Can Fam Physician. 2012 January; 58(1): 5557.

PMCID: PMC3264012

Too much of a good thing

Management of diabetic ketoacidosis in adults
Danielle Blouin, MD MHPE FRCP FCFP
A healthy 19-year-old man presents to your emergency department complaining of weakness
and lethargy for the past 2 weeks. He sleeps 10 hours a day, yet remains tired. His appetite
has been poor and he constantly feels thirsty. He voids frequently with no dysuria or
hematuria. For the past 24 hours, he has been experiencing moderately severe and diffuse
abdominal pain; he vomited 4 times in the past 2 hours. He has lost 10 kg over the past 2
weeks. He denies other symptoms or using drugs or medications, and he drinks alcohol only
socially. His personal and family medical histories are not relevant.
An examination reveals blood pressure of 115/60 mm Hg, heart rate of 135 beats per minute,
temperature of 36.9C, respiration rate of 24 breaths per minute, and oxygen saturation of
100% on room air. The patient is alert and appears uncomfortable, retching repeatedly. The
mucosae are dry and the abdomen soft but diffusely tender, with normal bowel sounds and no
peritoneal signs. There is no costovertebral angle tenderness. Findings from the remainder of
the examination are noncontributory.
A bedside glucometer displays High-High-High. Laboratory investigations reveal a white
blood cell count of 14.2 109/L, a hemoglobin level of 143 g/L, a platelet count of 365
109/L, a sodium level of 133 mmol/L, a potassium level of 2.9 mmol/L, a chloride level of
103 mmol/L, a blood urea nitrogen level of 17 mmol/L, a creatinine level of 144 mol/L, a
glucose level of 29.7 mmol/L, an arterial pH of 7.10, a Pco2 of 23 mm Hg, a Po2 of 95 mm
Hg, a bicarbonate level of 11 mmol/L, and an oxygen saturation of 95%. Urinalysis results
are positive for high levels of ketones and glucose. How would you approach this patient?
Diabetic ketoacidosis (DKA) occurs in 4.6 to 8 of 1000 diabetic patients.1 Up to 20% of
patients present without a previous diagnosis of diabetes.1 Primarily thought of as a
complication of type 1 diabetes, DKA is increasingly noted in type 2 diabetes.1 Mortality
ranges from 0.65% in young patients to greater than 25% in patients older than 70 years.13
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Pathophysiology
The underlying mechanism of DKA is a reduction in the effective concentration of circulating
insulin, coupled with a concomitant elevation of counterregulatory stress hormones. When
insulin is decreased, hyperglycemia develops as a result of increased gluconeogenesis,
accelerated glycogenolysis, and impaired glucose use by peripheral tissues.
The increased production of ketones results from the breakdown of triglycerides into glycerol
and free fatty acids, which are then oxidized to ketones (-hydroxybutyric acid and
acetoacetic acid). In DKA, the ratio of -hydroxybutyric acid to acetoacetic acid increases to

as much as 10:1, leading to an underestimation of ketones if the -hydroxybutyric acid is not

measured.3 In addition to their increased production, ketone clearance also appears to be
affected in DKA.4
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Diagnosis
There are no definitive criteria for the diagnosis of DKA.2 Typically, the arterial pH is less
than 7.3, serum bicarbonate levels are less than 15 mmol/L, and the anion gap is greater than
12 mmol/L, with positive serum or urine ketones. Plasma glucose levels are usually greater
than 14.0 mmol/L, but they can be lower.2
The ketoacids cause increased anion gap metabolic acidosis. The nitroprusside reaction
typically used to measure ketones provides a semiquantitative estimation of acetoacetate and
acetone only, resulting in an underestimation of the severity of ketoacidosis.1 Direct
measurement of -hydroxybutyric acid levels is preferable.
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Treatment
The use of standardized treatment protocols has improved care and decreased
morbidity.5,6 The Canadian Diabetes Association publishes guidelines and treatment
algorithms every 5 years on the management of DKA. The therapies highlighted below
reflect the current Canadian recommendations.2The mainstays of treatment are 1) fluid
replacement, 2) correction of potassium deficit, 3) correction of metabolic acidosis, and 4)
treatment of precipitating factors.
Fluid replacement
Hyperglycemia leads to osmotic diuresis, with loss of water exceeding that of sodium.4 In
addition, ketone excretion forces the excretion of sodium, potassium, and ammonium. The
typical water loss amounts to 5 to 7 L.4
Aggressive rehydration lowers serum glucose independently of insulin, decreases the levels
of counterregulatory hormones, restores intravascular volume, and reduces the insulin
resistance caused by the DKA hyperosmolar state.3 Start with 1 to 2 L/h of normal saline
solution to correct shock, followed by 0.5 L/h of normal saline solution for 4 hours, and then
decrease the rate to 250 mL/h. Add 5% dextrose in water (D5W) when serum glucose levels
reach 14 mmol/L in DKA so that insulin can be continued to achieve ketone clearance.2
Correction of potassium deficit
Diabetic ketoacidosis is associated with profound body potassium depletion, ranging from 3
to 15 mmol/kg, in spite of an initial plasma concentration typically normal or elevated at
presentation.4Potassium follows water as it shifts out of cells; acidosis further enhances this
shift. In addition, the lack of insulin impairs potassium entry into cells.4 Ketone excretion
accelerates the potassium loss owing to osmotic diuresis. Although treatment with hydration
and insulin leads to a rapid decrease in potassium, replacement should not be started until the
potassium level is less than 5.0 to 5.5 mmol/L and diuresis is well established.2,4 If the
patient is normokalemic or hypokalemic at presentation, potassium should be given

immediately at 10 to 40 mmol/L, at a maximum rate of 40 mmol/h.2 In the case of frank

hypokalemia (potassium level < 3.3 mmol/L), insulin should be withheld until potassium
replacement at 40 mmol/h has restored potassium to greater than 3.3 mmol/L.2,4 Electrolyte
levels must be monitored every 2 to 4 hours.
Correction of metabolic acidosis
Insulin: As presented above, serum potassium levels should be checked and corrected to
greater than 3.3 mmol/L before starting insulin.2
A bolus dose of insulin appears to be unnecessary and is no longer recommended if the
infusion rate is at least 0.1 U/kg/h.710
Serum glucose needs to be monitored every 1 to 2 hours. The target is a decrease of 3 to 4
mmol/L in the first hour (increase drip if necessary)2,4; a steeper decrease in hyperosmolarity
might be associated with a higher risk of cerebral edema. Decrease the infusion by 50% when
serum glucose levels reach 14 mmol/L and add D5W, aiming for a level between 12 and 14
mmol/L. Continue insulin until DKA is resolved (bicarbonate > 18 mmol/L, anion gap 12
mmol/L, and pH > 7.3).
Bicarbonate: Alkali therapy is usually not necessary because metabolic acidosis tends to be
corrected with insulin therapy. The administration of bicarbonate might actually lead to
rebound alkalosis, worsened hypokalemia, paradoxical central nervous system acidosis, an
increase in intracellular acidosis, and prolongation of ketosis.3 Because severe acidosis might
lead to important adverse side effects, and because of the small number of patients with a pH
less than 7.0 included in most studies, bicarbonate therapy seems prudent if the pH is less
than 7.0. Use 100 mmol (2 ampules) of bicarbonate in 400 mL of sterile water with 20mmol/L potassium chloride at 200 mL/h until the pH is greater than 7.0.2
Treatment of precipitating factors
The 2 main precipitating factors are infections (up to 60% of cases, with pneumonia and
urinary tract infections accounting for 30% to 50% of cases) and omission of or undertreatment with insulin (20% to 40%).1,3,4 Drugs such as -blockers, calcium channel
blockers, diuretics, loxapine, phenytoin, steroids, and cocaine are also common triggers.1,3
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Pediatric considerations
This article focuses on the treatment of adult DKA. Although the pediatric principles are
similar, most pediatric centres have strict protocols and they should be consulted before
initiating treatment.
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Complications of treatment
Hypoglycemia
Hypoglycemia is especially common if an insulin bolus has been administered.

Cerebral edema
Cerebral edema is more common in children, especially children newly diagnosed with
diabetes. The mortality rate is 20% to 40%. There is controversy regarding whether the
condition is present before initiation of treatment or whether it is related to the rapid change
in osmolarity.
Adult respiratory distress syndrome
Adult respiratory distress syndrome is rare. Fluid intake should be limited in patients with
rales or increased alveolar-arterial PO2 gradients.
Your patient was diagnosed with DKA and new-onset type 1 diabetes. After 8 hours of fluid
and insulin therapy, half of his fluid deficit had been restored and his serum glucose was
maintained at 12 mmol/L with D5W and continuous insulin. His abdominal pain and nausea
have resolved.
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Notes
BOTTOM LINE

Diabetic ketoacidosis is increasingly seen in patients with type 2 diabetes.

Treatment should be initiated with 1 to 2 L of normal saline solution over the first
hour. Serum potassium must be greater than 3.3 mmol/L before insulin is started.
Boluses of insulin are no longer recommended.
Reserve treatment with bicarbonate for patients with pH less than 7.0.

POINTS SAILLANTS

On observe de plus en plus de cas dacidoctose diabtique chez les patients

atteints de diabte de type 2.
Il faut initier un traitement au moyen de 1 2 litres de solution saline normale
pendant la premire heure. Le potassium srique doit excder 3,3 mmol/l avant de
commencer ladministration dinsuline. Les bolus dinsuline ne sont plus
recommands.
Rservez le traitement au bicarbonate aux patients dont le pH est de moins de 7,0.

Emergency Files is a quarterly series in Canadian Family Physician coordinated by the

members of the Emergency Medicine Program Committee of the College of Family
Physicians of Canada. The series explores common situations experienced by family
physicians doing emergency medicine as part of their primary care practice. Please send any
ideas for future articles to Dr Robert Primavesi, Emergency Files Coordinator,
at [email protected].
Footnotes
Competing interests
None declared