The goal of intensive care management of patients with head injury is to provide them with a favourable physiological and metabolic environment for recovery of injury-compromised cells, and to prevent secondary brain insults. Clinical intracerebral microdialysis has enabled documentation of the metabolic derangement after head injury. Treatment targeted at this derangement has emphasized maintenance of optimal cerebral perfusion pressure (CPP). To determine the relationships between CPP and five clinically relevant intracerebral extracellular metabolites (glucose, lactate, glycerol, glutamate and pyruvate) in relation to different therapy intensities, 23 moderate to severe head-injury patients with hourly microdialysis samples were studied. These five metabolites were correlated with CPP and showed a biphasic relation at CPP of 65 to 67 mmHg, which was believed to be the critical CPP indicating irreversible brain damage. Relationship between intracerebral metabolites and CPP in relation to different therapy intensities was studied and suggests the critical CPP threshold in head-injured patients with high ICP and maximum therapy is elevated and should be maintained above 70 mmHg to prevent irreversible brain damage.