Colloid osmotic pressure and the formation of posttraumatic cerebral edema.

IN the beginning, it was “Run ’em dry for Neurosurgery.” It was the fervent (but empiric) belief of many clinicians that all crystalloid administration aggravated edema in injured brain, and, as a result, aggressive fluid restriction was commonly the standard. But then, the evolution of cerebral blood flow methodology begat the awareness that the common cerebral injury states, including traumatic brain injury (TBI), often entail regions of low cerebral blood flow that might become frankly ischemic in the event of hypotension; and careful maintenance of normovolemia (and sometimes hypervolemia) became the credo. Accordingly, with the increased fluid administration, we must again be concerned about whether crystalloids can aggravate brain edema. A carefully conducted preclinical investigation that appears in this issue of ANESTHESIOLOGY adds additional insights to that discussion. First, let us review the facts to better evaluate all the fervor and speculation that has gone before. (1) Crystalloid administration that results in a reduction of serum osmolality will cause brain edema even in entirely normal brain; accordingly, whatever fluid regimen is chosen it should not have sufficient free water to cause reduction in osmolality; (2) Reduction of colloid osmotic pressure (COP) in isolation will not cause edema of normal brain. That latter assertion is in contradistinction to what happens in most peripheral tissues, in which reduction of COP is associated with tissue swelling. The explanation for the difference resides largely in the properties of the endothelium of cerebral capillaries that are largely responsible for the so-called blood-brain barrier (BBB). In the majority of the capillary beds in the human body, the configuration of the desmosomes that connect endothelial cells creates an effective intercellular pore size of 60–70 Å; small electrolyte molecules pass freely; colloid molecules also pass but with difficulty. In the event of reduction of COP by dilution, a transmembrane osmotic pressure difference does occur. The gradient is small. For example, a 50% reduction in COP produces a transmembrane pressure gradient equivalent to an osmolality difference of less than 1 mOsm/l, but because small solvents move easily and the elastance ( P/ V) of the interstitlum is usually modest, fluid moves extravascularly and edema forms. By contrast, the tight junctions of the capillary endothelium in the brain result in an almost continuous lipid barrier, with occasional pores of 5–7 Å. Lipid soluble materials pass by diffusion; small charged electrolyte molecules pass with difficulty, and the barrier is highly impermeable to all large hydrophilic molecules, for example, albumin and starches. In addition, the interstitial space of the brain is much “tighter.” With COP reduction, some transendothelial movement of water probably does occur, but dissolved solvent cannot follow and opposing osmolar and hydrostatic gradients develop immediately and measurable edema differences are prevented. But all of that applies to normal brain. One of the subcomponents of the seemingly endless crystalloid–colloid debate has been the issue of whether the administration of isotonic crystalloids, with the concomitant dilution of colloids and reduction of oncotic pressure, will aggravate edema in injured brain. Why might it? If TBI were to result in sufficient injury to the BBB to open it to an extent equivalent to that which occurs natively in most peripheral vascular beds, would the interstitium of the brain also develop edema as that occurs in the periphery? Although that edema might be less severe because of the “tighter” interstitial space in the brain, physiologic principles (and a prior investigation) argue that it almost certainly will. And, the carefully conducted study by Jungner et al. elsewhere in this issue reaffirms that expectation. In that study, after a 2.4 atm (moderately severe) fluid percussion injury, rats underwent hemorrhage and then