• IV acyl-ghrelin: a Phase 2 RCT (160 comatose post-arrest adults) suggested possible benefit but did not meet conventional statistical significance for neurological outcome (P = 0.06). It remains investigational, not standard care. GRECO trial, PMID 38709502
• Inhaled xenon with temperature control: investigational, limited Phase 2 imaging/biomarker data, not routine clinical therapy. Xe-Hypotheca substudy
• Selective brain cooling, steroids, erythropoietin, citicoline, magnesium, N-acetylcysteine, and similar agents have no established outcome benefit for routine post-arrest HIE treatment.

1. Strict fever prevention / protocolized temperature control. Avoid fever, particularly in the first 72 hours after ROSC. Do not start drug-induced hypothermia as a substitute for a protocol.
2. Avoid hypoxemia and hyperoxemia, and avoid major hypo/hypercapnia. T-piece is fine only if oxygenation, ventilation, airway protection, and secretion clearance are adequate. An ABG and continuous capnography are useful.
3. Maintain adequate MAP and perfusion, correct hypotension, arrhythmia, glucose extremes, fever, and metabolic derangements.
4. Continuous or repeated EEG if unresponsive, myoclonus, or unexplained impaired consciousness. Treat definite electrographic seizures/status epilepticus, but routine aggressive suppression of rhythmic/periodic EEG patterns did not improve 3-month neurological outcome in the TELSTAR RCT. TELSTAR, PMID 35196426
5. Treat the cause and post-arrest complications: coronary ischemia when indicated, infection/aspiration, renal failure, shock, etc.
6. Do not make definitive neurological prognosis early. Remove sedatives/confounders and use multimodal assessment, typically at least 72 hours after ROSC and after normothermia: serial exam, EEG, SSEP where available, biomarkers, CT/MRI. The 2025 AHA post-cardiac-arrest guidance emphasizes structured post-arrest care and multimodal neuroprognostication.

Adult post-cardiac-arrest care bundle

1. Airway, oxygenation, ventilation

• Secure/protect airway if consciousness or secretion clearance is inadequate. T-piece is appropriate only if the patient can maintain airway protection, ventilation, and adequate gas exchange.
• Use 100% oxygen only until reliable SpO2/ABG data are available, then titrate.
• Target SpO2 90%-98% or PaO2 60-105 mmHg.
• Target PaCO2 35-45 mmHg, unless a specific severe acidemia or lung strategy requires otherwise.
• Avoid hypoxemia, sustained hyperoxia, hypocapnia, and marked hypercapnia.
• ABG after major respiratory-support changes, plus continuous oximetry. Capnography is useful if intubated.

2. Hemodynamic and cardiac support

• Continuous telemetry and invasive arterial pressure monitoring where feasible.
• Target MAP at least 65 mmHg, individualized upward if chronic hypertension, poor urine output, rising lactate, or clinical evidence of inadequate perfusion.
• Use balanced fluids cautiously, then vasopressor/inotrope support guided by shock phenotype and echocardiography.
• Serial ECG, troponin trend, bedside echo, lactate, urine output, and electrolytes.
• Treat hypokalemia, hyperkalemia, magnesium and phosphate abnormalities promptly.
• Obtain a 12-lead ECG and actively investigate cause: acute coronary syndrome, pulmonary embolism, hemorrhage, hypoxia, sepsis, tamponade, intoxication, electrolyte abnormality, etc.
• Urgent coronary angiography/PCI is indicated for STEMI and considered for ongoing ischemia, cardiogenic shock, recurrent ventricular arrhythmia, or high suspicion of coronary occlusion.

3. Temperature control

• Start a deliberate temperature-control strategy promptly.
• Maintain 32°C to 37.5°C, with a protocol that reliably prevents fever.
• The 2025 AHA guidance considers maintaining temperature control for at least 36 hours reasonable in unresponsive adults.
• Use continuous core-temperature monitoring.
• Manage shivering with analgesia/sedation and a unit protocol. Avoid paralysis without adequate sedation.
• Avoid rapid rewarming and monitor carefully during rewarming for hypotension, arrhythmias, electrolyte shifts, hypoglycemia, and seizures.

4. Neurologic monitoring and seizure care

• Stop/minimize sedatives and neuromuscular blockers when clinically safe so serial examination is interpretable.
• In any patient not following commands, obtain EEG. Continuous EEG is preferred when coma, myoclonus, unexplained movements, or concern for non-convulsive seizures exists.
• Treat clinical seizures or electrographic status epilepticus with usual antiseizure therapy guided by ICU/neurology.
• Do not routinely use antiseizure drugs prophylactically.
• Do not pursue aggressive suppression of all rhythmic or periodic EEG patterns solely to normalize the EEG. In the TELSTAR randomized trial, this did not improve neurological outcome. TELSTAR trial

5. Metabolic and general ICU care

• Maintain glucose in a safe range and avoid both:
  • Hypoglycemia: <70 mg/dL
  • Marked hyperglycemia: >180 mg/dL
• Correct sodium, potassium, calcium, magnesium, phosphate, acid-base and renal abnormalities.
• Treat fever, infection, aspiration pneumonitis/pneumonia, renal injury, rhabdomyolysis, and other organ dysfunction.
• Analgesia first, then lightest safe sedation. Assess for pain, agitation, shivering, and delirium.
• Begin enteral nutrition when hemodynamically stable.
• Provide DVT prophylaxis, stress-ulcer prophylaxis only when indicated, pressure-area care, early physiotherapy, and infection-prevention measures.

6. Neuroprognostication: delayed and multimodal

• Do not give a definitive poor neurological prognosis early.
• Avoid basing withdrawal-of-life-support decisions on one sign, one EEG pattern, one biomarker, or early imaging.
• Make prognostic impressions only after confounders are addressed, including residual sedation, neuromuscular blockade, hypothermia, shock, metabolic derangement, and seizures.
• Use a multimodal assessment, generally at least 72 hours after ROSC or after return to normothermia:
  • serial neurological examination
  • EEG
  • SSEP where available
  • serial NSE or neurofilament light chain where locally validated
  • CT and/or MRI in appropriate time windows

For the patient currently on a T-piece

• ABG within targets
• stable MAP with acceptable perfusion and lactate trend
• adequate cough, secretion management, and airway protection
• no uncontrolled seizures or severe agitation
• a plan for fever prevention and EEG/neuro-monitoring
• no reversible cardiac, infectious, metabolic, or respiratory cause left untreated