Pstgraduate Medical Jurnal (June 1978) 54, 45-49. The effects f ptassium supplements, spirnlactne r amilride n the ptassium status f patients with heart failure C. DAVIDSON M.A., M.B., M.R.C.P. D. B. MORGAN M.D., M.R.C.Path. L. BURKINSHAW B.Sc., Ph.D. Departments f Medicine, Medical Physics and Chemical Pathlgy, General Infirmary, Leeds Summary xtra ptassium supplements, spirnlactne r amilride were given fr 5 mnths t frty-nine patients with heart failure wh were taking fursemide and were in a steady state. Plasma ptassium increased with all three treatments but there was n significant increase in ttal bdy ptassium r red cell ptassium. These findings tgether with ther studies suggest that patients with heart failure taking diuretics d nt have a significant depletin f bdy ptassium. Intrductin Ptassium depletin is generally accepted as ne f the hazards f lng-term treatment with ptent diuretics in patients with heart failure, and these patients are therefre usually als given either ptassium supplements r ne f the ptassiumsparing diuretics. The authrs recently measured the ttal bdy ptassium (TBK) f patients with chrnic heart disease with a ttal bdy radiatin cunter (Davidsn et al., 1976). The TBK in the patients with heart disease was nt significantly different frm the TBK in a grup f healthy subjects. Mrever, amng the patients with heart disease there was n difference between thse wh were taking diuretics and thse wh were nt, and in thse n diuretics there was n difference between thse taking small dses f ptassium supplements and thse taking large dses. These findings cntrasted with previus reprts in the literature, and did nt supprt the view that ptassium depletin was a cmplicatin f lng-term diuretic therapy. Nevertheless, it culd be argued that a crss-sectinal study is an insensitive apprach since it depends n the cmparisn f a grup f patients with a grup f cntrls; a mre sensitive apprach wuld be t study serial changes in individual patients. Ideally such a study shuld be carried ut frm the time the patients start diuretics Address fr reprint requests: Prfessr D. B. Mrgan, Department f Chemical Pathlgy, The General Infirmary, Leeds. but this is difficult lgistically and as far as the authrs knw it has nt been dne. Alternatively ne can attempt t crrect any deficit in bdy ptassium in patients already established n treatment by giving extra ptassium supplements r a ptassium-retaining diuretic. If ptassium depletin is present, these changes in treatment shuld cause an increase in TBK, even in a patient whse TBK is reduced but still lies within the nrmal range. Surprisingly this apprach has nly rarely been used in heart failure (De Deuchaisnes, Busset and Cllet, 1961; White, 197; Davidsn and Gillebrand, 1973). A grup f patients with heart failure have been studied wh had been taking a cnstant dse f fursemide and ptassium supplements fr at least 6 mnths. The ptassium supplements were either increased t 48 mml/day r replaced by spirnlactne r amilride. The dse f fursemide was kept cnstant thrughut the study. The ptassium status f the three treatment grups was assessed at mnthly intervals fr 5 mnths after the change f treatment. Patients The patients in this study came frm a larger crss-sectinal study f patients with heart failure (Davidsn et al., 1976). Sixty-six patients wh agreed t jin the study were allcated t ne f three treatment grups using randm tables. Six patients were subsequently excluded frm the ptassium grup because they were already taking 48 mml f ptassium r mre per day. leven patients did nt finish the trial; six required an increased dse f diuretic, three defaulted and tw died frm mycardial infarctin. The final analysis was therefre based n a ttal f frty-nine patients; thirteen patients had their ptassium supplements increased t 48 mml/day; sixteen tk spirnlactne (1 mg/day) and twenty tk amilride (2 mg/day). The patients in the spirnlactne and amilride grups stpped their ptassium supplements. The increase in ptassium supplements in 32-5473/78/6-45 $2. 1978 The Fellwship f Pstgraduate Medicine Pstgrad Med J: first published as 1.1136/pgmj.54.632.45 n 1 June 1978. Dwnladed frm http://pmj.bmj.cm/ n 13 August 218 by guest. Prtected by
46 the ptassium grup (given Slw K) was n average 25 mml/day (range 8-4 mml/day). Clinical details f the patients are shwn in Table 1. The patients were seen at least nce, but usually twice, befre their treatment was changed and then five times at mnthly intervals. At each visit the patients were asked abut symptms and the side effects f treatment, and their TBK, plasma ptassium, red cell ptassium and 24-hr urine ptassium excretin were measured. Details f these techniques are given elsewhere (Davidsn et al., 1976). Chest X-rays were taken at the beginning and end f the study. The ttal duratin f the study was 18 mnths. Results Table 2 shws that the plasma, electrlytes, urea and creatinine were the same n average in the three grups befre treatment was changed. The average TBK differed between the grups, but there were als differences in age and weight. The bserved TBK was cmpared with the TBK predicted frm sex, age, weight, height and skin fld thicknesses (Davidsn et al., 1976). There was a small apparent deficit f TBK in each grup (25, 79 and 183 mml respectively). Nne f the patients had any clinical r radilgical deteriratin during the study. Twelve patients (tw n ptassium supplements, three n spirnlactne, seven n amilride) had transient epigastric discmfrt r nausea when they changed treatment. In three patients (tw spirnlactne, ne amilride) these symptms persisted until the end f the study. Tw patients in the spirnlactne grup had persistent gynaecmastia. Figure 1 shws the changes in plasma ptassium, urinary ptassium excretin and TBK in the three grups f patients. The results have been calculated as the difference frm the mean value befre the treatment was changed. Plasma ptassium increased at first in all grups by.1-.2 mml/l but the rise was nt sustained in the ptassium grup. Urinary ptassium excretin increased by the expected 2 mml/day in the ptassium grup and decreased by the same amunt in the ther tw grups wh stpped their ptassium supplements when they changed treatment. There were n significant changes in TBK. In rder t summarize the changes in the ther measurements, the values befre treatment have been cmpared with the values at the furth mnth f treatment; the values at 4 mnths were representative f the values in the latter part f the study. There were small falls in bdy weight and bld pressure; the fall in weight was significant nly in the ptassium grup (P<.5), and the fall in bld pressure was significant nly in the spirnlactne C. Davidsn, L. Burkinshaw and D. B. Mrgan a. 'O mcd 2-2 ~: l -1 [-.A ll-.. 2 3 4 5 Mnths f tretment FIG. 1. The changes in plasma ptassium, urinary ptassium and ttal bdy ptassium (TBK) in the three grups f patients. Results calculated as the difference frm the mean value befre the treatment was changed: A - patients given ptassium supplements. - patients given spirnlactne. * - patients given amilride. grup (P<'1). There was a significant fall in plasma sdium (P< 1) and a rise in bicarbnate (P<-1) in the spirnlactne grup. There was a rise in bld urea in the amilride grup (P<.1) but n significant change in the plasma creatinine. Red cell ptassium did nt change in any grup. Discussin This lngitudinal study was undertaken because the previus crss-sectinal study f patients with heart failure had failed t detect large ptassium deficits and was therefre at variance with numerus previus reprts (Davidsn et al., 1976). The patients in the present study had apparent deficits which were similar t thse in the previus study (5-2 mml). Hwever, extra ptassium, spirnlactne r amilride failed t raise the ttal bdy r red cell K despite a rise in plasma ptassium, which makes it unlikely they were ptassium depleted. There have been several similar studies in heart failure in which either extra ptassium r a ptassium-sparing diuretic has been added t the diuretic Pstgrad Med J: first published as 1.1136/pgmj.54.632.45 n 1 June 1978. Dwnladed frm http://pmj.bmj.cm/ n 13 August 218 by guest. Prtected by
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regime. Mst studies have used exchangeable ptassium (Ke) as a measure f bdy ptassium. They have ften invlved small numbers f patients fllwed fr relatively shrt perids, and the results have been cnflicting. Three grups have studied the effect f ptassium supplements. De Deuchaisnes et al. (1961) gave eight patients 4-12 mml/day f extra ptassium fr ne t three weeks. The average Ke did nt change and the extra ptassium was excreted in the urine. White (197) gave seven patients with heart failure and an apparent ptassium deficit 48 mml/ day f extra ptassium fr 4 weeks. There was n change in plasma ptassium but Ke increased by an average f 2 mml. Dwn, Plak and Ra (1972) gave fur patients with heart failure and an apparent ptassium deficit 48 mml/day fr 2 mnths. There was n change in plasma ptassium r Ke. The results frm studies f ptassium-sparing diuretics have been equally incnclusive. Davidsn and Gillebrand (1973) gave amilride fr 6 mnths t twenty-fur patients with heart failure stabilized n fursemide. There was a sustained rise in plasma ptassium; Ke initially rse by 32 mml but at 6 mnths was n greater than befre the change in treatment. Nichlls, spiner and Hughes (1976) studied eleven patients with heart failure fr 2 mnths after substituting amilride fr ptassium supplements. There was n change in plasma ptassium r Ke. White (1969) reprted that spirnlactne prevented any fall in Ke in patients taking fursemide; Friis (1972) cncluded that it did nt increase Ke in patients with heart failure. There are several studies shwing that spirnlactne increases plasma ptassium (Gerge, Breckenridge and Dllery, 1973). The present study is thus in agreement with mst reprts frm the literature. xtra ptassium supplements r ptassium-sparing diuretics can increase plasma ptassium, but they d nt influence bdy ptassium. These drugs may therefre be unnecessary t maintain bdy ptassium in heart failure during lng-term diuretic treatment. Lawsn Bddy and Gray (1976) gave twenty-ne patients with heart failure diuretics but n ptassium supplements fr a year. There was a small fall in plasma ptassium but n change in TBK. Nevertheless, the general view is that patients with heart failure are depleted f ptassium and that the depletin is related t the use f ptent diuretics (Leading Article, 1977). This view seems t be based n the numerus reprts f lw K, in patients with heart failure taking diuretics and the demnstratin that these diuretics can increase the urine ptassium and lwer the plasma ptassium. The authrs have recently reviewed all published data n exchangeable Ptassium status in heart failure 49 ptassium in patients with heart disease (Mrgan, Burkinshaw and Davidsn, 1978). Althugh there was an apparent deficit f2-3% fbdy ptassium, this deficit was n greater in the patients taking diuretics than in thse wh were nt, and culd be explained by the muscle wasting which happens in chrnic heart disease. The findings in the present study, the authrs' previus study (Davidsn et al., 1976), the study f Lawsn et al. (1976) and the authrs' review f the literature (Mrgan et al., 1978) lead the authrs t cnclude that there is n true ptassium depletin in patients with heart disease, even thse taking diuretics. The nly reasn fr treating patients with ptassium supplements r ptassium-sparing agents is t prevent r treat a lw plasma ptassium. Acknwledgments We are grateful t Dr W. Whitaker, Dr D. Smith and Mr M. Inescu wh allwed us t study their patients; Mrs D. Davidsn wh had a majr respnsibility in the rganizatin f the study; Miss D. W. Krupwicz wh made the TBK measurements; and Miss S. Hassam and the many staff f the Departments f Chemical Pathlgy wh made the chemical measurements. The study was supprted in part by a grant frm G. D. Searle. References DAVIDSON, C. & GILLBRAND, I.M. (1973) Use f amilride as a ptassium cnserving agent in severe cardiac disease. British Heart Jurnal, 35, 456. DAVIDSON, C., MCLACHLAN, M.S.F., BURKINSHAW, L. & MORGAN, D.B. (1976) ffect f lng-term diuretic treatment n bdy-ptassium in heart disease. Lancet, i, 144. D DUCHAISNS, C.N., BUSST, R. & COLLT, R.A. (1961) xchangeable ptassium in wasting, amytrphy, heart disease, and cirrhsis f the liver. Lancet, ii, 681. DOWN, P.F., POLAK, A. & RAO, R. (1972) Fate f ptassium supplements in six utpatients receiving lng-term diuretics fr edematus disease. Lancet, ii, 721. FRIIS, TH. (1972) In: xtrarenal Activity f Aldsterne and its Antagnists xcerpta Medica, Amsterdam, 35. GORG, C.F., BRCKNRIDG, A.M. & DOLLRY, C.T. (1973) Cmparisn f the ptassium-retaining effects f amilride and spirnlactne in hypertensive patients with thiazide-induced hypkalaemia. Lancet, ii, 1288. LAWSON, D.H., BODDY, K. & GRAY, J.M.B. (1976) Ptassium supplements in patients receiving lng-term diuretics fr edema. Quarterly Jurnal f Medicine, 45, 469. LADING ARTICL (1977) Ptassium in heart failure. British Medical Jurnal, 1, 469. MORGAN, D.B., BURKINSHAW, L. & DAVIDSON, C. (1978) Ptassium depletin in heart failure and its relatin t lng-term treatment with diuretics: a review f the literature. Pstgraduate Medical Jurnal, 54, 72. NICHOLLS, M.G., SPINR,.A. & HUGHS, H. (1976) ffect f ptassium-sparing diuretics n the renin-angitensin-aldsterne system and ptassium retentin in heart failure. British Heart Jurnal, 38, 125. WHIT, R.J. (1969) The bdy electrlytes in heart failure and in systematic hypertensin. M.D. thesis, University f Cambridge. WHIT, R.J. (197) ffect f ptassium supplements n the exchangeable ptassium in chrnic heart disease. British Medical Jurnal, 3, 141. Pstgrad Med J: first published as 1.1136/pgmj.54.632.45 n 1 June 1978. Dwnladed frm http://pmj.bmj.cm/ n 13 August 218 by guest. Prtected by