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

Marion, Donald W. MD; Puccio, Ava RN; Wisniewski, Stephen R. PhD; Kochanek, Patrick MD; Dixon, C. Edward PhD; Bullian, Leann RN; Carlier, Patricia RN

Author Information

From the Brain Trauma Research Center, Departments of Neurological Surgery (DWM, AP, CED, LB, PC), Epidemiology (SRW), and Anesthesiology (PK), University of Pittsburgh School of Medicine, Pittsburgh, PA.

Supported, in part, by Public Health Service Grant 30318, National Institutes of Health, Bethesda, MD.

Address requests for reprints to: Donald W. Marion, MD, Brain Trauma Research Center, Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop Street, Suite B400, Pittsburgh, PA 15213. E-mail:[email protected]

We therefore continue to recommend that the acute care of patients with severe traumatic head injury focus on enhancing cerebral perfusion and avoiding therapies with the potential to cause ischemia, such as aggressive hyperventilation, whenever possible.

^*See also p. 2774.

Critical Care Medicine30(12):p 2619-2625, December 2002.

Abstract

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 ≥10% increase in the extracellular concentrations of glutamate in 14 of 20 patients, with concentrations in those 14 patients 13.7–395% above baseline; a ≥10% increase in lactate in 7 of 20 patients (11.6–211% above baseline); and a ≥10% 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 ≥10%, 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’st-test) at both time points after injury, as was the lactate/pyruvate ratio at 24–36 hrs. A ≥10% 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.