Influence of mannitol and furosemide, alone and in combination, on brain water content after fluid percussion injury.

BACKGROUND: Furosemide and mannitol are used to reduce intracranial pressure, but the impact of furosemide on edema of injured brain is unclear. The authors examined the effects of furosemide and mannitol, alone and in combination, on brain water content in brain-injured rats. METHODS: Anesthetized rats were subjected to a 2.2-atm left hemispheric fluid percussion injury. Two and three-quarters hours later, animals received 0.5, 1, 4, or 8 g/kg mannitol; 8 mg/kg furosemide; a combination of 4 g/kg mannitol plus 4 mg/kg furosemide; or 8 g/kg mannitol plus 8 mg/kg furosemide. One hour later (4 h after injury), plasma osmolality was measured, and hemispheric water content was determined by drying. Other animals were subjected to injury without drug treatment (impact only) or did not undergo injury (control). Pairwise group comparisons regarding the effects of mannitol and furosemide were restricted to only four groups: impact only, 8 g/kg mannitol, 8 mg/kg furosemide, and 8 g/kg mannitol plus 8 mg/kg furosemide. RESULTS: The water content of both hemispheres in the impact-only group was greater than in the control group (left greater than right). Mannitol, 8 g/kg, increased osmolality from 306 +/- 4 to 351 +/- 6 mOsm/kg (mean +/- SD) and reduced water content in the left hemisphere from 80.06 +/- 0.84% (impact only) to 78.24 +/- 0.73%. Furosemide, 8 mg/kg, had no effect on osmolality or water content. Brain water in animals treated with 8 g/kg mannitol plus 8 mg/kg furosemide did not differ from that seen with 8 g/kg mannitol alone. CONCLUSIONS: Mannitol increased plasma osmolality and reduced water content of the injured and contralateral hemispheres, whereas the authors observed no effect of furosemide when given either alone or in combination with mannitol.

Vasopressor agents without volume expansion as a safe alternative to venovenous bypass during cavaplasty liver transplantation.

BACKGROUND: Cavaplasty orthotopic liver transplantation (OLT) offers advantages for hepatectomy and implantation and eliminates the risk of outflow obstruction. However, it does require clamping of the cava. This study describes the use of a vasopressor without fluid expansion or venovenous bypass (VB) for hemodynamic control during the anhepatic phase. METHODS: The cavaplasty OLT technique was used routinely. A vasopressor was administered if the mean arterial blood pressure (MAP) was less than 60 mm Hg after clamping of the cava. If the MAP did not reach 60 mm Hg after adjusting the dosage of the vasopressor, femoro-axillary VB would be used. VB was also indicated for preexisting cardiac disease or for massive hemorrhage from severe portal hypertension and extensive adhesions. RESULTS: Among all the 121 adult cavaplasty OLTs, 33 were supported with VB and 50 received a vasopressor. The remaining 38 were excluded. However, baseline variables were well matched, except that preexisting cardiac disease was more frequent in the VB group. The median dosage of epinephrine was 0.07 microg/kg/min (range 0.01-0.6). The VB and vasopressor groups were similar in the reduction in mean MAP and the accumulation in arterial lactate upon clamping as well as in the central venous pressure upon unclamping. Postreperfusion hypotension was more frequent in the VB than in the vasopressor group (27.3% vs. 4.0%, P=0.006). There was no primary graft nonfunction or intraoperative right heart failure. One patient in the vasopressor group required postoperative temporary dialysis. Ninety-day patient and graft survival for the VB and vasopressor groups were 97.0% vs. 98.0% and 97.0% vs. 94.0%, respectively. CONCLUSION: Modest doses of vasopressor without volume expansion or VB can maintain hemodynamic stability during the anhepatic phase of cavaplasty OLT.

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.