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CHRONIC DEHYDRATION AND SODIUM DEPLETION IN PATIENTS WITH ESTABLISHED ILEOSTOMIES
740 There was no significant difference in the mean age of those with bradycardia compared with those who did not have this arrhythmia (56-3 years compared with 58-6
years). Discussion
The results confirm that bradycardia is significantly more common in posterior than in anterior myocardial infarction. James and Burch (1958) investigated the anatomy of the atrial arterial supply and found that in 60% of cases the right coronary artery, and in 40% the left coronary artery, gave rise to the sinus node artery. Since 90% of posterior infarcts are due to right coronary occlusion (James 1961) this can only account for a slight bias in incidence of sinus bradycardia in favour of posterior myocardial infarction. Bradycardia may be less common than expected in anterior myocardial infarction because the block is distal to the origin of the sinus node artery. Some cases of bradycardia may be due to other factors.
Drugs, especially morphine, may produce bradycardia (Fluck et al. 1967). Differences in drug dose and usage may account for the fact that, in contrast to the findings of Fluck et al. (1967), vasovagal syncope associated with severe pain was not seen at all during the present study, although it has, rarely, been observed since. No patient with sinus bradycardia alone died, although one had ventricular fibrillation treated successfully and there were a number of other serious arrhythmias. Table ill shows that the prognosis for patients with sinus bradycardia is good, as was noted by Julian et al. (1964). The association between posterior infarction and bradycardia due to nodal rhythm or heart-block is easier to explain since in 83% of cases the atrioventricular node is supplied from the right coronary artery (James and Burch 1958), and posterior infarction is usually due to occlusion of the right coronary artery. The high mortality in patients with non-sinus bradycardia is striking, and it should also be noted that 4 patients in this group had ventricular fibrillation which was successfully treated. Many of these patients were clinically shocked and moribund on admission. Harris and Bluestone (1966) consider that bradycardia due to nodal rhythm or heart-block is an indication for endocardial pacing, and some of the patients were paced. The value of pacing in this context is controversial: some patients undoubtedly benefit, but the procedure is not without considerable risk and difficulty (Paulk and Hurst 1966, Lassers and Julian 1967).
finding of an abnormally slow heart-rate, in the of myocardial infarction, is considered to be an urgent indication for E.C.G. investigation and, where possible, transference to a special unit for further care. The
context
We thank physicians in administrative charge of the coronary-care unit-Prof. K. W. Donald, Dr. M. F. Oliver, and Dr. D. G. Julianfor permission to publish the clinical data, and Dr. Julian and Dr. Oliver for their help and encouragement in the preparation of this paper. Requests for reprints should be addressed to M. G. REFERENCES
Fluck, D. C., Olsen, E., Pentecost, B. L., Thomas, M., Fillmore, S. J. Shillingford, J. P., Mounsey, J. P. D. (1967) Br. Heart J. 29, 170. Harris, A., Bluestone, R. (1966) ibid. 28, 631. James, T. N. (1961) Circulation, 24, 761. Burch, G. E. (1958) ibid. 17, 90. Julian, D. G., Valentine, P. A., Miller, G. G. (1964) Am. J. Med. 37, 915. Lassers, B. W., Julian, D. G. (1967) Br. med. J. ii, 506. Lawrie, D., Greenwood, T. W., Goddard, M. D., Harvey, A., Donald, K. W., Julian, D. G., Oliver, M. F. (1967) Lancet, ii, 109. Paulk, E. A., Jr., Hurst, T. W. (1966) Am. J. Cardiol. 17, 695. World Health Organisation (1959) Tech. Rep. Ser. W.H.O. no. 168, p. 18. —
CHRONIC DEHYDRATION AND SODIUM DEPLETION IN PATIENTS WITH ESTABLISHED ILEOSTOMIES A. M. CLARKE M.B. N.Z., F.R.A.C.S. SENIOR LECTURER IN SURGERY
A. CHIRNSIDE M.B. N.Z., F.R.C.S., F.R.A.C.S. RESIDENT SURGEON AND SURGICAL TUTOR, CHRISTCHURCH HOSPITAL
G. L. HILL M.B. Otago
GILLIAN POPE
RESEARCH FELLOW
LECTURER (SCIENCE), DEPARTMENT OF SURGERY
M.Sc.
IN SURGERY
M. K. STEWART M.Sc. SCIENTIFIC
OFFICER,
MASS SPECTROMETRY
INSTITUTE OF NUCLEAR
From the
SCIENCES,
SECTION,
LOWER HUTT
Department of Surgery, University of Otago Medical School, Dunedin, New Zealand Total
and total
Summary sodiumbody were measured in water
a
exchangeable
group of ileos-
tomy patients who were otherwise well. Compared with a control group, the ileostomy patients showed on the average an 11% reduction in total body water and a 7% deficit in total exchangeable sodium. The urinary excretion of water and sodium in the ileostomy patients was also significantly reduced. Introduction
PATIENTS who have
susceptible (Gallagher
long-established ileostomies are dehydration and sodium depletion al. 1962). The demonstration by these
to acute et
workers of diminished renal excretion of water and sodium in ileostomy patients who were otherwise in good health suggests that the increased risk of acute depletion is due in part to a pre-existing chronic deficit of water and sodium. This chronic dehydration may further contribute to the hazards of ileostomy by being responsible for the frequency of renal calculi in such patients (Deren et al. 1962, Maratka and Nedbal 1964, Bennett and Jepson
1966). The indirect evidence that ileostomy leads to chronic and sodium depletion is therefore strong, but this has not been confirmed by direct studies of body composition. We have therefore measured total body water (T.B.w.) and total exchangeable sodium (Nae) in a group of patients with established ileostomies who are otherwise well, and we have compared our findings with similar measurements made on a group of healthy controls. water
Methods
Twenty-one patients with established ileostomies and a control group of twenty-one were investigated as outpatients. All the patients had undergone total colectomy more than 3 months previously for chronic ulcerative colitis (nineteen patients) and polyposis coli (two patients). The investigation of each group extended through the spring of 1966 and autumn of 1967.
Climatic conditions for each group
were
therefore
comparable. No attempt was made to match patients accurately with controls, but the two groups were comparable (table I). The ileostomy group was on the average slightly larger than the control group, but this difference is not significant. Total exchangeable sodium was measured by the method described by Veall and Vetter (1958) using the isotope 24Na. The estimation of total body water was based on a 3-hour equilibration period after an oral dose of the isotope deuterium oxide (D2O).
741 TABLE I-COMPARABLE DATA
specimens were lost as a result of breakage). The correlation coefficient (r) for the combined data is 0-85 (n<001). Though there is considerable overlap, the two groups appear separate. Thus, when the regression lines of each group are fitted, only three ileostomy patients lie above the regression line for the controls. The slopes of the regression lines of the two groups are not significantly different, but the difference between their intercepts at either mean weight for the control group or the ileostomy Thus, when compared with group is significant (P<0-01). the controls, the ileostomy patients, as a group, are serum
the investigation diet and daily routine, apart from attendances at the laboratories, remained unchanged. At the first visit, patients and controls were weighed and measured, and were given a dose of 25 fLC24Na in physiological saline solution by mouth. The next day, 21 hours after the beginning of the investigation, a carefully weighed dose of about 10 g. D20 was taken by mouth, and at 24 hours 40 ml. of venous blood was collected, together with the 24-hour specimens of urine and fasces. The blood was allowed to clot, and the serum was separated. The sodium space was calculated from measurements of the radioactivity of the serum, urine, fxces, and counting standards which were made in a well-type scintillation counter (’ Echo N.664c ’). The concentrations of sodium in the serum and urine were determined by flame photometry (EEL). The total exchangeable sodium (Nae) was then calculated from the formula:
During
two
dehydrated. Mean body water for ileostomy patients is 0-485 litre per kg. B.w., and for the controls is 0-547 litre per kg. B.w. The " average " patient (weight 68 kg.) has therefore
Nae (mEq.)=Na-space (litres) x serum [Na] (mEq./litre). The concentration of D20 in body water was determined by a double-collection mass spectrometer of the ’ Nier II ’ type (Kirshenbaum 1951) built.at the Institute of Nuclear Sciences. The method used was that described by Friedman (1953), the sample of venous serum having previously been vacuum distilled and quantitatively converted to hydrogen gas over zinc at 395°C. Body water was then calculated from the formula:
The results
were
expressed
as
litres of
body
water.
Results
Total Body Water In fig. 1 T.B.W. is plotted against body-weight (B.W.) for the ileostomy patients and nineteen controls (two D20
Fig. 2-Relation of total exchangeable sodium
to
body-weight.
of 33-0 litres compared with that of his control counterpart of 372 litres-a deficit of 4-2 litres, or 11 % of normal T.B.w.
a T.B.w.
Fig. 1-Relation of total body
water to
body-weight.
Total Exchangeable Sodium Total exchangeable sodium of the ileostomy patients and twenty of the controls are plotted against B.w. in fig. 2. (An error in collection invalidated the measurement in one of the controls.) The correlation coefficient (r) for the combined data is 0-80 (p < 0-01). There is rather more overlap between the two groups than there is in the case of T.B.w. The slopes of the regression lines are not significantly different, but the difference between their intercepts at mean weight for either the control group or the ileostomy group is significant (p < 005). Thus, compared with the controls, the ileostomy patients as a group are sodium depleted. The mean total exchangeable sodium for ileostomy patients is 38-8 mEq. per kg. B.w. and for the controls 41-8 mEq. per kg. B.w. The hypothetical average patient (weight 68 kg.) has therefore a total exchangeable sodium of 2638 mEq. compared with that of his average control counterpart of 2842 mEq. This represents an average deficit of 204 mEq. or about 7% of normal total exchangeable sodium. The observed difference could be due to a lower " sodium space " in the ileostomy patients, or to a lowered
742 TABLE II-SERUM-SODIUM CONCENTRATIONS AND SODIUM SPACES
[Na+]. Table 11 shows that the sodium deficit associated with ileostomy is almost entirely due to the contraction of the " sodium space " or that fluid compartment through which sodium is distributed. When body water and exchangeable sodium are related to B.w., the most dehydrated patients are also the ones most depleted of sodium (fig. 3). This correlation is more apparent for the ileostomy patients who are spread than for the conover a wide range (r==0-77, p < 0001), trols who are collected more compactly at the upper end of the whole group (r==0-64, P < 001).
serum
estimation of T.B.W. primarily because of the availability of high resolution mass spectrometry. Additional to both and controls radioactivity by exposure patients Resolution to less than 5 p.p.m. was thus avoided. allowed the use of a small oral dose of D20 calculated to give serum concentrations of the order of twice the background concentration. Equilibration of deuterium oxide, after oral administration is extremely rapid (table III), and venous sampling at three hours is valid. This is supported by the data of Schloerb et al. (1950).
24-hour Urinary Volume and Sodium Excretion The 24-hour urinary volumes and sodium excretion for each group are plotted in fig. 4. The mean volume of the control group is 1447 ml. and the mean volume of the ileostomy group is 1097 ml. The difference is highly significant (P< 0-001). The mean sodium output of the control group is 147 mEq., and that of the ileostomy patients is 105 mEq. The difference is highly significant
(P < 0.001). There is no correlation between urinary volume or urinary sodium excretion on the one hand, and T.B.w. or total exchangeable sodium on the other. The ileostomy
4-24-hour excretion.
Fig.
urinary volume and 24-hour urinary sodium
Horizontal lines represent mean values for each group. nificance of difference between means.
r=sig-
The normal values for total exchangeable sodium and that we obtained are comparable to those obtained others by (Moore 1963). The deficit of body sodium and water in our ileostomy patients confirms the suspicion, based on indirect evidence, that ileostomy is associated with chronic sodium depletion and dehydration. This is the sort of body compositional change which might be expected in patients who suffer continued loss of abnormal amounts of alimentary secretions. The assessment of the magnitude of the chronic sodium " and water deficits by calculating these for the " average patient is at best very approximate. The information cannot readily be related to the individual patient. An average deficit of 7% exchangeable sodium and 11 % body water, however, is considerable; though many patients with ileostomies are probably not as depleted as this, many are likely to be considerably more so. None of our patients had significant symptoms attributable to dehydration or sodium depletion. No patient complained of chronic thirst. Normal tonicity of body fluids was probably preserved, and this is supported by T.B.W.
Fig. 3-Relation of body kg. body-weight).
water content to
exchangeable sodium (per
with low values for body water and body sodium exhibit random variation in urinary water and sodium excretion which are of the same magnitude as the patients whose body compositional measurements fall within the normal range. Discussion Measurement of total exchangeable sodium and T.B.W. in ileostomy patients and controls revealed considerable variability within each group. Nevertheless it was possible to demonstrate by direct measurement that the ileostomy patients, who are otherwise well, are as a group significantly dehydrated and sodium depleted. We used D20 in preference to tritium as a tracer for
patients
TABLE
III-EQUILIBRATION
OF DEUTERIUM OXIDE
DOSE OF
Estimated million and
AFTER AN ORAL
background concentration (151) is ± 1-0 parts per concentration of 365 is less than 5-0 p.p.m.
error at
at a
(D2O)
10 g
743 the normal concentrations of serum-sodium in the ileostomy group. Several of the patients showed lassitude, but this was not related to the severity of sodium depletion as measured by total exchangeable sodium. The findings suggest that there was considerable isotonic contraction of the space through which sodium is distributed. The remainder of the water deficit probably represents a much smaller reduction of the intracellular water. Nearly half of our patients were taking extra salt on our advice during the investigation; this, together with the possible effect of a cooler climate may have resulted in a greater output of sodium (105 mEq.) than that reported by Gallagher et al. (1962)-70 mEq. per day. None the less, there is no doubt that our ileostomy group also showed renal conservation of water and sodium when compared with the controls. Contrary to what might be expected, patients who are the most severely depleted of water and sodium do not exhibit the most pronounced renal conservation of sodium and water. The reduced renal excretion of these substances in the group as a whole probably reflects the situation where less water and sodium are available for excretion by the kidney after ileostomy loss has occurred. The average daily deficit in urinary volume (350 ml.) and sodium excretion (42 mEq.) comes very close to the normal daily loss of these substances in ileostomy effluent. Apparently, any functional adaptation by the kidney which might have resulted from chronic water and sodium depletion was still obscured by random variations in dietary intake. Sabo et al. (1967) reported that ileostomy in the dog produced considerable debility with gross loss of weight. During the 11-week period of study, a relative increase in body water and an absolute increase in extracellular fluid volume (measured by thiocyanate) was observed. These observations are in accord with changes in body composition after major operations (Lyon et al. 1949, Ariel et al. 1950, Shires et al. 1961) and during profound debilitating illness (Moore 1959), but the findings are in no way comparable to the present investigation where patients have long regained nutritional equilibrium. The study was supported by the Medical Research Council of New Zealand. The assistance of Mr. G. F. S. Spears with the statistical analyses is gratefully acknowledged. We are grateful for the cooperation of the surgeons in Dunedin and Christchurch whose patients are included in this study, and the assistance and encouragement of Mr. T. A. Rafter and Dr. J. R. Hulston of the Institute of Nuclear Sciences. Requests for reprints should be addressed to A. M. C. REFERENCES
Ariel, I. M., Kremen, A. J., Wangensteen, O. H. (1950) Surgery, St. Louis, 27, 827. Bennett, R. C., Jepson, R. P. (1966) Aust. N.Z. J. Surg. 36, 153. Deren, J. J., Porush, J. G., Levitt, M. F., Khilnani, M. T. (1962) Ann. intern. Med. 56, 843. Friedman, I. (1953) Geochim. Cosmochim, 4, 89. Gallagher, N. D., Harrison, D. D., Skyring, A. P. (1962) Gut, 4, 322. Kirshenbaum, I. (1951) Physical Properties and Analysis of Heavy Water. London. R. P., Stanton, J. R., Freis, E. D., Smithwick, R. H. (1949) Surgery Gynec. Obstet. 89, 9. Maratka, Z., Nedbal J. (1964) Gut, 5, 3. Moore, F. D. (1959) Metabolic Care of the Surgical Patient. Philadelphia. — (1963) The Body Cell Mass and its Supporting Environment.
Lyon,
Philadelphia. Sabo, J. C., Enquist, I. F., Golding, M. R., Solomon, N., Fierst, S. M. (1967) Am. J. Surg. 113, 149. Schloerb, P. R., Friis-Hansen, B. J., Edelman, I. S., Solomon, A. K., Moore, F. D. (1950) J. clin. Invest. 29, 1296. Shires, P., Williams, J., Brown, F. (1961) Ann. Surg. 154, 803. Veall, N., Vetter, H. (1958) Radioisotope Techniques in Clinical Research and
Diagnosis. London.
SERUM-CREATINE-KINASE IN CASES OF STROKE, HEAD INJURY, AND MENINGITIS H. DUBO M.D. Manitoba VISITING
FELLOW, REGIONAL NEUROLOGICAL CENTRE, NEWCASTLE GENERAL HOSPITAL
DOROTHY C. PARK M.Sc. Durh. SENIOR RESEARCH
BIOCHEMISTRY,
ASSOCIATE,
DEPARTMENT OF CLINICAL
UNIVERSITY OF NEWCASTLE UPON TYNE
R. J. T. PENNINGTON D.Sc. Birm., F.R.S.E. READER IN
NEUROCHEMISTRY, DEPARTMENT OF CLINICAL BIOCHEMISTRY, UNIVERSITY OF NEWCASTLE UPON TYNE
R. M. KALBAG F.R.C.S. NEUROSURGEON, REGIONAL NEUROLOGICAL CENTRE, NEWCASTLE GENERAL HOSPITAL
JOHN N. WALTON T.D., M.D. Durh., F.R.C.P. NEUROLOGIST, REGIONAL NEUROLOGICAL CENTRE, NEWCASTLE GENERAL HOSPITAL, NEWCASTLE UPON TYNE 4
serum-creatine-kinase (C.K.) was studied in cases of head injury, acute cerebrovascular accident, and meningitis. Each of 14 patients with a head injury had raised serum-C.K. values. Of 21 patients with acute strokes, 15 had raised values. Of 7 patients with meningitis, 2 had raised values. In all patients having sufficiently high levels of serum-C.K. for isoenzyme fractionation, the circulating enzyme was found to be derived largely from muscle. No definite clinical correlations or prognostic inferences could be determined from the serum-C.K. levels. There is no clear evidence that this enzyme leaks from the brain into the blood-serum in any of the neurological disorders studied. Why muscle C.K. is often much increased in the serum in such cases remains unclear. Summary
The
Introduction
IN the search for an enzyme which could be useful as a clinical guide to the diagnosis and prognosis of various forms of cerebral disease, previous studies using aspartate aminotransferase (G.O.T.) and lactate dehydrogenase have not been fruitful (Hsieh and Blumenthal 1956, Wakim and Fleischer 1956, Chinskey and Sherry 1957, Liebermann et al. 1957, Brodel et al. 1959). Creatine kinase (c.K.) has received the most attention of late, because it is present in high concentrations in brain tissue and relatively little is found in all other tissues except skeletal and cardiac muscle (Tanzer and Gilvarg 1959, Colombo et al. 1962). Acheson et al. (1965) found that the serum-c.K. level was raised during the acute phase of cerebral infarction and later returned to normal. Schiavone and Kaldor (1965) reported that more than 60% of patients with cerebral dysfunction have raised serum-c.K. values. In a preliminary study, Kalbag et al. (1966) found a significant rise of serum-c.K. levels in cases of acute head injury and in cerebrovascular accidents. However, the isoenzyme pattern of the serum-creatine-kinase in the cases studied corresponded with that of muscle-creatinekinase rather than the brain enzyme. Because of this unexpected finding, the present study was undertaken in order to try to correlate serial C.K. enzyme and isoenzyme levels in cerebral disorders with the clinical state of the
patients.
years). Discussion
The results confirm that bradycardia is significantly more common in posterior than in anterior myocardial infarction. James and Burch (1958) investigated the anatomy of the atrial arterial supply and found that in 60% of cases the right coronary artery, and in 40% the left coronary artery, gave rise to the sinus node artery. Since 90% of posterior infarcts are due to right coronary occlusion (James 1961) this can only account for a slight bias in incidence of sinus bradycardia in favour of posterior myocardial infarction. Bradycardia may be less common than expected in anterior myocardial infarction because the block is distal to the origin of the sinus node artery. Some cases of bradycardia may be due to other factors.
Drugs, especially morphine, may produce bradycardia (Fluck et al. 1967). Differences in drug dose and usage may account for the fact that, in contrast to the findings of Fluck et al. (1967), vasovagal syncope associated with severe pain was not seen at all during the present study, although it has, rarely, been observed since. No patient with sinus bradycardia alone died, although one had ventricular fibrillation treated successfully and there were a number of other serious arrhythmias. Table ill shows that the prognosis for patients with sinus bradycardia is good, as was noted by Julian et al. (1964). The association between posterior infarction and bradycardia due to nodal rhythm or heart-block is easier to explain since in 83% of cases the atrioventricular node is supplied from the right coronary artery (James and Burch 1958), and posterior infarction is usually due to occlusion of the right coronary artery. The high mortality in patients with non-sinus bradycardia is striking, and it should also be noted that 4 patients in this group had ventricular fibrillation which was successfully treated. Many of these patients were clinically shocked and moribund on admission. Harris and Bluestone (1966) consider that bradycardia due to nodal rhythm or heart-block is an indication for endocardial pacing, and some of the patients were paced. The value of pacing in this context is controversial: some patients undoubtedly benefit, but the procedure is not without considerable risk and difficulty (Paulk and Hurst 1966, Lassers and Julian 1967).
finding of an abnormally slow heart-rate, in the of myocardial infarction, is considered to be an urgent indication for E.C.G. investigation and, where possible, transference to a special unit for further care. The
context
We thank physicians in administrative charge of the coronary-care unit-Prof. K. W. Donald, Dr. M. F. Oliver, and Dr. D. G. Julianfor permission to publish the clinical data, and Dr. Julian and Dr. Oliver for their help and encouragement in the preparation of this paper. Requests for reprints should be addressed to M. G. REFERENCES
Fluck, D. C., Olsen, E., Pentecost, B. L., Thomas, M., Fillmore, S. J. Shillingford, J. P., Mounsey, J. P. D. (1967) Br. Heart J. 29, 170. Harris, A., Bluestone, R. (1966) ibid. 28, 631. James, T. N. (1961) Circulation, 24, 761. Burch, G. E. (1958) ibid. 17, 90. Julian, D. G., Valentine, P. A., Miller, G. G. (1964) Am. J. Med. 37, 915. Lassers, B. W., Julian, D. G. (1967) Br. med. J. ii, 506. Lawrie, D., Greenwood, T. W., Goddard, M. D., Harvey, A., Donald, K. W., Julian, D. G., Oliver, M. F. (1967) Lancet, ii, 109. Paulk, E. A., Jr., Hurst, T. W. (1966) Am. J. Cardiol. 17, 695. World Health Organisation (1959) Tech. Rep. Ser. W.H.O. no. 168, p. 18. —
CHRONIC DEHYDRATION AND SODIUM DEPLETION IN PATIENTS WITH ESTABLISHED ILEOSTOMIES A. M. CLARKE M.B. N.Z., F.R.A.C.S. SENIOR LECTURER IN SURGERY
A. CHIRNSIDE M.B. N.Z., F.R.C.S., F.R.A.C.S. RESIDENT SURGEON AND SURGICAL TUTOR, CHRISTCHURCH HOSPITAL
G. L. HILL M.B. Otago
GILLIAN POPE
RESEARCH FELLOW
LECTURER (SCIENCE), DEPARTMENT OF SURGERY
M.Sc.
IN SURGERY
M. K. STEWART M.Sc. SCIENTIFIC
OFFICER,
MASS SPECTROMETRY
INSTITUTE OF NUCLEAR
From the
SCIENCES,
SECTION,
LOWER HUTT
Department of Surgery, University of Otago Medical School, Dunedin, New Zealand Total
and total
Summary sodiumbody were measured in water
a
exchangeable
group of ileos-
tomy patients who were otherwise well. Compared with a control group, the ileostomy patients showed on the average an 11% reduction in total body water and a 7% deficit in total exchangeable sodium. The urinary excretion of water and sodium in the ileostomy patients was also significantly reduced. Introduction
PATIENTS who have
susceptible (Gallagher
long-established ileostomies are dehydration and sodium depletion al. 1962). The demonstration by these
to acute et
workers of diminished renal excretion of water and sodium in ileostomy patients who were otherwise in good health suggests that the increased risk of acute depletion is due in part to a pre-existing chronic deficit of water and sodium. This chronic dehydration may further contribute to the hazards of ileostomy by being responsible for the frequency of renal calculi in such patients (Deren et al. 1962, Maratka and Nedbal 1964, Bennett and Jepson
1966). The indirect evidence that ileostomy leads to chronic and sodium depletion is therefore strong, but this has not been confirmed by direct studies of body composition. We have therefore measured total body water (T.B.w.) and total exchangeable sodium (Nae) in a group of patients with established ileostomies who are otherwise well, and we have compared our findings with similar measurements made on a group of healthy controls. water
Methods
Twenty-one patients with established ileostomies and a control group of twenty-one were investigated as outpatients. All the patients had undergone total colectomy more than 3 months previously for chronic ulcerative colitis (nineteen patients) and polyposis coli (two patients). The investigation of each group extended through the spring of 1966 and autumn of 1967.
Climatic conditions for each group
were
therefore
comparable. No attempt was made to match patients accurately with controls, but the two groups were comparable (table I). The ileostomy group was on the average slightly larger than the control group, but this difference is not significant. Total exchangeable sodium was measured by the method described by Veall and Vetter (1958) using the isotope 24Na. The estimation of total body water was based on a 3-hour equilibration period after an oral dose of the isotope deuterium oxide (D2O).
741 TABLE I-COMPARABLE DATA
specimens were lost as a result of breakage). The correlation coefficient (r) for the combined data is 0-85 (n<001). Though there is considerable overlap, the two groups appear separate. Thus, when the regression lines of each group are fitted, only three ileostomy patients lie above the regression line for the controls. The slopes of the regression lines of the two groups are not significantly different, but the difference between their intercepts at either mean weight for the control group or the ileostomy Thus, when compared with group is significant (P<0-01). the controls, the ileostomy patients, as a group, are serum
the investigation diet and daily routine, apart from attendances at the laboratories, remained unchanged. At the first visit, patients and controls were weighed and measured, and were given a dose of 25 fLC24Na in physiological saline solution by mouth. The next day, 21 hours after the beginning of the investigation, a carefully weighed dose of about 10 g. D20 was taken by mouth, and at 24 hours 40 ml. of venous blood was collected, together with the 24-hour specimens of urine and fasces. The blood was allowed to clot, and the serum was separated. The sodium space was calculated from measurements of the radioactivity of the serum, urine, fxces, and counting standards which were made in a well-type scintillation counter (’ Echo N.664c ’). The concentrations of sodium in the serum and urine were determined by flame photometry (EEL). The total exchangeable sodium (Nae) was then calculated from the formula:
During
two
dehydrated. Mean body water for ileostomy patients is 0-485 litre per kg. B.w., and for the controls is 0-547 litre per kg. B.w. The " average " patient (weight 68 kg.) has therefore
Nae (mEq.)=Na-space (litres) x serum [Na] (mEq./litre). The concentration of D20 in body water was determined by a double-collection mass spectrometer of the ’ Nier II ’ type (Kirshenbaum 1951) built.at the Institute of Nuclear Sciences. The method used was that described by Friedman (1953), the sample of venous serum having previously been vacuum distilled and quantitatively converted to hydrogen gas over zinc at 395°C. Body water was then calculated from the formula:
The results
were
expressed
as
litres of
body
water.
Results
Total Body Water In fig. 1 T.B.W. is plotted against body-weight (B.W.) for the ileostomy patients and nineteen controls (two D20
Fig. 2-Relation of total exchangeable sodium
to
body-weight.
of 33-0 litres compared with that of his control counterpart of 372 litres-a deficit of 4-2 litres, or 11 % of normal T.B.w.
a T.B.w.
Fig. 1-Relation of total body
water to
body-weight.
Total Exchangeable Sodium Total exchangeable sodium of the ileostomy patients and twenty of the controls are plotted against B.w. in fig. 2. (An error in collection invalidated the measurement in one of the controls.) The correlation coefficient (r) for the combined data is 0-80 (p < 0-01). There is rather more overlap between the two groups than there is in the case of T.B.w. The slopes of the regression lines are not significantly different, but the difference between their intercepts at mean weight for either the control group or the ileostomy group is significant (p < 005). Thus, compared with the controls, the ileostomy patients as a group are sodium depleted. The mean total exchangeable sodium for ileostomy patients is 38-8 mEq. per kg. B.w. and for the controls 41-8 mEq. per kg. B.w. The hypothetical average patient (weight 68 kg.) has therefore a total exchangeable sodium of 2638 mEq. compared with that of his average control counterpart of 2842 mEq. This represents an average deficit of 204 mEq. or about 7% of normal total exchangeable sodium. The observed difference could be due to a lower " sodium space " in the ileostomy patients, or to a lowered
742 TABLE II-SERUM-SODIUM CONCENTRATIONS AND SODIUM SPACES
[Na+]. Table 11 shows that the sodium deficit associated with ileostomy is almost entirely due to the contraction of the " sodium space " or that fluid compartment through which sodium is distributed. When body water and exchangeable sodium are related to B.w., the most dehydrated patients are also the ones most depleted of sodium (fig. 3). This correlation is more apparent for the ileostomy patients who are spread than for the conover a wide range (r==0-77, p < 0001), trols who are collected more compactly at the upper end of the whole group (r==0-64, P < 001).
serum
estimation of T.B.W. primarily because of the availability of high resolution mass spectrometry. Additional to both and controls radioactivity by exposure patients Resolution to less than 5 p.p.m. was thus avoided. allowed the use of a small oral dose of D20 calculated to give serum concentrations of the order of twice the background concentration. Equilibration of deuterium oxide, after oral administration is extremely rapid (table III), and venous sampling at three hours is valid. This is supported by the data of Schloerb et al. (1950).
24-hour Urinary Volume and Sodium Excretion The 24-hour urinary volumes and sodium excretion for each group are plotted in fig. 4. The mean volume of the control group is 1447 ml. and the mean volume of the ileostomy group is 1097 ml. The difference is highly significant (P< 0-001). The mean sodium output of the control group is 147 mEq., and that of the ileostomy patients is 105 mEq. The difference is highly significant
(P < 0.001). There is no correlation between urinary volume or urinary sodium excretion on the one hand, and T.B.w. or total exchangeable sodium on the other. The ileostomy
4-24-hour excretion.
Fig.
urinary volume and 24-hour urinary sodium
Horizontal lines represent mean values for each group. nificance of difference between means.
r=sig-
The normal values for total exchangeable sodium and that we obtained are comparable to those obtained others by (Moore 1963). The deficit of body sodium and water in our ileostomy patients confirms the suspicion, based on indirect evidence, that ileostomy is associated with chronic sodium depletion and dehydration. This is the sort of body compositional change which might be expected in patients who suffer continued loss of abnormal amounts of alimentary secretions. The assessment of the magnitude of the chronic sodium " and water deficits by calculating these for the " average patient is at best very approximate. The information cannot readily be related to the individual patient. An average deficit of 7% exchangeable sodium and 11 % body water, however, is considerable; though many patients with ileostomies are probably not as depleted as this, many are likely to be considerably more so. None of our patients had significant symptoms attributable to dehydration or sodium depletion. No patient complained of chronic thirst. Normal tonicity of body fluids was probably preserved, and this is supported by T.B.W.
Fig. 3-Relation of body kg. body-weight).
water content to
exchangeable sodium (per
with low values for body water and body sodium exhibit random variation in urinary water and sodium excretion which are of the same magnitude as the patients whose body compositional measurements fall within the normal range. Discussion Measurement of total exchangeable sodium and T.B.W. in ileostomy patients and controls revealed considerable variability within each group. Nevertheless it was possible to demonstrate by direct measurement that the ileostomy patients, who are otherwise well, are as a group significantly dehydrated and sodium depleted. We used D20 in preference to tritium as a tracer for
patients
TABLE
III-EQUILIBRATION
OF DEUTERIUM OXIDE
DOSE OF
Estimated million and
AFTER AN ORAL
background concentration (151) is ± 1-0 parts per concentration of 365 is less than 5-0 p.p.m.
error at
at a
(D2O)
10 g
743 the normal concentrations of serum-sodium in the ileostomy group. Several of the patients showed lassitude, but this was not related to the severity of sodium depletion as measured by total exchangeable sodium. The findings suggest that there was considerable isotonic contraction of the space through which sodium is distributed. The remainder of the water deficit probably represents a much smaller reduction of the intracellular water. Nearly half of our patients were taking extra salt on our advice during the investigation; this, together with the possible effect of a cooler climate may have resulted in a greater output of sodium (105 mEq.) than that reported by Gallagher et al. (1962)-70 mEq. per day. None the less, there is no doubt that our ileostomy group also showed renal conservation of water and sodium when compared with the controls. Contrary to what might be expected, patients who are the most severely depleted of water and sodium do not exhibit the most pronounced renal conservation of sodium and water. The reduced renal excretion of these substances in the group as a whole probably reflects the situation where less water and sodium are available for excretion by the kidney after ileostomy loss has occurred. The average daily deficit in urinary volume (350 ml.) and sodium excretion (42 mEq.) comes very close to the normal daily loss of these substances in ileostomy effluent. Apparently, any functional adaptation by the kidney which might have resulted from chronic water and sodium depletion was still obscured by random variations in dietary intake. Sabo et al. (1967) reported that ileostomy in the dog produced considerable debility with gross loss of weight. During the 11-week period of study, a relative increase in body water and an absolute increase in extracellular fluid volume (measured by thiocyanate) was observed. These observations are in accord with changes in body composition after major operations (Lyon et al. 1949, Ariel et al. 1950, Shires et al. 1961) and during profound debilitating illness (Moore 1959), but the findings are in no way comparable to the present investigation where patients have long regained nutritional equilibrium. The study was supported by the Medical Research Council of New Zealand. The assistance of Mr. G. F. S. Spears with the statistical analyses is gratefully acknowledged. We are grateful for the cooperation of the surgeons in Dunedin and Christchurch whose patients are included in this study, and the assistance and encouragement of Mr. T. A. Rafter and Dr. J. R. Hulston of the Institute of Nuclear Sciences. Requests for reprints should be addressed to A. M. C. REFERENCES
Ariel, I. M., Kremen, A. J., Wangensteen, O. H. (1950) Surgery, St. Louis, 27, 827. Bennett, R. C., Jepson, R. P. (1966) Aust. N.Z. J. Surg. 36, 153. Deren, J. J., Porush, J. G., Levitt, M. F., Khilnani, M. T. (1962) Ann. intern. Med. 56, 843. Friedman, I. (1953) Geochim. Cosmochim, 4, 89. Gallagher, N. D., Harrison, D. D., Skyring, A. P. (1962) Gut, 4, 322. Kirshenbaum, I. (1951) Physical Properties and Analysis of Heavy Water. London. R. P., Stanton, J. R., Freis, E. D., Smithwick, R. H. (1949) Surgery Gynec. Obstet. 89, 9. Maratka, Z., Nedbal J. (1964) Gut, 5, 3. Moore, F. D. (1959) Metabolic Care of the Surgical Patient. Philadelphia. — (1963) The Body Cell Mass and its Supporting Environment.
Lyon,
Philadelphia. Sabo, J. C., Enquist, I. F., Golding, M. R., Solomon, N., Fierst, S. M. (1967) Am. J. Surg. 113, 149. Schloerb, P. R., Friis-Hansen, B. J., Edelman, I. S., Solomon, A. K., Moore, F. D. (1950) J. clin. Invest. 29, 1296. Shires, P., Williams, J., Brown, F. (1961) Ann. Surg. 154, 803. Veall, N., Vetter, H. (1958) Radioisotope Techniques in Clinical Research and
Diagnosis. London.
SERUM-CREATINE-KINASE IN CASES OF STROKE, HEAD INJURY, AND MENINGITIS H. DUBO M.D. Manitoba VISITING
FELLOW, REGIONAL NEUROLOGICAL CENTRE, NEWCASTLE GENERAL HOSPITAL
DOROTHY C. PARK M.Sc. Durh. SENIOR RESEARCH
BIOCHEMISTRY,
ASSOCIATE,
DEPARTMENT OF CLINICAL
UNIVERSITY OF NEWCASTLE UPON TYNE
R. J. T. PENNINGTON D.Sc. Birm., F.R.S.E. READER IN
NEUROCHEMISTRY, DEPARTMENT OF CLINICAL BIOCHEMISTRY, UNIVERSITY OF NEWCASTLE UPON TYNE
R. M. KALBAG F.R.C.S. NEUROSURGEON, REGIONAL NEUROLOGICAL CENTRE, NEWCASTLE GENERAL HOSPITAL
JOHN N. WALTON T.D., M.D. Durh., F.R.C.P. NEUROLOGIST, REGIONAL NEUROLOGICAL CENTRE, NEWCASTLE GENERAL HOSPITAL, NEWCASTLE UPON TYNE 4
serum-creatine-kinase (C.K.) was studied in cases of head injury, acute cerebrovascular accident, and meningitis. Each of 14 patients with a head injury had raised serum-C.K. values. Of 21 patients with acute strokes, 15 had raised values. Of 7 patients with meningitis, 2 had raised values. In all patients having sufficiently high levels of serum-C.K. for isoenzyme fractionation, the circulating enzyme was found to be derived largely from muscle. No definite clinical correlations or prognostic inferences could be determined from the serum-C.K. levels. There is no clear evidence that this enzyme leaks from the brain into the blood-serum in any of the neurological disorders studied. Why muscle C.K. is often much increased in the serum in such cases remains unclear. Summary
The
Introduction
IN the search for an enzyme which could be useful as a clinical guide to the diagnosis and prognosis of various forms of cerebral disease, previous studies using aspartate aminotransferase (G.O.T.) and lactate dehydrogenase have not been fruitful (Hsieh and Blumenthal 1956, Wakim and Fleischer 1956, Chinskey and Sherry 1957, Liebermann et al. 1957, Brodel et al. 1959). Creatine kinase (c.K.) has received the most attention of late, because it is present in high concentrations in brain tissue and relatively little is found in all other tissues except skeletal and cardiac muscle (Tanzer and Gilvarg 1959, Colombo et al. 1962). Acheson et al. (1965) found that the serum-c.K. level was raised during the acute phase of cerebral infarction and later returned to normal. Schiavone and Kaldor (1965) reported that more than 60% of patients with cerebral dysfunction have raised serum-c.K. values. In a preliminary study, Kalbag et al. (1966) found a significant rise of serum-c.K. levels in cases of acute head injury and in cerebrovascular accidents. However, the isoenzyme pattern of the serum-creatine-kinase in the cases studied corresponded with that of muscle-creatinekinase rather than the brain enzyme. Because of this unexpected finding, the present study was undertaken in order to try to correlate serial C.K. enzyme and isoenzyme levels in cerebral disorders with the clinical state of the
patients.