I2i / 15A10: Compare and contrast the pharmacology of mannitol and hypertonic saline

15A10: Exam Report

Compare and contrast the pharmacology of mannitol and hypertonic saline.

8% of candidates passed this question.

A structured approach is important and a table worked best for most candidates, although a few attempted this in free text. Despite attempting a structured answer very few candidates provided information in regards to preparation, dose, monitoring of osmolarity, adverse effects or contraindications. Understanding of the action of these drugs was expected and factual inaccuracies were common with many candidates suggesting hypertonic saline acts as an osmotic diuretic. Better answers mentioned other potential mechanisms of action of mannitol. Many candidates failed to appreciate the impact on raised intracranial pressure.

I2i / 15A10: Compare and contrast the pharmacology of mannitol and hypertonic saline

Mannitol

3% NaCl

Chemical

Mannitol

Osmotic diuretic

3% NaCl

A hypertonic crystalloid solution

Use

Mannitol

  1. ↓ICP
  2. Diuresis

3% NaCl

  1. ↓ICP
  2. Hyponatraemia <120mmol/L
  3. Large Na loss (ie cerebral salt wasting)

Presentation

Mannitol

100g in 1000mL or 500mL (10%, 20%)

Sterile solutions

10% = 596 mOsm/kg

20% = 1192 mOsm/kg

Dose 0.25-1.5g/kg

3% NaCl

Sterile solution of

NaCl MW = 58.4mg

3% NaCl = 30g/L

513mmol Na/L

513mmol Cl/L

Osmolarity 1026mOsm/L

Calculated osmolality 900mOsm/L

pH 5-8

Route

Mannitol

IV

3% NaCl

CVC

MoA

Mannitol

  • 6 carbon sugar
  • Small molecular weight substance
  • VD 34L → confined to extracellular space, cannot cross BBB
  • Freely filtered by glomerulus
  • Minimally reabsorbed
  • Exerts osmotic force → diuresis

3% NaCl

↑Na in ECF

Effects

Mannitol

Osmotic effects (due to hypertonicity)

  • Intracelular dehydration
  • Immediate plasma expansion (except brain ECF)
  • Haemodilution
  • Osmotic Diuresis

Non-Osmotic effects

  • Decreased blood viscocity
  • Free radical scavenging
  • CVS effects from initial rapid plasma expansion (HF, APO, HTN)

3% NaCl

TBW

Before Infusion

42L

After 1L 3%NaCL

+1L = 43L

ECF Solute

Before Infusion

290mOsm x 19L = 5510mOsm

After 1L 3%NaCL

+900mOsm = 6410 mOsm

ICF Solute

Before Infusion

290mOsm x 23 = 6670mOsm

After 1L 3%NaCL

Unchanged bc Na in ECF         = 6670mOsm

Final Osmolality

Before Infusion

ICF + ECF

5510 + 6670

= 12,180 in 42L

= 290mOsm/L

After 1L 3%NaCL

ICF + ECF

6670 + 6410

= 13080 in 43L

= 304mOsm/L

ECF Volume

Before Infusion

19L

After 1L 3%NaCL

6410/304 = 21.1L

ICF Volume

Before Infusion

23L

After 1L 3%NaCL

6670/304 = 21.9L

↑­tonicity = 304mOsm/L

­↑volume ECF = 21.1L → 25% intravascular (500ml)

↓volume ICF = 21.9L

­↑omsolality = 5% = activation of osmoreceptors (threshold 2%) = ↑ADH

­↑volume = 10% = activation of volume receptors = ↓ADH

Monitoring

Mannitol

Osmolar gap

3% NaCl

Plasma Na

Advantages

Mannitol

Cheap

Easy calculation by body weight

Rapid effect

Initial volume expansion

3% NaCl

Cheap

Very rapid effect

Equipotent to mannitol for ICP

Less potential for hypovoalemia cf mannitol

Some intrinsic anti-inflammatory effect

Easier to monitor

A/E

Mannitol

Fluid & electrolyte imbalance – Hypernatraemia

Metabolic acidosis (SID)

HF

Pulmonary congestion

Hypovolaemia

Hypotension

Thrombophlebitis

Skin necrosis w extravasation

Allergic reaction including anaphylaxis

Rebound ­ICP

3% NaCl

Metabolic acidosis (SID)

Overshoot hypernatraemia

Hypokalaemia

Coaguloopathy

Rebound ­ICP

Central pontine myelinolysis

Seizures