# Cerebral Perfusion and Hyperosmolar Therapy in Severe TBI — BTF 2016

## Hyperosmolar Therapy

### Mannitol

- Mannitol is effective for control of raised ICP at doses of **0.25 g/kg to 1 g/kg body weight** (Level II).
  - Administered as IV bolus over 15-20 minutes.
  - Repeat doses may be given every 4-6 hours as needed.
  - Each dose should be titrated to the ICP response.
- **Arterial hypotension (SBP < 90 mmHg) should be avoided** during mannitol administration (Level III).
  - Mannitol can cause osmotic diuresis leading to hypovolemia and hypotension.
  - Ensure adequate intravascular volume before and during mannitol therapy.
- **Restrict mannitol use prior to ICP monitoring** to patients with signs of transtentorial herniation or progressive neurological deterioration not attributable to extracranial causes (Level III).
  - Once ICP monitoring is established, mannitol should be titrated to ICP response.

### Mannitol Monitoring Parameters

| Parameter | Target / Limit |
|-----------|---------------|
| **Serum osmolality** | < 320 mOsm/L (some protocols allow up to 360 mOsm/L) |
| **Osmolar gap** | < 20 mOsm/L |
| **Serum sodium** | Monitor for hypernatremia |
| **Systolic blood pressure** | Maintain >= 90 mmHg |
| **Volume status** | Replace urinary losses to avoid hypovolemia |

### Hypertonic Saline

- Although hypertonic saline may lower ICP, there was insufficient evidence about effects on clinical outcomes to support a specific recommendation, or to support the use of any specific hyperosmolar agent, for patients with severe TBI.
- Concentrations used in clinical practice range from 3% to 23.4%:
  - **3% NaCl:** 150-250 mL IV bolus or continuous infusion at 0.5-2 mL/kg/hr
  - **23.4% NaCl:** 30 mL IV bolus via central venous catheter for acute herniation
- Serum sodium target generally 145-155 mEq/L (institution-dependent; not specified in guideline).

### Hyperosmolar Therapy Decision Algorithm

```
ICP > 22 mmHg despite first-line measures (HOB elevation, sedation, CSF drainage)
  --> Is ICP monitoring in place?
      --> YES: Administer mannitol 0.25-1 g/kg IV bolus
          --> Check SBP: must be >= 90 mmHg
          --> Monitor serum osmolality: hold if >= 320 mOsm/L
          --> Reassess ICP in 15-30 minutes
          --> If ICP remains elevated: may repeat mannitol q4-6h OR
              consider hypertonic saline
      --> NO: Signs of transtentorial herniation or progressive neurological deterioration?
          --> YES: Administer mannitol 0.25-1 g/kg IV bolus [Level III]
          --> NO: Establish ICP monitoring before initiating hyperosmolar therapy
  --> Refractory ICP elevation despite hyperosmolar therapy?
      --> Consider barbiturate coma, decompressive craniectomy, or other second-tier therapies
```

## Hyperventilation

### General Recommendations

- **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.
- **Hyperventilation should be avoided during the first 24 hours after injury** when cerebral blood flow (CBF) is often critically reduced (Level III).

### Mechanism and Risks

- Hyperventilation reduces ICP by inducing cerebral vasoconstriction, which decreases cerebral blood volume (CBV).
- Excessive or prolonged hyperventilation can cause cerebral ischemia by reducing CBF below critical thresholds.
- If hyperventilation is used, **SjO2 or BtpO2 monitoring is recommended** to monitor oxygen delivery and detect cerebral ischemia (Level III).

### Hyperventilation Targets

| Clinical Scenario | PaCO2 Target | Duration | Monitoring |
|-------------------|-------------|----------|------------|
| **General management** | 35-40 mmHg (normocapnia) | Ongoing | Standard |
| **Acute ICP crisis (temporizing)** | 30-35 mmHg (mild hyperventilation) | Brief periods only | SjO2 or BtpO2 recommended |
| **Acute herniation (bridge to definitive therapy)** | 25-30 mmHg (aggressive hyperventilation) | Minutes to hours | SjO2 or BtpO2 mandatory |
| **Prophylactic hyperventilation** | **Not recommended (PaCO2 <= 25 mmHg)** | -- | -- |

## Cerebrospinal Fluid (CSF) Drainage

### EVD-Based CSF Drainage

- An **external ventricular drain (EVD) system zeroed at the midbrain** with **continuous drainage of CSF** may be considered to lower ICP burden more effectively than intermittent use (Level III).
- Use of CSF drainage to lower ICP in patients with an initial **GCS < 6 during the first 12 hours after injury** may be considered (Level III).

### Practical Considerations

- EVD placement allows both ICP monitoring and therapeutic CSF drainage.
- **Antimicrobial-impregnated catheters** may be considered to prevent catheter-related infections during external ventricular drainage (Level III).
- CSF drainage is typically a first-line intervention before escalating to hyperosmolar therapy, assuming an EVD is already in place.

## Tiered Approach to ICP Management

```
Tier 1 (First-Line):
  --> Head of bed elevation to 30 degrees, midline head position
  --> Adequate sedation and analgesia
  --> CSF drainage via EVD (if in place)
  --> Ensure normothermia
  --> Treat systemic factors (pain, agitation, fever, seizures)

Tier 2 (Second-Line):
  --> Hyperosmolar therapy: mannitol 0.25-1 g/kg IV bolus
  --> Hypertonic saline (institution-dependent dosing)
  --> Mild hyperventilation (PaCO2 30-35 mmHg) -- temporizing only

Tier 3 (Refractory ICP):
  --> High-dose barbiturates (pentobarbital) for burst suppression
  --> Decompressive craniectomy
  --> Aggressive hyperventilation (PaCO2 25-30 mmHg) -- temporizing bridge
  --> Therapeutic hypothermia (limited evidence)
```

## Limitations

- The hyperosmolar therapy recommendations for mannitol are carried forward from prior guideline editions. There was insufficient new evidence to support updated recommendations, and no evidence to support one hyperosmolar agent (mannitol vs. hypertonic saline) over another.
- The optimal dose, concentration, and regimen for hypertonic saline remain undefined by evidence-based guidelines.
- Hyperventilation targets are based on physiological rationale and limited clinical evidence. The risk of cerebral ischemia from hyperventilation makes it a temporizing measure only, and advanced cerebral monitoring (SjO2 or BtpO2) is recommended but not universally available.
- CSF drainage recommendations are new to the 4th Edition and are based on limited evidence (Level III only). The comparison of continuous vs. intermittent drainage is supported by a single study.
