Targeted temperature management after cardiac arrest

Since TTM2 the emphasis has shifted from cooling to fever prevention. Lowering the body temperature to 33 °C has not been shown to improve survival or the neurological outcome compared with keeping the patient normothermic — but fever after cardiac arrest is harmful, it often arises spontaneously, and it must be actively prevented. The treatment has therefore not been abandoned, only redefined: continuous core temperature measurement and a target value that must never be exceeded, during the first 72 hours for as long as the patient remains unconscious.

The evidence

The current ERC and ESICM recommendation is continuous core temperature measurement and the active prevention of fever — defined as a temperature above about 37.7–37.8 °C — for at least 72 hours in patients who remain unconscious. The evidence is insufficient to recommend for or against active cooling to 32–36 °C. The HYPERION result means that active hypothermia is still used in some units with a non-shockable rhythm; this is the clearest area in which Swedish practice differs between hospitals, and the local care programme applies.

In practice the cooling device is set to a target of around 37.0–37.5 °C, that is, with a margin below the fever threshold, since a device set at the fever threshold is always behind.

Indications

• A patient who remains unconscious (with no meaningful response to speech) after the return of spontaneous circulation, whether the arrest occurred in or out of hospital and whatever the initial rhythm.
• It applies to both shockable and non-shockable initial rhythms.
• It is started as soon as possible after ROSC and continued for at least 72 hours for as long as the unconsciousness persists.

An awake patient who obeys commands after ROSC needs no targeted temperature management, but must still be kept free of fever.

Contraindications and caution

Active fever prevention has in practice no absolute contraindications. With active cooling to hypothermia, caution applies in:

• Ongoing uncontrolled bleeding or marked coagulopathy.
• Severe sepsis and septic shock.
• Already marked hypothermia from another cause — warm the patient instead.
• Refractory shock in which the bradycardia and reduced contractility of hypothermia are not tolerated.
• A decision to withhold further life-sustaining treatment.

Preparation and equipment

• Continuous core temperature measurement. An oesophageal probe or a urinary catheter with a temperature sensor are the first choice; rectal or intravascular measurement also works. Axillary, oral and tympanic measurement are not adequate — they lag behind and miss the fever.
• Equipment for temperature control: automated surface cooling with gel pads or a blanket, or alternatively an intravascular cooling catheter. Both are controlled by feedback from the core temperature.
• Simple measures that are often enough: undressing the patient, lowering the room temperature, a fan, paracetamol, cold infusions.
• A ventilator, an arterial line, a central venous catheter, ECG monitoring, blood gases.
• Drugs for sedation, analgesia and control of shivering.

Procedure

1. Start temperature management early — within the first hour after ROSC, in parallel with coronary angiography, the search for the cause and the rest of the intensive care.
2. Insert the core temperature probe and connect it to the feedback loop of the cooling device. Without continuous measurement the whole treatment is blind.
3. Set the target temperature according to the local care programme, in practice around 37.0–37.5 °C for fever prevention or 33 °C for active hypothermia according to local practice.
4. Maintenance phase: keep the temperature within the target range for at least 72 hours for as long as the patient is unconscious, and avoid swings. With active hypothermia, 33 °C is usually maintained for 24 hours.
5. Sedate and provide analgesia. Deep sedation is recommended for the first 24 hours or so, in practice with propofol and a short-acting opioid, so that the patient does not shiver and the oxygen consumption is kept down. With hypothermia, the elimination of most sedatives and neuromuscular blockers is markedly prolonged — use lower doses and expect a slower awakening.
6. Treat shivering actively. It is the commonest reason for the target temperature not being reached, and it increases oxygen consumption, intracranial pressure and metabolic stress. Escalate in this order: warm the skin with a blanket over the hands, feet and face while the core temperature is maintained, deepen the sedation, give magnesium or clonidine, and add a neuromuscular blocker as a last resort. Neuromuscular blockers mask seizures — add EEG monitoring.
7. Controlled rewarming. After active hypothermia the patient is rewarmed slowly, at no more than 0.25–0.5 °C per hour, and the cooling device is kept in feedback mode until 72 hours have passed. After rewarming, fever prevention continues.
8. Rebound hyperthermia is common once the device is disconnected. Continue to measure the temperature continuously and treat fever throughout the stay in intensive care, not just for the first 72 hours.
9. Attend at the same time to the other intensive care targets: normoxia and normocapnia, a mean arterial pressure according to the local target, a blood glucose without hypoglycaemia, and actively treated seizures.
10. Monitor the potassium, magnesium, phosphate and blood glucose at least every four to six hours during cooling and rewarming. Cooling drives potassium into the cells and rewarming drives it out again.

{
  "$schema": "https://vega.github.io/schema/vega-lite/v5.json",
  "description": "Target temperature over time after cardiac arrest with two strategies",
  "width": "container",
  "height": 260,
  "data": {
    "values": [
      {"t": 0, "temp": 36.8, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 2, "temp": 37.2, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 6, "temp": 37.3, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 12, "temp": 37.3, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 24, "temp": 37.4, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 36, "temp": 37.3, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 48, "temp": 37.4, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 60, "temp": 37.3, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 72, "temp": 37.4, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 84, "temp": 37.5, "strategi": "Active fever prevention (target about 37.5 °C)"},
      {"t": 96, "temp": 37.6, "strategi": "Active fever prevention (target about 37.5 °C)"},

      {"t": 0, "temp": 36.8, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 1, "temp": 35.6, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 2, "temp": 34.6, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 4, "temp": 33.2, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 6, "temp": 33.0, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 12, "temp": 33.0, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 24, "temp": 33.0, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 32, "temp": 35.0, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 40, "temp": 37.0, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 48, "temp": 37.2, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 60, "temp": 37.3, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 72, "temp": 37.4, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 84, "temp": 37.5, "strategi": "Hypothermia 33 °C for 24 hours"},
      {"t": 96, "temp": 37.6, "strategi": "Hypothermia 33 °C for 24 hours"}
    ]
  },
  "layer": [
    {
      "mark": {"type": "rule", "strokeDash": [6, 4], "color": "#f0668a"},
      "encoding": {"y": {"datum": 37.8}}
    },
    {
      "mark": {"type": "text", "align": "left", "dx": 6, "dy": -8, "color": "#f0668a", "fontSize": 11},
      "encoding": {
        "y": {"datum": 37.8},
        "x": {"datum": 0},
        "text": {"value": "Fever threshold 37.8 °C — must not be exceeded"}
      }
    },
    {
      "mark": {"type": "rule", "strokeDash": [4, 4], "color": "#9a9ea8"},
      "encoding": {"x": {"datum": 72}}
    },
    {
      "mark": {"type": "line", "point": true, "interpolate": "monotone"},
      "encoding": {
        "x": {"field": "t", "type": "quantitative", "title": "Hours after the return of spontaneous circulation", "scale": {"domain": [0, 96]}},
        "y": {"field": "temp", "type": "quantitative", "title": "Core temperature (°C)", "scale": {"domain": [32, 39]}},
        "color": {"field": "strategi", "type": "nominal", "title": "Strategy", "scale": {"range": ["#2451c9", "#3ec9a7"]}}
      }
    }
  ]
}

The figure shows the intended temperature courses, not measured patient data. The dashed vertical line marks 72 hours, the earliest point at which formal temperature management is stopped. With the hypothermia strategy, rewarming takes place at no more than 0.25–0.5 °C per hour and then passes into fever prevention for the remainder of the 72-hour period.

flowchart TD
  A[ROSC with persisting unconsciousness] --> B[Core temperature probe: oesophagus or bladder<br/>Continuous measurement]
  B --> C[Sedation and analgesia, ventilation<br/>Parallel search for the cause and coronary angiography]
  C --> D{The local care programme}
  D -- Fever prevention --> E[Target temperature about 37.0–37.5 °C]
  D -- Hypothermia with a non-shockable rhythm --> F[Cool to 33 °C, maintain for 24 hours]
  F --> G[Controlled rewarming<br/>no more than 0.25–0.5 °C per hour]
  G --> E
  E --> H[Maintain the target temperature for at least 72 hours<br/>for as long as the patient is unconscious]
  H --> I[Disconnect the device but continue to measure<br/>Treat rebound fever]
  I --> J[Neurological prognostication no earlier than 72 hours after the arrest]

Neurological prognostication

Prognostication must not begin until at least 72 hours after the arrest, and only once confounders have been excluded: residual sedation and neuromuscular blockade, hypothermia, marked hypotension, hypoglycaemia, marked electrolyte or acid–base disturbance, sepsis and ongoing seizures. With hypothermia and organ failure, sedatives and neuromuscular blockers can persist long after the infusion has been stopped, and prognostication is then postponed.

The assessment must be multimodal — no single modality may form the basis for withdrawing treatment:

• Clinical neurological examination: the pupillary reaction, the corneal reflex, the motor response.
• Status myoclonus within 48 hours indicates a poor prognosis; later, isolated myoclonus does not, and patients with it can wake.
• SSEP: bilateral absence of the cortical N20 responses with preserved peripheral responses.
• EEG no earlier than 24 hours; a malignant pattern such as burst suppression or a suppressed background without reactivity.
• Serum NSE, rising or markedly raised values at 48–72 hours; a value of at least 60 µg/L has been used as a guide. Haemolysis gives falsely high values.
• CT of the brain urgently to exclude another cause, and MRI of the brain after 2–5 days where uncertainty persists.

When in doubt: wait and re-examine. Late awakenings after a week or more do occur, and the consequence of a premature conclusion is final.

Complications

Aftercare and follow-up

• Continue to measure the temperature and treat fever throughout the intensive care stay, not just for the first 72 hours.
• Wake the patient from sedation only once the temperature target has been completed and the organ failure has stabilised; document the timing and the doses ahead of prognostication.
• Continued cardiological investigation of the cause of the arrest: coronary angiography, echocardiography, arrhythmia assessment, and consideration of an ICD.
• Structured follow-up of cognitive and emotional function within a few months. Fatigue, memory difficulties, impaired executive function, anxiety and depression are common even in patients who appear unaffected at discharge.
• Neurological function is assessed with the Cerebral Performance Category or the modified Rankin scale at discharge and at follow-up after three to six months.
• Offer support to relatives too, who have often witnessed the arrest.

Common pitfalls

• Believing that TTM2 meant that temperature management has been abandoned. Fever prevention remains recommended for at least 72 hours.
• Measuring the temperature in the axilla, the mouth or the ear. A core temperature is required, and it must be measured continuously.
• Setting the device at the fever threshold instead of with a margin below it.
• Disconnecting the device at 72 hours and stopping measurement. Rebound hyperthermia is common.
• Not treating shivering, or going straight to a neuromuscular blocker without first warming the skin and deepening the sedation.
• Giving a neuromuscular blocker without EEG monitoring and thereby missing ongoing seizures.
• Rewarming too quickly after active hypothermia; no more than 0.25–0.5 °C per hour.
• Prognosticating too early, before 72 hours or before sedatives and neuromuscular blockers have been eliminated.
• Making a decision on a single modality — particularly on an isolated NSE value or on an EEG alone.
• Forgetting that the potassium rises during rewarming, and therefore replacing it too generously at the end of the cooling phase.