Fluid Management During Craniotomy

Osmolality

Osmolality is one of the four colligative properties of a solution. (The other three are vapor pressure, freezing point depression, and boiling point elevation.) The addition of 1 osmole of any solute to 1 kg of water causes the vapor pressure to fall by 0.3 mmHg, the freezing point to drop by 1.85° C, and the boiling point to rise by 0.52° C. The colligative properties are determined solely by the number of particles in solution and are independent of the chemical structure of the solute. The solute may exist in either an ionized or a nonionized state, and the size (molecular weight) of the solute is of no importance. Although it may seem counterintuitive, equimolar concentrations of glucose, urea, and mannitol have the same effect on the colligative properties of a solution. Osmolality is strictly a function of the number of particles in solution.

For physiologic solutions, osmolality is commonly expressed as milliosmoles (mOsm) per kilogram of solvent , whereas the units of measure for osmolarity are milliosmoles per liter of solution . For dilute solutions (including most of those of physiologic importance), the two terms may be used interchangeably. Osmolarity can be calculated if the molecular weight of the solute and its tendency to disassociate in solution are known ( Boxes 9.1 and 9.2 ). The osmolarities of some commonly used intravenous fluids are listed in Table 9.1 .

Osmolarity is important in determining fluid movement between various physiologic compartments because of the osmotic pressure that is generated when solutions of unequal osmolarity are separated by a membrane permeable to water but not to solutes. According to the second law of thermodynamics, which states that all systems spontaneously change to maximize entropy, water has a tendency to move from the solution of lower osmolality, across the membrane, and into the solution of higher osmolality ( Fig. 9.1 ).

This process continues until the solutions are of equal osmolality or the hydrostatic pressure is sufficient to preclude any further net flow of water across the membrane. The hydrostatic pressure that can be generated by osmolar differences is formidable and may be calculated by the following equation:

where π is osmotic pressure in atmospheres, C is concentration of all osmotically active solutes in the solution (in moles per liter), R is gas constant (0.08206 liter-atm/mole-degree), and T is temperature in degrees Kelvin (° K).

On the basis of this formula, a pressure of more than 19 mmHg is generated for each milliosmole difference across a semipermeable membrane (see Box 9.2 ). Thus, osmolar differences can provide a potent driving force for the movement of water between the intracellular and extracellular spaces and, as seen later, across the blood–brain barrier. Although osmolar gradients can be produced by administering hypo-osmolar or hyperosmolar fluids, these gradients are fleeting; and water moves from one compartment to another so that all body fluids are again of equal osmolarity.

Oncotic Pressure

Oncotic pressure is the osmotic pressure generated by solutes larger than an arbitrary limit (usually 30,000 molecular weight [MW]). Albumin (69,000 approximate MW), hetastarch (480,000 mean MW), dextran 40 (40,000 mean MW), and dextran 70 (70,000 mean MW) are compounds of clinical interest that are capable of exerting oncotic pressure. Reported values for the oncotic pressures of plasma, mannitol, albumin, and hetastarch are listed in Table 9.1 . ^, The oncotic pressure produced by all plasma proteins (eg, albumin, globulins, fibrinogen) accounts for less than 0.5% of total plasma osmotic pressure. The oncotic pressure of various solutions can be easily measured with an electronic pressure transducer and a membrane that is freely permeable to low-molecular-weight (LMW) solutes but that prevents the passage of particles greater than 30,000 MW ( Fig. 9.2 ).

Determinants of Fluid Movement between Vasculature and Tissues

Nearly 100 years ago, Ernest Starling described the forces that determine the movement of water between tissues and the intravascular space. This description was subsequently formalized in what is now known as the Starling equation, as follows:

where Q _f is the net amount of fluid that moves between the capillary lumen and the surrounding extracellular space (interstitium), K _f is the filtration coefficient for the membrane, S is the surface area of the capillary membrane, P _c is the hydrostatic pressure in the capillary lumen, P _t is the hydrostatic pressure (usually negative) in the extracellular space of the surrounding tissue, σ is the coefficient of reflection—this number, which can range from 1 (no movement of the solute across the membrane) to 0 (free diffusion of the solute across the membrane), quantitates the “leakiness” of the capillary and is different for vessels in the brain and those in peripheral tissues, π _c is the oncotic pressure of the plasma, and π _t is the oncotic pressure of the fluid in the extracellular space.

Capillary pressure, tissue pressure (negative in nonedematous tissues), and tissue oncotic pressure all act to draw fluid from the capillaries and into the extracellular space of the tissue ( Fig. 9.3 ). In peripheral tissues, the only factor that serves to maintain intravascular volume is the plasma oncotic pressure, which is produced predominantly by albumin and to a lesser extent by immunoglobulins, fibrinogen, and other high-molecular-weight (HMW) plasma proteins (see Fig. 9.3 ).

Under most circumstances, the sum of the forces results in a Q _f value that is slightly greater than zero, indicating a net outward flux of fluid from the vessels into the tissue extracellular space. This fluid is cleared from the tissue by the lymphatic system, thereby preventing the development of edema ( Fig. 9.4 ).

The clinical effects of altering one or more of the variables in the Starling equation may frequently be observed in the operating room. Many patients who have been resuscitated from hemorrhagic hypovolemia with large volumes of crystalloid solutions demonstrate pitting edema, caused by a dilution of plasma proteins. This results in a decrease in intravascular oncotic pressure (π _c ). In the presence of relatively unchanged capillary hydrostatic pressure, an increased movement of fluid from the vasculature into the tissues occurs. When this fluid flux exceeds the drainage capacity of the lymphatics, clinically apparent edema results.

Another example of the Starling equation in action is the facial edema that is often seen in patients who have been placed in the Trendelenburg position for prolonged periods. In this case, the edema is due not to a decrease in plasma oncotic pressure but rather to an increase in the capillary hydrostatic pressure (P _c ), favoring an increased transudation of fluid into the tissue.

Fluid Movement between Capillaries and the Brain

The Starling equation describes the factors that govern fluid movement between the intravascular and peripheral extracellular spaces (eg, the interstitium of lung, bowel, and muscle). However, the brain and spinal cord are unlike most other tissues in the body in that they are isolated from the intravascular compartment by the blood–brain barrier. Morphologically, this barrier is now thought to be composed of endothelial cells that form tight junctions in the capillaries supplying the brain and spinal cord. Endothelial cells are surrounded by the layer of pericytes delineated by the foot processes of glial cells. In the normal brain, these tight junctions severely limit the diffusion of molecules between the intravascular space and the brain. By measuring the movement of water out of the central nervous system after abrupt changes in plasma osmolality, Fenstermacher and Johnson calculated the effective pore radius for the blood–brain barrier to be only 7 to 9 Å. This small pore size of the blood–brain barrier prevents movement not only of plasma proteins but also of sodium, chloride, and potassium ions between the intravascular compartment and the brain’s extracellular space ( Fig. 9.5 ). In effect, the blood–brain barrier acts like the semipermeable membrane of an osmometer, and movement of water across this membrane is determined by the relative concentrations of impermeable solutes.

This situation is markedly different in peripheral tissues, where endothelial cells do not form tight junctions and pore sizes in the capillaries may be as much as several orders of magnitude greater. Although these pores are small enough to preclude the movement of most protein components of plasma, electrolytes pass freely from the capillary lumen into the extracellular space. Thus, in peripheral tissues, movement of water between the intravascular space and the extravascular space is governed by the plasma concentration of large macromolecules (oncotic gradient) as defined by the Starling equation. In contrast, fluid moves in and out of the central nervous system according to the osmolar gradient (determined by relative concentrations of all osmotically active particles, including most electrolytes) between the plasma and the extracellular fluid. This difference in the determinants of fluid flux explains why the administration of large volumes of iso-osmolar crystalloid results in peripheral edema caused by dilutional reduction of plasma protein content, but does not increase brain water content or intracranial pressure (ICP).

There can be little doubt that osmolarity is the primary determinant of water movement across the intact blood–brain barrier. The administration of excess free water (either iatrogenically or as a result of psychogenic polydipsia) can result in an increased ICP and an edematous brain. Conversely, the intravenous administration of markedly hyperosmolar crystalloids (eg, mannitol) to increase plasma osmolarity results in a decrease in brain water content and ICP. Hyperosmolar solutions are used as standard therapeutic agents to treat intracranial hypertension.

In the presence of an intact blood–brain barrier, plasma osmolarity is the key determinant of water movement between the central nervous system and the intravascular space. However, what occurs when the brain is injured with disruption of the barrier? If the blood–brain barrier is partially disrupted, will blood vessels in the brain start to act more like peripheral capillaries? Experimental evidence is not conclusive, but if the injury is of sufficient severity to allow extravasation of plasma proteins into the interstitial space (ie, capillaries have become “leaky”), plasma oncotic pressure does not affect water movement, because no oncotic gradient between the plasma and the brain interstitial space can be produced (ie, the proteins leak out of the capillaries and into the brain tissue) ( Fig. 9.6 ). In an animal study using a cryogenic lesion as a model of acute brain injury, a 50% decrease in plasma oncotic pressure had no effect on regional water content or ICP. These results were confirmed in a subsequent study that demonstrated that reducing the plasma oncotic pressure from approximately 21 mmHg to 10 mmHg for 8 hours had no effect on ICP or brain water content in animals with a cryogenic brain injury despite the fact that the anticipated increase in water content was documented in peripheral tissues (muscle and jejunum).

Despite a lack of convincing experimental evidence that iso-osmolar crystalloids are detrimental, the neurosurgical literature is filled with admonitions to restrict the use of crystalloids in patients at risk for intracranial hypertension. In the case of the intact blood–brain barrier, neither theoretical nor experimental evidence suggests that colloids are more beneficial than crystalloids for either brain water content or ICP. The crystalloid-colloid question has been addressed in animal models of cerebral injury, with varying and sometimes conflicting results. Warner and Boehland studied the effects of hemodilution with either saline or 6% hetastarch in rats subjected to 10 minutes of severe forebrain ischemia. Despite an approximately 50% reduction in plasma oncotic pressure in the saline group (from 17.2 ± 0.8 to 9 ± 0.6 mmHg), no beneficial effect in terms of decreased edema formation was demonstrated in the hetastarch group. Similarly, in a study that used a cryogenic lesion as a model of cerebral injury, Zornow and colleagues found no differences in regional water content or ICP between animals that received saline, those that received 6% hetastarch, and those that received albumin.

In contrast, Korosue and associates found a smaller infarct volume and better neurologic status in dogs undergoing hemodilution with a colloid (LMW dextran) than in animals undergoing hemodilution with lactated Ringer’s solution after ligation of the middle cerebral artery. The researchers speculated (but did not provide evidence) that this beneficial effect was due to decreased edema formation in the ischemic zone. They further speculated that, in this model of moderate ischemic injury, the blood–brain barrier may become selectively permeable to ions with preservation of its impermeability to HMW compounds (eg, dextran and proteins). If this is the case, then the brain tissue in the ischemic region may act very much like tissues in the periphery (ie, decreases in plasma oncotic pressure result in increased water movement into the tissue). A study by Drummond and coworkers suggests that a similar situation may occur after traumatic brain injury (TBI). They subjected anesthetized rats to a 2.7 atm fluid percussion injury and then hemodilution with normal saline or a colloid. Brain water content was increased in the animals that received the normal saline. Thus, although the osmolality of the infused solution is the primary determinant of water movement between the vasculature and brain tissue in the noninjured state, apparently in cases of ischemic or traumatic injury, colloids may or may not be beneficial, depending on the severity and extent of the injury as well as the time at which brain water content is measured.

Beneficial effects of hypertonic solutions in cases of localized brain injury with disruption of the blood–brain barrier appear to be derived primarily from the ability of hypertonic solutions to cause a fluid flux out of brain tissue where the blood–brain barrier remains intact. In effect, the normal brain is dehydrated to compensate for the edema that forms in the vicinity of the lesion. The most likely mechanism for this beneficial effect is a decrease in brain water content in regions remote from the lesion.