OSMOTIC DIURETICS MANNITOL
Osmotically active diuretics are filtered at the glom-erulus and undergo limited or no reabsorption in the proximal tubule. Their presence in the proximal tubule limits the passive water reabsorption that nor-mally follows active sodium reabsorption. Although their major effect is to increase water excretion, in large doses, osmotically active diuretics also increase electrolyte (sodium and potassium) excretion. The same mechanism also impairs water and solute reab-sorption in the loop of Henle.
Mannitol is the most commonly used osmotic diuretic. It is a six-carbon sugar that normally undergoes little or no reabsorption. In additionto its diuretic effect, mannitol appears to increase RBF. The latter can wash out some of the medullary hypertonicity and interfere with renal concentrat-ing ability. Mannitol appears to activate the intrare-nal synthesis of vasodilating prostaglandins. It also appears to be a free radical scavenger.
Many clinicians continue to administer mannitol for renal protection and, less frequently, to convert oliguric acute kidney failure to nonoliguric kidney failure, with the goal of lowering associated mor-bidity and mortality. However, there is no evidence that such use of mannitol provides renal protec-tion, lessens the severity of AKI, or lessens the morbidity or mortality associated with AKI when compared with correction of hypovolemia and preservation of adequate renal perfusion alone. In addition, high-dose mannitol can be nephrotoxic, especially in patients with renal insufficiency.
Mannitol will augment urinary output in the set-ting of hypovolemia but will have little effect in the presence of severe glomerular or tubular injury. However, the optimal initial approach to evaluation of acute oliguria is to correct hypovolemia and opti-mize cardiac output and renal perfusion.
The intravenous dose for mannitol is 0.25–1 g/kg.
Mannitol solutions are hypertonic and acutely raise plasma and extracellular osmolality. A rapid intra-cellular to extracellular shift of water can transiently increase intravascular volume and precipitatecardiac decompensation and pulmonary edema in patients with limited cardiac reserve. Transient hyponatremia and reductions in hemoglobin con-centration are also common and represent acute hemodilution resulting from rapid movement of water out of cells; a modest, transient increase in plasma potassium concentration may also be observed. It is also important to note that the ini-tial hyponatremia does not represent hypoosmo-lality but reflects the presence of mannitol . If fluid and electrolyte losses are not replaced following diuresis, mannitol administra-tion can result in hypovolemia, hypokalemia, and hypernatremia. The hypernatremia occurs because water is lost in excess of sodium. As noted above, high-dose mannitol can be nephrotoxic, especially in patients with renal insufficiency.