The effect of urea and invert sugar (Urevert) on cerebral damage occurring after cardiac arrest.

The human brain usually suffers irreversible damage if it endures anoxia for a period in excess of five minutes under normothermic conditions. Cardiac resuscitation techniques, properly applied according to present concepts, make it possible to restore the heart beat after long periods of anoxia, but the patient often dies or remains decerebrate as a result of the pathologic changes in the brain. Any method that will reduce the cerebral edema which follows cerebral anoxia will either prevent neurologic injury or decrease its severity. Hypothermia is beneficial in this respect, as shown by reports published by Williams and Spencer’ in 1959, Zimmerman and Spencer2 in 1959, Rosomoff et al.3 in 1960, and Wolfe4 in 1960. Urea has been shown to be an effective agent for reducing intracranial pressure and should be applicable to this syndrome. Fremont-Smith and Forbes,3 in 1927, on the basis of experiments in which they injected 50 per cent urea intraperitoneally in three cats, suggested that urea might prove useful clinically. However, no clinical tests were reported prior to the study by Javid and Settlage’ in 1956. Several experimental studies in dogs and rabbits indicated that urea is toxic when injected intravenously. Extensive clinical experience7’8” along with experimenta.l work on monkeys9”#{176} resulted in the establishment of a technique for administering urea in combination with 10 per cent invert sugar.t This seems to be the treatment of choice in reducing intracranial tension in man. This appears to be the only combination that consistently does not produce hemoglobinuria. It consists of 70 ml. of 10 per cent invert sugar in water for each 30 grams of lyophilized urea. The usi al dosage is 1 gram of urea per kilogram of body weight, but 1.5 gram per kilogram of body weight can be given safely. It was first believed that the diuretic effect of urea was the important factor in the reduction of cerebrospinal fluid pressure. However, Javid” observed that diuresis was not essential, especially in the early phase of cerebrospinal fluid pressure reduction, because there was a reduction in brain volume after intravenous injection of this urea solution at the time of operation, before there was any urinary output; also, there was a drop in cerebrospinal fluid pressure after administration of urea by gastric tube, before there was any diuresis. It appears that urea acts primarily on the basis of osmotic pressure differential between blood and cerebrospinal fluid, although the exact mechanism seems more complicated and requires further study. The two factors which limit the maintenance of cerebrospinal fluid pressure reduction are: (1) the rate at which the urea diffuses from the blood stream, and (2) the rate at which urea is ex-