Extracellular Potassium and Its Correlates After Head Injury
Disturbed ionic and neurotransmitter homeostasis are now recognized to be probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brian injury (TBI). Evidence obtained from animal models indicates that posttraumatic neuronal excitation via excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with intracranial pressure (ICP), outcome, and also with the levels of dialysate glutamate, lactate, and cerebral blood flow (CBF) so as to determine the role of ischemia in this posttraumatic ionic dysfunction.

Eighty-five patients with severe TBI (Glasgow Coma Scale score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed by flame photometry, as were dialysate glutamate and dialysate lactate levels, which were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients respectively. Cerebral blood flow studies (stable Xenon--computerized tomography scanning) were performed in 59 patients.

In approximately 20% of the patients, potassium values were increased (dialysate potassium > 1.8 mmol). Mean dialysate potassium (> 2 mmol) was associated with ICP above 30 mm Hg and fatal outcome. Dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate levels (p < 0.0001). Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019).

Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase of potassium, together with dialysate glutamate and lactate, supports the hypothesis that glutamate induces ionic flux and consequently increases ICP due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered potassium reactivity in cerebral blood vessels after trauma.

Severe TBI leads to a sudden neuronal discharge--traumatic depolarization. As in any depolarizing cell, this results in an extracellular increase in potassium in exchange with sodium, which moves into the cell. Methods such as patch-clamp techniques or K-sensitive microelectrodes can be used to measure these millisecond physiological changes. The traumatic depolarization encountered after TBI, however, is a longer-lasting phenomenon. Patch-clamp studies have shown that traumatic depolarization persists for up to 24 hours in vitro. Using microdialysis, Katayama, et al., have demonstrated that after rat fluid-percussion injury, the increase in dialysate potassium was dependent on the magnitude of the injury. In cases of fatal fluid-percussion injury, potassium levels remained elevated but did not revert to baseline as observed in those with less severe injuries. This late increase was attributed to membrane breakdown and cell death, with failure to repolarize the membrane. It can be hypothesized that several different mechanisms can lead to an increase in dialysate potassium: 1) brief, transient membrane microporation by mechanical stress without membrane disruption; 2) potassium flux through voltage-gated and agonist-activated channels such as NMDA and AMPA receptors; 3) nonspecific membrane breakdown, as part of cell rupture and necrosis; and 4) ischemic depolarization due to inadequate CBF and consequent ATP reduction.

Astrocytes as neuronal energy providers and maintainers of ECF homeostasis are especially exposed to the influence of increased ECF [K], and they have been shown to respond to increased [K] by marked cell swelling. It has been shown that increasing extracellular potassium experimentally from 3 to 6 mmol causes normal astrocytes to swell to several times their normal volume. This is an important mechanism by which the increase in extracellular potassium is buffered to allow membrane repolarization. This mechanism may also influence CBF, because astrocytic perivascular foot processes have been shown to swell enough to compress the microvessels. Paulson and Newman have shown that potassium is taken up by astrocytes and transported into the endfeet of astrocytes surrounding blood vessels, thus causing them to swell, and that this may derange the normal cerebrovascular reactivity in the presence of increased extracellular potassium, as seen after severe head injury.

To test these hypotheses we have studied 85 severely head injured patients by using continuous intracerebral microdialysis, and we have related the ionic and neurochemical data to clinical parameters, ICP, and outcome.