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Neurocritical Care
Neurocritical Care
Ayush Batra
Terrance Kummer
Brian L. Edlow
COMA & DISORDERS OF CONSCIOUSNESS
Coma: A state of unarousable unresponsiveness, duration typically <2-4 wk; rare cases longer, up to 12 mo (Funct Neurol 2014;29:201).
Vegetative state (VS): Unawareness of self or environment, but preserved sleep/wake cycles & complete or partial preservation of hypothalamic & brainstem autonomic functions.
Persistent vegetative state (PVS): >1 mo in vegetative state.
“Permanent” vegetative state: 3 mo after nontraumatic brain injury, 1 yr after TBI, but descriptions of late recovery of responsiveness in pts w/TBI & nontraumatic brain injuries have undermined concept of permanence (Neurology 2010;75:239).
Minimally conscious state (MCS): Severely impaired consciousness w/minimal but definite behavioral evidence of awareness.
NOTE: Neuro exam a/w ˜40% misdiagnosis rate of VS compared to formal assessment w/Coma Recovery Scale-Revised—more sensitive for MCS (BMC Neurol 2009;9:35).
Locked-in syndrome: State of de-efferentation w/quadriplegia & loss of lower cranial nerve function but preservation of sensation, cognition, & eye mvmts.
Catatonia: Unresponsiveness due to psych disorder w/disturbance of motor behavior but maintained consciousness. Stuporous & hyperexcitable forms exist; stuporous form may resemble coma. Behavioral disturbances: mutism, posturing, waxy flexibility, & catalepsy.
Coma Scales: GCS most common scale used.
FOUR score validated for lower GCS, better for TBI & intubated pts
Pathophysiology, ddx, & clinical manifestations
Neuroanatomic localization: Dysfxn of brainstem reticular activating system, thalamic relay nuclei, and/or b/l diffuse dysfxn of cerebral hemispheres. In coma of unknown etiology, subsequently determined causes: diffuse and/or metabolic brain dysfxn > supratentorial lesion > infratentorial lesion > psychiatric “coma” (conversion Rxn, depression, catatonic stupor).
Etiologies of coma (Plum & Posner’s Diagnosis of Stupor & Coma 2007)
Structural (compressive/destructive): Hemispheres (EDH, SDH, SAH, ICH, stroke, HIE, tumor, abscess, meningitis, encephalitis, vasculitis, leukoencephalopathy, prion dz, PML), diencephalon (BG ICH, stroke, tumor, abscess, pituitary tumor, pineal tumor, encephalitis, fatal familial insomnia, paraneoplastic syndrome), & brainstem (cerebellar stroke, ICH, tumor, abscess; brainstem stroke, ICH, tumor, or infxn).
Diffuse, multifocal, or metabolic: Hypoxia, ischemia, hypoglycemia, & vitamin cofactor deficiency (thiamine, niacin, pyridoxine, B12, folate), endogenous metabolic products (hepatic coma, uremic coma, CO2 narcosis, exocrine pancreatic encephalopathy, myxedema-thyrotoxicosis, hypo- or hyperparathyroidism, adrenal dz), meds/poisons (sedatives, acids, psychotropic drugs, medication overdose), sepsis, hypo- or hypernatremia, acidosis/alkalosis, hypo-/hyper-Mg, hypo-/hyper-Ca, hypophos, temp dysreg (hypothermia or heat stroke), sz or postictal state, & diffuse axonal injury.
Initial management/evaluation of coma & impaired consciousness
CABs (circulation, airway, breathng), 1 g/kg IV dextrose, 1 mg/kg IV thiamine, & 0.01 mg/kg IV naloxone; comprehensive metabolic panel, CBC w/diff, coags, ABG/VBG, serum & urine tox screen, serum osms, EKG, TFTs, adrenal function tests, UA/UCx, Bld Cxs, head CT, and/or brain MRI; consider LP & EEG. Other tests based on clinical suspicion.
Natural history & prognosis of coma, VS, & MCS: Prognosis varies depending on cause. Post-TBI better outcomes than postanoxia. Prolonged coma rare; most progress to VS w/in 1 mo. Both VS & MCS can be permanent or transitional states. Likelihood of improvement ↓’s over time for both. VS life expectancy typically 2-5 yr; rarely >10 yr. MCS pts have better chance of fxnl recovery than VS; MCS from TBI more likely to improve than MCS from other etiologies (J Head Trauma Rehabil 1997;12:36).
Neuroimaging in disorders of consciousness: MRI can help predict which early post-TBI VS pts (6-8 wk) will recover: corpus callosum & dorsolateral brainstem injuries predict nonrecovery (Lancet 1998;351:1763). FDG-PET of VS shows ↓ global cerebral metabolism to 30%-50% of nl (J Neurosurg Anesthesiol 1999;11:17); FDG-PET of MCS shows high diagnostic se (93%) (Lancet 2014;384:514). EEG background rhythm & presence of sleep architecture may have diagnostic utility in VS & MCS (Ann Neurol 2014;76:869), but not validated as a prognostic tool. Functional MRI has demonstrated willful modulation of brain activity in some VS & MCS pts (NEJM 2010;362:579).
Therapies in disorders of consciousness: Amantadine improves rate of fxnl recovery over 4-wk period in pts w/TBI VS & MCS (NEJM 2012;366:819). ˜5% of VS & MCS pts respond to zolpidem (Am J Phys Med Rehabil 2014;93:101). Experimental approaches: Thalamic DBS has improved responsiveness in 1 pt w/MCS (Nature 2007;448:522) & transcranial direct current stimulation of L-dorsolateral prefrontal cortex showed improvement in MCS pt CRS-R scores (Neurology 2014;82:1112).
HYPOXIC-ISCHEMIC ENCEPHALOPATHY (HIE) AFTER CARDIAC ARREST
<10% survival for out-of-hospital cardiac arrest after CPR (NEJM 2004;351:632).
<20% survival to d/c for in-hospital cardiac arrest after CPR (Resuscitation 2003;58:297).
↑ duration of anoxia & ↑ duration of CPR → ↓ outcome (Crit Care Med 1995;23:18).
Neurological prognosis for coma after cardiac arrest
Goal of bedside exam & ancillary testing: predict poor vs. favorable neuro outcome. Strong predictors of poor prognosis are known. However, fever prevention (therapeutic hypothermia or targeted temperature management) alters the specificity of most prognostic indicators; thus, prognostication is more challenging in patients treated w/therapeutic hypothermia. Emerging evidence may eventually allow prediction of favorable prognosis. No single datum in isolation is entirely reliable. Concordant findings from multiple modalities (e.g., exam, EEG, SSEP, etc.) allow more reliable predictions and more informed medical decision making.
Suggested workup (note timing): Statistical value of tests in table below.
Neuro exam: Predictors of poor outcome: Absent pupillary, corneal, oculocephalic reflexes 1-3 days postarrest/postrewarming; diffuse myoclonus. Early eye opening & spont eye mvmts not predictive of good outcome; more predictive after 3 days. Single sz & intermittent focal myoclonus do NOT predict poor outcome (Neurology 2006;66:62).
EEG: Starting during hypothermia. Purpose: (1) monitor for szs; (2) prognosis. Duration: continue ≥24 h after completion of rewarming (findings can evolve). Persistent voltage suppression, burst suppression, epileptiform activity predict poor prognosis (Resuscitation 2014;85:1580). Alpha coma NOT invariably a/w poor outcome (Neurology 1988;38:773). Postanoxic status epilepticus NOT invariably a/w poor outcome (Neurology 2009;72:744).
SSEP: Wait ≥48 h after completion of rewarming to do somatosensory evoked potentials. Less reliable if done too early. B/l absence of N20 w/median nerve stim predicts poor outcome. Insufficient data for prognostic value of BAERs & VEPs alone.
Serum markers: Consider 48-72 h after rewarming. Neuron-specific enolase (NSE) > 33 µg/L at days 1-3 a/w poor outcome. Serum astroglial S-100B more predictive than NSE at 24 h after return of spontaneous circulation (ROSC) (Resuscitation 2011;82:26).
CT: Consider 48 h postrewarming if coma continues & prognosis remains unclear.
MRI: Consider at 72 h postrewarming if coma continues & prognosis remains unclear. Absence of DWI/ADC lesions a/w better outcome (Mayo Clin Proc 2007;82:828). ↓ whole-brain median ADC may predict poor outcome (Radiology 2009;252:173). Typical DWI/ADC abnls: cortical ribbon, watershed infarct, thalamus, BG. Findings follow characteristic temporal & spatial patterns involving BG & cerebellum followed by cortical & WM changes in early/late/subacute periods (Neurocrit Care 2011;14:61-67).
ICP & brain oxygen monitoring: Insufficient evidence for prognostic value.
THERAPEUTIC HYPOTHERMIA (TH) FOR COMA AFTER CARDIAC ARREST
Mechanisms of action: Reduces cerebral metabolic rate & oxygen demand. Reduces cerebral edema & ICP by preserving BBB integrity. Reduces excitotoxic neuronal injury. Minimizes free radical release & suppresses inflammation.
Supporting data: Mortality & neurologic recovery benefits demonstrated by multiple randomized trials (NEJM 2002;346:549; NEJM 2002;346:557). Data exist mostly for out-of-hospital VF/VT cardiac arrest; limited data for PEA, asystolic arrest, in-hospital arrest → TH for these types may be applied at discretion of clinician (Circulation 2003;108:118). Hyperthermia is detrimental—odds ratio for unfavorable outcome >2 for each 1°C ↑ in temp after arrest (Arch Int Med 2001;161:2007). More recent literature on out-of-hospital cardiac arrest w/coma—hypothermia targeted temp 33°C showed no benefit over 36°C (NEJM 2014;369:2197).
Basic principles & approach to therapeutic hypothermia: Initiate cooling rapidly. Multiple cooling methods may be required to meet temp goal of 33°C-36°C (91°F-96°F). Total cooling period 24 h begins when cooling is initiated, NOT when target temp reached. Shivering generates heat & contributes to neuronal injury by increasing cerebral metabolism → sedation & paralysis may be necessary.
Preparation for hypothermia: Lab eval: CMP, CBC, PT/PTT, fibrinogen, D-dimer. Place a-line for BP monitoring. Monitor core temp: bladder temp probe, or pulm artery temp probe if oliguric (bladder temp probe requires urine in bladder).
Inclusion criteria: Not following commands w/in 6 h of cardiac arrest.
Relative exclusion criteria (hypothermia may carry ↑ risk): Hemodynamic instability requiring high-dose pressors. Major head trauma → rule out ICH by head CT prior to TH if suspicion for head trauma. Recent major surgery (w/in 14 days). Systemic infxn/sepsis → hypothermia interferes w/immune function. Other etiology for coma → drug/EtOH, pre-existing coma prior to arrest. Active bleeding → hypothermia ↓ clotting factor activity. Admin of thrombolytic, antiplatelet, or anticoagulation meds for cardiac condition NOT a contraindication to hypothermia.
