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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 6  |  Page : 316-320

Role of capillary blood ketone assay in diagnosis and management of diabetic ketoacidosis in pediatric intensive care unit


Department of Pediatric Medicine, The Indus Hospital, Karachi, Pakistan

Date of Submission27-Jun-2020
Date of Decision16-Aug-2020
Date of Acceptance21-Aug-2020
Date of Web Publication11-Nov-2020

Correspondence Address:
Dr. Muhammad Shahzad
Department of Pediatric Medicine, The Indus Hospital, Karachi
Pakistan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JPCC.JPCC_105_20

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  Abstract 


Introduction: Diabetic ketoacidosis (DKA) is a life-threatening metabolic emergency in children. The capillary beta-hydroxybutyrate (BOHB) is increasingly used in the diagnosis and management of DKA. This study's objective is to assess the clinical and statistical correlation of BOHB with standard acidosis markers such as pH and HCO3.
Materials and Methods: We retrospectively reviewed the electronic medical record of children aged 2 months to 16 years with DKA from January 2018 to January 2020 admitted in the pediatric intensive care unit of The Indus Hospital which is a tertiary care specialized center. All children received the treatment according to the standard protocol. Capillary blood BOHB was measured on admission, q 4–6 hourly, and blood glucose was also measured. All parameters were recorded on a structured sheet.
Results: Among 1080 critically ill admissions, 26 patients (2.4%) were diagnosed as DKA. The mean age was 9.8 ± 3.8 years, and females were 54%. Half patients were newly diagnosed with Type 1-Insulin dependant diabetes mellitus (1DDM). Mild, moderate, and severe cases of DKA were 19%, 50%, and 31%, respectively. The median time to resolution of acidosis was 17 (10–39) h. At the time of resolution of acidosis, the correlation between capillary BOHB and blood pH (r = 0.11, P= 0.56), HCO3(r = 0.37, P = 0.86), AG (r = 0.37, P = 0.06), and base deficit (r = 0.04, P = 0.82) was noted. Hyperchloremia was present in 61.5% of cases. Five patients (19.2%) developed AKI that recovered. There was a strong clinical correlation of beta-hydroxybutyrate (BHOB) with standard acidosis markers of DKA management.
Conclusion: Bedside capillary blood BOHB is a simple, inexpensive, point-of-care test that helps diagnose and treat DKA, especially in resource-limited settings, for avoiding unnecessary delays.

Keywords: Beta-hydroxybutyrate, diagnosis, management, diabetic ketoacidosis


How to cite this article:
Shahzad M, Haque A, Mirza S, Jurair H, Ahmed AR, Khalid M. Role of capillary blood ketone assay in diagnosis and management of diabetic ketoacidosis in pediatric intensive care unit. J Pediatr Crit Care 2020;7:316-20

How to cite this URL:
Shahzad M, Haque A, Mirza S, Jurair H, Ahmed AR, Khalid M. Role of capillary blood ketone assay in diagnosis and management of diabetic ketoacidosis in pediatric intensive care unit. J Pediatr Crit Care [serial online] 2020 [cited 2020 Dec 1];7:316-20. Available from: http://www.jpcc.org.in/text.asp?2020/7/6/316/300573




  Introduction Top


Diabetic ketoacidosis (DKA) is the most common life-threatening metabolic–endocrine emergency in children. The current criterion for the diagnosis of DKA is characterized by a triad of hyperglycemia (blood glucose [BG] ≥200 mg/dL), metabolic acidosis (venous pH <7.3 or serum HCO3<15 mEq/L), and ketonemia (blood beta-hydroxybutyrate [BOHB] ≥3 mmol/L) or moderate-to-large ketonuria.[1] In DKA, BOHB is the primary ketone body, and its concentration increased to 4–10 times.[2] Urine ketone measurement in DKA has few limitations, such as delayed voiding leading to delay in diagnosis and unnecessarily prolonged insulin infusion because of continued excretion of ketoacid in the urine, despite the correction of ketosis.[3] The current literature strongly supports the use of capillary blood BHOB in the establishing diagnosis and response to the treatment of DKA both in children and adults.[4],[5],[6],[7] There is a paucity of data available for its use in the management of DKA in pediatric intensive care unit (PICU). This study's objective is to assess the clinical and statistical correlation of capillary blood BOHB level with the traditional standard acidosis such as pH, HCO3, anion gap (AG), and base deficit (BD) in the diagnosis and resolution of ketoacidosis in the management of DKA in the PICU.


  Materials and Methods Top


Study design, setting, and population

We retrospectively reviewed the electronic medical records of all children aged 2 months to 16 years admitted with DKA from January 2018 to January 2020 to compare the capillary blood ketone body (β-HOB) with other standard variables of DKA such as pH, HCO3, AG, and BD at the time of diagnosis and resolution of DKA. This study was approved by the institutional ethical committee (IRD_IRB_2020_03_008).

Definition

The criteria of DKA diagnosis in this study are, according to the ISPAD 2018 guidelines, defined as venous BG >200 mg/dL, pH <7.30, and HCO3<15 and severity is categorized as moderate DKA if venous BG >200 mg/dL, pH <7.20, and HCO3<10 and severe DKA if venous BG >200 mg/dL, pH <7.10, and HCO3<5 with the evidence of ketosis (either blood or urine).[1] Ketoacidosis was diagnosed when capillary blood β-HOB level ≥3.0 mmol/L. MediSense Optium Glucose Ketometer (Abbott Laboratories, UK) is a handheld device that has combined glucose and ketone body (BOHB) sensor device to measure both BG and ketone body from a drop of blood (50 μl) and result in 30 s on the bedside.

Acute kidney injury (AKI) was defined according to the Kidney Disease Improving Global Outcome (KIDGO) criteria based on the serum creatinine.[8]

Hyperchloremia is defined as serum chloride level >107 mEq/L (according to our laboratory reference).

Study protocol

All patients received structured standard protocol-based therapy of DKA in children as described by Shankar et al., including intravenous fluid therapy (two-bag system), continuous intravenous regular insulin infusion (0.1 unit/kg/h), frequent clinical (vital signs, Glasgow coma scale), laboratory hourly bedside BG, intermittent venous blood gas, electrolytes q 4–6 hourly till the resolution of acidosis (pH >7.3, HCO3>15, and AG <12), and switch to intermittent insulin therapy.[9] In addition, capillary blood BOHB was measured at bedside along with the capillary BG from the same skin prick at the time of diagnosis and 4–6 hourly intervals until the resolution of DKA [Figure 1] and [Figure 2]. It has been proven in studies that the capillary BOHB measurement is a valid method to compare the ketones with serum.[10]
Figure 1: Simple process for measuring the BOHB in blood

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Figure 2: Capillary beta-hydroxybutyrate value by ketometer

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Data analysis

Data were entered as means with standard deviation or frequency and percentages as appropriate and analyzed using Software Statistical Package for the Social Sciences Version-22. Pearson's correlation coefficient was performed to assess the association of capillary blood BOHB with other standard DKA parameters such as venous blood pH, serum bicarbonate, AG, and BD at diagnosis and resolution of DKA. P < 0.05 was considered statistically significant.


  Results Top


Of the total 1080 critically ill admissions, 26 patients (2.4%) diagnosed with DKA were enrolled during the study period. The patients' characteristics are described in [Table 1]. The mean age was 9.8 ± 3.8 years (range: 2 months to 16 years), and males were 46% (n = 12). Half of the patients (n = 13) were newly diagnosed with 1DDM. On admission, the mean BG was 477.3 ± 152.8 mg/dL, and the mean serum ketone levels were 5.5 ± 1.09 mmol/L. Arterial blood gas analysis on admission showed mean blood pH of 7.12 ± 0.11, base excess of −15 ± 6.6 mmol/L, AG of 19.5 ± 4.3, and mean HCO3 level of 8.3 ± 3.2 mmol/L. Mild, moderate, and severe cases of DKA were 19% (n = 5), 50% (n = 13), and 31% (n = 8) in our cohort, respectively. The median time to resolution of acidosis was 17 (10–39) h. Hyperchloremia (serum Cl >107 mEq/L) was present in 61.5% (n = 16), which masks the correction of ketosis. Five patients (19.2%) developed AKI; all of them have hyperchloremia which resolved with conservative management. Two children required continuous renal replacement therapy in the PICU. Renal function recovered in all cases. One patient had lactic acidosis due to septic shock along with DKA. There was no mortality in our cohort.
Table 1: Patients' demographic, clinical, and metabolic characteristics

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At the time of admission, the correlation between capillary BHOB and blood pH (r = −3.56, P = 0.05), HCO3(r = 0.37, P = 0.01), AG (r = 0.52, P = 0.06), BD (r = 1.57, P = 0.01) was noted. At the time of resolution of acidosis, the correlation between capillary BHOB and blood pH (r = 0.11, P = 0.56), HCO3(r = 0.37, P = 0.86), AG (r = 0.37, P = 0.06), and BD (r = 0.04, P = 0.82) was noted [Table 2].
Table 2: Comparison of β-HOB (ketone body) with acidosis markers (pH, HCO3, and anion gap)

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There was no overall statistical correlation of BOHB with other acidosis markers on the diagnosis and the time of resolution of ketoacidosis used in the management of DKA, except HCO3 and BD on admission. However, we observed a significant positive clinical correlation of BOHB with almost all acidosis markers, especially AG, both on making a diagnosis and resolving acidosis in the management of children with DKA. There were other factors, that contributed to the marked variability between BHOB and the standard traditional acid variables like (pH, HCO3, AG and BD), such as concurrent metabolic acidosis due to AKI with presence of hyperchloremic, non-anion gap acidosis and lactic acidosis.


  Discussion Top


It is a preliminary report in which we did not observe the statistical correlation of BHOB with the standard acidosis markers in the management of DKA in children. This correlation may be most likely due to the small sample size. However, we found the strong clinical correlation of BHOB with the standard variables of the acid assay in the management of DKA in children in this study project like other published reports.[11],[12],[13],[14] There is a high probability of missing other causes of high AG metabolic acidosis, such as AKI and lactic acidosis from septic shock. Many published reports identified a significant positive role of BHOB measurement in the diagnosis of DKA in the emergency room. Few published reports demonstrated its utility in the monitoring of ketonemia resolution and discontinuation of continuous insulin infusion.[14],[15] This testing can shorten the duration of continuous insulin infusion based on BHOB values, irrespective of pH, HCO3, and BD values that may be inconclusive because of hyperchloremia. It is “point-of-care testing,” straightforward to do, that can be measured from the same device used for BG measurement, less expansive. It requires only a drop of capillary blood (50 μl), and results will be available only in 30 s on a digital display. This testing can save several phlebotomies, blood conservation, and unnecessary laboratory testing and is ultimately cost-effective. Both patients/parents and healthcare professionals preferred this mode of testing in the management of DKA.[16] The home monitoring of capillary blood BHOB along with BG helps in preventing DKA episodes with reduced frequency of hospitalization during sick-day management.[17]

Hyperketonemia and DKA are not synonymous. We were able to differentiate other causes of persistent metabolic acidosis by using bedside BHOB during the treatment of DKA in children. We found hyperchloremia in more than 60% during the treatment of DKA in our case series. Taylor et al. described a similar situation and observed hyperchloremic metabolic acidosis in 94% by 20-h treatment and persistent metabolic acidosis based on the serum BD, HCO3, and pH, which misinterpreted as being due to ketoacidosis.[18] The use of a large volume of chloride-rich fluids can result in hyperchloremia and lead to the development of AKI.[19]

About one-fifth of (19.2%) cases developed AKI during the management of DKA. In the last decade, there was a high incidence (range 30%–64.2%) of AKI reported in children with DKA, and hyperchloremia is a possible risk factor.[5]

The measurement of ketone body as blood BHOB is an objective and quantitative information. There was a lack of relationship between BHOB and routinely measured acidosis markers such as pH and HCO3 in the present study due to concurrent metabolic acidosis secondary to AKI, lactic acidosis, and especially the presence of hyperchloremic metabolic acidosis, in addition to small sample size.

The bedside estimation of BHOB has a very high-performance efficacy in rapid diagnosis and response to the treatment in DKA management in adults and children.[3],[6],[7] Our clinical results followed other studies[15] and are especially helpful in identifying the other causes of metabolic acidosis in the management of DKA in children. This simple, low-cost biochemical assay can alter the management of DKA in children in the future.

Our study had several limitations, such as retrospective design, single center, and small sample size. Another limitation in this study is the mentioning of shortening of insulin duration based on previous study but not calculated here. The strength of this clinical report is the first study from PICU of low- and middle-income countries about the use of point-of-care capillary blood BOHB for rapid diagnosis, response to treatment, and ability to identify the causes of persistent metabolic acidosis in children with DKA.


  Conclusion Top


Bedside capillary blood BHOB is simple, easy to perform with instant results, very useful in rapid diagnosis, monitoring the treatment, discontinuation of insulin infusion, and inexpensive and helps in identifying other causes of metabolic acidosis children with DKA in the PICU. Further, extensive multicenter studies needed to implement the use of bedside BOHB along with BG.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes 2018;19 Suppl 27:155-77.  Back to cited text no. 1
    
2.
Wallace TM, Matthews DR. Recent advances in the monitoring and management of diabetic ketoacidosis. QJM 2004;97:773-80.  Back to cited text no. 2
    
3.
Misra S, Oliver NS. Utility of ketone measurement in the prevention, diagnosis and management of diabetic ketoacidosis. Diabet Med 2015;32:14-23.  Back to cited text no. 3
    
4.
Ham MR, Okada P, White PC. Bedside ketone determination in diabetic children with hyperglycemia and ketosis in the acute care setting. Pediatr Diabetes 2004;5:39-43.  Back to cited text no. 4
    
5.
Bektas F, Eray O, Sari R, Akbas H. Point of care blood ketone testing of diabetic patients in the emergency department. Endocr Res 2004;30:395-402.  Back to cited text no. 5
    
6.
Brooke J, Stiell M, Ojo O. Evaluation of the accuracy of capillary hydroxybutyrate measurement compared with other measurements in the diagnosis of diabetic ketoacidosis: A systematic review. Int J Environ Res Public Health 2016;13:837.  Back to cited text no. 6
    
7.
Klocker AA, Phelan H, Twigg SM, Craig ME. Blood β-hydroxybutyrate vs. urine acetoacetate testing for the prevention and management of ketoacidosis in Type 1 diabetes: A systematic review. Diabet Med 2013;30:818-24.  Back to cited text no. 7
    
8.
Kellum JA, Lameire N, Aspelin P, Barsoum RS, Burdmann EA, Goldstein SL, et al. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012;2:1-138.  Back to cited text no. 8
    
9.
Shankar V, Haque A, Churchwell KB, Russell W. Insulin glargine supplementation during early management phase of diabetic ketoacidosis in children. Intensive Care Med 2007;33:1173-8.  Back to cited text no. 9
    
10.
Kurup PM, Rameshkumar R, Soundravally R, Satheesh P. Capillary versus serum β-hydroxybutyrate in pediatric diabetic ketoacidosis. Indian Pediatr 2019;56:126-9.  Back to cited text no. 10
    
11.
Noyes KJ, Crofton P, Bath LE, Holmes A, Stark L, Oxley CD, et al. Hydroxybutyrate near-patient testing to evaluate a new end-point for intravenous insulin therapy in the treatment of diabetic ketoacidosis in children. Pediatr Diabetes 2007;8:150-6.  Back to cited text no. 11
    
12.
Pulungan AB, Juwita E, Pudjiadi AH, Rahmayanti S, Tsaniya I. diabetic ketoacidosis in adolescents and children: A prospective study of blood versus urine ketones in monitoring therapeutic response. Acta Med Indones 2018;50:46-52.  Back to cited text no. 12
    
13.
Turan S, Omar A, Bereket A. Comparison of capillary blood ketone measurement by electrochemical method and urinary ketone in treatment of diabetic ketosis and ketoacidosis in children. Acta Diabetol 2008;45:83-5.  Back to cited text no. 13
    
14.
Prisco F, Picardi A, Iafusco D, Lorini R, Minicucci L, Martinucci ME, et al. Blood ketone bodies in patients with recent-onset type 1 diabetes (a multicenter study). Pediatr Diabetes 2006;7:223-8.  Back to cited text no. 14
    
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Vanelli M, Chiari G, Capuano C, Iovane B, Bernardini A, Giacalone T. The direct measurement of 3-beta-hydroxy butyrate enhances the management of diabetic ketoacidosis in children and reduces time and costs of treatment. Diabetes Nutr Metab 2003;16:312-6.  Back to cited text no. 15
    
16.
Arora S, Menchine M. The role of point-of-care β-hydroxybutyrate testing in the diagnosis of diabetic ketoacidosis: A review. Hosp Pract (1995) 2012;40:73-8.  Back to cited text no. 16
    
17.
Laffel LM, Wentzell K, Loughlin C, Tovar A, Moltz K, Brink S. Sick day management using blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: A randomized clinical trial. Diabet Med 2006;23:278-84.  Back to cited text no. 17
    
18.
Taylor D, Durward A, Tibby SM, Thorburn K, Holton F, Johnstone IC, et al. The influence of hyperchloraemia on acid base interpretation in diabetic ketoacidosis. Intensive Care Med 2006;32:295-301.  Back to cited text no. 18
    
19.
Marttinen M, Wilkman E, Petäjä L, Suojaranta-Ylinen R, Pettilä V, Vaara ST. Association of plasma chloride values with acute kidney injury in the critically ill-A prospective observational study. Acta Anaesthesiol Scand 2016;60:790-9.  Back to cited text no. 19
    


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