Effect of mannitol and furosemide on blood-brain osmotic gradient and intracranial pressure.
ABSTRACT The effect of mannitol (1.0 gm/kg) and furosemide (0.7 mg/kg), alone and in combination, on the blood-brain extracellular fluid and cerebrospinal fluid (CSF) osmotic gradient, elevated intracranial pressure (ICP), CSF and serum osmolality, and urine output was studied in 26 mongrel dogs. Mannitol and furosemide, when used together, produced a greater (62.4% versus 56.6%) and more sustained (5 hours versus 2 hours) fall in ICP than mannitol alone. This correlated with a prolongation of the reversal of the blood-brain osmotic gradient (-3.4 to + 38.5 mOsm/kg) and a rate of urine formation 15 times control values. There was a transient but not significant fall in serum Na+ with the combined treatment, but the arterial pressure did not vary from pretreatment levels. The results from this present study suggest that the distal loop diuretics in a dose of less than 1.0 mg/kg act synergistically with mannitol by causing preferential excretion of water over solute in the renal distal tubule, and thereby sustaining the osmotic gradient initially established by the mannitol infusion. It is possible, but unlikely in the doses used, that the additive effect of furosemide on reducing ICP in the presence of mannitol is due to interference with CSF formation or Na+ and H2O movement across the blood-brain barrier.
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ABSTRACT: : Mannitol is often used during intracranial surgery to improve surgical exposure. Furosemide is often added to mannitol to augment this effect. The concern exists, however, that the augmented diuresis caused by the addition of furosemide to mannitol may cause hypovolemia and hypoperfusion, hypokalemia, and hyponatremia. We examined the intraoperative safety of low-dose furosemide (0.3 mg/kg) combined with mannitol (1 g/kg). : We observed 23 patients in a double-blind, block randomized, placebo-controlled study to examine the effects of furosemide (0.3 mg/kg) when combined with mannitol (1 g/kg) on surgical brain relaxation for tumor surgery. Mannitol and the study drug (furosemide or placebo) were administered, and arterial blood gases with electrolytes (sodium, potassium, and lactic acid) and urine output volume were recorded every 30 minutes for 3 hours. Plasma sodium, potassium, and lactic acid concentrations, and interval urine outputs, were compared across time and between furosemide-placebo assignment groupings, with a P<0.01 considered significant. : Although mannitol produced a large volume of diuresis (1533±335 mL), the addition of a low dose of furosemide substantially increased both the rate of production of urine for the first 90 minutes after administration and the total volume of urine produced (2561±611 mL, P<0.001, compared with placebo group). The addition of furosemide did not produce a serum potassium level below 3.8±0.7 mEq/L, a serum sodium level below 128.3±3.4 mEq/L, or a serum lactic acid level above 2.4±0.9 mmol/L. There were no differences in the plasma potassium concentration, sodium concentration, or lactic acid concentration between the drug groups at any time point. : Despite an increase in urine output by as much as 67%, adding low-dose furosemide to mannitol does not seem to produce significant electrolyte derangements or hypovolemia compared with the administration of mannitol alone.Journal of neurosurgical anesthesiology 01/2013; 25(1):51-4. · 2.41 Impact Factor
Chapter: Traumatic Brain Injury[Show abstract] [Hide abstract]
ABSTRACT: Trauma of the head is a common cause of morbidity and mortality and continues to be an enormous public health problem. Tagliaferri and colleagues  compiling data from 23 European reports including findings from national studies from Denmark, Sweden, Finland, Portugal, Germany, and from regions within Norway, Sweden, Italy, Switzerland, Spain, Denmark, Ireland, the U.K., and France derived an aggregate hospitalized plus fatal traumatic brain injury (TBI) incidence rate of about 235 per 100,000, an average mortality rate of about 15 per 100,000, and a case fatality rate of about 11 per 100. Prevalence is estimated to reach a 317 per 100,000 persons living in Denmark with a work-precluding TBI sequelae in 1989 .01/2011: pages 1-91;
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ABSTRACT: BACKGROUND:: Mannitol and hypertonic saline (HS) are used by clinicians to reduce brain water and intracranial pressure and have been evaluated in a variety of experimental and clinical protocols. Administering equivolume, equiosmolar solutions in healthy animals could help produce fundamental data on water translocation in uninjured tissue. Furthermore, the role of furosemide as an adjunct to osmotherapy remains unclear. METHODS:: Two hundred twenty isoflurane-anesthetized rats were assigned randomly to receive equivolume normal saline, 4.2% HS (1,368 mOsm/L 25% mannitol (1,375 mOsm/L), normal saline plus furosemide (8 mg/kg), or 4.2% HS plus furosemide (8 mg/kg) over 45 min. Rats were killed at 1, 2, 3, and 5 h after completion of the primary infusion. Outcome measurements included body weight; urinary output; serum and urinary osmolarity and electrolytes; and brain, lung, skeletal muscle, and small bowel water content. RESULTS:: In the mannitol group, the mean water content of brain tissue during the experiment was 78.0% (99.3% CI, 77.9-78.2%), compared to results from the normal saline (79.3% [99.3% CI, 79.1-79.5%]) and HS (78.8% [99.3% CI, 78.6-78.9%]) groups (P < 0.001), whereas HS plus furosemide yielded 78.0% (99.3% CI, 77.8-78.2%) (P = 0.917). After reaching a nadir at 1 h, brain water content increased at similar rates for mannitol (0.27%/h [99.3% CI, 0.14-0.40%/h]) and HS (0.27%/h [99.3% CI, 0.17-0.37%/h]) groups (P = 0.968). CONCLUSIONS:: When compared to equivolume, equiosmolar administration of HS, mannitol reduced brain water content to a greater extent over the entire course of the 5-h experiment. When furosemide was added to HS, the brain-dehydrating effect could not be distinguished from that of mannitol.Anesthesiology 01/2013; · 5.16 Impact Factor