# Ventilation and Supportive Care in Severe TBI — BTF 2016

## Ventilation Therapies

### Hyperventilation

- **Prolonged prophylactic hyperventilation** with PaCO2 of **25 mmHg or less is not recommended** (Level IIB).
- Hyperventilation is recommended only as a **temporizing measure** for the reduction of elevated ICP (Level III).
- **Hyperventilation should be avoided during the first 24 hours** after injury when cerebral blood flow (CBF) is often critically reduced (Level III).
- If hyperventilation is used, **jugular venous oxygen saturation (SjO2) or brain tissue oxygen partial pressure (BtpO2) monitoring** is recommended to monitor oxygen delivery (Level III).

### Mechanism and Rationale

- Hyperventilation reduces PaCO2, causing cerebral vasoconstriction, decreased cerebral blood volume (CBV), and consequently decreased ICP.
- Excessive vasoconstriction from hyperventilation can reduce CBF to ischemic levels, causing secondary brain injury.
- In the first 24 hours after severe TBI, CBF is already at its lowest point; further reduction through hyperventilation can be particularly harmful.

### Ventilation Targets by Clinical Scenario

| Clinical Scenario | PaCO2 Target | Evidence Level | Notes |
|-------------------|-------------|----------------|-------|
| **Routine management** | 35-40 mmHg (normocapnia) | Best practice | Standard of care |
| **Mild hyperventilation (temporizing)** | 30-35 mmHg | Level III | Brief periods for acute ICP elevation |
| **Aggressive hyperventilation (bridge)** | 25-30 mmHg | Level III | Only as bridge to definitive therapy (surgery, osmotherapy) |
| **Prophylactic hyperventilation** | **Not recommended** (PaCO2 <= 25 mmHg) | Level IIB | Associated with worse outcomes |

### Oxygenation

- Maintain PaO2 >= 60 mmHg (SpO2 >= 90%).
- Avoid hypoxia (PaO2 < 60 mmHg or SpO2 < 90%), which is independently associated with increased mortality and worse neurological outcomes in severe TBI.
- The guideline does not provide a specific recommendation regarding the routine use of high inspired oxygen concentrations or PaO2 targets beyond avoiding hypoxia.

## Anesthetics, Analgesics, and Sedatives

### Propofol

- Propofol is recommended for the **control of ICP** (Level IIB).
- Propofol is **not recommended for improvement in mortality or 6-month outcomes** (Level IIB).
- **High-dose propofol can produce significant morbidity** (propofol infusion syndrome).
  - Risk factors: doses > 5 mg/kg/hr, infusion duration > 48 hours.
  - Monitor: creatine kinase, lactate, triglycerides, acid-base status.

### Barbiturates

- **Prophylactic barbiturates** to induce burst suppression as prophylaxis against intracranial hypertension **are not recommended** (Level IIB).
- **High-dose barbiturate administration** is recommended to control **elevated ICP refractory to maximum standard medical and surgical treatment** (Level IIB).
  - Pentobarbital protocol:
    - Loading dose: **10 mg/kg IV over 30 minutes**
    - Then: **5 mg/kg/hr for 3 hours**
    - Maintenance: **1-3 mg/kg/hr**
    - Target: EEG burst suppression
  - **Hemodynamic stability is essential** before and during barbiturate therapy.
  - Vasopressor support is frequently required.
  - Continuous EEG monitoring is required to titrate to burst suppression.

### Sedation/Analgesia Summary

| Agent | Use | Considerations |
|-------|-----|---------------|
| **Propofol** | ICP control, sedation | Risk of PRIS at high doses; monitor CK, lactate |
| **Pentobarbital** | Refractory ICP only | Cardiovascular depression; requires vasopressor support |
| **Midazolam** | Sedation (alternative) | No specific BTF recommendation; commonly used |
| **Fentanyl** | Analgesia | Commonly used; may blunt ICP spikes from noxious stimuli |
| **Morphine** | Analgesia | May increase ICP transiently; use with caution |

## Prophylactic Hypothermia

- Early (within 2.5 hours), short-term (48 hours post-injury), **prophylactic hypothermia is not recommended** to improve outcomes in patients with diffuse injury (Level IIB).
- This refers specifically to prophylactic whole-body hypothermia as a neuroprotective strategy, not targeted temperature management for fever control or refractory ICP.

## Steroids

- The use of steroids is **not recommended** for improving outcome or reducing ICP (Level I).
  - This is the only Level I recommendation in the entire 4th Edition.
  - Based on the **CRASH trial**: high-dose methylprednisolone increased mortality (21.1% vs. 17.9%) in severe TBI.
  - **High-dose methylprednisolone is contraindicated** in severe TBI.

## Infection Prophylaxis

### Early Tracheostomy

- Early tracheostomy is recommended to reduce mechanical ventilation days when the overall benefit is felt to outweigh the complications associated with the procedure (Level IIB).
  - "Early" is generally defined as within 7-10 days of intubation, though the optimal timing is not precisely defined.
  - May reduce ICU length of stay and ventilator-associated pneumonia rates.

### Antimicrobial-Impregnated Catheters

- **Antimicrobial-impregnated catheters** may be considered to prevent catheter-related infections during external ventricular drainage (Level III).
  - Includes antibiotic- or silver-impregnated EVD catheters.
  - Systemic antibiotic prophylaxis for EVD placement alone is not specifically recommended.

## DVT Prophylaxis

- **LMWH or low-dose UFH** may be used in combination with **mechanical prophylaxis** (Level III).
- In addition to compression stockings, pharmacologic prophylaxis may be considered if the brain injury is stable and the benefit is considered to outweigh the risk of increased intracranial hemorrhage (Level III).
- There is insufficient evidence to support recommendations regarding the preferred agent, dose, or timing of pharmacologic prophylaxis for DVT (Level III).

## Nutrition

- Feeding patients to attain **basal caloric replacement at least by the fifth day and at most by the seventh day** post-injury is recommended to decrease mortality (Level IIA).
- **Transgastric jejunal feeding** is recommended to reduce the incidence of ventilator-associated pneumonia (Level IIB).

## Supportive Care Algorithm

```
Severe TBI patient admitted to neurocritical care
  --> Ventilation:
      --> Maintain PaCO2 35-40 mmHg (normocapnia)
      --> Avoid hypoxia: PaO2 >= 60 mmHg, SpO2 >= 90%
      --> DO NOT use prophylactic hyperventilation (PaCO2 <= 25 mmHg) [Level IIB]
      --> Avoid hyperventilation during first 24 hours [Level III]
      --> If brief hyperventilation needed: PaCO2 30-35 mmHg, monitor SjO2/BtpO2
  --> Sedation/Analgesia:
      --> Propofol for ICP control [Level IIB]
      --> If refractory ICP: pentobarbital infusion targeting burst suppression [Level IIB]
      --> DO NOT use prophylactic barbiturate coma [Level IIB]
  --> Steroids: NEVER use in severe TBI [Level I]
  --> Temperature: Maintain normothermia; prophylactic hypothermia NOT recommended [Level IIB]
  --> Seizure prophylaxis: Phenytoin for 7 days [Level IIA]; stop after day 7
  --> Nutrition: Achieve basal caloric needs by day 5-7 [Level IIA]
      --> Transgastric jejunal feeding preferred [Level IIB]
  --> DVT prophylaxis: Mechanical immediately; pharmacologic when stable [Level III]
  --> Tracheostomy: Consider early tracheostomy [Level IIB]
  --> EVD: Use antimicrobial-impregnated catheters [Level III]
```

## Summary of All Recommendation Levels

| Recommendation Level | Count | Key Recommendations |
|---------------------|-------|-------------------|
| **Level I** | 1 | Steroids are not recommended (CRASH trial) |
| **Level IIA** | 7 | Seizure prophylaxis (phenytoin 7 days), nutrition (basal calories by day 5-7), DC size (>= 12 x 15 cm), against bifrontal DC for diffuse injury |
| **Level IIB** | 10 | ICP threshold 22 mmHg, CPP 60-70 mmHg, propofol for ICP, barbiturates for refractory ICP, against prophylactic hypothermia, against prophylactic hyperventilation, against prophylactic barbiturates, early tracheostomy |
| **Level III** | 10 | CSF drainage, advanced monitoring (SjO2/BtpO2), mannitol dosing, DVT prophylaxis, antimicrobial catheters |

## Limitations

- The ventilation recommendations are based largely on physiological principles and limited clinical evidence. No RCT has compared specific PaCO2 targets in severe TBI.
- Sedation recommendations are limited. The guideline does not provide specific recommendations for commonly used agents such as midazolam, dexmedetomidine, or ketamine.
- The prophylactic hypothermia recommendation against use is based primarily on the Eurotherm trial. Targeted temperature management for refractory ICP remains a clinical option not explicitly addressed.
- Nutrition recommendations do not specify optimal macronutrient composition, protein targets, or the role of indirect calorimetry.
- DVT prophylaxis timing and agent selection remain poorly defined, reflecting the limited evidence and the tension between VTE prevention and hemorrhagic risk in TBI.
- The guideline predates several important trials and developments in TBI management, including the RESCUEicp trial results (2016, published after guideline finalization), and practice patterns have evolved since publication.
