Neurologic emergencies — status epilepticus, acute ischemic stroke, intracerebral hemorrhage, raised intracranial pressure, meningitis, autoimmune encephalitis, neuromuscular respiratory failure, and others — require rapid, protocolized pharmacologic intervention. The neurologist on call must know not only the indication and dose of each emergency drug but the timing, contraindications, and adjuncts. This page covers the major pharmacologic responses to neurologic emergencies.

Status Epilepticus

Definition

  • Continuous seizure activity ≥5 minutes OR multiple seizures without return to baseline.
  • “Refractory” if continues after first and second-line therapy (typically 30 minutes).
  • “Super-refractory” if continues despite >24 hours of anesthetic infusion.

First-Line (0-5 min)

  • Lorazepam: 0.1 mg/kg IV (max 4 mg per dose); may repeat.
  • Diazepam: 0.15-0.2 mg/kg IV; max 10 mg; less preferred (rapid redistribution).
  • Midazolam: 10 mg IM, IN, or buccal; useful when IV not available; 0.2 mg/kg IV.
  • Failure to control after 2 adequate doses (10-15 min): proceed to second-line.

Second-Line (10-30 min)

  • Fosphenytoin: 20 mg/kg PE IV at up to 150 mg/min; cardiac monitoring.
  • Phenytoin: 20 mg/kg IV at 50 mg/min; older, more risks.
  • Levetiracetam: 60 mg/kg IV (up to 4500 mg); rapid; well-tolerated; emerging as first-choice second-line.
  • Valproate: 40 mg/kg IV (up to 3000 mg); alternative.
  • Lacosamide: 200-400 mg IV; emerging alternative.
  • Recent evidence (ESETT trial): no significant difference among fosphenytoin, levetiracetam, valproate.

Refractory Status Epilepticus (after 30-60 min)

  • Intubation, continuous EEG monitoring.
  • Midazolam infusion: 0.2 mg/kg load, then 0.05-2 mg/kg/hr.
  • Propofol: 1-2 mg/kg load, then 5-10 mg/kg/hr; watch propofol infusion syndrome with prolonged use.
  • Pentobarbital: 5 mg/kg load, then 1-3 mg/kg/hr; significant CV depression.
  • Ketamine: emerging; NMDA antagonist; useful in cases not responding to GABAergic agents.
  • Burst suppression target on EEG.

Super-Refractory Status

  • Continued anesthetic infusion.
  • Add additional agents: lacosamide, brivaracetam, cenobamate, perampanel.
  • Consider: ketogenic diet, hypothermia, ECT, vagus nerve stim, immunotherapy if NORSE/FIRES.

Acute Ischemic Stroke

IV Thrombolysis

  • Alteplase: 0.9 mg/kg (max 90 mg); 10% bolus, 90% over 60 min; within 4.5 hours of last known well.
  • Tenecteplase: 0.25 mg/kg single bolus; increasingly preferred (similar/better than alteplase in some trials; logistically simpler).

Contraindications to tPA

  • Hemorrhage on imaging.
  • Recent significant bleeding.
  • SBP >185 or DBP >110 (must lower first).
  • Platelet count <100,000.
  • INR >1.7 (if on warfarin); recent DOAC use (depending on agent).
  • Heparin within 48 hours with aPTT prolonged.
  • Recent surgery, GI bleed, intracranial hemorrhage.
  • Various others — multiple inclusion/exclusion criteria.

Mechanical Thrombectomy

  • For large vessel occlusion within 6 hours.
  • Selected patients up to 24 hours based on imaging (DAWN, DEFUSE-3).
  • Stent retriever or aspiration; often combined.
  • Most powerful acute stroke intervention.

Blood Pressure Management

  • Pre-tPA: SBP <185 / DBP <110.
  • Post-tPA: <180 / <105 for 24 hours.
  • Non-tPA candidate: permissive HTN to SBP 220/DBP 120.
  • Drugs: labetalol IV, nicardipine IV.

Adjunctive

  • Statin: high-intensity within 24 hours.
  • Aspirin: within 24-48 hours (delay if tPA given).
  • DVT prophylaxis: heparin or LMWH 24 hours post-tPA.
  • Glucose: maintain 140-180; avoid hypoglycemia and severe hyperglycemia.

tPA Complications

  • Symptomatic ICH: ~6%; discontinue tPA; cryoprecipitate, platelets, aminocaproic acid.
  • Angioedema: discontinue; antihistamines, steroids, epinephrine if severe.

Intracerebral Hemorrhage (ICH)

BP Management

  • Target SBP <140; rapid lowering safe (INTERACT-2, ATACH-2).
  • Labetalol IV, nicardipine IV infusion.
  • Avoid hypotension.

Reversal of Anticoagulants

  • Warfarin: 4-factor PCC (25-50 IU/kg) + vitamin K 10 mg IV.
  • Dabigatran: idarucizumab (Praxbind).
  • Apixaban, rivaroxaban: andexanet alfa (Andexxa); alternative 4-factor PCC.
  • Edoxaban: andexanet not approved; PCC.

Reversal of Antiplatelet

  • Platelet transfusion: controversial benefit (PATCH trial — no benefit; some still use).
  • DDAVP: may reduce bleeding time.

Adjunctive

  • Surgical evacuation: indication-specific.
  • Hematoma expansion prevention: BP control; reversal; consider tranexamic acid (TICH-2 limited benefit).
  • Seizure prophylaxis: only if presenting seizure; levetiracetam.
  • VTE prophylaxis: pneumatic compression initially; medical prophylaxis 24-72 hours.

Subarachnoid Hemorrhage (SAH)

  • Aneurysm repair: clipping or coiling.
  • Nimodipine: 60 mg PO q4h × 21 days; prevents delayed cerebral ischemia from vasospasm.
  • BP management: SBP <160 typically; tailored.
  • Hydrocephalus: EVD if needed.
  • Anticonvulsant: short-term prophylaxis (controversial).
  • Glucocorticoids: NOT routinely used.
  • Vasospasm management: hypertensive therapy with phenylephrine, norepinephrine; endovascular angioplasty if refractory.

Raised Intracranial Pressure (ICP)

Pharmacologic Measures

  • Mannitol: 0.5-1.5 g/kg IV bolus; 20% solution; reduces brain water through osmotic effect; monitor serum osmolarity (target <320); urine output.
  • Hypertonic saline: 3%, 5%, 23.4% solutions; mannitol alternative; preserves intravascular volume.
  • Sedation: propofol, midazolam, fentanyl; reduce CMRO2 and ICP.
  • Hyperventilation: short-term emergency only (transient cerebral vasoconstriction); target PaCO2 30-35.
  • Steroids: dexamethasone for vasogenic edema (tumor, abscess); NOT for ischemic/traumatic.
  • Barbiturates: induced coma in refractory cases.

Non-Pharm

  • Head of bed at 30°.
  • Neutral neck position.
  • CSF drainage (EVD).
  • Decompressive craniectomy.

CNS Infections

Bacterial Meningitis

  • Empiric (adult community-acquired): vancomycin + ceftriaxone (or cefepime) + ampicillin (if Listeria risk: age >50, immunocompromised, pregnant).
  • Adjust based on culture.
  • Dexamethasone: 10 mg IV q6h × 4 days; start BEFORE or WITH first antibiotic dose; reduces mortality and neurologic sequelae in pneumococcal meningitis.
  • Don’t delay antibiotics for LP if not immediately available.

Viral Encephalitis

  • Acyclovir: 10 mg/kg IV q8h for suspected HSV encephalitis; start empirically when suspected.
  • Renal dose adjustment.
  • Continue 14-21 days if HSV confirmed.
  • Other viral: supportive.

Brain Abscess

  • Empiric: ceftriaxone + metronidazole; vancomycin if Staph risk.
  • Surgical drainage often needed.
  • 4-8 weeks total antibiotic course.

Tuberculous Meningitis

  • RIPE: rifampin + isoniazid + pyrazinamide + ethambutol.
  • Steroid adjunctive (dexamethasone): reduces mortality (TBM Lancet trial).
  • Long duration (12+ months).

Cryptococcal Meningitis

  • Amphotericin B + flucytosine induction.
  • Fluconazole maintenance.
  • HIV-associated: also ART.

Autoimmune Encephalitis (Acute)

  • Methylprednisolone 1 g IV daily × 3-5 days.
  • IVIG 2 g/kg over 2-5 days.
  • Plasmapheresis.
  • Second-line: rituximab, cyclophosphamide.
  • Search for and treat underlying tumor (especially anti-NMDA → ovarian teratoma).

Acute MS Relapse

  • Methylprednisolone 1 g IV daily × 3-5 days (or oral equivalent).
  • Plasmapheresis for steroid-refractory severe relapse.

Myasthenic Crisis

  • IVIG 2 g/kg over 2-5 days, or plasmapheresis (5 sessions).
  • Intubation if respiratory failure (FVC <15-20 mL/kg).
  • Steroids: may initially worsen (consider IVIG bridge).
  • Avoid drugs worsening MG.

GBS

  • IVIG 0.4 g/kg/day × 5 days OR plasmapheresis.
  • Respiratory monitoring (FVC, NIF).
  • Autonomic monitoring.
  • DVT prophylaxis.
  • Steroids NOT effective.

Neuroleptic Malignant Syndrome / Serotonin Syndrome

NMS

  • Discontinue D2 antagonist; reinitiate dopaminergic if PD withdrawal.
  • Dantrolene 1-2.5 mg/kg IV.
  • Bromocriptine 2.5-10 mg PO TID.
  • Supportive: cooling, hydration, ICU.

Serotonin Syndrome

  • Discontinue all serotonergic drugs.
  • Cyproheptadine 4-8 mg PO q1-4h (max 32 mg/day).
  • Benzodiazepines for agitation, myoclonus.
  • Aggressive cooling for hyperthermia.
  • ICU for severe.

Wernicke Encephalopathy / Wernicke-Korsakoff

  • IV thiamine BEFORE glucose; 500 mg TID × 3 days, then 250 mg daily.
  • Glucose without thiamine in deficient patient can precipitate Wernicke.

Cocaine/Stimulant Toxicity

  • Benzodiazepines for agitation, seizures, HTN.
  • Avoid pure β-blockers (unopposed α → hypertensive crisis).
  • Labetalol acceptable (combined α/β).
  • Vasodilators (nitrates, nicardipine) for HTN.

Hypoxic-Ischemic Encephalopathy (Post-Cardiac Arrest)

  • Targeted temperature management 32-36°C.
  • Address seizures (myoclonic, status).
  • Prognosis 72 hours after rewarming.

Toxic Encephalopathy

  • Lithium toxicity: dialysis.
  • Hepatic encephalopathy: lactulose, rifaximin.
  • Uremic: dialysis.
  • Specific toxin: specific antidote.

🔍 Did You Know?

The recognition that dexamethasone significantly reduces mortality and neurologic sequelae in pneumococcal meningitis when given BEFORE or WITH the first antibiotic dose has been one of the most important treatment advances in CNS infection over the past two decades. The de Gans/van de Beek European Dexamethasone Study (2002) demonstrated that early dexamethasone in adults with bacterial meningitis (especially pneumococcal) reduced mortality and neurologic sequelae. The mechanism involves reducing inflammatory response to bacterial lysis, which paradoxically can damage the brain even as antibiotics kill bacteria. The clinical implications are profound: dexamethasone (10 mg IV q6h × 4 days) should be given BEFORE or WITH the first antibiotic dose in any patient with suspected bacterial meningitis. Continuing dexamethasone is appropriate if pneumococcus identified; discontinue if other pathogens. The lesson generalizes: combining antimicrobial therapy with immunomodulation can produce better outcomes than either alone, and modulating host inflammatory response is increasingly important in modern infectious disease care. For practicing neurologists, the take-home: in suspected bacterial meningitis, dexamethasone should be in the IV alongside or before the antibiotics, not after. Hospital systems should optimize meningitis protocols to ensure this happens. The same principle of host immunomodulation also applies to tuberculous meningitis (dexamethasone), severe COVID (dexamethasone), and other infections.

Pitfalls and Pearls

  • Status epilepticus first-line: lorazepam, diazepam, midazolam.
  • Second-line: fosphenytoin, levetiracetam, valproate (similar efficacy ESETT).
  • Refractory: midazolam infusion, propofol, pentobarbital, ketamine; continuous EEG.
  • Acute ischemic stroke: tPA or tenecteplase within 4.5 hours; thrombectomy within 6-24 hours for LVO.
  • tPA BP: <185/110 before; <180/105 after.
  • ICH BP: SBP <140 (INTERACT-2, ATACH-2).
  • Warfarin reversal: 4-factor PCC + vitamin K.
  • Dabigatran reversal: idarucizumab.
  • Apixaban/rivaroxaban reversal: andexanet alfa or PCC.
  • SAH: nimodipine 60 mg PO q4h × 21 days for vasospasm prevention.
  • Raised ICP: mannitol, hypertonic saline; sedation; hyperventilation short-term.
  • Bacterial meningitis: dexamethasone BEFORE or WITH first antibiotic.
  • HSV encephalitis: acyclovir empirically when suspected.
  • Autoimmune encephalitis: steroids + IVIG/plasmapheresis; rituximab.
  • MG crisis: IVIG or plasmapheresis; respiratory monitoring.
  • GBS: IVIG or plasmapheresis; steroids NOT effective.
  • Wernicke: thiamine BEFORE glucose.
  • NMS: discontinue D2 antagonist; dantrolene.
  • Serotonin syndrome: discontinue; cyproheptadine.
  • Cocaine HTN: avoid pure β-blockers; labetalol acceptable.

References

  1. Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults. Epilepsy Curr. 2016;16(1):48-61.
  2. Kapur J, Elm J, Chamberlain JM, et al. Randomized trial of three anticonvulsant medications for status epilepticus (ESETT). N Engl J Med. 2019;381(22):2103-2113.
  3. Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update. Stroke. 2019;50(12):e344-e418.
  4. Anderson CS, Heeley E, Huang Y, et al. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage (INTERACT-2). N Engl J Med. 2013;368(25):2355-2365.
  5. de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med. 2002;347(20):1549-1556.
  6. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120.