Summary
Increased intracranial pressure due to brain oedema was produced in albino rabbits by combining a cryogenic lesion in the left hemisphere with the intraperitoneal administration of 6-aminonicotinamide (cytotoxic agent).
The most effective reduction in ICP (74%) was achieved when furosemide and mannitol were used in combination. When either mannitol or furosemide was employed alone, the average ICP reduction was approximately 53%. Peak ICP reduction occurred at 45 minutes with furosemide, 30 minutes with mannitol and furosemide combined, and at 60 minutes with a combination of mannitol and acetazolamide.
Also studied simultaneously in these animals were intracranial elastance (Em), brain water content, hemispheric water volume content, electrolytes, EEG, and gross pathology. Following therapy there was a statistically significant reduction of water content in the left hemisphere (cryogenic lesion) by all therapeutic modalities except with furosemide alone. In the right hemisphere the water content was reduced by furosemide and the furosemide-mannitol combination but not by the association of mannitol with acetazolamide. A significant decrease of brain sodium was noted only for the combination of mannitol and furosemide.
This study indicates that effective reduction of cytotoxic-cryogenic brain oedema and intracranial hypertension can be obtained with a variety of diuretic agents. From the standpoint of tissue dehydration, restoration of tissue electrolyte balance, and rate of ICP reduction, the combination of furosemide-mannitol appears to offer advantages over furosemide alone, or acetazolamide-mannitol.
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References
Baethmann, A., Lanksch, W., Schmiedek, P., Formation and treatment of cerebral edema. Neurochirurgia (Stuttg.)17 (1974), 37–47.
Baethmann, A., Reulen, H. J., Brendel, W., Die Wirkung des Antimetaboliten 6-Aminonicotinamid (6-ANA) auf Wasser- und Elektrolytgehalt des Rattenhirns und ihre Hemmung durch Nikotinsäure. Z. ges. exp. Med.146 (1968). 226–240.
Baethmann, A., van Harreveld, A., Water and electrolyte distribution in gray matter rendered edematous with a metabolic inhibitor. J. Neuropathol. Exp. Neurol.32 (1973), 408–423.
Bakey, L., Haque, I. U., Morphological and chemical studies in cerebral edema: I. Cold induced edema. J. Neuropathol. Exp. Neurol.23 (1964), 393–418.
Beks, J. W. F., ter Weeme, C. A., The influence of urea and mannitol on increased intraventricular pressure in cold-induced cerebral edema. Acta neurochir. (Wien)16 (1967), 97–107.
Bergland, R. M., Page, R. B., Howland, W. S., Furosemide: A non-osmotic diuretic for neurosurgical use. Presented at the 43rd Annual Meeting of the American Association of Neurological Surgeons, Miami Beach, Florida, April 8, 1975.
Billet, R., Injectable acetazolamide in neurosurgery. Sem. Hop. Ther.38 (1962), 248–251.
Blakemore, W. F., The fate of escaped plasma protein after thermal necrosis of the rat brain: An electron microscope study. J. Neuropathol. Exp. Neurol.28 (1969), 139–152.
Blasberg, R. G., Clearance of serum albumin from brain extracellular fluid: A possible role in cerebral edema. In: Dynamics of brain edema (Pappius, H. M., Feindel, W., eds.), pp. 98–102. New York: Springer. 1976.
Buhan, S., Effect of acetazolamide (Diamox) on the water content and distribution in various segments of the central nervous system. Acta Med. Jugosl.14 (1960), 341–352.
Buhrley, L., Reed, D. J., The effect of furosemide on sodium-22 uptake into cerebrospinal fluid and brain. Exp. Brain Res.14 (1972), 503–510.
Clasen, R. A., Cooke, P. M., Pandolfi, S., Boyd, D., Raimondi, A. J., Experimental cerebral edema produced by focal freezing: I. An anatomic study utilizing vital dye techniques. J. Neuropathol. Exp. Neurol.21 (1962), 579–596.
Clasen, R. A., Cooke, P. M., Pandolfi, S., Carnecki, G., Bryar, G., Hypertonic urea in experimental cerebral edema. Arch. Neurol.12 (1965), 424–434.
Clasen, R. A., Pandolfi, S., Casey, D., Jr., Furosemide and pentobarbital in cryogenic cerebral injury and edema. Neurology (Minneap.)24 (1974), 642–648.
Cottrell, J. E., Robustelli, A., Post, K., Turndorf, H., Furosemide- and mannitol-induced changes in intracranial pressure and serum osmolality and electrolytes. Anesthesiology47 (1977), 28–30.
Cserr, H., Cooper, D. N., Milhorat, T. H., Production, circulation, and absorption of brain interstitial fluid. In: Dynamics of brain edema (Pappius, H. M., Feindel, W., eds.), pp. 95–97. New York: Springer. 1976.
Demailly, P., Acetazolamide in intracranial hypertension. Gaz. Med. France69 (1962), 2123–2124.
Domer, F., Effects of diuretics on cerebrospinal fluid formation and potassium movement. Exp. Neurol.24 (1969), 54–64.
Ehrenrich, D. L., Burns, R. A., Alhman, R. W., Fazekas, J. F., Influence of acetazolamide on cerebral blood flow. Arch. Neurol.5 (1961), 227–232.
Einspruch, B. C., Clark, K., Further studies on the effectiveness of agents used to lower intracranial pressure. J. Neurosurg.23 (1965), 45–48.
Elliott, K. A. C., Jasper, H., Measurement of experimentally induced brain swelling and shrinkage. Amer. J. Physiol.157 (1949), 122–129.
Fenske, A., Samii, M., Reulen, H. M., Hey, O., Extracellular space and electrolyte distribution in cortex and white matter of dog brain in cold induced oedema. Acta neurochir. (Wien)29 (1973), 81–94.
Fishman, R. A., Brain edema. N. Engl. J. Med.293 (1975), 706–711.
Fossati, P., Delandtscheer, J. M., Galibert, P., Lopez-Pinto, C. M., Linguette, C., Laine, E., Importance of acetazolamide in the resuscitation of subjects with head injuries. Lille Med.8 (1963), 501–506.
Giacobini, E., Localization of carbonic anhydrase in the nervous system. Science134 (1961), 1524–1525.
Goluboff, B., Shenkin, H. A., Haft, H., The effects of mannitol and urea on cerebral hemodynamics and cerebrospinal fluid pressure. Neurology (Minneap.)14 (1964), 891–898.
Gray, W. D., Rauh, C. E., Shanahan, R. W., The intracellular localization of carbonic anhydrase and a carbonic anhydrase inhibitor in the brains of mice. Biochem. Pharmacol.8 (1961), 307–316.
Harbaugh, R. D., James, H. E., Marshall, L. F., Shapiro, H. M., Laurin, R., Acute therapeutic modalities for experimental vasogenic edema. Neurosurgery5 (1979), 656–665.
Harper, A. M., Bell, R. A., The failure of intravenous urea to alter the blood flow through the cerebral cortex. J. Neurol. Neurosurg. Psychiat.26 (1963), 69–70.
Herrmann, H. D., Neuenfeldt, D., Development and regression of a disturbance of the blood-brain barrier and of edema in tissue surrounding a circumscribed cold lesion. Exp. Neurol.34 (1972), 115–120.
James, H. E., Bruce, D. A., Welsh, F., Cytotoxic edema produced by 6-aminonicotinamide and its response to therapy. Neurosurgery3 (1978), 196–200.
James, H. E., Laurin, R., Intracranial hypertension and brain oedema in albino rabbits: Part I: Experimental models. Acta neurochir. (Wien)55 (1981), 213–226.
James, H. E., Langfitt, T. W., Kumar, V. S., Ghostine, S. Y., Treatment of intracranial hypertension: Analysis of 105 consecutive, continuous recordings of intracranial pressure. Acta neurochir. (Wien)36 (1977), 189–200.
Javid, M., Anderson, J., The effect of urea on cerebrospinal fluid pressure in monkeys before and after bilateral nephrectomy. J. Lab. Clin. Med.53 (1959), 484–489.
Johnston, I. H., Harper, A. M., The effect of mannitol on cerebral blood flow: An experimental study. J. Neurosurg.36 (1973), 461–471.
Kirkendall, W. M., Stein, J. H., Clinical pharmacology of furosemide and ethacrynic acid. Amer. J. Cardiol.22 (1968), 162–167.
Kister, S. J., Carbonic anhydrase inhibition: VI. The effect of acetazolamide on cerebrospinal fluid flow. J. Pharmacol. Exp. Ther.117 (1956), 402–405.
Klatzo, I., Neuropathological aspects of brain edema. J. Neuropathol. Exp. Neurol.26 (1967), 1–14.
Klatzo, I., Pathophysiological aspects of brain edema. In: Steroids and brain edema (Reulen, H. J., Schurmann, K., eds.), pp. 1–8. New York: Springer. 1972.
Klatzo, I., Piraux, A., Laskowski, E. J., The relationship between edema, blood-brain barrier and tissue elements in a local brain injury. J. Neuropathol. Exp. Neurol.17 (1958), 548–564.
Klatzo, I., Wisniewski, H., Steinwall, O., Streicher, E., Dynamics of cold injury edema. In: Brain edema (Klatzo, I., Seitelberger, F., eds.), pp. 554–563. New York: Springer. 1967.
Knopp, L. M., Atkinson, J. R., Ward, A. A., Jr., Effect of diamox on cerebrospinal pressure of cat and monkey. Neurology (Minneap.)7 (1957), 119–123.
Koch, A., Woodbury, D. M., Carbonic anhydrase inhibition and brain electrolyte composition. Amer. J. Physiol.198 (1960), 434–440.
Leech, P., Miller, J. D., Intracranial volume-pressure relationships during experimental brain compression in primates: I. Pressure responses to changes in ventricular volume. J. Neurol. Neurosurg. Psychiat.37 (1974), 1093–1098.
Leech, P., Miller, J. D., Intracranial volume-pressure relationships during experimental brain compression in primates: 3. Effect of mannitol and hyperventilation. J. Neurol. Neurosurg. Psychiat.37 (1974), 1105–1111.
Long, D., Maxwell, R., Choi, K. S., A new therapy regimen for brain edema. In: Dynamics of brain edema (Pappius, H. M., Feindel, W., eds.), pp. 293–300. New York: Springer. 1976.
Long, D. M., Maxwell, R. E., Choi, K. S., Cole, H. O., French, L. A., Multiple therapeutic approaches in the treatment of brain edema induced by a standard cold lesion. In: Steroids and brain edema (Reulen, H. J., Schurmann, K., eds.), pp. 87–94. New York: Springer. 1972.
Lopez-Pinto, C., Fosati, P., Galibert, P., Delandtsheer, J., Acetazolamide (Diamox) immediately following craniocerebral injuries. Acta Neurol. Belg.63 (1963), 298–314.
Maren, T. H., Carbonic anhydrase: Chemistry, physiology, and inhibition. Physiol. Rev.47 (1967), 595–781.
Maren, T. H., Robinson, B., Pharmacology of acetazolamide in man, with particular reference to the cerebrospinal fluid. Amer. J. Med.27 (1959), 317 (abstr.).
Miller, J. D., Volume and pressure in the craniospinal axis. Clin. Neurosurg.22 (1974), 76–105.
Miller, J. D., Leech, P., Effects of mannitol and steroid therapy on intracranial volume-pressure relationships in patients. J. Neurosurg.42 (1975), 274–281.
Pappius, H. M., Dayes, L. A., Hypertonic urea: Its effect on the distribution of water and electrolytes in normal and edematous brain tissue. Arch. Neurol.13 (1965), 395–402.
Pollay, M., Formation of cerebrospinal fluid: Relations of studies of isolated choroid plexus to the standing gradient hypothesis. J. Neurosurg.42 (1975), 665–673.
Raimondi, A. J., Evans, J. P., Mullan, S., Studies of cerebral edema: III. Alteration in the white matter: An electron microscopic study using ferritin as a labeling compound. Trans. Amer. Neurol. Assoc.87 (1962), 143–146.
Reed, D. J., The effect of furosemide on cerebrospinal fluid flow in rabbits. Arch. Int. Pharmacodyn. Ther.178 (1969), 324–330.
Reed, D. J., Woodbury, D. M., Effect of urea and acetazolamide on brain volume and cerebrospinal fluid pressure. J. Physiol. (Lond.)164 (1962), 265–273.
Reulen, H. J., Vasogenic brain oedema: New aspects in its formation, resolution and therapy. Brit. J. Anaesth.48 (1976), 741–752.
Reulen, H. J., Graham, R., Spatz, M., Klatzo, I., Role of pressure gradients and bulk flow in dynamics of vasogenic brain edema. J. Neurosurg.46 (1977), 24–35.
Rose, A. L., Millac, P., The treatment of benign intracranial hypertension with furosemide. J. Neurol. Sci.3 (1966), 606–608.
Schaul, N., Ball, G., Gloor, P., Pappius, H. M., The EEG in cerebral edema. In: Dynamics of brain edema (Pappius, H. M., Feindel, W., eds.), pp. 144–149. New York: Springer. 1976.
Shenkin, H. A., Goluboff, B., Haft, H., The use of mannitol for the reduction of intracranial pressure in intracranial surgery. J. Neurosurg.19 (1962), 897–901.
Steicher, E., Ferris, P. J., Prokop, J. D., Klatzo, I., Brain volume and thiocyanate space in local cold injury. Arch. Neurol.11 (1964), 444–448.
Thilmann, J., Zeumer, H., Untersuchungen zur Behandlung des Hirnödems mit hohen Dosen Furosemid. Dtsch. Med. Wochenschr.99 (1974), 932–935.
Torack, R. M., Terry, R. D., Zimmerman, H. M., The fine structure of cerebral fluid accumulation. I. Swelling secondary to cold injury. Amer. J. Pathol.35 (1959), 1135–1147.
Trotot, R., Remarks on the action of acetazolamide on certain closed cranial injuries. Gaz. Med. France68 (1961), 945–949.
Tschirgi, R. D., Frost, R. W., Taylor, J. L., Inhibition of cerebrospinal fluid formation by a carbonic anhydrase inhibitor, 2-acetylamino-1,3,4-thiadiazole-5-sulfonamide (Diamox). Proc. Soc. Exp. Biol. Med.87 (1954), 373–376.
Tutt, H. P., Pappius, H. M., Studies on the mechanisms of action of steroids in traumatized brain. In: Steroids and brain edema (Reulen, H. J., Schurmann, K., eds.), pp. 147–151. New York: Springer. 1972.
Vassallo, A., Cioffi, F., Strukelj, S., Il fursemid nel trattamento dell'edema cerebrale durante l'intervento chirurgico. Minerva Neurochir.15 (1971), 165–167.
Vernadakis, A., Woodbury, D. M., Electrolyte and amino avid changes in rat brain during maturation. Amer. J. Physiol.203 (1962), 748–752.
Weed, L. H., McKibben, P. S., Pressure changes in the cerebrospinal fluid following intravenous injection of solutions of various concentrations. Amer. J. Physiol.48 (1919), 512–530.
Wilkinson, H. A., Wepsic, J. G., Austin, G., Diuretic synergy in the treatment of acute experimental cerebral edema. J. Neurosurg.34 (1971), 203–208.
Wise, B. L., Effects of infusion on hypertonic mannitol on electrolyte balance and on osmolarity of serum and cerebrospinal fluid. J. Neurosurg.20 (1963), 961–967.
Wise, B. L., Chater, N., The value of hypertonic mannitol solution in decreasing brain mass and lowering cerebrospinal fluid pressure. J. Neurosurg.19 (1962), 1038–1043.
Wistrand, P., Nechay, B. R., Maren, T. H., Effects of carbonic anhydrase inhibition on cerebrospinal and intraocular fluids in the dog. Acta Pharmacol. (Kbh.)17 (1961), 315–336.
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Millson, C., James, H.E., Shapiro, H.M. et al. Intracranial hypertension and brain oedema in albino rabbits. Acta neurochir 56, 167–181 (1981). https://doi.org/10.1007/BF01407228
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DOI: https://doi.org/10.1007/BF01407228