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hyperosmolar diabetes mellitus, already receiving insulin therapy and refusal ..... Diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic syndrome.
ORIGINAL ARTICLE

β-hydroxybutirate Levels as a Determinant for The Success of Diabetic Ketoacidosis Management Ika Prasetya Wijaya*, Pradana Soewondo**, Djoko Widodo***, Aru W. Sudoyo****

ABSTRACT Aim: to obtain a greater understanding of the diagnosis and evaluation of success in diabetic ketoacidosis management. Methods: a prospective observational study was performed on patients with diabetic ketoacidosis at the Emergency Unit of Cipto Mangunkusumo General Hospital. All patients that were admitted were had their blood glucose, β--hydroxybutirate, acetoacetate, pH, pCO2, HCO3, anion gap and consciousness levels serially monitored on upon admittance (0 hour) and the 2nd, 6th, 12th, 18th and 24th hours. The correlation coefficient of each examination was also calculated. The benefit of serial examination of each variable was also determined for each ketoacidosis undergoing the study. Results: Out of the 19 available samples, a strong negative correlation was found between β--hydroxybutirate and pH with a value of r>0.5 (from –0.524 to –0.833 with p 250 mg/dL, b. positive blood acetoacetate, c. blood pH < 7.35 and or d. serum bicarbonate level < 18 mEq/L who were willing to participate in the study. Exclusion criteria: pregnant patient, alcoholic ketoacidosis, salisilate overdose, isopropyl alcohol intoxication, non-ketotic hyperosmolar diabetes mellitus, already receiving insulin therapy and refusal to participate in the study. The studied variables were b-hydroxybutirate, blood glucose, acetoacetate, pH, pCO2, HCO3, anion gap and level of consciousness. Samples were taken by consecutive sampling. The sample size was calculated using a formula to determine a single sample in different means and with single samples to determine the correlation coefficient. Patients who met the inclusion criteria for diabetic ketoacidosis have received diabetic ketoacidosis

β-hydroxybutirate Levels as a Determinant for The Success

management based on the diabetic ketoacidosis management scheme (protocol for diabetic ketoacidosis management at Cipto Mangunkusumo General Hospital). Blood samples were obtained for hemoglobin, hematocryte, leukocyte, platelet count, ureum, creatinine, cito blood glucose, blood gas analysis, and acetoacetate performed on 0 hour (upon admittance to the Emergency Unit) and was performed at the laboratory of the Emergency Unit, on the second floor of the Emergency Unit building. Afterwards, examination of blood glucose and serum keton body levels, particularly βhydroxybutirate was performed using a Precision Optium instrument (from PT. Abbot Diagnostic), and pH, HCO3, anion gap examination with a I-Stat Analyser instrument (from PT. Abbot Diagnostic). The limitation of using Precision Optium is the maximum blood glucose level detected is 600 mg/dl and the maximum b-hydroxybutirate level detected is 6 mmol/L. Above those levels, the instrument displayed “High”. Blood glucose and b-hydroxybutirate levels were examined using capillary blood without anticoagulant, where the first drop was removed using tissue, while the next drop was used as sample. Measurement was performed directly at the patient’s bed side. Acetoacetate was examined at the laboratory of the emergency unit (on the second floor) using uristix (the instrument usually used at the emergency unit laboratory to analyze blood acetoacetate) using 1 ml of venous blood transported immediately after being obtained in a closed compartment, and then centrifuged to obtain the serum. For pH, HCO3 and anion gap evaluation, 0.5 ml of arterial blood with lithium heparin anticoagulant (with approximately 0.05 ml of anticoagulant) was obtained, and the examination was performed less than 10 minutes after the sample was obtained. The sample was examined using I-Stat Analyser in a special instrument to insert approximately 0.2 ml of blood and insert it into the I-Stat Analyser slot to be read. The examination takes approximately 2 minutes. The bicarbonate level obtained from the calculation using the standard instrument could be read immediately on the instrument’s LCD screen. The examination was performed directly at the patient’s bed side. On the patient, blood glucose, keton (acetoacetate and beta hydroxybutirate), pH and anion gap as well as bicarbonate calculation were performed on 0, the 2nd, 6th, 12th, 18th and 24th hours. Consciousness was determined by a single researcher based on the criteria for being fully conscious, apathetic, somnolent, soporous or comatose. 71

Ika P Wijaya, etal

During the examination and treatment at the beginning of the study, history was obtained from the patient or the patient’s family on age, the duration of type 2 diabetes mellitus, and the duration of current illness. Information was provided on the procedure of the study and the benefit both for the sample as well as for the community outside of the study, and consent was obtained. Consent was obtained directly from the patient or from the patient’s family if the patient could not provide direct consent. This study received consent from the research ethics committee of the Faculty of Medicine of the University of Indonesia. Patients with diabetic ketoacidosis who did not participate in the study received the same treatment as the study participants. The data that was obtained then underwent univariate analysis to determine the mean and standard deviation (CD). Serial changes in the values or condition of each variable were tested using the paired t-test for numeric variables and the Marginal Homogeneity test for categorical variables. Bivariate analysis was performed to determine the correlation between beta hydroxybutirate, acetoacetate and blood glucose with pH, pCO2, HCO3, anion gap and level of consciousness, using the Pearson test for numeric variables and the Spearman’s rank test for categorical variables. If both variables are categorical, they were tested using the contingency coefficiency test. All statistical analyses were performed using SPSS version 10.05 and the results of the study were reported in the form of text, tables, and graphs.

Acta Med Indones-Indones J Intern Med Table 1. Patient Demographical Characteristics

Age (years) Sex Duration of DM (months) Duration of illness(days) Hemoglobin (g/dL) Hematocryte (vol%) Leukocyte (/mL) Platelet (/mL) Ureum (mg/dL) Creatinine (mg/dL)

Mean

SD

48.1 Male : 8 Female : 11 8

12.5

8.5

9.6

12.84

3.47

37.05

10.29

19.926 340.736

10.585 189.51 2 51.7 3.56

70.8 2.48

14.6

Note

Min : 0 Max: 60 Min : 1 Max: 30

Min : 0.6 Max: 16.8

Table 2. The Medical Problems Found Among Patients with Diabetic Acidosis

Problem

Frequency

Pneumonia Diabetic ulcer Lung tuberculosis Acute renal failure Acute pancreatitis Urinary tract infection Stroke Chronic renal failure Cessation of Insulin Cessation of Oral Hypoglycemic agent Liver abscess Meningitis Septic shock Respiratory failure

12 6 5 3 2 2 2 2 1 1 1 1 1 1

RESULTS General Characteristics

From January to June 2002, 39 diabetic ketoacidosis patients were recruited. Out of the 39 patients, 19 were included in the study. The rest could not be included due to technical problems, such as prior administration of insulin treatment, bolus or infusion. Out of the 19 people who were included in the study, 8 (42%) were male and 11 (58%) female. The age ranged between 25 and 72 years with a mean age of 48.1 years. The complete data on patient characteristics can be found in Table 1. Out of the 19 patients included in the study, 3 patients died during observation. The medical problems that the patients had aside from diabetic acidosis varied. These medical problems could be found in Table 2.

72

The Correlation Between Beta Hydroxybutirate, Blood Glucose and Acetoacetate Levels and pH

From table 3, it was found that there was a significant (p 0.5} negative correlation between level beta hydroxybutirate, blood glucose and acetoacetate level and blood pH in patients with diabetic ketoacidosis upon admission to the hospital. Beta hydroxybutirate has a significant and relatively strong correlation with blood pH within 24 hours. The Correlation Between Beta Hydroxybutirate, Blood Glucose and Acetoacetate Levels and pCO2

In table 4, it was found that only beta hydroxybutirate and acetoacetate were negatively correlated with blood pCO2. The correlation was strong and significant only up to the 6th hour.

Vol 36 • Number 2 • April-June 2004

β-hydroxybutirate Levels as a Determinant for The Success

Table 6. The Correlation Coefficient Beta Hydroxybutirate, Blood Glucose and Acetoacetate Level and Serial Anion Gap

Table 3. The Correlation Between Beta Hydorxybutirate, Blood Glucose and Acetoacetate Levels and pH nd

0 hour - 0,590**

th

th

6 hour -0,081

2 hour -0,198

th

th

18 hour

12 hour

Blood -0,173 Glucose Beta -0,656** -0,779** -0,524* -0,833** hydroxy butirate a a a a -0,701** -0,515* -0,528* Acetoac -0,731** etate * : p < 0,05 **: p < 0,01 a All were tested using Pearson’s correlation test, except a : with Spearman’s correlation test.

-0,182

24 hour -0,316

-0,713**

-0,598**

-0,470

a

-0,334

a

Table 4. The Correlation Coefficient for Beta Hydroxybutirate, Blood Glucose and Acetoacetate and Serial pCO2

Blood glucose Beta hydroxyb utirate Acetoac etate

nd

th

th

th

th

0 hour -0,302

2 hour -0,366

6 hour -0,356

12 hour

18 hour

24 hour

0,042

-0,087

-0,038

-0,723**

-0,646**

-0,623**

-0,494*

-0,376

-0,384

a

-0,634**

a

-0,499*

a

-0,120

-0,568*

a

-0,583*

* : p < 0,05 **: p < 0,01 All were tested using Pearson’s correlation test, except a : with Spearman’s correlation test.

a

-0,359

a

a

The Correlation Between Beta Hydroxybutirate, Blood Glucose and Acetoacetate Levels and HCO3

From Table 5, it was found that beta hydroxybutirate has a strong and significant negative correlation { r > -0.5 } with HCO3 compared to acetoacetate and blood glucose level. Table 5. The Correlation Coefficient Between Beta Hydroxybutirate, Blood Glucose and Acetoacetate Levels and HCO3 Serial 0 hour

nd

2 hour

th

6 hour

th

12 hour

th

18 hour

Blood -0,446* -0,375 -0,287 -0,033 -0,128 glucose -0,729** -0,737** -0,573** -0,603** -0,554* Beta hydroxy butirate a a a a a Acetoac -0,664** -0,698** -0,561* -0,502* -0,165 etate * : p < 0,05 **: p < 0,01 a All were tested using Pearson’s correlation test, except a : with Spearman’s correlation test.

0 hour 0,360

nd

2 hour 0,160

th

6 hour 0,247

th

-0,263 -0,502*

-0,272

a

The Correlation Between Beta Hydroxybutirate, Blood Glucose and Acetoacetate Level and Anion Gap

In Table 6, a negative correlation > 0.5 was more freqeuntly found among beta hydroxybutirate levels compared to blood glucose and acetoacetate levels. The level of significance even reached p < 0.01 for the positive correlation between beta hydroxybutirate and anion gap. The correlation between beta hydroxybutirate and anion gap weakened after the 6th hour.

th

24 hour 0,035 0,072

0,131

a

The Correlation Between Beta Hydroxybutirate, Blood Glucose and Acetoacetate Levels and The Level of Consciousness

From Table 7, a weak correlation was found between acetoacetate and the level of consciousness. The correlation was positive. However, the correlation did not occur sequentially, since it only appeared on the 2nd and 12th hours. Table 7. The Correlation Coefficient Beta Hydroxybutirate, Blood Glucose and Acetoacetate Levels and Serial Level of Consciousness

Blood Glucose Beta hydroxy butirate Acetoac etate

th

nd

-0,026

0,025

0,499*

-0,010

0,075

0,432

0,385

0,160

0,241

0,322

0,362

0,528*

b

th

24 hour

-0,033

b

th

18 hour

6 hour

0,493*

th

12 hour

2 hour

0 hour

0,109

b

0,573*

b

All were tested using Pearson’s correlation test, except a : with the contingency coefficient test.

24 hour

18 hour

Blood -0,192 0,310 Glucose 0,588** 0,544** 0,623** 0,481* 0,362 Beta hydroxy butirate a a a a a 0,485* 0,496* 0,678** 0,283 0,295 Acetoac etate * : p < 0,05 **: p < 0,01 a All were tested using Pearson’s correlation test, except a : with Spearman’s correlation test.

* : p < 0,05 **: p < 0,01 th

th

12 hour

0,396

b

0,068

b

a

Changes in The Median Values for Keton Body, Blood Glucose and Metabolic Profile

It can be seen in Table 8 that changes in mean value were significant at the 6th hour compared to those at the 2nd hour. From the six numeric variables in the metabolic profile studied, only the mean changes in pH and anion gap turned out to be not significant at the 6th hour. Changes in the mean blood glucose level were still significant up to the 12th hour. From the examination results with repeated measurement, significant serial results from the statistical tests performed in this study was obtained for blood glucose, beta hydroxybutirate and serial HCO3. In study it was also found in the second and third patients that even though the blood glucose level had reached below 200 mg/dL, beta hydroxybutirate was still found to exceed 3 mmol/L up to the 24th hour. Even though the result was not significant, improvement in the patient’s consciousness was found along with treatment. 73

Ika P Wijaya, etal

Acta Med Indones-Indones J Intern Med

Table 8. Changes in Mean Metabolic Profile for Numeric Variables

Blood Glucose Beta hydroxy butirate PH pCO2 HCO3 Anion gap

nd

th

th

th

th

0 hour

2 hour

6 hour

12 hour

18 hour

24 hour

400 (113) 3,31 (2,41)

382 (136) 3,13 (2,49)

248* (137) 1,72* (2,40)

195* (90) 1,01 (1,92)

202 (95) 1,38 (2,08)

211 (89) 0,83 (1,31)

7,24 (0,21) 18,87 (7,19) 10,17 (6,37) 16,51 (8,00)

7,29 (0,14) 19,14 (7,45) 10,56 (5,98) 13,11 (9,36)

7,34 (0,10) 22,45* (6,23) 12,92* (5,37) 13,69 (5,69)

7,35 (0,08) 22,92 (5,98) 13,27 (5,00) 11,89 (7,26)

7,37 (0,09) 23,55 (5,38) 13,81 (4,46) 11,56 (7,44)

7,38 (0,07) 23,72 (5,71) 14,87 (3,99) 12,06 (9,12)

p repeated measure 0,000 0,041

0,138 0,259 0,048 0,152

Number of patients

* : p < 0,05 (for paired t-test ) (…) : standard deviation 14 12 10 8 6 4 2 0

KM A Sm S 0

2

6 12 hour

18

K

24

Figure 1. Changes in The Level of Consciousness in 24 Hours

7.4

Blood pH

7.35 7.3

pH

hydroxybutirate and acetoacetate levels were accompanied by elevations in pH, pCO2 and HCO3. It was also found that when acetoacetate was zero and beta hydroxybutirate was still over the normal value (0.6 mmol/L), changes in metabolic profile was still taking place. The results of the beta hydroxybutirate and acetoacetate during admission demonstrated that at beta hydroxybutirate levels of > 3.0 mmol/L, acetoacetate was found to be ++ and +++. Complete results can be found in Table 9. Table 9. The Comparison Between Beta Hydroxybutirate and Acetoacetate Results at The Time Diabetic Ketoacidosis was Established

7.25

Beta hydroxybutirate (mmol/L) >3 1,5 – 3 0,6 – 1,5 < 0,6

7.2 7.15

0

2

6

12

18

24

25.0

20.0

8 0 0 0

Acetoacetate ++ + ± 2 1 1 0

0 1 4 0

0 0 0 2

0 0 0 0

3HB

15.0 Median

pCO2 HCO3 AG

10.0

AsAs

5.0

0.0 0

2

6

12

18

24

Hour

Figure 2. Changes in The Median of Each Variable in 24 Hours

When compared, there were changes in the mean of all numeric and categorical variables except the level of consciousness, as demonstrated in Figure 2. It can be seen that each reduction in blood glucose, beta 74

+++

DISCUSSION

Thirty nine cases of diabetic ketoacidosis were admitted to the Emergency Unit of Cipto Mangunkusumo General Hospital from January 2000 to June 2000. This was the greatest number of cases compared to previous reports at the same hospital. Batubara8 found 55 cases of diabetic ketoacidosis in 48 months from 1984 to1988. Noor9 found 37 cases in one year (1999). From this study, an increase in the number of diabetic ketoacidosis cases admitted to Cipto Mangunkusumo General Hospital was discovered. The cause of this increase is unknown.

Vol 36 • Number 2 • April-June 2004

From this study, beta hydroxybutirate was found to be the only variable with a strong correlation with blood pH, compared to blood glucose and acetoacetate. This is in line with the opinions of Oster and Epstein.10 Both of them believed that beta hydroxybutirate is a keton body with a greater similarity compared to acetoacetate. They stated that beta hydroxybutirate has a pKa 4.7 and acetoacetate has a pKa of only 3.58. The difference in pKa causes a difference in the titration process to blood acidity from HCO3. Beta hydroxybutirate more easily undergoes protonization and HCO3 buffering. Beta hydroxybutirate was mentioned to be the most common keton body in the blood, compared to acetoacetate or acetone. According to Suryaatmaja,11 beta hydroxybutirate makes up 75%, acetoacetate 20-25% and acetone 2%. Thus, in diabetic ketoacidosis the role of beta hydroxybutirate is even greater. For CO2, the results of this study were in line with the results of the study by Fullop et al 3 . What differentiates this study from that by Fullop et al is in the CO2 that was measured. This study utilized arterial blood CO2, correlated with blood beta hydroxybutirate. On the other hand, Fullop et al used serum CO2 with blood beta hydroxybutirate. Fullop et al found a correlation of r = -0.60 between CO 2 serum and serum beta hydroxybutirate in diabetics and diabetic ketoacidosis patients. In diabetic ketoacidosis patients the r value was -0.69. In our study, we found that a correlation between beta hydroxybutirate and arterial blood CO2 of r = -0.723 at 0 hour. This result is better than that of Fullop. According to that previous study, in diabetic ketoacidosis, many things influences the blood/serum CO2 level, such as hyperchloremia, which also induces acidosis, and the effects of the clinical symptom of vomiting, a complaint that often accompanies diabetic acidosis, which causes alkalosis.3 Thus, even though the beta hydroxybutirate has dropped, serum CO2 levels remain low. This is the cause of the lack of strong correlation between beta hydroxybutirate and CO2 during subsequent monitoring. In the mean time, Halperin and Goldstein12 believe that the drop in arterial pCO2 in diabetic ketoacidosis in caused by acidemia-induced hyperventilation. Arterial pCO2 levels are often lower than venous pCO2. This is because in the peripheral tissue, there is little blood flow due to lack of extracellular fluid, so that each liter of venous blood carries more CO 2. In addition, CO 2 production is also low, since keton body from ketogenesis of free fatty acid oxidation is used as an energy source instead of glucose in diabetic

β-hydroxybutirate Levels as a Determinant for The Success

ketoacidosis. Keton body processing does not produce CO 2. 13,14 Many references associated the drop in HCO3 with blood pH reduction in diabetic ketoacidosis.6,12,15-17 This is associated with the function of HCO3 as a hydrogen ion buffer. Thus, the correlation between HCO3 and beta hydroxybutirate is better than acetoacetate for the same reason as blood pH. In addition, HCO3 level is also associated with anion gap. Adrogue et al18 described how the ratio between the increase in anion gap to the reduction in bicarbonate equals 1. It is expected that the higher the anion gap, the more HCO3 is excreted. In reality, we often find a ratio exceeding or below 1. Androgue et al mentioned that if the ratio exceeds 1, there are several possible causes, as follows: 1) vomiting or bicarbonate administration, 2) hyperproteinemia, 3) tissue titration, 4) renal excretion, and 5) selective hydrogen ion cellular uptake. If the ratio is less than 1, it may be caused by: 1) Renal excretion of keton body from sodium salts, 2) chloride-containing infusion, 3) hypocapnia, 4) renal tubular acidosis, and 5) differences in the distribution of hydrogen ions and accompanying anions.18,19 The correlation between HCO 3 and beta hydroxybutirate and acetoacetate is very similar with the correlation between pH and beta hydroxybutirate and acetoacetate. Blood glucose is not correlated with HCO3. In relation to anion gap, beta hydroxybutirate has a correlation that is in line with theory. After 6 hours of treatment, the correlation is reduced. Blood chloride levels increases slightly after administration of 0.9% NaCl, and disturbs the anion gap and bicarbonate level, aside from other causes mentioned above, when in fact anion gap is up to now still recommended to use as a determinant of the success of diabetic ketoacidosis management. Fleckman 5 stated that calculation of effective serum osmolality very important to monitor changes in the level of consciousness of diabetic ketoacidosis patients. The proposed calculation is as follows: Effective serum osmolality = 2 [Na- + K+] + blood glucose (mg/dL)/18 Meanwhile, for serum sodium level, the recommended calculation is derived from the following corrected formula: Corrected serum sodium = [Na-] + 1.6 x {[blood glucose (mg/dL) – 100]/100} If the osmolality value is over 330, this is hyperosmolar, and is associated with reduced consciousness due to intracellular dehydration. Evaluation of the level of consciousness cannot be estimated only 75

Ika P Wijaya, etal

according to the patient’s blood glucose level. This is because hyperglycemia does not indicate true blood hyperosmolarity.5,12 Another cause for reduced consciousness in diabetic ketoacidosis is cerebral edema. The cause for one of such complication of diabetic ketoacidosis is uncertain.20-22 Glaser et al21 stated that one of the suspected causes is low arterial pCO2 and high serum blood urea nitrogen (BUN) concentration. This study was performed in children up to 18 years of age. The Benefits of Serial Examination

Not many people mention the benefits of serial examinations in diabetic acidosis management. A common examination is hourly blood glucose test. This serial examination is performed to avoid the development of the complication of hypoglycemia. Wiggam et al2 performed serial blood glucose and beta hydroxybutirate examination to find an effective value for insulin management that is adapted with the results of beta hydroxybutirate. Meanwhile, the American Diabetes Association recommends hourly serial examination of electrolyte, BUN, creatinine and blood glucose, blood osmolality and venous blood pH at the commencement of treatment and afterwards every 2-4 hours until the patient’s diabetic ketoacidosis stabilizes. 23 The pH is not examined from the artery but instead from the vein, which is 0.03 less than the artery. Serial blood gas analysis examination is not recommended for monitoring of diabetic ketoacidosis. Kitabchi and Wall12 wrote that blood glucose could noly reach a stable value after 7.5 hours of treatment. This is because the physiological rate for insulin to reduce the blood glucose level is mg/dL/hours, while HCO3 level and blood pH could only stabilize after twice the time (15 hours). On the other hand, Oster and Epstein10 stated that that level of beta hydroxybutirate that is excreted through urine will drop after 8 hours of management. If it is combined with the results of this study, there is harmony in the benefit of serial blood glucose examination, HCO3 and beta hydroxybutirate. Attention needs to be paid for the perfect time to examine blood keton body. Kitabchi12 recommended for the examination to be performed only at the initial diagnosis and at the end of diabetic ketoacidosis. On the other hand, Wiggam et al2 stated that a repeat beta hydroxybutirate examination should be performed after the blood glucose is controlled (approaching normoglycemia) for 24 hours. The results of this study demonstrate that after the 76

Acta Med Indones-Indones J Intern Med

6th hour, all serial examinations except blood glucose have become not significant for comparison between 2 different points in time. However, for 24-hour serial examination, serial blood glucose, beta hydroxybutirate and HCO3 examinations were statistically significant. The Comparison Between Beta Hydroxybutirate and Acetoacetate at The Time of Diagnosis of Diabetic Ketoacidosis

Regarding the correlation between beta hydroxybutirate and acetoacetate at the diagnosis of diabetic ketoacidosis, it was found that not all patients with trace or positive one or two results of acetoacetate has a beta hydroxybutirate level of >3 mmol. When brochure of the instrument to examine beta hydroxybutirate used is consulted, then suspicions of diabetic ketoacidosis begins when measured levels of beta hydroxybutirate exceed 1.5 mmol. This may be because when samples enter, interconversion has occurred from beta hydroxybutirate to acetoacetate, or in other words, the process of ketogenesisnya has diminished.13,14 In this study, the interaction between acetoacetate and beta hydroxybutirate was not investigated, because the aim of the study was not to compare the two as diagnostic modalitites. Nevertheless, from the available data, the diagnosis of diabetic ketoacidosis should be based on beta hydroxybutirate, because all beta hydroxybutirate levels exceeding 3 mmol/L has a pH of less than 7.35 and an HCO3 level of less than 18 mEq/L. On the other hand, if we only base our decisions on the results of the acetoacetate examination, the diabetic ketoacidosis protocol is initiated too early, since the results of acetoacetate examination from trace up to (++) sometimes still have a beta hydroxybutirate level of less than 1.5 mmol/L. Thus, if we rely on beta hydroxybutirate, we could save on the costs of treatment by only administering sliding scale insulin. CONCLUSION

Based on this study a strong and significant negative correlation was found between βhydroxybutirate level and pH, pCO2 and HCO3 compared to the correlation between blood glucose level and acetoacetate and pH, pCO2 and HCO3. A positive strong and significant correlation between β-hydroxybutirate level and anion gap was found compared to the correlation between blood glucose level and acetoacetate and anion gap. A weak and insignificant correlation was found between β-hydroxybutirate, blood glucose and acetoacetate levels and the level of

Vol 36 • Number 2 • April-June 2004

consciousness. Beneficial serial examination modality for the management of diabetic ketoacidosis are blood glucose, β-hydroxybutirate and HCO3 examination.

β-hydroxybutirate Levels as a Determinant for The Success

9.

SUGGESTIONS

Examination of β-hydroxybutirate level should be performed in patients with diabetic ketoacidosis. The present management protocol for diabetic ketoacidosis should be continued, with the addition of βhydroxybutirate examination. Further study using a larger sample and comparison with a gold standard examination is needed to determine a better diagnostic procedure. REFERENCES 1.

2.

3.

4.

5. 6.

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Soewondo P. Ketoasidosis diabetik. Dalam: Markum HMS, Sudoyo AW, Effendie S, eds. Naskah lengkap pertemuan ilmiah tahunan ilmu penyakit dalam 1997. Bagian ilmu penyakit dalam FKUI, RSUPN CM 1997: 181-8. Wiggam MI, O’Kane MJ, Harper R, Atkinson AB, Hadden DR, Trimble ER, et al. Treatment of diabetic ketoacidosis using normalization of blood 3-hydroxybutyrate concentration as the endpoint of emergency management. Diabetes Care 1997; 20(9):1347-52. Fulop M, Murthy V, Michili A, Nalamati J, Qian Q, Saitowitz A. Serum â-hidroksibutirat measurement in patients with uncontrolled diabetes mellitus. Arch Intern Med 1999;159:381-4. Ennis ED, Kreisberg RA. Diabetic ketoacidosis and the hyperglycemic hyperosmolar syndrome. In: LeRoith D, Taylor SI, Olefsky JM, eds. Diabetes mellitus a fundamental and clinical text. Philadelphia: Lippincot Williams&Wilkins; 2000. p. 336-46. Fleckman AM. Diabetic ketoacidosis. Endocrinol and Metab Clinics North Am 1993; 22(2):181-207. Delaney MF, Zisman A, Kettyle WM. Diabetic ketoacidosis and hyperglycemic hyperosmolar nonketotic syndrome. Endocrinol and Metab Clinics North Am 2000; 29(4):683-705. Kitbachi AE, Umpierrez GE, Murphy MB, Barret EJ, Kreiberg RA, Malone JI, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care 2001;24(1):131-61. Batubara M. Faktor-faktor yang mempengaruhi hasil penatalksanaan ketoasidosis diabetik di UPF penyakit dalam

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