Question 10(p.2)

Outline the mechanism of action of drugs used to control raised intracranial pressure.

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College Answer

The answers to this question were generally not broad enough. Only one or two drugs were
discussed rather than the range of drugs used in this situation. Discussion should have included benzodiazepines, intravenous induction agents, opioid narcotics, diuretics including
loop diuretics and mannitol. Hypertonic saline also gained marks. Generally the discussions
on the drugs mentioned were done well.
Some candidates discussed the physiological control of intracranial pressure which was not
required and gained no marks.


  • Agents which act directly on cerebral metabolic demand:
    • General anaesthetics, eg. propofol and thiopentone
      • Produce a dose-related decrease in CMRO2 and ICP
      • This is because cerebral blood flow is closely tied to cerebral metabolic rate
    • Anticonvulsants, eg. benzodiazepines:
      • Mitigate the risk of seizures, which would increase cerebral metabolic rate and therefore also increase ICP
  • Agents which act on cerebral blood flow by decreasing response to noxious stimuli:
    • Opioids, and to a lesser extent benzodiazepines:
      • Ablate the sympathetic response to noxious stimuli
      • This decreases the blood pressure, and therefore decreases cerebral bloodflow to areas of vulnerable brain, where autoregulation is impaired
  • Agents which improve venous efflux:
    • Opioids dampen the cough reflex, and cough can transiently increase venous pressure
    • Muscle relaxants (eg. neuromuscular junction blockers):
      • Decrease the intrathoracic pressure and therefore improve venous drainage
      • Also abolish the cough reflex
    • Diuretics decrease total body circulating volume and decrease venous pressure
  • Agents which influence the volume of brain tissue:
    • Osmotherapy agents (hypertonic saline, mannitol, urea) are used to increase the systemic osmolality and therefore produce an osmotic shift of water out of brain parenchyma, decreasing its volume
    • Dexamethasone is used to decrease the cerebral oedema associated with intracranial malignancy
  • Agents which influence the production of CSF:
    • Acetazolamide inhibits carbonic anhydrase and therefore decreases the production of CSF at the choroid plexus
    • Loop diuretics are thought to have a similar effect


Colton, Katharine, et al. "Intracranial pressure response after pharmacologic treatment of intracranial hypertension." Journal of Trauma and Acute Care Surgery 77.1 (2014): 47-53.

Roberts, Derek J., et al. "Sedation for critically ill adults with severe traumatic brain injury: A systematic review of randomized controlled trials*." Critical care medicine 39.12 (2011): 2743-2751.

Majdan, Marek, et al. "Barbiturates use and its effects in patients with severe traumatic brain injury in five European countries.Journal of neurotrauma 30.1 (2013): 23-29.

de Nadal, Miriam, et al. "Cerebral Hemodynamic Effects of Morphine and Fentanyl in Patients with Severe Head Injury Absence of Correlation to Cerebral Autoregulation.The Journal of the American Society of Anesthesiologists 92.1 (2000): 11-11.

Papazian, L., et al. "Effect of bolus doses of midazolam on intracranial pressure and cerebral perfusion pressure in patients with severe head injury.British journal of anaesthesia 71.2 (1993): 267-271.