Diabetic ketoacidosis (DKA)

Diabetic ketoacidosis (DKA) is a serious, life-threatening metabolic complication of diabetes mellitus, which, whilst most common in type 1 diabetes mellitus, can on rare occasions present in patients with type 2 diabetes mellitus.
DKA develops in those patients with either an absolute deficiency of insulin or a relative lack of insulin brought about by an excess of counter regulatory hormones.
Diabetic ketoacidosis (DKA) is the most common cause of hospitalization of children with diabetes and of death in the pediatric years in this group. Most deaths can be attributed to intracerebral crises. From 20 to 40% of newly diagnosed patients are admitted in DKA, depending on the adequacy and availability of medical services to diagnose the diabetes early. Recurrent DKA in established patients has been reduced in frequency by the intervention of multidisciplinary teams. Unfortunately, there is no evidence of a decrease in case fatality below the 1-2% achieved by the early 1970s, despite improvements in fluid and insulin therapy and more careful monitoring. Thus, a major goal of diabetes management is to prevent DKA by a high index of suspicion with early symptoms of diabetes and close supervision of established patients.
This article provides guidelines to serve as a checklist and reminder, particularly for those who do not regularly treat DKA or hyperosmolar coma in diabetes. Guidelines cannot be written for all circumstances and for rigid adherence. It should be obvious that a diagnosis does not carry with it the assumption that either the patient or the treatment regimen will follow the book. This article is a supplement to, not a substitute for, clinical judgment.

DKA is always caused by insulin deficiency, either relative or absolute. Many previously undiagnosed patients have been seen in physicians’ offices or emergency rooms where an adequate history and laboratory study could have made the diagnosis before they became critically ill. A high index of suspicion is particularly important for infants and young children. An interesting phenomenon is the occasional marked delay in diagnosis seen in medical families and in the siblings or offspring of people with diabetes, reflecting denial. A simple urine test may turn out to be lifesaving by preventing the initial episode of ketoacidosis, particularly in the high-risk infant and preschool child.

In the established patient, DKA results from:
  • Failing to take insulin, the most common cause of recurrent DKA, particularly in adolescents.
  • Acute stress, which can be trauma, febrile illness, or psychological turmoil, with elevated counter regulatory hormones (glucagons, epinephrine, cortical, growth hormone).
  • Poor sick-day management, typically not giving insulin because the child is not eating or failing to increase insulin for the illness, as dictated by blood glucose monitoring. Home testing of urine for ketones with test strips may be misleading and result in delayed institution of sick-day management; the strips can deteriorate and give false-negative readings. Nitroprusside tablets are less convenient but very stable and reliable.

The combination of hyperglycemia (greater than 12 mmol/L), hyperketonemia (large serum ketones-acetone or betahydroxybutyrate) or large ketonuria, with acidosis (venous pH <7.3 or serum bicarbonate <15 mmol/L).
Occasionally, DKA can occur with normoglycemia when there is vomiting, reduced intake of carbohydrate, and continued insulin therapy. There are also pediatric instances of coma in which ketosis is mild but the blood glucose level very high (often referred to as hyperosmolar nonketotic coma; this occurs typically in very young patients, in those with brain disorders that may affect thirst responses, and in older adolescents with new-onset non insulin-dependent diabetes. These treatment guidelines also apply to these variants.

Pathogenesis of DKA:

Precipitating factors:

One of the most important aspects of care of the patient with DKA is isolation of trigger factors associated with the condition.
Research has repeatedly demonstrated infection as the most common precipitating factor in DKA, with factors such as missed insulin dose, new onset of diabetes and drugs and alcohol also identified.
Whilst it must be acknowledged that it is not always possible to identify a cause for DKA, a full investigation is warranted if further episodes are to be avoided.

DKA diagnosis:
  • Blood Glucose >12 mmol/l9
  • Presence of ketonuria, or positive serum ketones greater 1:210
  • Arterial blood Ph <7.359
  • Serum bicarbonate level <15mmol/l10
Signs and symptoms:
Patients suffering from DKA may present with varying symptoms depending upon the severity of the condition:
  • Hyperglycemia
  • Raised blood glucose
  • Polydipsia
  • Polyuria
  • Fatigue and weakness
  • Abdominal pain and vomiting
  • Other complaints may include abdominal pain and vomiting which are believed to be a result of ketoacidosis and gastric stasis.
Therapeutic goals appear to remain consistent within recent research literature for treatment of DKA.
  • Replacing of fluid loss.
  • Decreasing serum blood glucose.
  • Reversing acidosis and ketosis.
  • Correcting electrolyte imbalances.
  • Identifying underlying causes are the main priorities of care.

Initial treatment should assess the patients airway, with intubations and ventilation a possible requirement for those severely comatosed.
A nasogastric tube may be required if the patient is vomiting to prevent aspiration.

In tissues: Insulin deficiency results in decreased glucose uptake with tissue starvation resulting in proteolysis and lipolysis providing amino acids and glycerol for gluconeogenesis, enhanced by counter regulatory hormone response to both the precipitating and tissue starvation stress.
In the liver: Insulin deficiency results in glycogenolysis and enhanced gluconeogenesis, also stimulated by counter regulatory hormones.

Dehydration and thirst:
Results from osmotic diuresis due to hyperglycemia and hyperketonemia, hyperventilation, and vomiting as part of the primary precipitating illness or resulting from the ketosis; since dehydration is usually hyperosmolar and mostly intracellular, dehydration may be underestimated by clinical examination.

Due to ketonemia from overproduction of ketones, which cannot be metabolized in the absence of insulin, and lactic acidosis from tissue hypo-perfusion.
Rapid deep respiration (Kussmaul):
Compensatory response to the metabolic acidosis, contributing to dehydration.

Results from hyperosmolality, not acidosis; calculated osmolality greater than 320 mosm/L is associated with coma.

Largely due to hyperglycemia; calculated as:
  • Na (mmol/L) x 2 + glucose / 18 (mg/dL) + BUN / 2.8 (mg/dL)
  • Na (mmol/L) x 2 + glucose (mmol/L) + urea (mmol/L)

Due to counter-regulatory-hormone- stimulated lipolysis and hypoinsulinemia.
Electrolyte disturbances:
Spuriously low Na level due to osmolar dilution by glucose and sodium-free lipid fraction. Corrected Na (i.e., for normal glucose level) can be estimated as:
Measured Na + (glucose in mmol/L-5.6) / 2(Na deficit is estimated at 10 mmol/kg body weight).
Potassium may be spuriously normal because of acidosis-related exudation from tissues and obligatory urinary losses; estimate total K deficit at 5 mmol/kg. Potassium deficits in newly diagnosed patients may be greater than in established patients because of the longer duration of polyuria before admission.