Multiple interstitial substances measured by microdialysis in patients with subarachnoid hemorrhage

Intracerebral microdialysis is a tool to monitor metabolic disturbances in the brains of patients with severe head injuries or subarachnoid hemorrhage (SAH). In the search for putative indicators of primary and secondary brain damage, we measured multiple metabolites in the dialysates of patients with SAH, to elucidate their significance for the outcomes of the patients as well as their temporal profiles of liberation after the insult.

Microdialysis probes were placed, with a ventriculostomy catheter for drainage of cerebrospinal fluid, into a frontal lobe of 10 patients with aneurysmal SAH, for 4.6 +/- 0.5 days. Amino acids, metabolites of glycolysis, purines, catecholamines, and nitric oxide oxidation byproducts were measured by high-performance liquid chromatography. Spearman's correlation coefficient and Student's t test were used to compare the levels of the metabolites with the outcomes of the patients, as assessed using the Glasgow Outcome Scale, 3 months after the ictus.

For patients with unfavorable outcomes (Glasgow Outcome Scale scores of 1-3), which were primarily associated with the development of large infarctions, dialysate levels of excitatory amino acids increased up to 30-fold, those of lactate up to 10-fold, and those of nitrite up to 5-fold, compared with normal levels observed for patients with favorable outcomes (Glasgow Outcome Scale scores of 4 or 5). When average peak concentrations in the dialysates of patients with favorable and unfavorable outcomes were compared, significantly higher levels of excitatory amino acids, taurine, lactate, and nitrite, but not of purines and catecholamines, were observed for those with poor outcomes (P < 0.05). With respect to the temporal profiles of the average metabolite concentrations, the significantly increased levels of amino acids observed for patients with poor outcomes followed a biphasic course, with maximal concentrations on the first and second days or the seventh day after the insult (P < 0.01).

These data confirm the usefulness of excitatory amino acids and lactate as major parameters for neurochemical monitoring for patients threatened by acute cerebral disorders. Other substances, such as taurine and nitrite, were also demonstrated to be potentially predictive. Release of these substances into the extracellular fluid of the brain might be particularly relevant for the development of secondary brain damage after SAH, e.g., infarction or brain swelling.