This document provides a clinical review of diabetic ketoacidosis (DKA) in adults. It begins with an introduction to DKA, defining it as a state of insulin deficiency causing extreme metabolic changes. It then covers diagnosis, epidemiology, pathophysiology, etiology, clinical presentation, laboratory evaluation, management, complications, topics for discussion, and references. The management section outlines the key treatment approach of correcting fluid loss, hyperglycemia, electrolyte disturbances, and acid-base balance primarily through intravenous fluids and insulin therapy. Controversies discussed include whether to use arterial or venous blood gases, the use of bicarbonate therapy, and choice of intravenous fluids.

1. DIABETIC KETOACIDOSIS IN ADULTS
A CLINICAL REVIEW
BRITISH MEDICAL JOURNAL
DR. SUJAY IYER
I YEAR POSTGRADUATE
GENERAL MEDICINE

2. TABLE OF CONTENT
• INTRODUCTION
• DEFINITION
• DIAGNOSIS
• EPIDEMIOLOGY
• PATHOPHYSIOLOGY
• ETIOLOGY
• CLINICAL PRESENTATION
• LABORATORY EVALUATION
• MANAGEMENT
• COMPLICATIONS
• TOPICS OF DISCUSSION
• REFERENCES

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.
• Described by Dr. Julius Dreschfeld in 1886.

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, high 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 Diabetes.
• 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 diabetes-related fatalities.
• DKA is frequently observed in diagnosis of type 1 diabetes and often
indicates this diagnosis (3%).
• The overall mortality rate for DKA is 0.2-2%, being at the highest in
developing countries.
• 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.

9. ETIOLOGY
• Inadequate insulin treatment or noncompliance.
• New onset diabetes (20-25%)
• Acute illness
• Infection (30 to 40%)
• CVA
• Acute Myocardial Infarction
• 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.

11. CLINICAL PRESENTATION: SIGNS
• Ill appearance.
• Labored respiration (Kussmaul).
• Dry mucous membranes, dry skin and decreased skin turgor.
• Decreased reflexes.
• Characterstic ketotic breath odor.
• Tachycardia
• Hypotension
• Tachypnea
• Hypothermia/ Fever (if infection is present)
• Confusion
• Coma
• Abdominal tenderness.

12. LABORATORY EVALUATION
• Blood test for glucose every 1-2 hour.
• ABG/ VBG.
• Serum electrolytes (includes phosphate)
• Renal function test.
• Urine dipstick test (acetoacetate).
• Serum ketones (3-hydroxybetabutyrate).
• CBC.
• Anion gap.
• Osmolarity.
• Cultures.
• Amylase.
Repeat lab investigations are key!

14. 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 present.

15. MANAGEMENT ALGORITHM

16. 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.

18. INSULIN THERAPY
• Insulin therapy to be initiated only if potassium levels are above 3.3 mEq/L.
• Intravenous regular insulin preferred.
• Initiated with IV bolus 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).

19. 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.

20. 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.

21. COMPLICATIONS
• CVT
• Myocardial Infarction
• DVT
• Acute gastric dilatation
• Erosive gastritis
• Late hypoglycemia
• Respiratory distress
• Infection (UTI)
• Hypophosphatemia
• Mucormycosis
• CVA
• Cerebral edema (rare in adults)

22. TOPICS OF DISCUSSION
• ABG or VBG?
• Bicarbonate therapy: to use or not to use?
• Insulin when?
• Utility of insulin bolus.
• Which Insulin?
• Insulin How?
• Transition from IV to SC insulin.
• Euglycemic DKA: It’s not a myth.
• Which fluid?

23. ABG OR VBG?
THE CASE FOR VENOUS RATHER THAN ARTERIAL BLOOD GASES IN DIABETIC
KETOACIDOSIS - Kelly AM et al (2006).
• There is reasonable evidence that venous and arterial pH have sufficient
agreement as to be clinically interchangeable in patients with DKA who are
hemodynamically stable and without respiratory failure.
ARTERIAL BLOOD GAS RESULTS RARELY INFLUENCE EMERGENCY PHYSICIAN
MANAGEMENT OF PATIENTS WITH SUSPECTED DIABETIC KETOACIDOSIS -
Ma OJ et al (2003).
• ABG results rarely influenced emergency physicians' decisions on diagnosis,
treatment, or disposition in suspected DKA patients. Venous pH correlated
well and was precise enough with arterial pH to serve as a substitute.

24. 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 Allen’s
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., 2011).

25. BICARBONATE THERAPY
BICARBONATE IN DIABETIC KETOACIDOSIS : A SYSTEMATIC REVIEW - Chua et al
(2011).
• Transient improvement in metabolic acidosis.
• No improved glycemic control.
• Risk of cerebral edema in pediatric patients.
• No studies with pH <6.85.
INTRAVENOUS SODIUM BICARBONATE THERAPY IN SEVERELY ACIDOTIC
DIABETIC KETOACIDOSIS - Duhon et al (2013).
• No Difference In: Time to resolution of acidemia, time to hospital discharge,
time on IV insulin, potassium requirement in first 24hrs.
• Subgroup Analysis of pH < 6.9 showed no statistical difference in time to
resolution of acidemia.

26. BICARBONATE THERAPY
CLINICAL BOTTOM LINE
• Intravenous bicarbonate therapy may transiently make acidemia better,
but there is no improvement of glycemic control, time on insulin, time
to hospital discharge, and in children can worsen cerebral edema.

27. INSULIN WHEN?
PREVALENCE OF HYPOKALEMIA IN ED PATIENTS WITH DIABETIC
KETOACIDOSIS - S. Arora et al (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
DKA.

28. UTILITY OF INSULIN BOLUS
UTILITY OF INITIAL BOLUS INSULIN IN THE TREATMENT OF DIABETIC
KETOACIDOSIS – Goyal et al (2010).
• Insulin bolus at the start of an insulin infusion IS EQUIVALENT to no
insulin bolus at the start of an insulin infusion in several endpoints
including:
• Decrease normalization of glucose
• Affect the rate of change of anion gap
• Reduce ED or hospital length of stay
• Insulin bolus at the start of an insulin infusion DOES:
• Increase hypoglycemic events by 6 fold (6% vs 1%).

29. WHICH INSULIN?
INSULIN ANALOGS VERSUS HUMAN INSULIN IN THE TREATMENT OF
PATIENTS WITH DIABETIC KETOACIDOSIS: A RANDOMIZED
CONTROLLED TRIAL – Umpierrez et al (2009)
• IV treatment with Regular & Glulisine Insulin.
• SC treatment with Regular Insulin/ NPH & Glargine/ Glulisine.
Conclusion:
• Equally effective in acute treatment of DKA.
• Lower rate of hypoglycemia with Glargine & Glulisine.

30. INSULIN HOW?
DIABETIC KETOACIDOSIS: LOW-DOSE INSULIN THERAPY BY VARIOUS
ROUTES - Fisher JN et al (1977).
• Intravenous infusion of Insulin is superior to subcutaneous route.
TREATMENT OF DIABETIC KETOACIDOSIS WITH SUBCUTANEOUS INSULIN
ASPART - Umpierrez et al (2004).
• The use of subcutaneous insulin Aspart every 1 or 2 h represents a safe
and effective alternative to the use of intravenous regular insulin in the
management of patients with uncomplicated DKA.

31. INSULIN HOW?
EFFICACY OF SUBCUTANEOUS INSULIN LISPRO VERSUS CONTINUOUS
INTRAVENOUS REGULAR INSULIN FOR THE TREATMENT OF PATIENTS WITH
DIABETIC KETOACIDOSIS - Umipierrez et al (2004).
• Treatment of uncomplicated DKA with SC lispro every hour in a non-intensive
care setting may be safe and more cost-effective than treatment with IV
regular insulin in the intensive care unit.
SUBCUTANEOUS LISPRO AND INTRAVENOUS REGULAR INSULIN TREATMENTS
ARE EQUALLY EFFECTIVE AND SAFE FOR THE TREATMENT OF MILD AND
MODERATE DIABETIC KETOACIDOSIS IN ADULT PATIENTS - Ersoz et al (2006).
• Treatment of mild and moderate DKA with SC insulin lispro is equally effective
and safe in comparison with IV regular insulin.

32. TRANSITION FROM IV TO SC
BRIDGE OVER TROUBLED WATERS: SAFE AND EFFECTIVE TRANSITIONS OF THE
INPATIENT WITH HYPERGLYCEMIA - O’Malley et al (2008).
• First dose of SC insulin to be given atleast 1 hour prior to discontinuation of IV insulin
infusion, failing which allows development of rapid rebound hyperglycemia.
TRANSITION FROM INTRAVENOUS TO SUBCUTANEOUS INSULIN: EFFECTIVENESS AND
SAFETY OF A STANDARDIZED PROTOCOL - Avanzini et al (2011).
• Stable blood glucoses which are less than 180 mg/dL for at least 4–6 h consecutively
(Some studies suggest 24 hours).
• Normal anion gap and resolution of acidosis in DKA.
• Stable clinical status; hemodynamic stability.
• Not on Vasopressors.
• Stable nutrition plan or patient is eating.
• Stable IV drip rates (low variability).

33. EUGLYCEMIC DKA: IT’S NOT A MYTH!
• It is essentially DKA without hyperglycemia (Glucose< 200).
• Euglycemic DKA is a rare entity that mostly occurs in patients with Type
1 Diabetes, but also in Type 2 Diabetes.
• It has been associated with partial treatment of diabetes, carbohydrate
food restriction, alcohol intake, and with Sodium-Glucose Cotransporter
2 (SGLT-2) inhibitor medications [Glifozins].
• The exact mechanism of euDKA is not entirely known.

34. EUGLYCEMIC DKA
• EUGLYCEMIC DKA EXISTS IN PATIENTS WHO ARE NOT ON SGLT-2
INHIBITORS - Munro JF et al (1973).
• Vomiting was the most common symptom.
• Most of the cases were Type 1 DM.
• Management was same as DKA.
• SGLT-2 Inhibitors cause DKA – Peters A L et al (2015).

36. WHICH FLUID TO USE?
PLASMA-LYTE 148 VS 0.9% SALINE FOR FLUID RESUSCITATION IN
DIABETIC KETOACIDOSIS - Chua et al. (2012)
• PL had faster initial resolution of metabolic acidosis and less
hyperchloremia, with a transiently improved blood pressure profile and
urine output.
RESUSCITATION WITH BALANCED ELECTROLYTE SOLUTION PREVENTS
HYPERCHLOREMIC METABOLIC ACIDOSIS IN PATIENTS WITH DIABETIC
KETOACIDOSIS - Mahler et al (2011).
• Resuscitation of DKA patients with BES results in lower serum
chloride and higher bicarbonate levels than patients receiving NS,
consistent with prevention of hyperchloremic metabolic acidosis.

37. WHICH FLUID TO USE?
FLUID MANAGEMENT IN DIABETIC-ACIDOSIS--RINGER'S LACTATE VERSUS
NORMAL SALINE - Van Zyl et al (2012).
• This study failed to indicate benefit from using RL compared to 0.9% NS
regarding time to normalization of pH in patients with DKA.
• The time to reach a blood glucose level of 14 mmol/l took significantly
longer with RL.

38. REFERENCES
• Harrison’s Principles of Internal Medicine
• British Medical Journal
• www.diabetes.org
• www.uptodate.com
• www.medscape.com
• www.rebelem.com
• www.ncbi.nlm.nih.gov

39. THANK YOU 