Effect of hyperventilation on extracellular concentrations of glutamate, lactate, pyruvate, and local cerebral blood flow in patients with severe traumatic brain injury

Objective., To determine the potential adverse effects of brief periods of hyperventilation commonly used for acute neurologic deterioration. Design: Prospective clinical trial. Setting: University medical school. Patients: Twenty patients with severe traumatic brain injury. Interventions: The effect of 30 mins of hyperventilation (mean PaCO2, 24.6 mm Hg) on the extracellular metabolites associated with ischemia, and on local cerebral blood flow was studied by using microdialysis and local cerebral blood flow techniques. Normal appearing brain adjacent to evacuated hemorrhagic contusions or underlying evacuated subdural hematomas was studied. Hyperventilation trials were done 24-36 hrs after injury and again at 3-4 days after injury. Dialysate concentrations of glutamate, lactate, and pyruvate were measured before and for 4 hrs after the hyperventilation trials. Measurements and Main Results., At 24-36 hrs, hyperventilation led to a greater than or equal to10% increase in the extracellular concentrations of glutamate in 14 of 20 patients, with concentrations in those 14 patients 13.7-395% above baseline; a greater than or equal to10% increase in lactate in 7 of 20 patients (11.6-211% above baseline); and a greater than or equal to10% increase in the lactate/pyruvate ratio in eight of 20 patients (10.8-227% above baseline). At 3-4 days after injury, ten of 13 patients had an increase in glutamate of greater than or equal to10%, while only three of 13 patients had an increase in extracellular lactate and two of 13 patients had an increase in the lactate/pyruvate ratio of this magnitude. The hyperventilation associated increases in extracellular glutamate and lactate concentrations were significant (P <.05; one-sample Student's t-test) at both time points after injury, as was the lactate/pyruvate ratio at 24-36 hrs. A greater than or equal to10% decline in local cerebral blood flow was observed with hyperventilation in five of 20 patients at 24-36 hrs (range, 10.2-18.7% below baseline), and in ten of 13 patients studied at 3-4 days (11.3-54% below baseline). There was no correlation with the presence or absence of local CO2 vasoresponsivity and increases in the extracellular metabolites at either the early or late time points. Conclusions: In brain tissue adjacent to cerebral contusions or underlying subdural hematomas, even brief periods of hyperventilation can significantly increase extracellular concentrations of mediators of secondary brain injury. These hyperventilation-induced changes are much more common during the first 24-36 hrs after injury than at 3-4 days.