1. JOURNAL CLUB BRITISH MEDICAL JOURNAL: DIABETIC KETOACIDOSIS
Dr. Sujay Iyer
2. TABLE OF CONTENT Introduction Definition Diagnosis
Epidemiology Pathophysiology Etiology Clinical Presentation
Laboratory Evaluation Management Complications Topics of discussion
3. INTRODUCTION Diabetic Ketoacidosis is an acute, major, life-
threatening complication of Diabetes. It mainly occurs in patients
with Type 1 Diabetes but it is not uncommon in some patients with
type 2 diabetes. The overall mortality rate for DKA is 0.2-2%,
being at the highest in developing countries.
4. DEFINITION DKA is an extreme metabolic state caused by
insulin deficiency. It is defined as an acute state of severe
uncontrolled diabetes associated with ketoacidosis that requires
emergency treatment. It is a state of absolute or relative insulin
deficiency aggravated by ensuing hyperglycemia, dehydration and
acidosis-producing derangements in intermediary metabolism.
5. DIAGNOSIS Triad of hyperglycemia, anion gap metabolic
acidosis and ketonemia. ADA (2009) Glucose> 13.9 mmol/L (250
mg/dl). Bicarbonate< 18mmol/L; pH< 7.3. Ketones positive
result for urine or serum ketones by nitroprusside reaction. JBDS
(2013) Glucose> 11 mmol/L (200 mg/dl) or known Diabestes.
Bicarbonate< 15mmol/L or pH< 7.3 or both. Ketones> 3mmol/L
or (++) in urine dipstick.
6. EPIDEMIOLOGY DKA accounts for 14% of all hospital admissions
of patients with diabetes and 16% of all diabeties- related
fatalities. DKA is frequently observed in diagnosis of type 1
diabetes and often indicates this diagnosis (3%). It occurs
primarily in patients with type 1 diabetes, but can also occur in
type 2 patients. The incidence of DKA in developing countries is
higher. It is far more common in young patients.
7. PATHOPHYSIOLOGY DKA is a complex disordered metabolic state
characterized by hyperglycemia, ketoacidosis and ketonuria. It
usually occurs as a consequence of absolute or relative insulin
deficiency that is accompanied by an increase in counter-regulatory
hormones (i.e, glucagon, cortisol, growth hormone, epinephrine).
This imbalance enhances hepatic gluconeogenesis, glycogenolysis,
lipolysis and ketogenesis.
8. PATHOGENESIS ALGORITHM
9. ETIOLOGY Inadequate insulin treatment or noncompliance. New
onset diabetes (20-25%) Acute illness - Infection (30 to 40%) - CVA
- Acute MI - Acute pancreatitis Drugs - Clozapine or olanzapine -
Cocaine - Lithium - SGLT2 inhibitors - Terbutaline
10. CLINICAL PRESENTATION: SYMPTOMS DKA usually evolves
rapidly, over a 24 hour period. Earliest symptoms are polyuria,
polydipsia and weight loss. Nausea, vomiting and abdominal pain are
usually present. Malaise, generalized weakness and fatigability. As
the duration of hyperglycemia progresses, neurologic symptoms,
including lethargy, focal signs, and obtundation can develop. Frank
coma is uncommon in DKA.
12. LABORATORY EVALUATION Blood test for glucose every 1-2
hour. ABG/ VBG. Serum electrolyes (includes phosphate) Renal
function test. Urine dipstick test (acetoacetate). Serum ketones
(3-hydroxybetabutyrate). CBC. Anion gap. Osmolarity. Cultures.
Amylase. Repeat lab investigations are key!
13. MANAGEMENT Correction of fluid loss with intravenous
fluids. Correction of hyperglycemia with insulin. Correction of
electrolyte disturbances, particularly potassium loss. Correction
of acid-base balance. Treatment of concurrent infection, if
14. MANAGEMENT ALGORITHM
15. CORRECTION OF FLUID LOSS It is a critical part of treating
patients with DKA. Use of isotonic saline. 15-20mL/kg/hour for the
first few hours. Recommended schedule: - Administer 1-3 L during
first hour. - Administer 1 L during second hour. - Administer 1 L
during the following 2 hours. - Administer 1 L every 4 hours,
depending on the degree of dehydration and CVP. When patient
becomes euvolemic, switch to 0.45% saline is recommended,
particularly if hypernatremia exists.
16. INSULIN THERAPY Insulin therapy to be initiated only if
potassium levels are above 3.3 mEq/L. Intravenous regular insulin
preferred. Initiated with IV blous of regular insulin (0.1
units/kg) followed by continuous infusion of regular insulin of 0.1
units/kg/hour. SC route may be taken in uncomplicated DKA (0.3 U/kg
then 0.2 U/kg one hour later). When serum glucose reaches 200
mg/dl, reduce insulin infusion to 0.02-0.03 U/kg/hour and switch
the IV saline solution to dextrose in saline. Revert to SC insulin,
after patient begins to eat (continue IV infusion simultaneously
for 1 to 2 hours).
17. POTASSIUM REPLACEMENT If the initial serum potassium is
below 3.3 mEq/L, IV potassium chloride is started with saline (20
to 40 mEq/hour). If the initial serum potassium is between 3.3 and
5.3 mEq/L, IV KCl (20 to 30 mEq) is added to each liter of IV
replacement fluid and continued until the serum potassium
concentration has increased to the 4.0 to 5.0 mEq/L range. If the
serum potassium is initially greater than 5.3 mEq/L, then potassium
replacement should be delayed.
18. CORRECTION OF ACIDOSIS Bicarbonate therapy is a bone of
contention among physicians and still remains a controversial
subject, as clear evidence of benefit is lacking. Bicarbonate
therapy is only administered if the arterial pH is less than 6.9.
100 mEq of sodium bicarbonate in 400 mL sterile water is
administered over two hours. Repeat doses until pH rises above 7.0.
Bicarbonate therapy has several potential harmful effects.
20. TOPICS OF DISCUSSION ABG or VBG (Kelly Am et al. & Ma
OJ et al.) Insulin when? (S Arora et al.) Bicarbonate therapy: to
use or not to use? (Chua et al. & Duhon et al.) Utility of
insulin bolus (Goyal et al.) Euglycemic DKA: Its not a myth (Peters
et al.) Which fluid? (3 Studies) Insulin How? (4 Studies)
Transition from IV to SC insulin (O Malley et al. & Avanzini et
21. ABG OR VBG? Study #1: Kelly AM et al. Review Article Can
Venous Blood Gas Analysis Replace Arterial in Emergency Medical
Care (2010) For pH, mean difference was found to be 0.02. For
bicarbonate, mean difference was found to be -1.41 mmol/L. Study
#2: Ma OJ et al. - Arterial Blood Gas Results Rarely Influence
Emergency Physician Management of Patients with Suspected Diabetic
Ketoacidosis ABG analysis changed ED physicians diagnosis in 1% of
patients. ABG analysis changed ED physicians treatment in 3.5% of
patients (Change from SQ to IV insulin or vice versa). ABG analysis
changed patient disposition in 2.5% of patients. Venous pH
correlated well with arterial pH with difference of - 0.015 +/-
0.006 pH units.
22. ABG OR VBG Other Reasons ABGs can cause radial artery
spasm, infarct, and/or aneurysms ABGs are painful to patients, even
more so than IV access By the way, when is the last time you
checked a Modified Allens Test before doing a radial ABG? The
VBG-electrolytes were 97.8% sensitive and 100% specific for the
diagnosis of DKA in hyperglycemic patients (Menchine M et al.,
23. INSULIN WHEN? Study: S. Arora et al - Prevalence of
hypokalemia in ED patients with diabetic ketoacidosis (2012)
Hypokalemia was observed in 5.6% of patients with DKA. These
findings support the ADA recommendation to obtain a serum potassium
before initiating intravenous insulin therapy in a patient with
24. BICARBONATE THERAPY Study #1: Chua et al. - Bicarbonate in
Diabetic Ketoacidosis A Systematic Review (2011). Transient
improvement in metabolic acidosis. No improved glycemic control.
Risk of cerebral edema in pediatric patients. No studies with