[Cerebral neuroprotection and ketamine]

Ketamine is said to increase intracranial pressure (ICP), cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) and hence to be unsuitable for neuroanaesthesia. This may require reconsideration in the light of the neuroprotective properties mediated by the interaction of ketamine with the N-methyl-D-aspartate receptor (NMDA). Meta-analysis of published experimental rodent studies yields contradictory conclusions. Ketamine does not provide neuroprotection against hypoxic hypoxaemia or focal cerebral ischaemia. During complete forebrain ischaemia of 10 min duration, ketamine offers some degree of protection only if administered before (i.e. prophylactically) and after (i.e. therapeutically) a transient ischaemic episode. In experimental head injury, ketamine may be protective if administered therapeutically within 2 h after the trauma. In the case of incomplete forebrain ischaemia, ketamine provides neuroprotection if administered both before and during ischaemia. Clinical or primate studies are not available; extrapolation of results derived from rodent studies requires caution and has limitations. With respect to the pharmacodynamic action providing neuroprotection, NMDA-receptor antagonism may be just one of several mechanisms; others include scavenging of free radicals, a central sympatholytic effect and augmentation of dopamine metabolism in the caudate. The suitability of ketamine for neuroanaesthesia, which must also take account of its effects on ICP, CBF and CMRO2, is--for the time being--questionable.