Original Article Diabetic Ketoalkalosis in Children and Adults Emily A. Huggins, MD, Shawn A. Chillag, MD, Ali A. Rizvi, MD, Robert R. Moran, PhD, and Martin W. Durkin, MD, MPH and DR are calculated because the pH and bicarbonate may be near Objectives: Diabetic ketoacidosis (DKA) with metabolic alkalosis normal or even elevated. In addition to having interesting biochemical (diabetic ketoalkalosis [DKALK]) in adults has been described in the features as a complex acid-base disorder, DKALK can pose diagnostic literature, but not in the pediatric population. The discordance in the and/or therapeutic challenges. change in the anion gap (AG) and the bicarbonate is depicted by an Key Words: delta ratio, diabetic ketoacidosis, diabetic ketoalkalosis, elevated delta ratio (DR; rise in AG/drop in bicarbonate), which is metabolic alkalosis normally approximately 1. The primary aim of this study was to de- termine whether DKALK occurs in the pediatric population, as has been seen previously in the adult population. The secondary aim was iabetic ketoacidosis (DKA), a common and serious dis- to determine the factors that may be associated with DKALK. Dorder that almost always results in hospitalization, is de- Methods: A retrospective analysis of adult and pediatric cases with a fined by the presence of hyperglycemia, reduced pH, metabolic 1 primary or secondary discharge diagnosis of DKA between May 2008 and acidosis, elevated anion gap (AG), and serum or urine ketones. August 2010 at a large urban hospital was performed. DKALK was as- In some situations, a metabolic alkalosis coexists with DKA sumedtobepresentiftheDRwas91.2 or in cases of elevated bicarbonate. and may normalize the pH and serum bicarbonate; therefore, the usual definition of DKA is not met. Bleicher coined the Results: Of 190 DKA cases, 91 were children, with 21% fulfilling term diabetic ketoalkalosis (DKALK) for this entity in 1967,2 the criterion for DKALK. There were 99 adult cases, 35% of which although DKA with metabolic alkalosis had been described fulfilled the criterion for DKALK. Our final logistic model revealed first in 1959.3 Since Bleicher’sdescription, more than 30 cases that among patients with a discharge diagnosis of DKA, male patients, have been published in the English-language literature. patients with a history of renal failure, and patients presenting with Although criteria for the presence of DKALK have been abdominal findings on physical examination were at greater odds of insufficiently studied and are not generally established, the use of 4 having a concomitant metabolic alkalosis. the delta ratio (DR) is favored. DR denotes the rise in the AG, divided by the drop in serum bicarbonate, when this value is Conclusions: Although DKALK has been described in adults, it can below the normal range. The serum bicarbonate may be higher occur in a significant number of children presenting with DKA. The than the normal value in some cases, assuming that serum bi- recognition of DKA can be obscured in such situations unless the AG carbonate did indeed decrease by the same number that the AG increased but started at a higher level.5 In such cases, when an AG From the Department of Medicine, University of South Carolina School of Medicine, the Department of Epidemiology and Biostatistics, University is present, in the appropriate clinical setting a metabolic alkalosis of South Carolina Arnold School of Public Health, and the Department of and DKA are present; however, DR cannot be calculatedV Clinical Research, Palmetto Health Richland, Columbia, South Carolina. instead, an excess AG is present. Some authors have objected to Reprint requests to Dr Shawn A. Chillag, Department of Medicine, Uni- the term DKALK because the metabolic alkalosis is not directly versity of South Carolina School of Medicine, 2 Medical Park, Suite 502, Columbia, SC 29203. Email: [email protected] This article has been developed as a Journal CME Activity by the Southern Key Points Medical Association. Visit http://sma.inreachce.com to view instructions, & documentation, and the complete necessary steps to receive CME credit Diabetic ketoalkalosis (DKALK) is seen with diabetic for reading this article. Fees may apply. CME credit will be available ketoacidosis and a concomitant metabolic alkalosis. for 2 years after date of publication. & DKALK may be recognized by calculating the delta ratio, The study was funded by a Summer Research Internship grant (E.A.H.) and which may illustrate the possible discordance between the the Department of Medicine, University of South Carolina School of Medi- cine, Columbia. change in anion gap and the change in bicarbonate, in com- The authors have no financial relationships to disclose and no conflicts of bination with considering additional information from a interest to report. medical history and physical examination. Accepted July 10, 2013. & Recognition of DKALK may prevent diabetic ketoacidosis Copyright * 2014 by The Southern Medical Association cases from being unrecognized. 0038-4348/0Y2000/107-6 & DKALK is seen in both pediatric and adult patients. DOI: 10.1097/SMJ.0000000000000040 6 * 2014 Southern Medical Association Copyright © 2013 The Southern Medical Association. Unauthorized reproduction of this article is prohibited. Original Article Table 1. Candidate predictor variables Table 1. (Continued) Demographics Demographics Age (dichotomized at younger than 18 years) Admission studies Sex Abdominal films ordered Race Precipitating cause Medicaid insurance New diagnosis of diabetes mellitus Admission information Noncompliance Primary diagnosis of diabetic ketoacidosis Infection Type 1 diabetes mellitus Diet Diagnosis of acute or chronic renal failurea Other Diagnosis of cellulitis aScreened in simple logistical regression as acute renal failure, chronic renal Diagnosis of urinary tract infection failure, and renal failure (acute or chronic). Diagnosis of pneumonia linked to the ketosis6; rather, it may be related to the volume First admission of diabetic ketoacidosis depletion seen in DKA. Diagnosis of dehydration There was no large, systematic study of this entity until our Diagnosis of history of noncompliance brief report in adults.7 A review of the pediatrics literature and Diagnosis of streptococcal pharyngitis textbooks does not describe this association of two primary Diagnosis of gastroparesis acid-base disorders in children, nor was it familiar to our pe- Admission vitals diatrics colleagues. It is unclear whether this is a failure to Temperature recognize or to report the metabolic alkalosis and DKA in Systolic blood pressure children. Although there is a report of ketoalkalosis occurring Body mass index in a 9-year-old, this was a central respiratory alkalosis related Pulse to Rett syndrome that persisted after correction of the DKA.8 Diastolic blood pressure The primary aim of this study was to determine whether Admission symptoms DKALK occurs in the pediatric population, as has been seen Nausea and vomiting previously in the adult population. The secondary aim was to Abdominal pain determine the factors that may be associated with DKALK. We Excessive thirst or polydipsia report the findings of a retrospective chart review conducted Change in mental status using a liberal definition of DKALK. Change in weight Objective signs on physical examination Methods Dehydration Abdominal Study Design Neurologic A retrospective review of records for all pediatric and Infection adult patients with a primary or secondary diagnosis of DKA Chest admitted between May 2008 and August 2010 was performed Admission laboratory values at a 650-bed teaching hospital. The institutional review board Arterial pH granted study approval based upon its exempt status. The hos- pO2 pital informatics department mined 213 cases and provided Potassium these to the study team. A total of 23 cases were excluded from Creatinine data collection secondary to incomplete or absent serum so- Urine specific gravity dium, chloride, and bicarbonate. Information from the remain- Hemoglobin ing 190 cases was deidentified and data acquisition sheets were Hemoglobin A1c completed for each case. pCO2 Percent O2 saturation Statistical Analysis Blood urea nitrogen DKALK was defined as having a DR 91.2 or a serum Glucose bicarbonate Q24 mEq/dL. AG was calculated using the con- White blood cell count ventional formula of [Na Y (Cl + HCO3j)]. DR was calculated Platelet count based upon the following formula [(calculated AG Y 12)/(24 Y Urine ketones serum bicarbonate)], with 12 and 24 accepted as the normal value for AG and serum bicarbonate, respectively. Southern Medical Journal & Volume 107, Number 1, January 2014 7 Copyright © 2013 The Southern Medical Association. Unauthorized reproduction of this article is prohibited. Huggins et al & Diabetic Ketoalkalosis in Children and Adults nausea and vomiting, subjective thirst or polydipsia, and blood Table 2. Final regression model with DKALK as outcome glucose level. By using the likelihood ratio test with > = 0.05, age, ORa 95% CI P race, change in mental status, nausea and vomiting, subjective thirst or polydipsia, and blood glucose level were dropped from Sex 2.92 1.40Y6.10 0.004 the model. The final model, including odds ratios with 95% con- Renal failure 5.14 2.18Y2.13 G0.001 fidence limits and P values, is displayed in Table 2. Abdominal findings 2.90 1.27Y6.60 0.011 There were 190 cases with a primary or secondary dis- aOdds of a patient with discharge diagnosis of DKA having superimposed charge diagnosis of DKA. Ninety-one of the 190 were pediat- metabolic alkalosis is 2.92 times greater for male patients than for female ric cases (patients younger than 18 years) with a mean age of patients, after adjusting for other two factors. CI, confidence interval; DKA, diabetic ketoacidosis; DKALK, diabetic 12 years; 89 (97.8%) had type 1 diabetes mellitus and 19 (21%) ketoalkalosis; OR, odds ratio. fulfilled the criteria for DKALK with a DR 91.2 or serum bi- carbonate Q 24. There were 99 cases in the adult group with a Seventy-two potential predictor variables (demographic, mean age of 38 years; 67 (68%) had type 1 diabetes mellitus clinical, and laboratory data) were initially collected.