Summary
An i.v. infusion of mannitol was given over 15 min to 12 patients before they underwent intracranial surgery under general anesthesia. Samples of blood, CSF and urine were taken over 4 h.
Mannitol disappeared from plasma in a bi-exponential manner. The mean maximal plasma concentration was 4.08 mg/ml at 15 min, and at 4 h it had declined to 0.53 mg/ml. The mean distribution rate constant was 11.2 h−1, corresponding to a plasma distribution half-life of 0.11 h. The mean elimination rate constant was 0.41 h−1, the plasma half-life was 2.2 h, the central distribution volume was 16.31, and total plasma clearance was 100.4 ml/min. The mean concentration of mannitol in CSF during the 4 h period increased up to 0.10 mg/ml. There were marked interindividual differences in the concentration ratio blood/CSF, and the CSF concentration varied 7.5 fold between patients.
Optimal use of mannitol during neurosurgery requires further prolonged study of its pharmacokinetics.
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Smith WW, Finkelstein N, Smith HW (1940) Renal excretion of hexitols (sorbitol, mannitol and dulcitol) and their derivates (sorbitan, isomannide and sorbide) and of exogenous creatinine like chromogen in dogs and man. J Biol Chem 125: 231–250
Newman EV, Bordley J, Winternitz J (1944) Interrelationships of glomerularfiltration rate (mannitol clearance), extracellular fluid volume, surface area of body, and plasma concentration of mannitol; definition of extracellular fluid clearance determined by following plasma concentration after single injection of mannitol. Bull Johns Hopkins Hosp 75: 253–268
Wise BL, Chater N (1962) The value of hypertonic mannitol solution in decreasing brain mass and lowering cerebrospinal fluid pressure, J Neurosurg 19: 1038–1043
Simmons DH, Harvey RB, Hoshiko T (1954) Effect of sodium intake on sodium loss due to mannitoldiuresis. Am J Physiol 178: 182–188
Hostnik WJ, Powers SR Jr, Boba A, Stein AA (1960) Observations on the effect of mannitol on renal hemodynamics and 02 tension in the urine and renal vein. Surg Forum 10: 872–875
Stahl WM (1965) Effect of mannitol on the kidney. N Engl J Med 272: 381–386
Wendling MG, Eckstein JW, Abboud FM (1969) Effects of mannitol on the renal circulation. J Lab Clin Med 74: 541–547
Schettini A, Stahurski B, Young HF (1982) Osmotic and osmotic-loop diuresis in brain surgery. Effects on plasma and CSF electrolytes and ion excretion. J Neurosurg 56: 679–684
Barry KG, Berman AR (1961) Mannitol infusion. The acute effect of the intravenous infusion of mannitol on blood and plasma volumes. Engl J Med 264: 1085–1088
Schenkin HA, Goluboff B, Haft H (1962) The use of mannitol for the reduction of intracranial pressure in intracranial surgery. J Neurosurg 19: 897–901
Miller JD, Leech P (1975) Effects of mannitol and steroid therapy on intracranial volume-pressure relationship in patients. J Neurosurg 42: 274–281
James HE, Langfitt ThW, Kumar VS, Ghostine SY (1977) Treatment of intracranial hypertension. Analysis of 105 consecutive, continuous recordings of intracranial pressure. Acta Neurochir 36: 189–200
McGraw CP, Howard G (1983) Effect of mannitol on increased intracranial pressure. Neurosurg 13: 269–271
Pollav M, Fullenwider C, Roberts PA, Stevens FA (1983) Effect of mannitol and furosemide on blood-brain osmotic gradient and intracranial pressure. J Neurosurg 59: 945–950
Muizelaar JP, Lutz HA, Becker DP (1984) Effect of mannitol on ICP and CBF and correlation with pressure autoregulation in severely head-injured patients. J Neurosurg 61: 700–706
Rudehill A, Lagerkranser M, Lindquist C, Gordon E (1983) Effects of mannitol on blood volume and central hemodynamics in patients undergoing cerebral aneurysm surgery. Anesth Analg 62: 875–880
Gibaldi M, Perrier D (1975) Pharmacokinetics. Drugs and the pharmaceutical sciences. Marcel Dekker, New York
Laker MF, Bull HJ, Menzies IS (1982) Evaluation of mannitol for use as a probe marker of gastrointestinal permeability in man. Eur J Clin Invest 12: 485–491
Dominguez R, Corcoran AC, Page I (1947) Mannitol: Kinetics of distribution, excretion and utilization in human beings. J Lab Clin Med 32: 1192–1202
Cloyd JC, Snyder BD, Cleermans B, Bundlie SR, Blomquist CH, Lakatua DJ (1986) Mannitol pharmacokinetics and serum osmolality in dogs and humans. J Pharmacol Exp Ther 236: 301–306
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Anderson, P., Boréus, L., Gordon, E. et al. Use of mannitol during neurosurgery: Interpatient variability in the plasma and CSF levels. Eur J Clin Pharmacol 35, 643–649 (1988). https://doi.org/10.1007/BF00637601
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DOI: https://doi.org/10.1007/BF00637601