Adverse Effect of Antipyretic Agent on Serum Zinc*

Transcription

1 ANNALS O F CLINICAL AND LABORATORY SCIENCE, Vl. 23, N. 2 Cpyright 1993, Institute fr Clinical Science, Inc. Adverse Effect f Antipyretic Agent n Serum Zinc* SIN ICI SOJI, Ph.D, M.D.,t ID EO MIYAMOTO, M.D.,i and SOZO NOMOTO, Ph.D.'1 Departments f Medicine, f and Surgery,t Schl f Medicine, and Divisin f Clinical Chemistry, Schl f Medical TechnlgyJ1 Shinshu University, Matsumt, 390, Japan ABSTRACT T study the pathgenesis f the inc deficiency that is smetimes fund pstperatively, the serum cncentratin f inc was determ ined in 35 patients befre, during, and after thracabdminal surgery. Preperatively, a serum inc level belw 60 jig per 100 ml was recrded in fur f 16 patients tested and was assciated w ith severe anrexia. Pstperatively, the serum inc level was significantly reduced fr up t fur days, when the patient was unable t eat. After the start f ral feeding, the average serum inc level returned t nrmal. The serum inc level decreased rapidly in tw patients after buts f severe sweating prduced by an antipyretic agent (diclfenac). In anther patient, the serum inc level decreased rapidly fllwing the lss f a large vlume f intestinal fluid via an intestinal stma. Factrs leading t lw serum cncentratins f inc thus include anrexia, peratins, antipyretic agents, and the lss f intestinal fluid. Intrductin Zinc, an essential elem ent, has been reprted t be depleted in patients fllwing surgery.1,3,4 This study was cnducted t investigate the alteratins in serum inc level fllw ing thracab * Send reprint requests t: Shin ichi Shji, Ph.D., M.D., Department f Neurlgy, Institute f Clinical Medicine, University f Tsukuba, Tennhdai, Tsukuba, 305, Japan. Dr.. Miyamt s present address: Divisin f Surgery, kushin General spital, Nishi, Nakan, 383, Japan. dm inal surgery and t evaluate the pathgenesis f the lw serum inc level that may exist during the pstperative perid. Subjects and M ethds A ttal f 35 patients, 27 m en and eight wmen, aged frm 41 t 81 years, participated in this study. Each was scheduled fr a thracabdm inal peratin, including surgery n the esphagus (7), stmach (7), small intestine (1), cln and rectum (3), biliary tract and gall bladder (5), /93/ $00.90 Institute fr Clinical Science, Inc.

2 ADVERSE EFFECT OF ANTIPYRETIC AGENT ON SERUM ZINC 107 jig/100ml 100 t * < Z w u : 3 V. 50 F ig u r e 1. Serum cncentratin f inc in surgical patients during the p st p erativ e perid, b efre resum ing ral feeding. Black circles and bars represent mean ± standard deviatin (SD). N represents the number f patients. Prep. refers t th e p r e p e r a tiv e perid. The 1-2,3-4,5-8, and 9-20 days refers t thse pstperative days. *Indicates a statistically significant d ifferen ce frm the mean preperative value fr serum inc (p < 0.001). Nrmal value fr serum inc: 80.4 ± 3.3 jig per 100 ml (66.7 t 87.9 jig per 100 ml). pre p days pstp. liver (9), and pancreas (3), including m alignant disease. T he serum inc cncentratin was determ in ed preperatively (18 ccasins) and pstperatively: (a) befre resum ptin f eating (41 ccasins) and (b) fllwing resum ptin f eating (47 ccasins). Sixty-seven healthy adults, 35 m en and 32 w m en, p a rticip a te d as nrmal cntrls. B ld sam ples w ere c lle cte d by venus puncture using a inc free evacuated plastic tu b e. Im m ediately after drawing bld, the tubes were allwed t stand fr 30 min. until the cltting was cm pleted. T hen the serum was separated by centrifugatin. Serum samples w ere discarded if any hem lysis was bserved. Atmic absrptin spectrphtmetry f serum inc was perfrm ed by the m ethd f Nmt.6 The samples were deprteinied w ith hydrchlric acid and trichlracetic acid. The prtein free extracts were subjected t analysis f inc with use f M del Z-8000 flame type atmic absrptin spectrmeter.* T h e s ig n ific a n c e f d iffe re n c e s betw een means was determ ined by Student s t-test. A level f p < 0.05 was accepted as statistically significant. Results Reference interval fr serum inc level was frm 66.7 t 87.9 ig per 100 ml and the average ± SD was 80.4 ± 3.3 jig per 100 ml. Preperatively, fur f the 16 patients exhib ited lw levels f serum inc, being; 43, 45, 49, and 58 xg per 100 ml. All fur patients had severe anrexia withut preperative inc supplem ents, wing (in ne case each) t chlecystitis * itachi Crp., Japan.

3 108 SOJI, MIYAMOTO, AND NOMOTO with chlelithiasis, carcinma f the gall bladder, gastric carcinma, and esphaggastric carcinma. Pstperatively, befre the patients resum ed ral feeding, the serum inc level was significantly lwer than that during the preperative perid (figure 1). T h is w as ra te d fr up t fur days pstperatively. T w i n t e r e s t i n g p a tie n ts w e re bserved t develp lw serum levels f inc re la te d t fev er and sw eatin g induced by diclfenac, while ne patient exhibited this finding related t the lss f intestinal fluid. Case Reprts A 66-year-ld man with acute chlecystitis with chlelithiasis exhibited a rapid decline in serum inc frm 72 t 35 (ig per 100 ml within ne week pstperatively, even thugh he was taking fd by muth. During this perid, he had a high fever and received diclfenac sdium, an antipyretic agent, by the rectal rute. Such treatment was fllwed by prfuse sweating (figure 2), thught t have been a pssible factr in the decline in serum inc level. A 68-year-ld wman wh was perated n fr chlangicarcinma, develped a hepatic abscess pstperatively. She had a fever, and was repeatedly treated with diclfenac by the rectal rute. The serum inc level shwed a relatively rapid drp n tw ccasins; the first was frm 61 t 43 jig per 100 ml within 10 days. N inc supplements were administered during the 9 days f this 10-day perid. A secnd drp in serum inc level, frm 69 t 42 jxg per 100 ml, was bserved in the next 26 days, fllwed by an additinal decline t 30 jig per 100 ml ver the next 14 days. During the latter part f this perid, n inc supplem ent was given (figure 3). A 56-year-ld man wh had been perated n fr a rectal carcinma had a secnd peratin, this time fr ileus. Pstperatively, during the perid he was unable t take fd by muth, his serum inc level shwed a rapid drp frm 77 t 36 xg per 100 ml within 16 days, despite the daily administratin f an intravenus inc supplement (1.3 mg per day). wever, during this perid he lst a ttal vlume f 2,680 ml f intestinal fluid via an intestinal stma (figure 4). 39 C' ZBL.*,V, (3,9mg X Iday) ORAL INTAKE w s» < C3 PU SB Ed >* a ffl Serum inc le v e l (pg/100ml) F i g u r e 2. Pstperative curse f a 66-year-ld man with acute chlecystitis and chlelithiasis. e received 3.9 mg f inc intravenusly n secnd pstperative day. e began the ral intake f fd and water n the furth pstperative day. The X refers t 25 mg f diclfenac sdium, an antipyretic agent, administered by the rectal rute. Serum inc levels were 34, 72, and 35 jig per 100 ml n the 3rd, 18th, and 25th pstperative days, respectively.

4 ADVERSE EFFECT OF ANTIPYRETIC AGENT ON SERUM ZINC 109 ORAL INTAKE ZINC I.V. (1.3mg/dav X 3»d«vs) Serum in c le v e l (fig/100ml) FIGURE 3. Curse f a 68-year-ld wman fllwing peratin fr chlangicarcinma cmplicated by liver abscess. During this time, the patient tk fd and water rally, but she had persistent anrexia. Frm days 10 t 47, a supplement cntaining 1.3 mg inc was given intravenusly each day. The X refers t 25 mg f diclfenac sdium, an antipyretic agent, given by the rectal rute. Serum levels f inc were 61, 43, 69, 42, and 30 p-g per 100 ml n days 1, 11, 17, 43, and 57, respectively. Discussin T he im prtance f inc in hum an health is well dcumented. The rate f wund healing is shw n t be accelerated by a inc supplem ent.1 The bservatin that all fur patients f any patients with severe anrexia shw ed lw serum inc lev els p re p e ra tiv e ly suggests severe anrexia m ay cause inc d e ficiency judging frm serum levels even befre the peratin. Surgery r tissue injury influences inc metablism. enel et al reprted that m arked incuria ccurred in thse individuals wh had undergne majr sur- 2 INC I.V. (1.3ag/day) _> [*. < M C/5 t/3 O -1 f- Ul m l/d ay Serum in c l e v e l ( pg/100m l) F i g u r e 4. Pstperative curse f a 56-year-ld man wh develped ileus fllwing an peratin fr rectal carcinma. An intestinal stma was created in the latter prcedure. During this perid, the patient did nt take fd r water rally. e received a inc supplement given intravenusly, 1.3 mg per day, during his entire curse. Between the 26th and the 35th pstperative days, he excreted a ttal vlume f 2,680 ml f intestinal fluid thrugh the stma. Serum inc levels were 18, 64, 77, and 36 fj-g per 100 ml n the first, 13th, 20th, and 36th pstperative days, respectively.

5 110 SOJI, MIYAMOTO, AND NOMOTO gery; a decrease in their bdy inc stres was bserved pstperatively.1 Kahn et al reprted that the mean serum cncentratin f inc and f the 24 hur inc in urine were unchanged during the first pstperative week, but were elevated during the secnd pstperative week.3 L indem an e t al fund that the m ean plasm a inc level in surgical patients declined frm nrmal t lw 24 hurs pstperatively; thereafter, plasma levels rse steadily tward nrmal n the furth pstperative day.4 The present study shw ed that during the pstperative perid, while the patient was unable t take fd by muth, the serum inc level decreased significantly t abut ne-half the preperative level betw een the first and furth pstperative days. An additinal im prtant finding was that the administratin f an antipyretic agent, such as diclfenac, t febrile patients can lead t prfuse sweating and a marked lss f inc. hnadel et al cllected sw eat frm h ealth y m en and wmen during sauna bathing and fund inc levels f 500 ± 480, and 1,250 ± 770 (xg per 1, respectively. Thse investigatrs suggested that sweating is an imprtant rute fr th e excretin f inc. M cdnald et al wh analyed inc in sweat fllwing strenuus exercise, als bserved that a cnsiderable amunt f inc was lst during excessive sweating.5 The present study is the first clinical reprt t dcum ent that excessive sweating prduced by an antipyretic agent can lead t lw serum cncentratins f inc. Wlman et al reprted that abnrmal inc lss frm the gastrintestinal tract ccurred in diarrheal stl and frm the intestinal fluid that was lst thrugh suctin and fistulus discharge.7 In additin, a patient f urs was bserved with an intestinal stma wh exhibited a rapid drp in serum inc level fllwing the excretin f a large vlum e f in testinal fluid. Severe anrexia, pstperative days, usage f an antipyretic agent, and lss f intestinal fluid may cause lw serum inc level. References 1. e n e l, J.., D e W e e s e, M. S., and P r i e s, M. W. J.: Significance f magnesium and inc metablism in the surgical patient. II. Zinc. Arch. Surg. 95: , h n a d e l, D. C., S u n d e r m a n, F. W., N e c h a y, M. W., and M c N e e l y, M. D.: Atmic absrptin spectrphtmetry f nickel, cpper, inc, and lead in sweat cllected frm healthy subjects during sauna bathing. Clin. Chem. 19: , Ka h n, A. M., and G r d n,. E.: Alteratins f inc metablism fllwing surgical peratins. Surg. Gynecl. Obstet. 128:88-90, L i n d e m a n, R. D., B t t m l e y, R. G C r - NELISON, R. L., and JACOBS, L. A.: Influence f acute tissue injury n inc metablism in man. J. Lab. Clin. Med. 79: , M c D n a l d, J. T., and M a r g e n, S.: Wine versus ethanl in human nutritin. IV. Zinc balance. Am. J. Clin. Nutr. 33: , NOMOTO, S.: A simplified methd fr trace metal analysis f bilgical materials. J. UOE 9(Suppl.): , W l m a n, S. L., A n d e r s n, G.., M a r l i s s, E. B., and Je e j e e b h y, K. N.: Zinc in ttal parenteral nutritin: requirements and metablic effects. Gastrenterlgy 76: , 1979.