Effect of mannitol and furosemide on plasma osmolality and brain water.

BACKGROUND: Mannitol and furosemide are used to reduce increased intracranial pressure (ICP) and to reduce brain bulk during neurosurgery. One mechanism by which these changes might occur is via a reduction in brain water content. Although mannitol and furosemide are commonly used in combination, there has been no formal evaluation of the interactive effects of these two drugs on brain water. The effect of mannitol and furosemide alone and in combination on water content of normal rat brain was examined. METHODS: The lungs of rats anesthetized with halothane were mechanically ventilated to maintain normal physiologic parameters. After baseline measurement of plasma osmolality, mannitol (1, 4, or 8 g/kg), furosemide (2, 4, or 8 mg/kg), or a combination of furosemide (8 mg/kg) and mannitol (1, 4, or 8 g/kg) was administered intravenously over approximately 15 min. One hour later, plasma osmolality was measured, the animals were killed, and brain water content was determined by wet and dry weight measurements. RESULTS: Mannitol produced a dose-dependent increase in plasma osmolality and reduction of brain water content. There was a linear relation between plasma osmolality and brain water content. Furosemide alone did not affect plasma osmolality or brain water at any dose. The combination of furosemide with mannitol resulted in a greater increase in plasma osmolality than seen with mannitol alone and a greater decrease in brain water at 4 and 8 g/kg of mannitol. CONCLUSIONS: The doses of mannitol and furosemide utilized were much larger than clinically applicable doses and were selected to maximize the ability to detect effect on brain water. The combination of mannitol and furosemide resulted in greater reduction of brain water content than did mannitol alone. Furosemide enhanced the effect of mannitol on plasma osmolality, resulting in a greater reduction of brain water content. Potential interaction (if any) of smaller, clinically used doses of mannitol and furosemide cannot be surmised from the current study.

Effect of the degree of quaternisation of N-trimethyl chitosan chloride on absorption enhancement: in vivo evaluation in rat nasal epithelia.

Five TMC polymers with different degrees of quaternisation (12-59%) were synthesised and administered together with [14C]-mannitol in the nasal route of rats at a pH of 6.20 and 7.40, respectively. All the TMC polymers increased the nasal absorption of [14C]-mannitol significantly at pH 6.20, but only TMC polymers with higher degrees of quaternisation (>36%) were able to increase the absorption of this hydrophilic model compound at pH 7.40. The absorption of [14C]-mannitol at pH 7.40 increased with an increase in the degree of quaternisation of TMC until a maximum absorption value was reached with TMC with a degree of quaternisation of 48%. The absorption of [14C]-mannitol did not increase further, even when TMC with a higher degree of quaternisation (59%) was used. This can probably be explained by steric effects caused by the attached methyl groups and changes in the flexibility of the TMC molecules with an increase in the degree of quaternisation above an optimum value for absorption enhancement in a neutral environment. It was concluded that the degree of quaternisation of TMC plays an important role in the absorption enhancement properties of this polymer across nasal epithelia in a neutral environment.

Quantification and predictors of plasma volume expansion from mannitol treatment.

OBJECTIVE: To determine the effects of acute hypertonic mannitol infusion on intravascular volume expansion and to identify potential predictors of hypervolemia. DESIGN: Measurements of plasma volume and volume regulatory hormones were performed in healthy volunteers before and over 90 min after acute infusion of 20% mannitol solution in a therapeutic dose of 0.5 g/kg body weight, equalling an average infusion volume of 180 ml. SETTING: Clinical research unit in an 800-bed teaching hospital in the eastern part of Switzerland. PARTICIPANTS: Eight normal male volunteers. MEASUREMENTS AND RESULTS: Baseline plasma volume was determined by the indocyanine green dye dilution technique. Serial plasma protein measurements were performed after mannitol infusion to calculate intravascular volume changes. Mannitol administration resulted in a plasma expansion that persisted for more than 90 min and peaked at 112% of the baseline plasma volume 15 min after infusion. Concomitantly, an increase in systolic blood pressure and a fall in plasma sodium concentration occurred. Pharmacokinetic analyses of mannitol distribution and elimination revealed a close relation between plasma volume expansion and mannitol serum concentrations. While renin activity and aldosterone concentrations were suppressed proportionally to the intravascular volume increase, antidiuretic hormone was increased despite notable volume expansion and hyponatremia. Similarly, a rise in atrial natriuretic peptide was detected. CONCLUSIONS: Therapeutic doses of hypertonic mannitol cause substantial plasma volume expansion, resulting in increased blood pressure. Plasma volume expansion is related to mannitol serum concentrations and mannitol clearance determines the time required to restore normovolemia. ADH and ANP are potentially aggravating factors of mannitol-induced hyponatremia.

Kinetics of peritoneal dialysis with glycerol and glucose as osmotic agents.

The kinetics of peritoneal dialysis with dialysis fluid containing either glucose (1.36, 2.27, or 3.86 g/dl) or glycerol (0.85, 1.40, or 2.50 g/dl) as an osmotic agent was investigated in 24 single dwell studies of 360 min on four uremic patients. To compare the effects of glycerol and glucose on the transport of fluid and solutes across the peritoneal barrier, a new mathematical method for calculation of intraperitoneal dialysate volumes and diffusive mass transport coefficients (KBD) was developed. Radioisotopically tagged albumin (RISA) was added to the dialysate and the rate of fluid transfer was determined by the dilution principle with corrections applied for elimination of RISA from the peritoneal cavity. The elimination rate of RISA varied between 1 and 2 ml/min. KBD values for urea, creatinine, glucose, glycerol, and total protein were calculated during dialysate isovolemia. Glycerol appeared to increase the peritoneal permeability as indicated by an increased KBD value for total protein. The osmotic effect during the initial part of the dwell was similar to that of glucose, but the duration of effective ultrafiltration was shorter because glycerol was absorbed more rapidly than glucose, and ultrafiltered volumes after 6 h were significantly smaller than with glucose.