 4.0-4.5; Mg >2.0; Ca normal; Phos normal Aggressive replacement; arrhythmia risk if uncorrected STAT STAT - STAT
Lactate clearance q4-6h until normal <2 mmol/L; clearance >20% at 6h Optimize perfusion; volume; vasopressors STAT STAT - STAT
NSE (neuron-specific enolase) At 24h, 48h, 72h post-ROSC; check for hemolysis (invalidates result) <33 ug/L at 48-72h; rising trend unfavorable Interpret as part of multimodal prognostication; >60 ug/L highly predictive of poor outcome - URGENT - URGENT
Pupillary light reflex (including automated pupillometry if available) q1h during acute phase; formal assessment at >=72h after rewarming Present and reactive; NPi >=3.0 on automated pupillometry Absent at >=72h after rewarming is poor prognostic sign; automated pupillometry more quantitative; reduce confounder effect STAT STAT ROUTINE STAT
Serum sodium q6h during osmotherapy; q12h otherwise 135-155 mEq/L (higher if on hypertonic saline) Adjust osmotherapy; free water restriction vs replacement - ROUTINE - STAT
Serum osmolality q6h during mannitol therapy <320 mOsm/kg; osmolar gap <10 Hold mannitol if >320 - ROUTINE - STAT
Shivering assessment (BSAS) q1h during TTM BSAS 0 (no shivering) Stepwise anti-shivering protocol - - - STAT
ICP (if monitoring in place) Continuous ICP <22 mmHg; CPP 60-70 mmHg Tiered ICP management; osmotherapy; sedation - - - STAT

7. DISPOSITION CRITERIA

Disposition Criteria
Admit to ICU (ALL comatose post-arrest) ALL comatose cardiac arrest survivors require ICU admission for: TTM, cEEG, hemodynamic monitoring, mechanical ventilation, neuroprognostication at >=72h after rewarming
Remain in ICU Ongoing TTM or rewarming phase; hemodynamic instability requiring vasopressors; active seizures; mechanical ventilation; pending formal neuroprognostication
Step down to floor (monitored bed) Completed TTM and rewarming; hemodynamically stable off vasopressors; no active seizures; extubated with adequate airway; neuroprognostication suggests potential recovery; awaiting rehabilitation placement
Transfer to acute inpatient rehabilitation Following commands consistently; medically stable; can tolerate 3 hours/day of therapy; motivated for rehabilitation; functional deficits amenable to rehabilitation interventions
Transfer to skilled nursing facility (SNF) Unable to tolerate 3h/day of rehabilitation therapy; chronic disorders of consciousness (vegetative or minimally conscious state) requiring ongoing medical management; tracheostomy/PEG care
Transfer to long-term acute care (LTAC) Requires prolonged ventilator weaning; ongoing complex medical needs; not yet stable enough for SNF or rehabilitation
Discharge home Alert, communicating; ambulatory or safe with home support; seizures controlled; cardiac workup complete; medications reconciled; follow-up arranged; home AED placed if indicated
Comfort care / withdrawal of life-sustaining treatment Multimodal neuroprognostication at >=72h post-rewarming confirms poor outcome by at least 2 independent modalities (exam, EEG, SSEP, MRI, NSE); family informed and goals of care aligned; palliative care involved
Brain death evaluation Clinical suspicion of brain death (absent brainstem reflexes, no respiratory drive); proceed with formal brain death protocol (see Brain Death Evaluation template)
Organ donation consideration When brain death confirmed or withdrawal of life-sustaining treatment planned; OPO notified per federal requirement; family approached by OPO designated requestor

8. EVIDENCE & REFERENCES

Recommendation Evidence Level Source
TTM at 32-36C for at least 24h in comatose cardiac arrest survivors Class I, Level B-R TTM2 Trial Investigators. NEJM 2021 — hypothermia at 33C vs normothermia (37.5C): no significant difference in mortality or neurological outcome at 6 months; Bernard et al. NEJM 2002 — initial trial showing benefit of 33C; HACA Trial. NEJM 2002
Avoid fever (target <37.7C) for at least 72h post-ROSC Class I, Level B-NR AHA/ILCOR 2020 Guidelines; Dankiewicz et al. NEJM 2021 (TTM2)
Multimodal neuroprognostication no earlier than 72h after rewarming Class I, Level B-NR Sandroni et al. Intensive Care Med 2014; ERC/ESICM 2021 Guidelines; AAN Practice Parameter Update 2023
Bilateral absence of N20 on SSEP predicts poor outcome (FPR <1%) Class I, Level A Sandroni et al. Intensive Care Med 2014; Zandbergen et al. Neurology 2006 — PROPAC study; Bouwes et al. Neurology 2012
NSE >33 ug/L at 48-72h predicts poor outcome Class IIa, Level B Stammet et al. JACC 2015 — TTM biomarker substudy; Sandroni et al. Intensive Care Med 2014
Highly malignant EEG patterns (suppression, burst-suppression without reactivity) predict poor outcome Class IIa, Level B Westhall et al. Neurology 2016 — TTM EEG substudy; ERC/ESICM 2021; Hofmeijer et al. Clin Neurophysiol 2015
Absent pupillary reflexes at >=72h after rewarming predicts poor outcome Class I, Level B ERC/ESICM 2021; Sandroni et al. Intensive Care Med 2014; Automated pupillometry (NPi) more reliable than manual assessment
Extensive DWI restriction on MRI at 2-7 days predicts poor outcome Class IIa, Level B Wijman et al. Neurology 2009; Mlynash et al. Neurocrit Care 2010
CT gray-white ratio <1.10 at 24-48h predicts poor outcome Class IIb, Level B Metter et al. Resuscitation 2011; Lee et al. Resuscitation 2016
Emergent coronary angiography for STEMI post-arrest Class I, Level B AHA 2020 Guidelines; Lemkes et al. NEJM 2019 (COACT trial) — immediate vs delayed angiography in non-STEMI shockable arrest: no difference
Target normoxia (PaO2 75-100) and normocapnia (PaCO2 35-45) Class IIa, Level B Kilgannon et al. JAMA 2010 — hyperoxia associated with increased mortality; Roberts et al. JAMA 2018
Glucose target 140-180 mg/dL; avoid hypoglycemia Class IIb, Level B AHA 2020 Guidelines; NICE-SUGAR Trial. NEJM 2009 — intensive glucose control increases mortality in ICU
Post-anoxic status myoclonus within 72h associated with poor outcome but not invariably fatal Class IIb, Level C Elmer et al. JAMA Neurology 2016; Seder et al. Crit Care Med 2015 — some patients with early myoclonus survive with good outcome
Lance-Adams syndrome (chronic post-hypoxic myoclonus in awake patients) compatible with good neurological outcome Class IIa, Level C Lance and Adams. Brain 1963; Freund et al. Medicine 2017
Amantadine accelerates recovery in disorders of consciousness Class IIa, Level B Giacino et al. NEJM 2012 — primarily TBI patients; extrapolated to ABI
Self-fulfilling prophecy avoidance: early WLST biases outcome data Expert consensus Geocadin et al. Circulation 2019 — AHA scientific statement; Steinberg et al. Neurology 2020
Levetiracetam first-line for post-anoxic seizures Class IIa, Level C Ruijter et al. JAMA Neurology 2022 (TELSTAR trial) — aggressive vs standard treatment of electrographic status epilepticus: no difference in primary outcome; treat clinical and electrographic seizures
cEEG monitoring recommended for all comatose post-arrest patients Class I, Level B Claassen et al. Neurology 2004; AHA/AAN guidelines
Avoid early withdrawal of life-sustaining treatment (<72h post-rewarming) Class I, Level C Sandroni et al. Intensive Care Med 2020; ERC/ESICM 2021

APPENDIX A: NEUROPROGNOSTICATION ALGORITHM

Multimodal Prognostication Protocol (>=72h After Rewarming)

Prerequisites before prognostication:

  1. At least 72h have elapsed since return to normothermia
  2. All sedation discontinued for at least 5 half-lives (or drug levels measured)
  3. Neuromuscular blocking agents discontinued for at least 5 half-lives (confirm with train-of-four)
  4. Core temperature 36-37.5C
  5. No severe metabolic derangements (glucose, electrolytes, renal/hepatic failure)
  6. No residual hypothermia effects

Step 1: Clinical Examination

Finding Interpretation
Absent pupillary light reflex bilaterally at >=72h POOR prognosis indicator (FPR <5%)
Absent corneal reflexes bilaterally at >=72h POOR prognosis indicator (use with other modalities)
Motor response M1 (no motor) or M2 (extension) at >=72h POOR prognosis indicator (FPR 10-20% if used alone)
Status myoclonus within 48h (continuous >30 min) POOR prognosis indicator (but not 100% — some survivors reported)
Any motor response M3 or better at >=72h May indicate potential for recovery; continue monitoring

Step 2: Ancillary Testing (At Least 2 Concordant Findings Required)

Test Poor Outcome Indicator False Positive Rate
SSEP: Bilateral N20 absence Highly predictive of poor outcome <1% (most reliable single test)
EEG: Burst-suppression without reactivity at >=72h Highly predictive of poor outcome ~5%
EEG: Suppression (<10 uV) at >=72h Highly predictive of poor outcome ~2%
EEG: Absent reactivity at >=72h Supportive of poor prognosis ~10%
NSE: >33 ug/L at 48-72h (confirm no hemolysis) Supportive of poor prognosis ~10% at 33; <5% at >60
CT: GWR <1.10 at 24-48h Supportive of poor prognosis ~5-10%
MRI DWI: Extensive cortical/subcortical restriction (day 2-7) Highly predictive of poor outcome <5%

Step 3: Interpretation

  • Poor prognosis confirmed: >=2 concordant poor prognostic indicators from DIFFERENT modalities (e.g., bilateral N20 absent + highly malignant EEG + NSE >60)
  • Indeterminate: Discordant results or only 1 modality abnormal; continue observation, repeat testing, consider additional modalities
  • Potentially favorable: Improving clinical exam, present N20 on SSEP, continuous reactive EEG background, normal or mildly elevated NSE

CRITICAL REMINDERS: - No single test is sufficient to declare poor prognosis - Always use at least 2 concordant modalities from different categories - Account for ALL confounders (sedation, temperature, metabolic, NMBAs) - Self-fulfilling prophecy: premature WLST biases outcome literature — allow adequate time - Some patients with early myoclonus make meaningful recovery; myoclonus alone is NOT sufficient for poor prognostication


APPENDIX B: TARGETED TEMPERATURE MANAGEMENT (TTM) PROTOCOL

Initiation Phase (Target: Reach Goal Temperature Within 4 Hours)

Step Action Details
1 Select target temperature 32-36C (based on institutional protocol; TTM2 trial supports 36C with strict fever prevention)
2 Initiate cooling Surface: Arctic Sun, cooling blankets. Intravascular: Thermogard XP, CoolGard. Cold saline (4C, 30 mL/kg) NOT recommended as sole cooling method (RINSE trial: no benefit, possible harm)
3 Insert temperature probe Esophageal (most accurate) or bladder catheter with temp probe
4 Start anti-shivering protocol Meperidine 25-50 mg IV PRN; buspirone 30 mg q8h; Mg infusion; escalate to NMBAs if refractory
5 Order cEEG Mandatory; seizures undetectable clinically in sedated/paralyzed patients
6 Check electrolytes K, Mg, Ca, Phos q4-6h (hypothermia shifts K intracellularly; hypokalemia risk)

Maintenance Phase (24-48 Hours at Target Temperature)

Parameter Target Action
Temperature Within 0.5C of target Adjust cooling device; check probe position
Potassium 4.0-4.5 mEq/L Aggressive replacement; caution — K will rise during rewarming
Shivering (BSAS) 0 Stepwise: acetaminophen -> meperidine -> buspirone -> Mg -> dexmedetomidine -> NMBAs
Glucose 140-180 mg/dL Insulin resistance increases with hypothermia; may need higher doses
Bradycardia HR 40-60 acceptable Sinus bradycardia expected at 33C; only treat if hemodynamically significant

Rewarming Phase (CRITICAL — Controlled and Slow)

Parameter Details
Rewarming rate 0.25C/hour (NEVER >0.5C/hour); rapid rewarming associated with rebound cerebral edema, ICP elevation, and rebound hyperthermia
Duration 12-16h from 33C to 37C; 4-8h from 36C to 37C
Potassium Reduce replacement during rewarming; K rises as it shifts extracellularly; risk of HYPERKALEMIA
Post-rewarming Maintain normothermia (<37.7C) for at least 72h post-ROSC using acetaminophen and cooling devices

APPENDIX C: MYOCLONUS CLASSIFICATION IN ANOXIC BRAIN INJURY

Type Timing Features Prognosis
Early status myoclonus Within 24-72h post-arrest Generalized, continuous or near-continuous myoclonic jerking; often involves face, limbs, axial muscles; typically in deeply comatose patients; may be stimulus-sensitive Generally associated with POOR outcome; however, NOT invariably fatal — some survivors with good recovery reported (especially if other prognostic indicators are favorable)
Acute cortical myoclonus Within 72h Focal or multifocal; stimulus-sensitive; cortical origin on EEG (time-locked cortical discharges) Variable; may respond to ASMs; use multimodal prognostication
Lance-Adams syndrome Days to weeks after arrest (during recovery) Action myoclonus in CONSCIOUS patients; triggered by voluntary movements; intention myoclonus; may be severely disabling but patient is AWAKE GOOD prognosis for survival (patient is conscious); may improve with clonazepam, valproic acid, levetiracetam; long-term disability varies
Subcortical/reticular myoclonus Variable Generalized; no cortical correlate on EEG; brainstem origin Variable

KEY PRINCIPLE: Myoclonus alone is NEVER sufficient for prognostication. Always integrate with multimodal assessment. The distinction between status myoclonus (continuous, generalized, in comatose patient) vs Lance-Adams (action myoclonus in awake patient) has critical prognostic implications.


CHANGE LOG

v1.1 (January 30, 2026) - Fixed column order in all lab tables (1A, 1B, 1C) to place venue columns (ED/HOSP/OPD/ICU) as last 4 columns per style guide - Fixed column order in all imaging tables (2A, 2B, 2C) to place venue columns as last 4 columns per style guide - Fixed column order in Section 6 Monitoring to place venue columns as last 4 columns per style guide - Standardized structured dosing format (dose :: route :: frequency :: instructions) across all treatment tables (3A, 3B, 3C, 3D) - Added OPD coverage for follow-up labs (CBC, CMP, glucose, Mg, Ca, Phos) in Section 1A for survivor clinic visits - Added ICU column to Sections 4B and 4C for setting consistency - Updated section dividers to Unicode box-drawing characters - Added Pre-Treatment Requirements to Section 3D medications (amantadine, sertraline, methylphenidate, modafinil, baclofen, tizanidine, botox) - Cleaned up treatment names to remove redundant section headers (e.g., "Shivering management:" prefix removed) - Fixed pneumatic compression devices Route column (was "-", now "External") - Added REVISED date to header metadata - Updated version to 1.1

v1.0 (January 30, 2026) - Initial template creation - Comprehensive post-cardiac arrest care bundle including TTM protocol - Multimodal neuroprognostication algorithm (clinical exam, EEG, SSEP, MRI, NSE, CT GWR) - Confounder identification and elimination checklist - Myoclonus classification (early status myoclonus vs Lance-Adams syndrome) - Rehabilitation pathway for survivors (amantadine, spasticity management, cognitive rehab) - Seizure management protocol including refractory status epilepticus - Family communication and goals of care guidance - Organ donation considerations - All citations include PubMed links where available