The fundamental clinical obstacle to the use of ketamine for neuroprotection is the historical textbook dogma that ketamine is contraindicated in patients at risk of increases in intracranial pressure (ICP) [1, 2]. Early studies in animals and man revealed an increase in cerebral oxygen consumption (CMRO2), cerebral blood flow (CBF) and ICP after ketamine [3–5]. However, various experimental and clinical data show that these findings lack consistency, which seems to be attributable to different study designs [6, 7], the absence or presence of controlled ventilation [8–11] and background anaesthetics or other medication [12–15]. Apart from practical use in haemorrhagic shock based on stimulatory effects on the cardiovascular system [16, 17], the well-known experimental neuroprotective efficacy of ketamine [18–20] has long remained clinically unexploited, with apparently having few if any implications for use in patients with intracranial lesions. When the classic concept of suppression of brain metabolism as the mainstay of cerebral protection by anaesthetics was questioned in recent years, interest in ketamine increasingly started to revive. The new pathophysiological thinking focused on a key role of glutamate signalling in the injury cascade, suggesting that neuronal death results from toxic concentrations of glutamate in the extracellular space and metabolic imbalances leading to apoptosis or delayed degeneration [21, 22]. Ketamine blocks the activation of excitatory glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype by binding non-competitively to the phencyclidine site in the receptor channel in humans [23] and may have further effects of unknown clinical relevance [24, 25].


Cerebral Blood Flow NMDA Receptor Cerebral Perfusion Pressure Severe Head Injury Cerebral Blood Flow Velocity 
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© Springer-Verlag Italia, Milano 2004

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  • S. Himmelseher
  • E. Kochs

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