K1ii: Drugs used to control raised ICP

Definition ICP & Normal Values

  • ICP = the pressure within the cranial vault
    • N = 5 – 15mmHg

Determinants of ICP

  • Brain tissue (80% volume)
  • CSF (5% volume)
  • Blood (10% volume)

Drugs to ↓ ICP

  • Aim to ↓one or more of these volumes
  • Generally 2 categories

↓Parenchymal Volume

Hypertonic saline

Diuretics (mannitol, acetazolamide)

Steroids

↓CMRO2

IV sedatives

BZDs

Opioids

Anticonvulsants

↓ Parenchymal Volume

Hypertonic Saline

  • Solution of high osmolality
  • Causes fluid shift from ICF → ECF
  • In nervous tissue, flow of H2O into plasma = ↓CSF production
    • ↓ICP

Diuretics

  • Mannitol
    • Physiologically inert, large MW 182
    • Confined to ECF
    • Cannot cross BBB
    • Exerts osmotic force
    • Draws H2O out of parenchyma & CSF into plasma
    • Mannitol is freely filtered & poorly absorbed by kidneys
    • ∴↑H2O excretion
    • ↓ICP
  • Acetazolamide
    • Non-competitive inhibition of CA
    • ↓rate of CSF & aqueous humor formation
    • ↓ICP
  • Steroids
    • Tumour assoc cerebral oedema arises because of lack of normal BBB function in tumour capillaries
    • Dexamethasone = glucocorticoid
    • Tries to normalise endothelial permeability
    • Inhibits COX2 which is important enzyme of eicosanoid formation
    • ↓cellular oedema
    • ↓ICP

IV Sedatives

Thiopentone

  • Hyperpolarises neuron
  • Dose dependent ↓CMRO2
  • O2/flow coupling → ↓CBF
  • ↓ICP

Propofol

  • Potentiates actions of GABA/glycerine
  • ↓CMRO2
  • O2/flow coupling → ↓CBF
  • ↓ICP

Benzodiazepines

  • Bind BZD receptor
  • Facilitates GABAergic transmission
  • Dose-related ↓CMRO2
  • O2/flow coupling → ↓CBF
  • ↓ICP

Opioids

  • Minimal effects on ↓CMRO2
  • May ↑PaCO2 → ↑CBF
  • Pain management

Anticonvulsants

  • Prevent seizure activity
  • ∴ ↓CMRO2
  • O2/flow coupling
  • ∴↓ICP

NB: Thiopentone, PPF & midazolam also have anticonvulsant effects