Neurosurgical forum vertebral disc disease. J Neurosurg 42:389-396, 1975 3. Sussman BJ, Verly G" Collagenase and chymopapain 1975: a study of toxicity. Presented at the Annual Meeting of the American Association of Neurological Surgeons, Miami, 1975 RESPONSE: In our experimental protocol, we operated on monkeys with normal intervertebral disc spaces and have no information concerning the effects of collagenase upon degenerated monkey disc material. Comparison of our data with such studies (if available) might or might not show differences. Although there is always the possibility of misinterpretation of what an author wrote in his article, we believe no inaccuracies exist in the reference citations. We did not, as Dr. Sussman suggests, offer the opinion that the aim is to eliminate the predominantly mucopolysaccharide nucleus pulposus. We posed a question which still remains a valid and unanswered challenge. We believe that Dr. Sussman's own work is worthy of study. We do not believe that his critique in any way invalidates the results we have reported. W. EUGENESTERN, M.D. Los Angeles, California
Diabetes lnsipidus in Neurosurgical Patients To THE EDITOR: The paper by Drs. Shucart and Jackson (Shucart WA, Jackson I: Management of diabetes insipidus in neurosurgical patients. J Neurosurg 44:65-71, January, 1976) brings to mind an example of Pitressin-resistant diabetes insipidus that may be worth adding to the differential diagnoses listed by the authors in their excellent article. One year ago a patient of mine required emergency transfrontal decompression for pituitary apoplexy. He had been treated with 100 gm of mannitol intravenously at the beginning of the procedure for brain relaxation. An early expected diuresis resulted, but later as tumor mass was being gutted, the patient suddenly developed total diabetes insipidus with a maximum urine flow rate of 5 liters in one 45-minute period. This diuresis was completely unresponsive to a total of 50 units of aqueous Pitressin given in 5- and 10unit doses. A 5-unit intramuscular dose of Pitressin tannate in oil also had no effect. The total acute diuresis was 12 liters and ceased 768
about 2 hours postoperatively without further treatment. Within the first postoperative day urine-concentrating ability became normal on response to water deprivation, no further Pitressin was administered, and the patient had no clinical or laboratory evidence of diabetes insipidus thereafter. Consultation with the Division of Endocrinology, Wadsworth VA Hospital Los Angeles, California, led to the intriguing suggestion that this might have been an example of mannitol toxicity to the distal tubules in the kidneys? If such an effect of mannitol does indeed exist, then there may be a basis for recommending that mannitol be avoided and urea be substituted as an intraoperative osmotic agent, particularly in high-risk patients undergoing operations in the pituitary and hypothalamic regions. PETER SCHOSSBERGER,M.D. Pocatello, Idaho
Reference 1. Seely JF, Dirks JH: Micropuncture study of hypertonic mannitol diuresis in the proximal and distal tubule of the dog kidney. J Clin Invest 48:2330-2340, 1969 RESPONSE: Dr. Schossberger's fascinating case presents several problems. There are many data unavailable which makes an analytical discussion difficult. Particularly in the case of pituitary apoplexy, which we assume was in a pituitary tumor, there are questions raised of previously unrecognized hypopituitarism, possible hyponatremia, and perhaps hypotension. Changes in these factors with large doses of corticosteroids will have a significant effect on renal function. It would also be necessary to know the patient's preoperative electrolyte status and the composition of the fluids administered during surgery. The lack of response to Pitressin and the rapid recovery suggest a nephrogenic problem. We assume that disorders such as hypokalemia and hypercalcemia were not present. We would be very reluctant to question the use of mannitol for it is so commonly used and the described problem so rarely encountered. Neither of us has seen this previously. The term "toxicity" of the distal tubules in regard to mannitol therapy is ambiguous. Mannitol, particularly when given rapidly, normally markedly impairs distal J. Neurosurg. / Volume 44 / June, 1976
Neurosurgical forum tubule function. The tubules do not recapture any significant portion of the increased sodium and water load they receive. The causes for this are not perfectly understood but likely include the osmotic restraining effect of mannitol on water reabsorption and reduced interstitial osmolality in the renal medulla. Sodium transport appears to be rate-limited in the distal tubule, unlike the proximal tubule and Henle's loop where it is gradient-limited, and the current feeling is that this sodium-transport process in the distal tubules is overwhelmed by the high flow rates generated with osmotic diuretics. Mannitol also exerts effects on the proximal tubule and loop of Henle by mechanisms similar to those with which it affects the distal tubule; the major difference is the dilution of the extracellular sodium which diminishes the effectiveness of the gradient-induced sodium reabsorption. If we had to postulate an explanation based on the limited data available we would guess that this patient was mildly hyponatremic, and when given a dose of mannitol had an exaggerated response. This problem can easily be compounded by rapid administration of fluids to make up for the loss so the kidney becomes little more than a conduit for the parenterally administered fluids. Particularly if the administered fluids contain a lot of solute there will be an obligate diuresis which the already burdened kidney would not be able to handle. WILLIAMA. SHUCART, M.D. IVOR JACKSON, M.D. Boston, Massachusetts
In Memory of Henry L. Heyl To THE EDITOR: The superb obituary by J. L. Pool (Pool JL: Henry L. Heyl, 1906-1975. J Neurosurg 42:625-627, June 1975) would urge anyone who knew Henry Heyl long and well to recall and share personal remembrances of that remarkable man who somehow surmounted cruel iatrogenic cutoff of a top-flight neurosurgical career to become an international leader of the whole profession. I came under his benign influence at the MGH. Having absorbed 3 years of highpowered tutelage under Profs. Cushing and German (New Haven) followed by high priests Horrax, Poppen, and Ingraham (BosJ. Neurosurg. / Volume 44 / June, 1976
ton), he was the ideal chief resident to help genial Dr. J. C. White organize the MGH training program established by the kindest of chiefs, Jason Mixter. The willing-with-gusto underlings were treated as equals on the service. The hospital was rebuilding. I slept at the end of a patient corridor in an expanded closet across from HLH, who occupied a converted utility room which had a sunken mop-tub near the door. Up at 6:00 he would pump ship into that sink which would alert me to awaken the other galleymen for rounds and program huddle at 7:00 before breakfast and morning "cutting time" at 8:00. Per diem assignments were checked as to the OR, patients, teaching, do's and dont's re senior staffmen and cohorts, gripes, crits, and credits. We were faulted or commended wherever due with probity. HLH meted out time off with each one's recreationa', habitude in mind, himself included, which was usually for some venturesome sport. That spring he tried gliding north of Boston until his instructor got himself hung up in a treetop and had to be rescued by HLH and volunteer firemen. Later he hit the White Mountain snow trails and became the first MGH resident to crack an ankle skiing. Back on the floors with crutches after a week he became the first recipient of a new hospital rule: Any house ofricer sidelined by athletic trauma was suspended for the duration of his disability. This regulation ensued upon an era when the Director had decreed that all white pants pockets be sewed up to deter the house staff from standing around with hands in same. HLH departed Boston late 1939 for Birmingham, England, where he worked during the British blitz replacing neurosurgeons urgently needed for military duty. He returned to start a service at the Dartmouth Medical School, Hanover, N.H. Then came Pearl Harbor and another shift to North Africa with the MGH field unit until he was transferred to Colorado to cure a tuberculous spot. There, an avid fisherman, he found himself at bedrest, unable to cast for western steelheads. So he took up tying fly lures at bedside (which maintained finger dexterity). Henry got back to Dartmouth with regained health and in 5 years had developed a service second to one in New England. He also continued his off-time quest for wily and vexing trout and salmon. 769
Diabetes lnsipidus in Neurosurgical Patients To THE EDITOR: The paper by Drs. Shucart and Jackson (Shucart WA, Jackson I: Management of diabetes insipidus in neurosurgical patients. J Neurosurg 44:65-71, January, 1976) brings to mind an example of Pitressin-resistant diabetes insipidus that may be worth adding to the differential diagnoses listed by the authors in their excellent article. One year ago a patient of mine required emergency transfrontal decompression for pituitary apoplexy. He had been treated with 100 gm of mannitol intravenously at the beginning of the procedure for brain relaxation. An early expected diuresis resulted, but later as tumor mass was being gutted, the patient suddenly developed total diabetes insipidus with a maximum urine flow rate of 5 liters in one 45-minute period. This diuresis was completely unresponsive to a total of 50 units of aqueous Pitressin given in 5- and 10unit doses. A 5-unit intramuscular dose of Pitressin tannate in oil also had no effect. The total acute diuresis was 12 liters and ceased 768
about 2 hours postoperatively without further treatment. Within the first postoperative day urine-concentrating ability became normal on response to water deprivation, no further Pitressin was administered, and the patient had no clinical or laboratory evidence of diabetes insipidus thereafter. Consultation with the Division of Endocrinology, Wadsworth VA Hospital Los Angeles, California, led to the intriguing suggestion that this might have been an example of mannitol toxicity to the distal tubules in the kidneys? If such an effect of mannitol does indeed exist, then there may be a basis for recommending that mannitol be avoided and urea be substituted as an intraoperative osmotic agent, particularly in high-risk patients undergoing operations in the pituitary and hypothalamic regions. PETER SCHOSSBERGER,M.D. Pocatello, Idaho
Reference 1. Seely JF, Dirks JH: Micropuncture study of hypertonic mannitol diuresis in the proximal and distal tubule of the dog kidney. J Clin Invest 48:2330-2340, 1969 RESPONSE: Dr. Schossberger's fascinating case presents several problems. There are many data unavailable which makes an analytical discussion difficult. Particularly in the case of pituitary apoplexy, which we assume was in a pituitary tumor, there are questions raised of previously unrecognized hypopituitarism, possible hyponatremia, and perhaps hypotension. Changes in these factors with large doses of corticosteroids will have a significant effect on renal function. It would also be necessary to know the patient's preoperative electrolyte status and the composition of the fluids administered during surgery. The lack of response to Pitressin and the rapid recovery suggest a nephrogenic problem. We assume that disorders such as hypokalemia and hypercalcemia were not present. We would be very reluctant to question the use of mannitol for it is so commonly used and the described problem so rarely encountered. Neither of us has seen this previously. The term "toxicity" of the distal tubules in regard to mannitol therapy is ambiguous. Mannitol, particularly when given rapidly, normally markedly impairs distal J. Neurosurg. / Volume 44 / June, 1976
Neurosurgical forum tubule function. The tubules do not recapture any significant portion of the increased sodium and water load they receive. The causes for this are not perfectly understood but likely include the osmotic restraining effect of mannitol on water reabsorption and reduced interstitial osmolality in the renal medulla. Sodium transport appears to be rate-limited in the distal tubule, unlike the proximal tubule and Henle's loop where it is gradient-limited, and the current feeling is that this sodium-transport process in the distal tubules is overwhelmed by the high flow rates generated with osmotic diuretics. Mannitol also exerts effects on the proximal tubule and loop of Henle by mechanisms similar to those with which it affects the distal tubule; the major difference is the dilution of the extracellular sodium which diminishes the effectiveness of the gradient-induced sodium reabsorption. If we had to postulate an explanation based on the limited data available we would guess that this patient was mildly hyponatremic, and when given a dose of mannitol had an exaggerated response. This problem can easily be compounded by rapid administration of fluids to make up for the loss so the kidney becomes little more than a conduit for the parenterally administered fluids. Particularly if the administered fluids contain a lot of solute there will be an obligate diuresis which the already burdened kidney would not be able to handle. WILLIAMA. SHUCART, M.D. IVOR JACKSON, M.D. Boston, Massachusetts
In Memory of Henry L. Heyl To THE EDITOR: The superb obituary by J. L. Pool (Pool JL: Henry L. Heyl, 1906-1975. J Neurosurg 42:625-627, June 1975) would urge anyone who knew Henry Heyl long and well to recall and share personal remembrances of that remarkable man who somehow surmounted cruel iatrogenic cutoff of a top-flight neurosurgical career to become an international leader of the whole profession. I came under his benign influence at the MGH. Having absorbed 3 years of highpowered tutelage under Profs. Cushing and German (New Haven) followed by high priests Horrax, Poppen, and Ingraham (BosJ. Neurosurg. / Volume 44 / June, 1976
ton), he was the ideal chief resident to help genial Dr. J. C. White organize the MGH training program established by the kindest of chiefs, Jason Mixter. The willing-with-gusto underlings were treated as equals on the service. The hospital was rebuilding. I slept at the end of a patient corridor in an expanded closet across from HLH, who occupied a converted utility room which had a sunken mop-tub near the door. Up at 6:00 he would pump ship into that sink which would alert me to awaken the other galleymen for rounds and program huddle at 7:00 before breakfast and morning "cutting time" at 8:00. Per diem assignments were checked as to the OR, patients, teaching, do's and dont's re senior staffmen and cohorts, gripes, crits, and credits. We were faulted or commended wherever due with probity. HLH meted out time off with each one's recreationa', habitude in mind, himself included, which was usually for some venturesome sport. That spring he tried gliding north of Boston until his instructor got himself hung up in a treetop and had to be rescued by HLH and volunteer firemen. Later he hit the White Mountain snow trails and became the first MGH resident to crack an ankle skiing. Back on the floors with crutches after a week he became the first recipient of a new hospital rule: Any house ofricer sidelined by athletic trauma was suspended for the duration of his disability. This regulation ensued upon an era when the Director had decreed that all white pants pockets be sewed up to deter the house staff from standing around with hands in same. HLH departed Boston late 1939 for Birmingham, England, where he worked during the British blitz replacing neurosurgeons urgently needed for military duty. He returned to start a service at the Dartmouth Medical School, Hanover, N.H. Then came Pearl Harbor and another shift to North Africa with the MGH field unit until he was transferred to Colorado to cure a tuberculous spot. There, an avid fisherman, he found himself at bedrest, unable to cast for western steelheads. So he took up tying fly lures at bedside (which maintained finger dexterity). Henry got back to Dartmouth with regained health and in 5 years had developed a service second to one in New England. He also continued his off-time quest for wily and vexing trout and salmon. 769
