β-hydroxybutirate Levels as a Determinant for The Success of Diabetic Ketoacidosis Management

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1 ORIGINAL ARTICLE β-hydroxybutirte Levels s Determinnt for The Success of Dibetic Ketocidosis Mngement Ik Prsety Wijy*, Prdn Soewondo**, Djoko Widodo***, Aru W. Sudoyo**** ABSTRACT Aim: to obtin greter understnding of the dignosis nd evlution of success in dibetic ketocidosis mngement. Methods: prospective observtionl study ws performed on ptients with dibetic ketocidosis t the Emergency Unit of Cipto Mngunkusumo Generl Hospitl. All ptients tht were dmitted were hd their blood glucose, β--hydroxybutirte, cetocette, ph, pco, HCO3, nion gp nd consciousness levels serilly monitored on upon dmittnce (0 ) nd the nd, 6th, th, 8th nd 4 th s. The correltion coefficient of ech exmintion ws lso clculted. The benefit of seril exmintion of ech vrible ws lso determined for ech ketocidosis undergoing the study. Results: Out of the 9 vilble smples, strong negtive correltion ws found between β--hydroxybutirte nd ph with vlue of r>0.5 (from 0.54 to with p<0.05) for 4 s, compred to cetocette with the lowest r of 0.55 to 0.73 lsting up to s. glucose nd ph is correlted only t 0, the sme with the correltion between β--hydroxybutirte nd HCO 3. pco nd nion gp is better compred to tht of blood glucose nd cetocette. There is no correltion between the three nd the level of consciousness. Significnt seril exmintions to perform re blood glucose, β- hydroxybutirte, nd HCO 3. * Deprtment of Internl Medicine of the Fculty of Medicine of the University of Indonesi/Cipto Mngunkusumo Generl Hospitl **Division of Endocrinology nd Metbolic Diseses ***Division of Tropicl nd Infectious Diseses ****Division of Hemtology nd Medicl Oncology of the Deprtment of Internl Medicine of the Fculty of Medicine of the University of Indonesi/Cipto Mngunkusumo Generl Hospitl Conclusion: β--hydroxybutirte hs stronger correltion compred to blood glucose nd or cetocette towrds ph, pco, HCO 3, nd nion gp. Ptients with ketocidosis re recommended to undergo blood β- hydroxybutirte exmintion. Seril exmintion should be performed for blood glucose, β--hydroxybutirte, nd bicrbonte. Key words: dibetic ketocidosis, blood glucose, cetocette, β--hydroxybutirte, correltion coefficient INTRODUCTION Dibetic ketocidosis is severe compliction for dibetes mellitus. This compliction is commonly found mong ptients with uncontrolled dibetes mellitus. A study t Cipto Mngunkusumo Generl Hospitl stted tht the mortlity rte due to dibetic ketocidosis will drop ccordingly with the increse in dibetic ketocidosis mngement. In type dibetes mellitus, dibetic ketocidosis occurs with reltive insulin deficiency nd increse in contr regultory hormone. The most influentil contr regultory hormone is glucgon. Glucgon increses the production nd reduces the utiliztion of glucose, cusing hyperglycemi. In ddition to glucgon, growth hormone nd cortisol lso ply role. There is lso n increse in lypolysis, cusing the formtion of keton bodies in lrge numbers, in the form of cetocette nd β-hydroxybutirte (lso known s 3-hydroxybutirte), the ccumultion of which would cuse metbolic cidosis. - 6 Under norml conditions, the rtio between β- hydroxybutirte:cetocette is -3:.4 while during cidosis, prticulrly dibetic cidosis, the rtio could increse up to 0:.7 This rtio illustrtes reductionoxidtion in the mitochondri. If the metbolic disturbnce is corrected, the rtio will return to norml. This is ssocited with reltive ccess of NADH compred to NAD, -7 which occurs during inter-conversion of cetocette to β-hydroxybutirte. 70

2 Vol 36 Number April-June 004 β-hydroxybutirte Levels s Determinnt for The Success Acetocette is keton body tht cn be exmined using sodium-nitropruside, while β-hydroxybutirte hs not been exmined in dibetic ketocidosis ptients t Cipto Mngunkusumo Generl Hospitl. In ddition, nion gp ws exmined while pying ttention to serum sodium, potssium, nd chloride levels. Up to now, keton body or lctic cid hs been detected using nion gp exmintion. In study by Wiggm et l, longer insulin infusion ws obtined by noting β-hydroxybutirte levels to indicte more rpid improvement in ketosis compred to by noting blood glucose level lone. This study imed to determine the correltion between β-hydroxybutirte level nd metbolic profile (ph, pco, HCO 3, nd nion gp) nd level of consciousness, compred to the correltion between blood glucose level nd cetocette nd metbolic profile nd level of consciousness. This study imed to obtin greter understnding of the dignosis nd evlution of success in dibetic ketocidosis mngement. METHODS A prospective observtionl study ws performed on group to compre b-hydroxybutirte level with blood glucose nd cetocette in dibetic ketocidosis. The study ws performed t the Internl Medicine section of the Emergency Unit of Cipto Mngunkusumo Generl Hospitl. The study took plce from Jnury to June 00. The trget popultion is dibetic ketocidosis ptients dmitted t the Deprtment of Internl Medicine of Cipto Mngunkusumo Generl Hospitl during tht time frme. The inclusion criteri were s follows: dibetic ketocidosis ptients with:. A blood glucose level of > 50 mg/dl, b. positive blood cetocette, c. blood ph < 7.35 nd or d. serum bicrbonte level < 8 meq/l who were willing to prticipte in the study. Exclusion criteri: pregnnt ptient, lcoholic ketocidosis, slisilte overdose, isopropyl lcohol intoxiction, non-ketotic hyperosmolr dibetes mellitus, lredy receiving insulin therpy nd refusl to prticipte in the study. The studied vribles were b-hydroxybutirte, blood glucose, cetocette, ph, pco, HCO3, nion gp nd level of consciousness. Smples were tken by consecutive smpling. The smple size ws clculted using formul to determine single smple in different mens nd with single smples to determine the correltion coefficient. Ptients who met the inclusion criteri for dibetic ketocidosis hve received dibetic ketocidosis mngement bsed on the dibetic ketocidosis mngement scheme (protocol for dibetic ketocidosis mngement t Cipto Mngunkusumo Generl Hospitl). smples were obtined for hemoglobin, hemtocryte, leukocyte, pltelet count, ureum, cretinine, cito blood glucose, blood gs nlysis, nd cetocette performed on 0 (upon dmittnce to the Emergency Unit) nd ws performed t the lbortory of the Emergency Unit, on the second floor of the Emergency Unit building. Afterwrds, exmintion of blood glucose nd serum keton body levels, prticulrly β- hydroxybutirte ws performed using Precision Optium instrument (from PT. Abbot Dignostic), nd ph, HCO 3, nion gp exmintion with I-Stt Anlyser instrument (from PT. Abbot Dignostic). The limittion of using Precision Optium is the mximum blood glucose level detected is 600 mg/dl nd the mximum b-hydroxybutirte level detected is 6 mmol/l. Above those levels, the instrument displyed High. glucose nd b-hydroxybutirte levels were exmined using cpillry blood without nticogulnt, where the first drop ws removed using tissue, while the next drop ws used s smple. Mesurement ws performed directly t the ptient s bed side. Acetocette ws exmined t the lbortory of the emergency unit (on the second floor) using uristix (the instrument usully used t the emergency unit lbortory to nlyze blood cetocette) using ml of venous blood trnsported immeditely fter being obtined in closed comprtment, nd then centrifuged to obtin the serum. For ph, HCO 3 nd nion gp evlution, 0.5 ml of rteril blood with lithium heprin nticogulnt (with pproximtely 0.05 ml of nticogulnt) ws obtined, nd the exmintion ws performed less thn 0 minutes fter the smple ws obtined. The smple ws exmined using I-Stt Anlyser in specil instrument to insert pproximtely 0. ml of blood nd insert it into the I-Stt Anlyser slot to be red. The exmintion tkes pproximtely minutes. The bicrbonte level obtined from the clcultion using the stndrd instrument could be red immeditely on the instrument s LCD screen. The exmintion ws performed directly t the ptient s bed side. On the ptient, blood glucose, keton (cetocette nd bet hydroxybutirte), ph nd nion gp s well s bicrbonte clcultion were performed on 0, the nd, 6th, th, 8th nd 4 th s. Consciousness ws determined by single resercher bsed on the criteri for being fully conscious, pthetic, somnolent, soporous or comtose. 7

3 Ik P Wijy, etl Act Med Indones-Indones J Intern Med During the exmintion nd tretment t the beginning of the study, history ws obtined from the ptient or the ptient s fmily on ge, the durtion of type dibetes mellitus, nd the durtion of current illness. Informtion ws provided on the procedure of the study nd the benefit both for the smple s well s for the community outside of the study, nd consent ws obtined. Consent ws obtined directly from the ptient or from the ptient s fmily if the ptient could not provide direct consent. This study received consent from the reserch ethics committee of the Fculty of Medicine of the University of Indonesi. Ptients with dibetic ketocidosis who did not prticipte in the study received the sme tretment s the study prticipnts. The dt tht ws obtined then underwent univrite nlysis to determine the men nd stndrd devition (CD). Seril chnges in the vlues or condition of ech vrible were tested using the pired t-test for numeric vribles nd the Mrginl Homogeneity test for ctegoricl vribles. Bivrite nlysis ws performed to determine the correltion between bet hydroxybutirte, cetocette nd blood glucose with ph, pco, HCO3, nion gp nd level of consciousness, using the Person test for numeric vribles nd the Spermn s rnk test for ctegoricl vribles. If both vribles re ctegoricl, they were tested using the contingency coefficiency test. All sttisticl nlyses were performed using SPSS version 0.05 nd the results of the study were reported in the form of text, tbles, nd grphs. RESULTS Generl Chrcteristics From Jnury to June 00, 39 dibetic ketocidosis ptients were recruited. Out of the 39 ptients, 9 were included in the study. The rest could not be included due to technicl problems, such s prior dministrtion of insulin tretment, bolus or infusion. Out of the 9 people who were included in the study, 8 (4%) were mle nd (58%) femle. The ge rnged between 5 nd 7 yers with men ge of 48. yers. The complete dt on ptient chrcteristics cn be found in Tble. Out of the 9 ptients included in the study, 3 ptients died during observtion. The medicl problems tht the ptients hd side from dibetic cidosis vried. These medicl problems could be found in Tble. Tble. Ptient Demogrphicl Chrcteristics Men SD Note Age (yers) Sex Mle : 8 Femle : Durtion of DM (months) Min : 0 Mx: 60 Durtion of illness(dys) Min : Mx: 30 Hemoglobin (g/dl) Hemtocryte (vol%) Leukocyte (/ml) Pltelet (/ml) Ureum (mg/dl) Cretinine (mg/dl) Min : 0.6 Mx: 6.8 Tble. The Medicl Problems Found Among Ptients with Dibetic Acidosis Problem Pneumoni Dibetic ulcer Lung tuberculosis Acute renl filure Acute pncretitis Urinry trct infection Stroke Chronic renl filure Cesstion of Insulin Cesstion of Orl Hypoglycemic gent Liver bscess Meningitis Septic shock Respirtory filure Frequency The Correltion Between Bet Hydroxybutirte, Glucose nd Acetocette Levels nd ph From tble 3, it ws found tht there ws significnt (p <0.0) nd strong {r = >0.5} negtive correltion between level bet hydroxybutirte, blood glucose nd cetocette level nd blood ph in ptients with dibetic ketocidosis upon dmission to the hospitl. Bet hydroxybutirte hs significnt nd reltively strong correltion with blood ph within 4 s. The Correltion Between Bet Hydroxybutirte, Glucose nd Acetocette Levels nd pco In tble 4, it ws found tht only bet hydroxybutirte nd cetocette were negtively correlted with blood pco. The correltion ws strong nd significnt only up to the 6 th

4 Vol 36 Number April-June 004 β-hydroxybutirte Levels s Determinnt for The Success Tble 3. The Correltion Between Bet Hydorxybutirte, Glucose nd Acetocette Levels nd ph Glucose Bet hydroxy butirte Acetoc ette **: p < 0,0 0 nd 6 th th 8 th 4 th - 0,590** -0,98-0,08-0,73-0,8-0,36-0,656** -0,779** -0,54* -0,833** -0,73** -0,598** -0,73** -0,70** -0,55* -0,58* -0,470-0,334 All were tested using Person s correltion test, except : with Spermn s correltion test. Tble 4. The Correltion Coefficient for Bet Hydroxybutirte, Glucose nd Acetocette nd Seril pco glucose Bet hydroxyb utirte Acetoc ette 0 nd 6 th th 8 th 4 th -0,30-0,366-0,356 0,04-0,087-0,038-0,73** -0,646** -0,63** -0,494* -0,376-0,384-0,568* -0,634** -0,583* -0,499* -0,0-0,359 **: p < 0,0 All were tested using Person s correltion test, except : with Spermn s correltion test. The Correltion Between Bet Hydroxybutirte, Glucose nd Acetocette Levels nd HCO3 From Tble 5, it ws found tht bet hydroxybutirte hs strong nd significnt negtive correltion { r > -0.5 } with HCO 3 compred to cetocette nd blood glucose level. Tble 5. The Correltion Coefficient Between Bet Hydroxybutirte, Glucose nd Acetocette Levels nd HCO 3 Seril 0 nd The Correltion Between Bet Hydroxybutirte, Glucose nd Acetocette Level nd Anion Gp In Tble 6, negtive correltion > 0.5 ws more freqeuntly found mong bet hydroxybutirte levels compred to blood glucose nd cetocette levels. The level of significnce even reched p < 0.0 for the positive correltion between bet hydroxybutirte nd nion gp. The correltion between bet hydroxybutirte nd nion gp wekened fter the 6th. 6 th th 8 th 4 th glucose -0,446* -0,375-0,87-0,033-0,8-0,63 Bet -0,79** -0,737** -0,573** -0,603** -0,554* -0,50* hydroxy butirte Acetoc -0,664** -0,698** -0,56* -0,50* -0,65-0,7 ette **: p < 0,0 All were tested using Person s correltion test, except : with Spermn s correltion test. Tble 6. The Correltion Coefficient Bet Hydroxybutirte, Glucose nd Acetocette Level nd Seril Anion Gp Glucose Bet hydroxy butirte Acetoc ette **: p < 0,0 0 th 8 th 4 th 0,360 0,60 0,47-0,9 0,30 0,035 nd 6 th 0,588** 0,544** 0,63** 0,48* 0,36 0,07 0,485* 0,496* 0,678** 0,83 0,95 0,3 All were tested using Person s correltion test, except : with Spermn s correltion test. The Correltion Between Bet Hydroxybutirte, Glucose nd Acetocette Levels nd The Level of Consciousness From Tble 7, wek correltion ws found between cetocette nd the level of consciousness. The correltion ws positive. However, the correltion did not occur sequentilly, since it only ppered on the nd nd th s. Tble 7. The Correltion Coefficient Bet Hydroxybutirte, Glucose nd Acetocette Levels nd Seril Level of Consciousness 0 nd 6 th th 8 th 4 th Glucose -0,033 0,4-0,06 0,05 0,499* -0,00 Bet 0,3 0,36 0,075 0,43 0,385 0,60 hydroxy butirte Acetoc 0,493* b 0,58* b 0,09 b 0,573* b 0,396 b 0,068 b ette **: p < 0,0 All were tested using Person s correltion test, except : with the contingency coefficient test. Chnges in The Medin Vlues for Keton Body, Glucose nd Metbolic Profile It cn be seen in Tble 8 tht chnges in men vlue were significnt t the 6th compred to those t the nd. From the six numeric vribles in the metbolic profile studied, only the men chnges in ph nd nion gp turned out to be not significnt t the 6th. Chnges in the men blood glucose level were still significnt up to the th. From the exmintion results with repeted mesurement, significnt seril results from the sttisticl tests performed in this study ws obtined for blood glucose, bet hydroxybutirte nd seril HCO 3. In study it ws lso found in the second nd third ptients tht even though the blood glucose level hd reched below 00 mg/dl, bet hydroxybutirte ws still found to exceed 3 mmol/l up to the 4 th. Even though the result ws not significnt, improvement in the ptient s consciousness ws found long with tretment. 73

5 Ik P Wijy, etl Act Med Indones-Indones J Intern Med Number of ptients Tble 8. Chnges in Men Metbolic Profile for Numeric Vribles Glucose 400 (3) Bet 3,3 hydroxy (,4) butirte PH 7,4 (0,) pco 8,87 (7,9) HCO3 0,7 (6,37) Anion 6,5 gp (8,00) 0 nd 38 (36) 3,3 (,49) 7,9 (0,4) 9,4 (7,45) 0,56 (5,98) 3, (9,36) (for pired t-test ) ( ) : stndrd devition th 48* (37),7* (,40) 7,34 (0,0),45* (6,3),9* (5,37) 3,69 (5,69) KM Figure. Chnges in The Level of Consciousness in 4 Hours A Sm S K th 95* (90),0 (,9) 7,35 (0,08),9 (5,98) 3,7 (5,00),89 (7,6) 8 th 0 (95),38 (,08) 7,37 (0,09) 3,55 (5,38) 3,8 (4,46),56 (7,44) 4 th (89) 0,83 (,3) 7,38 (0,07) 3,7 (5,7) 4,87 (3,99),06 (9,) hydroxybutirte nd cetocette levels were ccompnied by elevtions in ph, pco nd HCO3. It ws lso found tht when cetocette ws zero nd bet hydroxybutirte ws still over the norml vlue (0.6 mmol/l), chnges in metbolic profile ws still tking plce. The results of the bet hydroxybutirte nd cetocette during dmission demonstrted tht t bet hydroxybutirte levels of > 3.0 mmol/l, cetocette ws found to be ++ nd +++. Complete results cn be found in Tble 9. p repeted mesure 0,000 0,04 0,38 0,59 0,048 0,5 ph ph Tble 9. The Comprison Between Bet Hydroxybutirte nd Acetocette Results t The Time Dibetic Ketocidosis ws Estblished Bet hydroxybutirte (mmol/l) Acetocette > , ,6, < 0, Medin Hour Figure. Chnges in The Medin of Ech Vrible in 4 Hours When compred, there were chnges in the men of ll numeric nd ctegoricl vribles except the level of consciousness, s demonstrted in Figure. It cn be seen tht ech reduction in blood glucose, bet 3HB pco HCO3 AG AsAs DISCUSSION Thirty nine cses of dibetic ketocidosis were dmitted to the Emergency Unit of Cipto Mngunkusumo Generl Hospitl from Jnury 000 to June 000. This ws the gretest number of cses compred to previous reports t the sme hospitl. Btubr 8 found 55 cses of dibetic ketocidosis in 48 months from 984 to988. Noor 9 found 37 cses in one yer (999). From this study, n increse in the number of dibetic ketocidosis cses dmitted to Cipto Mngunkusumo Generl Hospitl ws discovered. The cuse of this increse is unknown. 74

6 Vol 36 Number April-June 004 β-hydroxybutirte Levels s Determinnt for The Success From this study, bet hydroxybutirte ws found to be the only vrible with strong correltion with blood ph, compred to blood glucose nd cetocette. This is in line with the opinions of Oster nd Epstein. 0 Both of them believed tht bet hydroxybutirte is keton body with greter similrity compred to cetocette. They stted tht bet hydroxybutirte hs pk 4.7 nd cetocette hs pk of only The difference in pk cuses difference in the titrtion process to blood cidity from HCO 3. Bet hydroxybutirte more esily undergoes protoniztion nd HCO 3 buffering. Bet hydroxybutirte ws mentioned to be the most common keton body in the blood, compred to cetocette or cetone. According to Surytmj, bet hydroxybutirte mkes up 75%, cetocette 0-5% nd cetone %. Thus, in dibetic ketocidosis the role of bet hydroxybutirte is even greter. For CO, the results of this study were in line with the results of the study by Fullop et l 3. Wht differentites this study from tht by Fullop et l is in the CO tht ws mesured. This study utilized rteril blood CO, correlted with blood bet hydroxybutirte. On the other hnd, Fullop et l used serum CO with blood bet hydroxybutirte. Fullop et l found correltion of r = between CO serum nd serum bet hydroxybutirte in dibetics nd dibetic ketocidosis ptients. In dibetic ketocidosis ptients the r vlue ws In our study, we found tht correltion between bet hydroxybutirte nd rteril blood CO of r = t 0. This result is better thn tht of Fullop. According to tht previous study, in dibetic ketocidosis, mny things influences the blood/serum CO level, such s hyperchloremi, which lso induces cidosis, nd the effects of the clinicl symptom of vomiting, complint tht often ccompnies dibetic cidosis, which cuses lklosis. 3 Thus, even though the bet hydroxybutirte hs dropped, serum CO levels remin low. This is the cuse of the lck of strong correltion between bet hydroxybutirte nd CO during subsequent monitoring. In the men time, Hlperin nd Goldstein believe tht the drop in rteril pco in dibetic ketocidosis in cused by cidemi-induced hyperventiltion. Arteril pco levels re often lower thn venous pco. This is becuse in the peripherl tissue, there is little blood flow due to lck of extrcellulr fluid, so tht ech liter of venous blood crries more CO. In ddition, CO production is lso low, since keton body from ketogenesis of free ftty cid oxidtion is used s n energy source insted of glucose in dibetic ketocidosis. Keton body processing does not produce CO. 3,4 Mny references ssocited the drop in HCO 3 with blood ph reduction in dibetic ketocidosis. 6,,5-7 This is ssocited with the function of HCO 3 s hydrogen ion buffer. Thus, the correltion between HCO 3 nd bet hydroxybutirte is better thn cetocette for the sme reson s blood ph. In ddition, HCO 3 level is lso ssocited with nion gp. Adrogue et l 8 described how the rtio between the increse in nion gp to the reduction in bicrbonte equls. It is expected tht the higher the nion gp, the more HCO3 is excreted. In relity, we often find rtio exceeding or below. Androgue et l mentioned tht if the rtio exceeds, there re severl possible cuses, s follows: ) vomiting or bicrbonte dministrtion, ) hyperproteinemi, 3) tissue titrtion, 4) renl excretion, nd 5) selective hydrogen ion cellulr uptke. If the rtio is less thn, it my be cused by: ) Renl excretion of keton body from sodium slts, ) chloride-contining infusion, 3) hypocpni, 4) renl tubulr cidosis, nd 5) differences in the distribution of hydrogen ions nd ccompnying nions. 8,9 The correltion between HCO 3 nd bet hydroxybutirte nd cetocette is very similr with the correltion between ph nd bet hydroxybutirte nd cetocette. glucose is not correlted with HCO 3. In reltion to nion gp, bet hydroxybutirte hs correltion tht is in line with theory. After 6 s of tretment, the correltion is reduced. chloride levels increses slightly fter dministrtion of 0.9% NCl, nd disturbs the nion gp nd bicrbonte level, side from other cuses mentioned bove, when in fct nion gp is up to now still recommended to use s determinnt of the success of dibetic ketocidosis mngement. Fleckmn 5 stted tht clcultion of effective serum osmollity very importnt to monitor chnges in the level of consciousness of dibetic ketocidosis ptients. The proposed clcultion is s follows: Effective serum osmollity = [N - + K + ] + blood glucose (mg/dl)/8 Menwhile, for serum sodium level, the recommended clcultion is derived from the following corrected formul: Corrected serum sodium = [N-] +.6 x {[blood glucose (mg/dl) 00]/00} If the osmollity vlue is over 330, this is hyperosmolr, nd is ssocited with reduced consciousness due to intrcellulr dehydrtion. Evlution of the level of consciousness cnnot be estimted only 75

7 Ik P Wijy, etl Act Med Indones-Indones J Intern Med ccording to the ptient s blood glucose level. This is becuse hyperglycemi does not indicte true blood hyperosmolrity. 5, Another cuse for reduced consciousness in dibetic ketocidosis is cerebrl edem. The cuse for one of such compliction of dibetic ketocidosis is uncertin. 0- Glser et l stted tht one of the suspected cuses is low rteril pco nd high serum blood ure nitrogen (BUN) concentrtion. This study ws performed in children up to 8 yers of ge. The Benefits of Seril Exmintion Not mny people mention the benefits of seril exmintions in dibetic cidosis mngement. A common exmintion is ly blood glucose test. This seril exmintion is performed to void the development of the compliction of hypoglycemi. Wiggm et l performed seril blood glucose nd bet hydroxybutirte exmintion to find n effective vlue for insulin mngement tht is dpted with the results of bet hydroxybutirte. Menwhile, the Americn Dibetes Assocition recommends ly seril exmintion of electrolyte, BUN, cretinine nd blood glucose, blood osmollity nd venous blood ph t the commencement of tretment nd fterwrds every -4 s until the ptient s dibetic ketocidosis stbilizes. 3 The ph is not exmined from the rtery but insted from the vein, which is 0.03 less thn the rtery. Seril blood gs nlysis exmintion is not recommended for monitoring of dibetic ketocidosis. Kitbchi nd Wll wrote tht blood glucose could noly rech stble vlue fter 7.5 s of tretment. This is becuse the physiologicl rte for insulin to reduce the blood glucose level is mg/dl/s, while HCO 3 level nd blood ph could only stbilize fter twice the time (5 s). On the other hnd, Oster nd Epstein 0 stted tht tht level of bet hydroxybutirte tht is excreted through urine will drop fter 8 s of mngement. If it is combined with the results of this study, there is hrmony in the benefit of seril blood glucose exmintion, HCO3 nd bet hydroxybutirte. Attention needs to be pid for the perfect time to exmine blood keton body. Kitbchi recommended for the exmintion to be performed only t the initil dignosis nd t the end of dibetic ketocidosis. On the other hnd, Wiggm et l stted tht repet bet hydroxybutirte exmintion should be performed fter the blood glucose is controlled (pproching normoglycemi) for 4 s. The results of this study demonstrte tht fter the 6th, ll seril exmintions except blood glucose hve become not significnt for comprison between different points in time. However, for 4- seril exmintion, seril blood glucose, bet hydroxybutirte nd HCO 3 exmintions were sttisticlly significnt. The Comprison Between Bet Hydroxybutirte nd Acetocette t The Time of Dignosis of Dibetic Ketocidosis Regrding the correltion between bet hydroxybutirte nd cetocette t the dignosis of dibetic ketocidosis, it ws found tht not ll ptients with trce or positive one or two results of cetocette hs bet hydroxybutirte level of >3 mmol. When brochure of the instrument to exmine bet hydroxybutirte used is consulted, then suspicions of dibetic ketocidosis begins when mesured levels of bet hydroxybutirte exceed.5 mmol. This my be becuse when smples enter, interconversion hs occurred from bet hydroxybutirte to cetocette, or in other words, the process of ketogenesisny hs diminished. 3,4 In this study, the interction between cetocette nd bet hydroxybutirte ws not investigted, becuse the im of the study ws not to compre the two s dignostic modlitites. Nevertheless, from the vilble dt, the dignosis of dibetic ketocidosis should be bsed on bet hydroxybutirte, becuse ll bet hydroxybutirte levels exceeding 3 mmol/l hs ph of less thn 7.35 nd n HCO 3 level of less thn 8 meq/l. On the other hnd, if we only bse our decisions on the results of the cetocette exmintion, the dibetic ketocidosis protocol is initited too erly, since the results of cetocette exmintion from trce up to (++) sometimes still hve bet hydroxybutirte level of less thn.5 mmol/l. Thus, if we rely on bet hydroxybutirte, we could sve on the costs of tretment by only dministering sliding scle insulin. CONCLUSION Bsed on this study strong nd significnt negtive correltion ws found between β- hydroxybutirte level nd ph, pco nd HCO 3 compred to the correltion between blood glucose level nd cetocette nd ph, pco nd HCO 3. A positive strong nd significnt correltion between β-hydroxybutirte level nd nion gp ws found compred to the correltion between blood glucose level nd cetocette nd nion gp. A wek nd insignificnt correltion ws found between β-hydroxybutirte, blood glucose nd cetocette levels nd the level of 76

8 Vol 36 Number April-June 004 β-hydroxybutirte Levels s Determinnt for The Success consciousness. Beneficil seril exmintion modlity for the mngement of dibetic ketocidosis re blood glucose, β-hydroxybutirte nd HCO 3 exmintion. SUGGESTIONS Exmintion of β-hydroxybutirte level should be performed in ptients with dibetic ketocidosis. The present mngement protocol for dibetic ketocidosis should be continued, with the ddition of β- hydroxybutirte exmintion. Further study using lrger smple nd comprison with gold stndrd exmintion is needed to determine better dignostic procedure. REFERENCES. Soewondo P. Ketosidosis dibetik. Dlm: Mrkum HMS, Sudoyo AW, Effendie S, eds. Nskh lengkp pertemun ilmih thunn ilmu penykit dlm 997. Bgin ilmu penykit dlm FKUI, RSUPN CM 997: Wiggm MI, O Kne MJ, Hrper R, Atkinson AB, Hdden DR, Trimble ER, et l. Tretment of dibetic ketocidosis using normliztion of blood 3-hydroxybutyrte concentrtion s the endpoint of emergency mngement. Dibetes Cre 997; 0(9): Fulop M, Murthy V, Michili A, Nlmti J, Qin Q, Sitowitz A. Serum â-hidroksibutirt mesurement in ptients with uncontrolled dibetes mellitus. Arch Intern Med 999;59: Ennis ED, Kreisberg RA. Dibetic ketocidosis nd the hyperglycemic hyperosmolr syndrome. In: LeRoith D, Tylor SI, Olefsky JM, eds. Dibetes mellitus fundmentl nd clinicl text. Phildelphi: Lippincot Willims&Wilkins; 000. p Fleckmn AM. Dibetic ketocidosis. Endocrinol nd Metb Clinics North Am 993; (): Delney MF, Zismn A, Kettyle WM. Dibetic ketocidosis nd hyperglycemic hyperosmolr nonketotic syndrome. Endocrinol nd Metb Clinics North Am 000; 9(4): Kitbchi AE, Umpierrez GE, Murphy MB, Brret EJ, Kreiberg RA, Mlone JI, et l. Mngement of hyperglycemic crises in ptients with dibetes. Dibetes Cre 00;4(): Btubr M. Fktor-fktor yng mempengruhi hsil pentlksnn ketosidosis dibetik di UPF penykit dlm RSCM thun (lporn penelitin), Fkults Pscsrjn Universits Indonesi, Noor R. Fktor-fktor yng mempengruhi hrpn hidup 4 jm pertm penderit ketosidosis dibetik di instlsi gwt drurt RSUP Dr. Cipto Mngunkusumo: Studi nlisis prmeter metbolik wl.(lporn penelitin ). IPD FKUI RSUPN CM Oster JR, Epstein M. Acid-bse spects of ketocidosis. Am J Nephrol 984;4: Surytmdj M. Ketone metbolism nd its clinicl implifiction. Proceeding JDM 00. Jkrt, 00.. Kitbchi AE, Wll BM. Dibetic ketocidosis. Med Clin of North Am 995;79(): Hlperin ML, Goldstein MB. Fluid, electrolyte nd cid-bse physiology problem bsed pproch. Edisi ke-. Phildelphi: WB Sunders Compny; 994. p McGrry JD, Foster DW. Regultion of heptic ftty cid oxidtion nd ketone body production. Ann Rev Biochem 980;49: Kitbchi AE, Fisher JN, Murphy MB, Rumbk MJ. Dibetic ketocidosis nd the hyperglycemic, hyperosmolr nonketotic stte. In: Khn CR, Weir GC, eds. Joslin s dibetes mellitus. Edisi 3. Phildelphi: Le & Febiger; 994. p Mitchell GA, Fuko T. Inborn errors of ketone body metbolism. In: Scriver CR, Beudet AL, Vlle D, Sly WS, Childs B, Kinzler KN, Vogelstein B, eds. The metbolic & moleculr bses of inherited disese. Edisi 8. New York: McGrw-Hill; 00. p Rose BD, Post TWP. Clinicl physiology of cid-bse nd electrolyte disorders. Edisi ke-5. Singpur: McGrw-Hill; 00. p Adrogue HJ, Eknoyn G, Suki WK. Dibetic ketocidosis: role of the kidney in the cid-bse homeostsis re-evluted. Editoril review. Kidney Int. 984;5: Adrogue HJ, Wilson H, Boyd AE, Suki WN, Eknoyn G. Plsm cid-bse ptterns in dibetic ketocidosis. N Engl J Med 98;307(6): Lebovitz HE. Dibetic ketocidosis. Lncet 995;345: Glser N, Brnett P, McCslin I, Nelson D, Trinor J, Louie J, Kufmn F et l. Risk fctors for cerebrl edem in children with dibetic ketocidosis. N Engl J Med 00;344(4): Edge JA, Hwkins MM,Winter DL, Dunger DB. The risk nd outcome of cerebrl oedem developing during dibetic ketocidosis. Arch Dis Child 00;85: Americn Dibetes Assocition. Hyperglycemic crises in ptients with dibetes mellitus. Dibetes Cre 00;4():