Mannitol

Mannitol is a sugar alcohol (polyol) used as an osmotic diuretic.

• Pharmacologic class: Osmotic diuretic
• Does NOT cross intact BBB
• Freely filtered at glomerulus → not reabsorbed

Mechanism of Action 

1. Intravascular Osmotic Effect

• Increases plasma osmolality
• Pulls water from:
• Brain parenchyma → ↓ cerebral edema
• Intraocular fluid → ↓ IOP

2. Renal Effect

• Filtered in glomerulus → remains in tubule
• Creates osmotic gradient → prevents water reabsorption
• → Osmotic diuresis

 Effect on Brain 

Phase-wise effects:

1. Immediate (minutes)
• Plasma expansion → ↓ blood viscosity
• → Reflex cerebral vasoconstriction
• → ↓ cerebral blood volume → ↓ ICP

2. Delayed (15–30 min)

• Osmotic gradient → water shifts from brain → plasma
• → ↓ brain bulk → ↓ ICP

3. Rebound phenomenon 

• Occurs if BBB disrupted
• Mannitol enters brain → reverses gradient
• → Worsening cerebral edema

 Pharmacokinetics

Parameter	Detail
Onset	5–10 min
Peak	20–60 min
Duration	4–6 hr
Half-life	~1.5–2 hr (↑ in renal failure)
Excretion	Renal (unchanged)

 Indications 

 Neurocritical Care

• Raised ICP:
• Traumatic brain injury
• Intracranial Hemorrhage
• Brain tumors
• Impending herniation (emergency bolus)

 Ophthalmology

• Acute angle-closure glaucoma → ↓ IOP

  Renal / ICU

• Prevention of AKI (controversial, NOT routine now)
• Rhabdomyolysis (selected cases)

 Dose 

Raised ICP

• 0.25–1 g/kg IV bolus
• Repeat based on ICP / osmolality

Target Monitoring:

• Serum osmolality: <320 mOsm/kg
• Osmolar gap: <55 mOsm/kg

 Re-dosing 

Instead of fixed timing:

 Repeat 0.25–0.5 g/kg ONLY if:

• ICP still elevated (>20–22 mmHg)
• Clinical signs persist:
• Pupillary changes
• Low GCS
• CT worsening

 Minimum interval

• Usually 4–6 hours
• BUT depends on:
• Serum osmolality
• Urine output
• Hemodynamics

 Tapering strategy 

1. Increase dosing interval
• From 4 hourly → 6 hourly → 8 hourly

2. Reduce dose

• From 1 g/kg → 0.5 g/kg → 0.25 g/kg

3. Stop when:

• ICP stable
• Osmolality approaching 300–310
• Risk of AKI or hypovolemia

 4. When to STOP immediately

• Serum osmolality >320 mOsm/kg
• Osmolar gap >55
• AKI / rising creatinine
• Hypotension / hypovolemia
• Pulmonary edema

Hemodynamic Effects

• Initial:
• Plasma expansion → ↑ preload
• May cause transient hypertension
• Later:
• Diuresis → ↓ intravascular volume
• Risk → hypotension

 Adverse Effects

1. Volume-related

• Early: Fluid overload → pulmonary edema
• Late: Hypovolemia → hypotension

2. Electrolyte disturbances

• Hyponatremia (dilutional, early)
• Hypernatremia (late due to water loss)
• Hypokalemia / Hyperkalemia

3. Renal

• Osmotic nephrosis
• AKI (especially if repeated high doses)

4. CNS

• Rebound ICP ↑ (BBB disruption)

 Contraindications

• Anuria / severe renal failure
• Pulmonary edema / CHF
• Active intracranial bleeding (relative; except perioperative neurosurgery)
• Severe dehydration

 Monitoring 

• Serum osmolality (keep <320)
• Urine output
• Electrolytes
• Renal function
• ICP (if available)

 Mannitol vs Hypertonic Saline 

Feature	Mannitol	Hypertonic Saline
Mechanism	Osmotic diuresis	Osmotic + volume expansion
Volume status	Causes diuresis	Expands intravascular volume
BP	May ↓ later	Improves BP
ICP effect	Good	Often superior
Rebound ICP	Possible	Less common
Use in shock	Avoid	Preferred

 Guidelines (Neurocritical Care Society / TBI guidelines):

• Both acceptable
• Hypertonic saline increasingly preferred, especially in hypotension

 Clinical Pearls 

• Mannitol works only if BBB intact
• Avoid repeated doses → risk of accumulation + rebound ICP
• If serum osmolality >320 → STOP
• Prefer hypertonic saline in:
• Hypotension
• Renal dysfunction

 Special ICU Considerations

• Warm solution before use (crystallization common)
• Use inline filter
• Avoid in:
• ARDS
• Heart failure