Hyperthermia & Hypothermia in Brain Injury

Hyperthermia in Brain Injury

• Hyperthermia increases cerebral metabolic demand by 8–13% per °C.
• It escalates glutamate release, oxygen free radical production, cytoskeletal breakdown, blood-brain barrier disruption, and vasogenic edema.
• Mnemonic: "HOT BRAIN" (BBB breakdown, Release of glutamate, Antioxidant depletion, Temperature-driven metabolic demand, Brain injury exacerbation).

Treatment of Post-Ischemic Patients

• Initiate aggressive treatment for temperatures >38°C.
• Interventions include acetaminophen and surface cooling.

Neuroprotective Mechanisms of Therapeutic Hypothermia

• Reduces glutamate release, metabolic demand, free radicals, inflammatory cytokines, and programmed cell death.

Target Temperature and Duration for Comatose Adults After Cardiac Arrest

• Target 33°C for 24 hours.
• Recent trials suggest 33°C provides better neuroprotection than 36°C, though safety outcomes are similar.
• Mnemonic: "COOL 33" (Cooling to 33°C, Optimal outcomes, Length 24h).

Initiating Cooling

• Rapid infusion of 2 L cold (4°C) IV saline immediately after ROSC.
• Follow with surface/endovascular cooling devices.
• Avoid blankets or heated ventilator circuits.

Preventing Shivering During Therapeutic Hypothermia

• Use sedation and nondepolarizing paralytics (e.g., bolus in ED, drip in ICU).

Rewarming

• Begin at 24 hours post-cooling.
• Rewarm to 36.5°C at 0.15°C/hour.
• Avoid rebound hyperthermia.

Actions on Day 0 (ROSC) for Neuroprognostication

• Initiate TTM.
• Perform CT brain.
• Start long-term EEG.
• Document status myoclonus.
• Assess motor response (flexion/better = indeterminate prognosis).

Strong Predictors of Poor Outcome >72 Hours Post-Normothermia

• Bilateral absent pupillary reflexes OR absent pupillary + corneal reflexes, OR bilateral absence of N20 waves on SSEP.
• False-positive rate <5%.

"Moderate predictors" of poor outcome

• Requires ≥2 findings

Status Myoclonus

• Status myoclonus <48h, unreactive/burst-suppression EEG, diffuse anoxic injury on CT/MRI.

Prognostication

• Prognostication is unreliable before 72 hours post-cardiac arrest due to sedatives/paralytics from TTM confounding exams.
• Early withdrawal of care creates a self-fulfilling prophecy.
• Mnemonic: "72 HRS" (Hours for Reliable Signs).

DNR Orders

• Avoid assigning new DNR status within the first 24 hours to prevent self-fulfilling prophecies.

SSEP Timing

• Perform SSEP after rewarming or 24–72h post-arrest in TTM patients.
• Obtain earlier (Day 2) in non-TTM patients.

Neuron-Specific Enolase (NSE)

• Higher NSE correlates with worse outcomes, but thresholds lack standardization.
• Do not rely on NSE alone.

Cooling Methods

• Use intranasal, intravascular, or surface temperature-modulating devices, or cold saline infusions instead of ice packs or fans

When to Avoid Therapeutic Hypothermia

• After ischemic stroke (no proven benefit).

During Rewarming

• Avoid rebound hyperthermia (common with passive rewarming).

Brain Death Evaluation

• If brainstem reflexes are absent >24h post-ROSC and temperature >36°C.

Prognostication Takeaway

• Avoid nihilism.
• Delay prognostication until ≥72h post-arrest using a multimodal approach (exam, EEG, SSEP, imaging).

First Steps in Induced Hypothermia After Cardiac Arrest

• Rapidly infuse 2 L of cold (4°C) IV saline.
• Expose the patient (no blankets/heated ventilator).
• Place temperature probes (urinary catheter + esophageal).
• Initiate cooling via surface/endovascular devices.

Cooling in Post-Arrest Patients Requiring Coronary Intervention

• Cooling should not delay door-to-balloon time for acute MI.
• Initiate cooling in the ED if time permits; otherwise, start in the catheterization lab.

Monitoring During Therapeutic Hypothermia

• Temperature: Esophageal + bladder probes.
• Continuous EEG for seizures.
• SSEPs after rewarming (TTM patients) or by Day 2 (non-TTM patients).
• Arterial blood gases (pH stat or alpha stat).

Managing Shivering During Cooling

• Use sedation (e.g., midazolam/propofol) and nondepolarizing paralytics (e.g., rocuronium).
• Bolus paralytics in the ED; transition to drips in the ICU.

Managing Rewarming

• Start at 24 hours post-cooling.
• Rate: 0.15°C/hour to a target of 36.5°C.
• Avoid rebound hyperthermia (use active rewarming if needed).
• Discontinue paralytics at rewarming onset; use sedation/narcotics for shivering.

Key Contraindications to Therapeutic Hypothermia

• Ischemic stroke (no proven benefit) and unstable hemodynamics (avoid hypotension/hypoxia during cooling).

Actions Required on Day 1 Post-ROSC

• Begin rewarming.
• Document status myoclonus.
• Continue EEG monitoring.
• Evaluate for absent brainstem reflexes (if present, perform brain death assessment once temperature >36°C).

Brain Death Evaluation

• If brainstem reflexes (e.g., pupillary, corneal) are absent >24 hours post-ROSC AND temperature is >36°C.

Diagnostic Tests Recommended by Day 3–5 for Prognostication

• SSEPs (if TTM-treated).
• Noncontrast CT/MRI for anoxic injury. EEG reactivity testing.

Strong Predictors of Poor Outcome

• Bilateral absent pupillary reflexes OR absent pupillary + corneal reflexes OR absent N20 waves on SSEP.
• Mnemonic: "3 Absents" (Pupils, Corneas, N20).

Counseling Families During Early Post-Arrest Care

• Avoid discussing prognosis before 72 hours due to sedation/TTM confounders.
• Emphasize multimodal testing (exam, EEG, SSEP, imaging) and avoid early DNR orders.

Institutional Framework for Successful Hypothermia Protocols

• A comprehensive post-arrest program spanning the ED, ICU, and rehab, with protocols for cooling, hemodynamic stability, and neuroprognostication.

Prehospital Cooling

• Trials show no benefit, and transport must prioritize avoiding rewarming en route.
• Cooling should only begin at facilities equipped to maintain TTM.

Role of NSE in Prognostication

• Higher levels correlate with poor outcomes, but thresholds vary.
• Use only in combination with clinical/EEG/imaging data.

Duration of Therapeutic Hypothermia

• Maintain for 24 hours at 33°C.
• A 48-hour duration showed no added benefit.

Critical Factors for ICU Management During Cooling

• Avoid hypotension/hypoxia.
• Lighten sedation gradually during rewarming.
• Minimize sedation by 72 hours for neurologic evaluation.

TTM Trials

• Both 33°C vs. 36°C are equally safe, but 33°C has stronger biologic evidence for neuroprotection

Impact of Status Myoclonus on Prognosis

• Status myoclonus <48 hours post-ROSC is a moderate predictor of poor outcome when combined with EEG/imaging abnormalities.

Final Step in the Hypothermia Protocol

• Remove sedation by 72 hours for neurologic evaluation and involve neurology for prognostication.

Mnemonics

• COLD SALINE: Cooling Initiated, Oxygenation maintained, Labs monitored, Devices (temperature probes), Sedation/Paralytics, Avoid blankets, Line (IV access), Infuse 2L cold saline, Neurologic monitoring, EEG/SSEP.
• 72-HOUR RULE: Prognostication requires 72 hours post-rewarming for reliable signs.
• SSEP Timing: "TTM patients: Post-rewarm or Day 3; Others: Day 2."