The Use of Continuous Intravenous Administration of Hypotonic Sodium Chloride (Retan Treatment) in Acute Experimental Poliomyelitis in Monkeys
Authors: Kramer S. D. , Geer H. A. , Himes A. T. 
Published: January 2023

Discussion and Summary

Although our problem was primarily concerned with the effect of the continuous intravenous administration of large quantities of hypotonic salt solution upon monkeys infected with poliomyelitis virus, it was difficult for us to reconcile the underlying principles experimentally established by McKibbin, Kubie and others with the procedures now applied by Retan in human beings and recommended by this author to be used in experimentally infected monkeys. The original concept propounded by the earlier investigators suggested that continuous intravenous administration of hypotonic salt solution when carried out in conjunction with continuous spinal fluid drainage should, theoretically at least, accomplish a two-fold purpose. In the first place continuous spinal drainage should prevent hydration of the cerebrospinal axis, and in the second place it was expected that such drainage would serve to “wash out” some products of inflammatory reaction. In a personal communication from Doctor Retan we were informed that except for an occasional lumbar puncture for purposes of following the course of the disease the procedure as applied to human beings no longer includes spinal fluid drainage, and he furthermore recommended that continuous drainage be omitted in the experimental procedure in monkeys; lumbar or cistern taps to be done before treatment is begun and at the end of treatment, only a small portion of fluid being removed each time. It would appear, therefore, that the mechanism of the theoretical principles originally invoked in justification of the treatment is either imperfectly understood or does not apply. The explanation for the favorable results claimed by Retan following the application of this treatment to a variety of human ailments involving the central nervous system must await a clearer understanding of the mechanism or perhaps a more careful consideration of other factors that might have contributed to the favorable outcome in patients treated by this method.

In the seven experiments reported in this communication 25 infected and 2 uninfected monkeys were used. In the infected group 11 received treatment and 14 served as controls. Of the 11 treated monkeys, 3 died during the first treatment, 1 withstood 3, 1 withstood 4, and the remaining 6 animals all received 5 or more treatments. All of the treated monkeys that survived more than one treatment developed either frank paralysis (monkeys nos. 184, 186, 197, 201, 204 and 205) before death or gave definite histologic evidence of acute experimental poliomyelitis (monkeys nos. 178, 182, 184, 186, 197, 201, 204, and 205). Except for control monkey no. 206 which developed a severe diarrhea and died on the fourth day and treated monkey no. 186 which died on the same day as its corresponding control, the treated monkeys that withstood the treatment and lived long enough to develop paralysis consistently died at an earlier date than their controls. In fact one control monkey recovered, and a second one survived, although extensively paralyzed, until it was sacrificed two months later.

It would appear that the rate of administration of fluid as recommended by Doctor Retan (10 ml per pound per hour) was rather rigorous in the presence of infection, since in addition to the severe general edema of the subcutaneous tissues which developed in all of the treated animals, free fluid was found on autopsy in the pleural or abdominal cavities of at least two animals (monkeys nos. 178 and 182). That infection may have contributed to the unfavorable outcome in the treated animals is suggested by the relatively better reaction to the treatment of the two normal uninfected animals (experiment IV).

Although Retan recommends that treatment be commenced with the first evidence of pleocytosis in the spinal fluid, failure of the first two experiments to give favorable results led to initiation of treatment before the appearance of pleocytosis. In the case of monkey no. 201 treatment was initiated 12 hours after infection and when examination of the spinal fluid showed no pleocytosis. This animal received 8 full treatments and a total of 4700 ml of hypotonic salt solution. In spite of the treatment it developed paralysis before either control and died 10 days after infection whereas both controls survived; one control (monkey no. 200) made an excellent recovery and the second animal (monkey no. 202) survived for two months when it was finally sacrificed. Similarly, monkeys nos. 186, 194, 195, and 197 were all placed on treatment at varying intervals following infection but before the appearance of abnormal changes in the spinal fluid. In none of the 4 animals was there any observable benefit from this earlier treatment.

In order that the treatment might be given every possible chance to exhibit a sparing effect on the course of the disease, two recently isolated strains of virus were used in addition to the highly virulent and fatal monkey laboratory strain. However, no favorable effect due to treatment was apparent with the less virulent strains.

Furthermore, although it is conceded that the experimental infection in monkeys is more severe and only approximates the human disease, it must be also pointed out that this disease in the human being is so unpredictable as to make proper evaluation of the effect of this or any treatment difficult, particularly in the absence of comparable controls.

As indicated in the text, effort was made to observe the effects of the administration of large quantities of fluid upon the histologic structure of the central nervous system, as well as upon certain blood elements. Histologic study of comparable sections from the cords and medullae of treated and untreated animals failed to show any evidence of appreciable hydration of the treated animals over the controls. The changes which occurred in the hemoglobin and some of the other blood constituents (table 2) were not in excess of what might be expected as a result of dilution by the large quantities of fluid administered.