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
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.
In the established patient, DKA results from:
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
- 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:
One of the most important
aspects of care of the patient with DKA is
isolation of trigger factors associated with
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.
Signs and symptoms:
- 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
Patients suffering from DKA may present with varying symptoms depending upon the severity of the condition:
- Raised blood glucose
- 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
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
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
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.
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
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