Plasma osmotic concentration consists of colloidal osmotic concentration and crystalloid osmotic concentration. The former is formed by the excess amount of proteins in the plasma, which, because of their large molecular weight, produce very little osmotic pressure but play an important role in maintaining the water balance inside and outside the blood vessels. The latter is formed by crystalline substances dissolved in plasma, i.e. electrolytes and small molecules, especially electrolytes, which are the main source of plasma osmotic pressure, accounting for about 99.5%. The concentrations of crystalline substances in plasma and tissues are almost equal, and therefore their crystal osmotic concentrations are also essentially equal. Most of the crystalline material does not readily pass through the cell membrane. The relative stability of the crystal osmotic concentration of the extracellular fluid is extremely important for maintaining the water balance inside and outside the cells. The osmotic concentrations of electrolytes and glucose in plasma also basically reflect the osmotic concentrations of extracellular liquid crystals. The relative stability of the physicochemical properties of the extracellular fluid, called the internal environment, is very important for maintaining the normal function of the entire body and all cells in the body, and abnormalities in the osmotic concentrations also destabilize the internal environment. In the acute phase of stroke and traumatic brain injury, changes in the patient’s PCO are closely related to the concentration of glucose in the blood, and less affected by the osmotic concentration of electrolytes. Although its osmotic concentration is small, the effect of glucose on plasma osmotic concentration is obvious, with the latter increasing with the former concentration. Martin also observed 25 cases of diabetic ketoacidosis and found that only 7% of extracellular fluid osmolality was increased if the osmolality was calculated by blood sodium alone, but 52% of extracellular fluid osmolality was increased if the osmolality of blood glucose was added together. Mannitol is a commonly used drug in the treatment of stroke and traumatic brain injury cranial hypertension. The 20% mannitol used clinically is a highly osmotic fluid, which does not easily penetrate into tissues after intravenous injection, and it produces dehydration by rapidly increasing plasma osmolality and transferring tissue fluid to plasma, and diuresis via the kidneys. The diuresis of mannitol combined with the formation of osmotic diuresis via the kidneys of sugar exceeding the renal sugar threshold, it excretes a large amount of water, sodium and potassium from the body, especially water more than electrolytes. If the intake cannot be maintained, it will inevitably result in the reduction of extracellular and intracellular fluid, forming a hypertonic state. Glucose cannot penetrate freely into the cell membrane. When hyperglycemia occurs, the osmotic concentration of extracellular fluid increases and intracellular fluid is transferred to extracellular fluid, while mannitol increases the osmotic concentration of plasma and tissue fluid is transferred to the blood vessels, which is eventually excreted again, thus making intracellular dehydration more serious and causing serious disorders in intracellular biochemical reactions and physiological functions, especially in elderly patients with pre-existing atherosclerosis. After dehydration, the cells may crumple, for example, red blood cells crumple and clump together, resulting in “embolism” in the blood vessels, which will aggravate the lack of blood supply and hypoxia in tissues and organs, with a dangerous prognosis. Studies have shown that mannitol has no significant effect on the plasma osmolality of patients with normal blood glucose in the treatment of stroke and traumatic brain injury. However, in patients with hyperglycemia, plasma osmolality is significantly altered, and as the dosage of mannitol increases, the patient’s PCO also increases, and there is a linear positive correlation between the two. Therefore, for acute stroke and traumatic brain injury patients with hyperglycemia, first, long-term use of large amounts of 20% mannitol is not recommended. As for the effect of small doses of short-term use of mannitol on plasma osmotic concentration, further study is needed; secondly, in view of the insignificant effect of mannitol on PCO in patients with normal blood glucose stroke and traumatic brain injury, it is safer to closely monitor blood glucose in the acute phase of stroke and traumatic brain injury and to use mannitol to lower cranial pressure when blood glucose is effectively controlled in the normal range. In clinical practice, some people use 50% glucose intravenously with mannitol to lower the cranial hypertension in patients with stroke and traumatic brain injury, which is not beneficial but harmful.