# Surgical and Medical Management of Severe TBI — BTF 2016

## Decompressive Craniectomy

### Bifrontal Decompressive Craniectomy

- Bifrontal decompressive craniectomy (DC) is **not recommended** to improve outcomes as measured by the Glasgow Outcome Scale-Extended (GOS-E) score at 6 months post-injury in severe TBI patients with **diffuse injury** (without mass lesions) and with **ICP elevation to values > 20 mmHg for more than 15 minutes within a 1-hour period** that are refractory to first-tier therapies (Level IIA).
  - Based on findings from the **DECRA trial** (2011), which showed that early bifrontal DC in patients with diffuse injury and refractory ICP elevation resulted in lower ICP but worse functional outcomes at 6 months compared with standard care.

### Large Frontotemporoparietal Decompressive Craniectomy

- A **large frontotemporoparietal DC (not less than 12 x 15 cm or 15 cm diameter)** is recommended over a small frontotemporoparietal DC for reduced mortality and improved neurologic outcomes in patients with severe TBI (Level IIA).
  - When DC is performed, bone flap size matters. Small craniectomies are less effective at reducing ICP and are associated with higher rates of brain herniation through the bone defect.

### Late Decompressive Craniectomy for Refractory ICP

- A **large frontotemporoparietal DC** (not less than 12 x 15 cm or 15 cm diameter) is recommended over a small frontotemporoparietal DC for reducing mortality and improving neurologic outcomes (Level IIA).
  - Note: The 2020 update to these guidelines (based on the **RESCUEicp trial**) subsequently added that DC for refractory late ICP elevation (> 25 mmHg for 1-12 hours) reduces mortality but increases the proportion of patients surviving with severe disability.

## 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).
  - Based on the Eurotherm trial and earlier negative studies.
  - This recommendation applies specifically to prophylactic hypothermia initiated as a neuroprotective strategy, not to targeted temperature management for refractory ICP elevation.

## Anesthetics, Analgesics, and Sedatives

### Propofol

- Although propofol is recommended for the **control of ICP**, it is **not recommended for improvement in mortality or 6-month outcomes** (Level IIB).
  - Propofol reduces cerebral metabolic rate of oxygen (CMRO2) and ICP.
  - **High-dose propofol can produce significant morbidity**, including propofol infusion syndrome (PRIS).
  - **Propofol infusion syndrome** presents with metabolic acidosis, rhabdomyolysis, hyperkalemia, cardiac failure, and renal failure. Risk increases with doses > 5 mg/kg/hr or infusion durations > 48 hours.
  - Monitor creatine kinase, lactate, and triglycerides during prolonged propofol infusion.

### Barbiturates

- **Administration of barbiturates to induce burst suppression measured by EEG as prophylaxis** against the development of intracranial hypertension **is 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** loading dose: 10 mg/kg IV over 30 minutes, then 5 mg/kg/hr for 3 hours, then maintenance at 1-3 mg/kg/hr.
  - Target: EEG burst suppression (bursts of 3-5 seconds between suppression periods).
  - **Hemodynamic stability is essential** before and during barbiturate therapy. Barbiturates cause significant cardiovascular depression and hypotension.
  - Requires continuous arterial blood pressure monitoring and often vasopressor support.

## Steroids

- The use of steroids is **not recommended** for improving outcome or reducing ICP in patients with severe TBI (Level I).
  - This is the **only Level I recommendation** in the entire 4th Edition of the BTF Guidelines.
  - Based on the **CRASH trial** (2004): high-dose methylprednisolone (2 g loading dose, then 0.4 g/hr for 48 hours) was associated with **increased mortality** at 2 weeks (risk of death 21.1% vs. 17.9%) and at 6 months in patients with severe TBI.
  - **High-dose methylprednisolone is specifically contraindicated** in severe TBI.

## Seizure Prophylaxis

### Early Post-Traumatic Seizures (Within 7 Days)

- Prophylactic treatment with **phenytoin** is recommended to decrease the incidence of **early post-traumatic seizures** (within 7 days of injury) (Level IIA).
  - Phenytoin loading dose: 15-20 mg/kg IV at a rate not exceeding 50 mg/min.
  - Maintenance: 100 mg IV/PO every 8 hours (target serum level 10-20 mcg/mL).
  - Levetiracetam is increasingly used as an alternative due to fewer drug interactions and no need for serum monitoring, though the BTF 2016 guideline specifically references the evidence base for phenytoin.

### Late Post-Traumatic Seizures (After 7 Days)

- Prophylactic use of phenytoin or valproate is **not recommended** for preventing **late post-traumatic seizures** (Level IIA).
  - The Temkin et al. landmark trial demonstrated that phenytoin reduced early seizures but had no effect on late seizure rates.

### Risk Factors for Post-Traumatic Seizures

- GCS < 10
- Cortical contusion
- Depressed skull fracture
- Subdural hematoma
- Epidural hematoma
- Intracerebral hematoma
- Penetrating head wound
- Seizure within 24 hours of injury

> **OpenMedicine Calculator:** `calculate_gcs` -- available via MCP for automated GCS scoring to identify patients at higher seizure risk (GCS < 10).

## Nutrition

### Timing

- 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).
  - Early enteral nutrition (within 24-48 hours) is preferred when feasible, but the critical mortality-reducing threshold is achieving basal caloric needs by day 5-7.

### Route

- **Transgastric jejunal feeding** is recommended to reduce the incidence of ventilator-associated pneumonia (VAP) (Level IIB).
  - Jejunal feeding bypasses gastroparesis, which is common in severe TBI patients.
  - If transgastric jejunal access is not feasible, gastric feeding with prokinetic agents (e.g., metoclopramide 10 mg IV every 6 hours) may be used with aspiration precautions.

## Deep Vein Thrombosis (DVT) Prophylaxis

### Mechanical Prophylaxis

- **Low-molecular-weight heparin (LMWH)** or **low-dose unfractionated heparin (UFH)** may be used in combination with mechanical prophylaxis (Level III).
  - There is insufficient evidence to support recommendations regarding the preferred agent, dose, or timing of pharmacologic prophylaxis for DVT (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).
  - "Stable brain injury" typically means: stable or improving ICP, no evidence of hemorrhagic progression on repeat imaging, and at least 24-48 hours post-injury or post-craniotomy.

### Practical DVT Prophylaxis Approach

```
Day 0 (Admission):
  --> Apply intermittent pneumatic compression (IPC) devices
  --> Apply graduated compression stockings
Day 1-2:
  --> Assess hemorrhagic stability: repeat CT head, stable ICP trend
  --> If stable: consider initiating pharmacologic prophylaxis
      --> LMWH (e.g., enoxaparin 40 mg SC daily) OR
      --> UFH 5,000 units SC every 8-12 hours
  --> If hemorrhage expanding or ICP unstable: delay pharmacologic prophylaxis, continue mechanical only
```

## Surgical and Medical Management Decision Algorithm

```
Severe TBI patient (GCS 3-8)
  --> Elevated ICP (> 22 mmHg) refractory to Tier 1-2 measures?
      --> Is this diffuse injury with early refractory ICP?
          --> Bifrontal DC is NOT recommended [Level IIA] (based on DECRA)
      --> Is this focal or late refractory ICP?
          --> Consider large frontotemporoparietal DC (>= 12 x 15 cm) [Level IIA]
  --> Sedation for ICP control needed?
      --> Propofol: effective for ICP but not for mortality improvement [Level IIB]
      --> Watch for propofol infusion syndrome at high doses
  --> Refractory ICP after all Tier 1-2 therapies?
      --> High-dose barbiturates (pentobarbital) targeting EEG burst suppression [Level IIB]
      --> Ensure hemodynamic stability first
  --> Do NOT use prophylactic barbiturates to prevent ICP elevation [Level IIB]
  --> Do NOT use steroids [Level I] -- CRASH trial: increased mortality
  --> Seizure prophylaxis: phenytoin for first 7 days only [Level IIA]
  --> Nutrition: achieve basal caloric replacement by day 5-7 [Level IIA]
      --> Transgastric jejunal feeding preferred [Level IIB]
  --> DVT prophylaxis: mechanical immediately; pharmacologic when brain injury stable [Level III]
  --> Prophylactic hypothermia: NOT recommended for diffuse injury [Level IIB]
```

## Limitations

- The DECRA trial informed the recommendation against bifrontal DC for early refractory ICP in diffuse injury, but its applicability to all clinical scenarios of refractory ICP has been debated. The RESCUEicp trial (published after the 4th Edition) provides additional data on late DC that was incorporated in the 2020 update.
- Seizure prophylaxis evidence is primarily based on phenytoin studies from the 1990s. Newer agents (levetiracetam, lacosamide) are widely used in practice but were not supported by sufficient evidence at the time of the 4th Edition to receive a specific recommendation.
- The Level I recommendation against steroids is the strongest recommendation in the entire guideline and is supported by the CRASH trial, one of the largest RCTs in TBI.
- Nutrition recommendations do not specify exact caloric formulas. "Basal caloric replacement" is used as the target, and the guideline does not address optimal protein intake or the use of indirect calorimetry.
- DVT prophylaxis recommendations are all Level III, reflecting the substantial uncertainty about optimal timing and agents in the TBI population, where the risk of hemorrhagic progression must be balanced against VTE prevention.
