Pediatric Diabetic Ketoacidosis 

  • Author: William H Lamb, MBBS, MD, FRCP(Edin), FRCP, FRCPCH; Chief Editor: Timothy E Corden, MD   more...
 
Updated: Aug 19, 2011
 

Background

Diabetic ketoacidosis (DKA) is a metabolic derangement caused by the absolute or relative deficiency of the anabolic hormone insulin. Together with the major complication of cerebral edema, diabetic ketoacidosis is the most important cause of mortality and severe morbidity in children with diabetes, particularly at the time of first diagnosis. Early recognition and careful management are essential if death and disability are to be avoided.[1]

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Pathophysiology

Insulin is the pivotal hormone of blood glucose regulation, increasing peripheral glucose uptake, switching off hepatic gluconeogenesis, while stimulating glycogen synthesis and peripheral fat deposition.

Insulin deficiency exaggerates the normal response to fasting, which is to increase liver production of glucose by gluconeogenesis from fat and protein together with breakdown of liver glycogen stores by glycogenolysis. Peripheral glucose uptake is impaired and levels of the main counter-regulatory hormones (ie, glucagon, cortisol, catecholamines, growth hormone) increase. Various metabolic consequences follow.[2]

Hyperglycemia

Glucagon stimulates glycogenolysis and gluconeogenesis, doubling liver glucose production. Hyperglycemia further impairs peripheral glucose uptake and inhibits any residual insulin synthesis. Blood glucose levels rise above the renal threshold for glucose reabsorption, causing an osmotic diuresis.

Fluid and electrolytes

Although they tend to be overestimated, fluid losses can be considerable, typically 3-8% of body weight.[3] Most water is lost by osmotic diuresis, with important contributions from hyperventilation and vomiting. The diuresis also leads to significant urinary losses of potassium, sodium, phosphate, and magnesium ions.

Ketoacidosis

Insulin inhibits the lipolytic action of cortisol and growth hormone; thus, insulin deficiency increases circulating levels of fatty acids. These are oxidized in the liver, producing the acidic ketone bodies beta-hydroxybutyrate and acetoacetate, from which acetone spontaneously forms. The resulting acidosis primarily is due to circulating ketone bodies, with additional contributions from excess fatty acids and lactic acidosis, as a consequence of poor tissue perfusion.

Eventually, hyperventilation no longer can compensate for the metabolic acidosis, which, together with dehydration, leads to renal failure and circulatory collapse followed by coma and death.

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Epidemiology

Frequency

United States

Exact figures for the incidence of diabetic ketoacidosis are not available; however, a multicenter, population-based study reported that around 25% of new cases of type I diabetes mellitus presented with ketoacidosis, resulting in an approximate annual incidence of 4 cases per 100,000 children.[4] The youngest children were at greatest risk, with more than 37% presenting with diabetic ketoacidosis; the rates for children with established diabetes increase with age.[5, 6]

International

As in the United States, few data are available. A large European multicentre study showed widely varying rates of diabetic ketoacidosis at diagnosis (26-67%), with rates inversely related to the overall incidence of childhood diabetes.[7] Diabetic ketoacidosis rates in children with established diabetes widely vary; in a United Kingdom national prospective study, 60% of all cases occurred in patients with known diabetes.[8] Diabetic ketoacidosis at the time of diagnosis is more likely in the most deprived communities. Despite an increased incidence of diabetes, the incidence of ketoacidosis remains high.[9]

A recent analysis of 46 published reports[10] serves to reinforce the above statements. The groups most likely to present with diabetic ketoacidosis at diagnosis were the youngest children, particularly those younger than 2 years, and children from the most deprived communities, including children from ethnic minorities or without health insurance. Factors protecting against diabetic ketoacidosis at diagnosis were having a first-degree relative with type 1 diabetes, better-educated parents, and children living in communities with a high background incidence of childhood diabetes.

Another enormous multicenter study from Germany and Austria used a database containing information on 28,770 children aged 19 years or younger.[11] They also reported the greatest risk of diabetic ketoacidosis in established cases of type 1 diabetes was in the early teenage years, particularly in girls and children from immigrant families.

Mortality/Morbidity

Diabetic ketoacidosis is the most common cause of diabetes-related death in childhood. Without insulin therapy, the mortality rate is 100%, but current mortality rates are around 2-5%.[12, 13, 14]

Treatment for diabetic ketoacidosis may cause life-threatening, predictable, and avoidable acute complications such as hypokalemia, hypoglycemia, hyponatremia, and fluid overload. Other complications, such as cerebral edema, are not as predictable but are very important.

Cerebral edema is the most serious complication of diabetic ketoacidosis. Its causes are not known, but associated factors include duration and severity of diabetic ketoacidosis before treatment, overaggressive fluid replacement, the use of sodium bicarbonate to treat the acidosis, too early an introduction of insulin therapy, cerebral anoxia, and degree of hyperglycemia.[15, 16, 17, 18, 19] Cerebral edema is the most important cause of mortality and long-term morbidity with diabetic ketoacidosis.

Other rare complications of diabetic ketoacidosis include acute respiratory distress syndrome (ARDS) with pulmonary edema,[20, 21] pneumediastinum (secondary to hyperventilation), rhabdomyolysis, and acute renal failure.

Race

Race alone does not appear to have any influence on the likelihood of developing diabetic ketoacidosis,[22] but immigrant communities may be at a higher risk of problems in established cases.[11]

Sex

Although no difference in diabetic ketoacidosis rates between the sexes is observed at diagnosis and during early childhood, adolescent girls with diabetes are more likely to develop diabetic ketoacidosis than adolescent boys.[11, 23]

Age

Infants and children younger than 5 years are at greatest risk of presenting with diabetic ketoacidosis because the diagnosis of diabetes in younger children is more difficult and is more likely to be delayed.[10, 24] Adolescents are more likely to develop diabetic ketoacidosis after diagnosis of diabetes.

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Contributor Information and Disclosures
Author

William H Lamb, MBBS, MD, FRCP(Edin), FRCP, FRCPCH  Clinical Lecturer, Department of Child Health, The General Hospital, Bishop Auckland, UK

William H Lamb, MBBS, MD, FRCP(Edin), FRCP, FRCPCH is a member of the following medical societies: British Medical Association, British Society of Paediatric Endocrinology and Diabetes, International Society of Pediatric and Adolescent Diabetes, Royal College of Paediatrics and Child Health, and Royal College of Physicians

Disclosure: Roche Diabetes Care Honoraria Speaking and teaching

Specialty Editor Board

G Patricia Cantwell, MD, FCCM  Professor of Clinical Pediatrics, Chief, Division of Pediatric Critical Care Medicine, University of Miami, Leonard M Miller School of Medicine; Medical Director, Palliative Care Team, Director, Pediatric Critical Care Transport, Holtz Children's Hospital, Jackson Memorial Medical Center; Medical Manager, FEMA, Urban Search and Rescue, South Florida, Task Force 2; Pediatric Medical Director, Tilli Kids – Pediatric Initiative, Division of Hospice Care Southeast Florida, Inc

G Patricia Cantwell, MD, FCCM is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Heart Association, American Trauma Society, National Association of EMS Physicians, Society of Critical Care Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry J Evans, MD  Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children's Medical Center

Barry J Evans, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Mary E Cataletto, MD  Director of Children's Sleep Services, Winthrop Sleep Disorders Center, Mineola, NY; Professor of Clinical Pediatrics, State University of New York at Stony Brook, Stony Brook, NY

Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians

Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

Chief Editor

Timothy E Corden, MD  Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society

Disclosure: Nothing to disclose.

Additional Contributors

The author would like to thank Debbie Matthews and Tim Cheetham for reading the manuscript and for all their support.

References

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A graphical representation of the ECG changes of hypokalemia.
A graphical representation of the ECG changes of hyperkalemia (due to overcorrection of potassium loss).
Glasgow Coma Scale, modified for age of verbal response.
Page 1 (of 4), diabetic ketoacidosis (DKA) treatment and results flow chart.
Page 2 (of 4), diabetic ketoacidosis (DKA) treatment and results flow chart.
Page 3 (of 4), diabetic ketoacidosis (DKA) treatment and results chart.
Page 4 (of 4), diabetic ketoacidosis (DKA) treatment and results flow chart.
Carbs for Kids-Count Them In: The Constant Carbohydrates Diet.
Diabetes Sick Day Rules.
Taking Diabetes Back to School.
Table 1. Clinical Assessment of Dehydration
Mild < 3%Moderate



3-8%



Severe 8% and



Shock >10%



AppearanceThirsty, alertThirsty lethargicDrowsy, cold
Tissue turgorNormalAbsentAbsent
Mucous membranesMoistDryVery dry
Blood pressureNormalNormal or lowLow for age
PulseNormalRapidRapid and weak
EyesNormalSunkenGrossly sunken
Anterior fontanelleNormalSunkenGrossly sunken
Table 2. Suggested daily maintenance fluid replacement rates.
WeightInfusion rate
0-12.9 kg80 mL/kg/24 h
13-19.9 kg65 mL/kg/24 h
20-34.9 kg55 mL/kg/24 h
35-59.945 mL/kg/24 h
Adult (>60 kg)35 mL/kg/24 h
Table 3. Infusion Rates of Potassium Chloride
Serum/Plasma K+ (mEq/L)Potassium Chloride (KCL) Dose in Infusion Fluids
< 2.5 mEq/LCarefully monitored administration of 1 mEq/kg body weight by separate infusion over 1 h
2.5-3.5 mEq/L40 mEq/L
3.5-5 mEq/L20 mEq/L
5-6 mEq/L10 mEq/L (optional)
Over 6 mEq/LStop K+ and repeat level in 2 h
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