Question 8

Critically evaluate the use of hypertonic saline and mannitol in the management of severe closed head injury.

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College Answer

Hypertonic Saline has theoretical advantages in the initial resuscitation of head injured patients because smaller volumes of fluid are required and blood pressure restoration is more effective. Brain oedema may be decreased to lower ICP and CPP may be increased. Post resuscitation use is less clear. In this setting, reduction in intracranial hypertension is due to improved systemic and cerebral haemodynamics and modulation of vasospasm. Adverse effects include renal impairment, rebound ICP rise and osmotic myelinolysis. Trials are continuing and a well defined role is not apparent as yet.

Mannitol has a long history of use in the management of head injuries. It lowers ICP initially by increasing CBF and producing a compensatory vasoconstriction. An osmotic effect and diuresis produce delayed fall in ICP. Efficacy would be dependent initially on the presence of adequate brain with intact autoregulation. Prolonged use may lead to leak into damaged brain with concomitant increase in ICP and swelling. The accepted role is in the urgent lowering of ICP before definitive therapy (eg. evacuate haematoma or perform decompression craniectomy). Chronic use is not supported by evidence.


Another question is very similar- Question 4 from the first paper of 2007. It asks one to discuss hypertonic saline, which of course is impossible without discussing mannitol.

In brief:

aised intracranial pressure falls within the realm of osmotherapy, which enjoys a thorough discussion elsewhere:

From those summary, a table of comparison can be compiled, which is presented below.



Hypertonic saline

A Comparison of Mannitol and Hypertonic Saline Osmotherapy
  • Still fairly cheap
  • Rapid effect
  • Seems to have some sort of rheological benefit (increaes red cell deformability)
  • Acts as a transient volume expander
  • May have a better effect on cerebral blood flow for a given reduction in ICP.
  • Safe endpoint (serum sodium) is easily monitored with ABGs.
  • Cheap
  • Stable in storage
  • Very rapid effect
  • Seems to have some sort of intrinsic anti-inflammatory effect
  • May also have some rheological benefits
  • At least as potent as mannitol when it comes to reducing intracranial pressure
  • Less potential for hypovolemia than with mannitol- the diuretic effect is less potent
  • May have a better effect on cerebral blood flow for a given reduction in ICP.
  • Safe endpoint (serum sodium around 145-155) is easily monitored with serial ABGs.
  • Unstable in storage: at low temperatures and at altitude, it precipitates.
  • Medium for bacteria and fungus.
  • Causes a brief state of volume overload
  • Causes torrential diuresis and hypovolemia
  • Causes hyponatremia while in the serum, and hypernatremia after the inevitable diuresis
  • Endpoint is serum osmolality(320), which is cumbersome to measure
  • May cause ICP to "rebound" after prolonged use
  • Need for central venous access
  • No standards for which concentration to use, or how to give it
  • Hypokalaemia
  • Hyperchloraemic acidosis
  • Should not be used if the patient is chronically hyponatremic
  • Possible seizures due to wild fluctuations in serum sodium
  • Increase in circulating volume with risk of fluid overload.
  • Coagulopathy (APTT and INR)
  • Altered platelet aggregation.
  • May affect normal brain more that injured brain which theoretically may worsen herniation


Oh's Intensive Care manual:

Chapter 43 (pp. 563) Cerebral protection by Victoria Heaviside and Michelle Hayes, and

Chapter 67 (pp. 765) Severe head injury by John A Myburgh.

Francony, Gilles, et al. "Equimolar doses of mannitol and hypertonic saline in the treatment of increased intracranial pressure*." Critical care medicine 36.3 (2008): 795-800.

Kamel, Hooman, et al. "Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: A meta-analysis of randomized clinical trials*."Critical care medicine 39.3 (2011): 554-559.

Nau, Roland. "Osmotherapy for elevated intracranial pressure." Clinical pharmacokinetics 38.1 (2000): 23-40.

Rickard, A. C., et al. "Salt or sugar for your injured brain? A meta-analysis of randomised controlled trials of mannitol versus hypertonic sodium solutions to manage raised intracranial pressure in traumatic brain injury." Emergency Medicine Journal (2013).

Lazaridis, Christos, et al. "High-Osmolarity Saline in Neurocritical Care: Systematic Review and Meta-Analysis*." Critical care medicine 41.5 (2013): 1353-1360.

Bhardwaj, Anish, and John A. Ulatowski. "Hypertonic saline solutions in brain injury." Current opinion in critical care 10.2 (2004): 126-131.

Arbabi, Saman, et al. "Hypertonic saline induces prostacyclin production via extracellular signal-regulated kinase (ERK) activation." Journal of Surgical Research 83.2 (1999): 141-146.

R LAWRENCE REED, I. I., et al. "Hypertonic saline alters plasma clotting times and platelet aggregation." Journal of Trauma-Injury, Infection, and Critical Care 31.1 (1991): 8-14.