MANNITOL AND RENAL FUNCTION

1310 MANNITOL AND RENAL FUNCTION SIR,-Your leading article (June 1, p. 1183) draws welcome attention to the value of prophylactic mannitol in the prevention of acute reversible intrinsic renal failure (acute tubular necrosis) in certain high-risk situations such as operation on deeply jaundiced patients. However, we believe that the management suggested for the patient who has already been exposed to an often unforeseeable renal insult is defective. We have recently published our own views and recommendations on this important topic.1 If the patient is exposed to a known renal poison such as carbon tetrachloride and renal failure has not yet occurred, then a mannitol diuresis should immediately be instituted. But if the patient has had a shock " incident (surgical, traumatic, obstetric, or medical), and is oliguric and has a rising blood-urea, the first essential is to ensure that there is no deficit of water, electrolytes, plasma, or blood. It has been increasingly recognised in recent years that such deficits may be of greater magnitude than previously suspected and replacement must be prompt and adequate; monitoring of central In many venous pressure is often helpful in this regard. individuals diuresis will occur after appropriate correction of deficits, and mannitol should certainly not be used until one is sure that any deficiencies have been made good; indeed, if mannitol is used in prerenal failure, it may interfere with the conservation of sodium and water by the kidneys. However, when prerenal factors are corrected and oliguria persists, mannitol can, in certain patients, induce a diuresis.3 4 Your leader states that mannitol can do no good " Once acute tubular necrosis is established ", but gives no guide to the clinician as to how to determine that this stage has been reached. Consideration of the urine urea and urine osmolality in relation to the patient’s plasma urea and osmolality are of 4-s We believe that, when properly great value in this regard. administered, intravenous hypertonic mannitol solutions can be safely used, and will produce a diuresis in many patients during the earlier stages of acute reversible intrinsic renal failure and so forestall the development of the full-blown syndrome of " established acute tubular necrosis " with its still significant mortality. We have evidencethat a combination of three main factors determines the likelihood of such a response: the urine/plasma osmolality ratio, the time-lapse since the onset incident, and the circulatory state. While the infusion of 5% or 10% mannitol solution is appropriate for prophylactic administration over a 24-48-hour period,8 there is theoretical 9 10 and practical support for the use of small-volume infusions of hypertonic mannitol (e.g., 100 ml. 20% mannitol) in the patient in the early stages of intrinsic renal failure. We have used such infusions for 5 years without any evidence of untoward effects. In summary, we would advocate the use of mannitol in three distinct situations: (1) for prophylaxis in the high-risk patient, as you describe; (2) for immediate treatment of known renal poisons; and (3) to attempt to induce a diuresis, with appropriate safeguards, in suitable patients during the early stages of acute reversible intrinsic renal failure. R. G. LUKE University Department of Medicine, A. C. KENNEDY Royal Infirmary, Glasgow C.4.

will be avoided." May we warn your readers not infer that a diuresis will safeguard the patient from circulatory overloading ? If mannitol is given in hypertonic (e.g., 10%) solution, it may cause considerable expansion of the extracellular fluid even when the urine flow exceeds 5 ml. per minute. This is because mannitol retention occurs, and the retained mannitol draws water from the cells into the interstitial fluid and the plasma. Severe oliguria may follow, and the patient may then need dialysis for the relief of pulmonary aedema.1 Wessex Regional Renal Unit, Saint Mary’s General Hospital, A. POLAK Milton, A. G. MORGAN. Portsmouth.

overloading

to

"

SIR,-Your leading article states: " Provided the administration of mannitol is stopped as soon as it is apparent that it is not producing a diuresis, then circulatory

5. 6. 7.

Luke, R. G., Kennedy, A. C. Post-Grad. med. J. 1967, 43, 280. Stahl, W. M. N. Engl. J. Med. 1965, 272, 381. Barry, K. G., Malloy, J. P. J. Am. med. Ass. 1962, 179, 510. Luke, R. G., Linton, A. L., Briggs, J. D., Kennedy, A. C. Lancet, 1965, i, 980. Eliahou, H. E. Br. med. J. 1964, i, 807. Eliahou, H. E., Bata, A. Nephton, 1965, 2, 287. Luke, R. G., Briggs, J. D., Allison, M. A., Kennedy, A. C. Unpub-

8. 9. 10.

Moore, F. D. Surg. Clins N. Am. 1963, 43, 577. Braum, W. E., Lilienfield, L. S. Proc. Soc. exp. Biol. Med. 1963, 114, 1. Goldberg, A. H., Lilienfield, L. S. ibid. 1965, 119, 635.

1. 2. 3. 4.

lished.

MEDICAL ADMINISTRATION to Dr. Whitney’s letter (May 25, p. 1158). I write as chairman of the committee which drew up the memorandum which appears as Appendix xi of the British Medical Association’s evidence to the Review Body. This committee included all grades of administrative medical staff of regional hospital boards. While all R.H.B. administrative medical staff will share Dr. Whitney’s disappointment at the findings of the Review Body, it must be pointed out that the B.M.A. incorporated in their written evidence all that our committee eventually submitted to them. One of my colleagues and I discussed the memorandum with the negotiating committee of the B.M.A. and received every help from the committee and its officers. I was also given the opportunity of presenting our evidence direct to the Review Body and replying to questions put to me. Serious consideration was given to the proposal which Dr. Whitney makes that the assistant senior medical officer (A.S.M.O.) grade should have the consultant salary scale. The decision to put forward the principal-A.s.M.o. grade, which involved an increase in salary of 67% at the maximum of the grade, elicited from the Review Body the statement that they saw no justification at present (my italics) for the very large increases proposed. The Review Body stated that they did not underestimate the importance of administrative doctors, and one must hope that the thorough examination of the structure which the Health Department has proposed will do something towards giving effect to a recognition of their worth. I am sure that Dr. Whitney is right when he says there ought to be a better opportunity for the exchange of views at junior level of R.H.B. medical staff. It should not be impossible to arrange this. Chislehampton, Oxford. J. O. F. DAVIES.

SIR,-Irefer

IMMUNOGLOBULINS AND HYPOGAMMAGLOBULINÆMIA SIR,-In families in which sex-linked hypogammaglobulinasmia occurs it is of interest both to the family and to the physician to establish the presence or absence of the d;sorder in newborn boys. Dr. Soothill has measured serum immunoglobulins serially after birth in infants from families with hypogammaglobulinxmia of various types (May 11, p. 1001). In 4 children who subsequently were shown to have congenital sex-linked hypogammaglobulinxmia, the earliest deficiencies were found in serum IgM. The statement is made that IgM was present at birth, but the starting level was too low, and the rise was late and less than normal. These data are difficult to assess because the normal limits of IgM in healthy infants were not given--only a single line for

" healthy populations ". Recent developments in immunoglobulin quantitation have made it simple to measure immunoglobulins in minute quantities of unconcentrated saliva by electroimmunodiffusion. 1.

Morgan, A. G., Bennett, J., Polak, A. Q. Jl Med. (in the press).