Diabetic Ketoacidosis as a complication of Diabetes

Diabetic ketoacidosis
By
Ayodeji Temilade

Outline
• Introduction
• Definition
• Epidemiology
• Pathogenesis
• Etiology
• Clinical Presentation
• Investigation
• Diagnosis
• Principles of Treatment
• Complications
• DKA vs HHS
• Other differential diagnosis
• Conclusion
• References

INTRODUCTION
• Diabetic ketoacidosis (DKA) is a medical emergency and remains a serious
cause of morbidity, It is the hallmark of type 1 diabetes.
• Is an acute complication of diabetes that can result in increased morbidity and
mortality if not efficiently and effectively treated.
• It is usually seen in the following circumstances:
• previously undiagnosed diabetes (10%)
• interruption of insulin therapy (15%)
• the stress of intercurrent illness (30%)

Epidemiology
• Mortality is low in the UK (approximately 2%) but remains high in
developing countries and among non-hospitalised patients.
• DKA is characteristic of type 1 diabetes and is often the presenting
problem in newly diagnosed patients.
• However, an increasing number of patients presenting with DKA have
underlying type 2 diabetes. This appears to be particularly prevalent in
African-American and Hispanic populations

Pathogenesis
• A clear understanding of the biochemical basis and pathophysiology
of DKA is essential for its efficient treatment.
• The cardinal biochemical features are:
• hyperketonaemia (≥ 3 mmol/L) and ketonuria (more than 2+ on
standard urine sticks)
• hyperglycaemia (blood glucose ≥ 11 mmol/L (~200 mg/dL))
• metabolic acidosis (venous bicarbonate < 15 mmol/L and/or venous
pH < 7.3).

• The hyperglycaemia causes a profound osmotic diuresis leading to
dehydration and electrolyte loss, particularly of sodium and potassium.
• Potassium loss is exacerbated by secondary hyperaldosteronism as a result of
reduced renal perfusion.

• In parallel to the hyperglycemia occurring, Ketosis results from insulin
deficiency, exacerbated by elevated catecholamines and other stress
hormones, leading to unrestrained lipolysis and supply of FFAs for hepatic
ketogenesis.
• When this exceeds the capacity to metabolise acidic ketones, these
accumulate in blood. The resulting metabolic acidosis forces hydrogen ions
into cells, displacing potassium ions.

• Vomiting leads to further loss of fluid and electrolytes.
• The excess ketones are excreted in the urine but also appear in the breath,
producing a distinctive smell similar to that of acetone.
• Respiratory compensation for the acidosis leads to hyperventilation,
graphically described as ‘air hunger’.
• Progressive dehydration impairs renal excretion of hydrogen ions and ketones,
aggravating the acidosis.
• As the pH falls below 7.0 ([H+] >100 nmol/L), pH-dependent enzyme systems
in many cells function less effectively.
• Untreated, severe ketoacidosis is invariably fatal.

Etiology
In patients with established diabetes, precipitating factors for DKA
include;
• infections (Urinary tract infection and pneumonia)
• Stress of intercurrent illnesses
• psychological stress
• poor compliance with therapy

Acute conditions that may precipitate DKA include;
• cerebrovascular accident
• alcohol/drug abuse (cocaine)
• pancreatitis
• pulmonary embolism
• myocardial infarction
• trauma.

Drugs that affect carbohydrate metabolism, such as;
• corticosteroids
• thiazides
• sympathomimetic agents
• pentamidine
• may also precipitate the development of DKA.

CLINICAL PRESENTATIONS
Clinical features of diabetic ketoacidosis Clinical features of diabetic ketoacidosis
Symptoms Signs
• Polyuria, thirst
• Weight loss
• Weakness
• Nausea, vomiting,, decreased appetite, and
anorexia
• Leg cramps
• Blurred vision
• Abdominal pain
• Hx of non compliance with insulin therapy or
missed insulin, or mechanical failure of insulin
infusion pump
• Dehydration
• Hypotension (postural or supine)
• Cold extremities/peripheral cyanosis
• Tachycardia or bradycardia
• Air hunger (Kussmaul breathing)
• Smell of acetone
• Hypothermia
• Confusion, drowsiness, coma (10%)

Investigation
• The following are important but should not delay the institution of
intravenous fluid and insulin replacement:
Venous blood:
• for Serum electrolytes, urea and creatinine
• glucose and bicarbonate (severe acidosis is indicated by a venous
plasma bicarbonate < 12 mmol/L).
• Urinalysis or blood analysis for ketones.
• Arterial blood gases

• ECG.
Infection screen:
• full blood count,
• blood and urine culture,
• C-reactive protein,
• chest X-ray.
N.B: Although leucocytosis invariably occurs in DKA, this represents a
stress response and does not necessarily indicate infection.

Diagnosis
• DKA is confirmed by demonstrating hyperglycaemia with ketonaemia or heavy ketonuria,
and acidosis.
• Clinical assessment of severity;
The presence of one or more of the following features is indicative of severe DKA;
• Blood ketone >6mmol/l
• Bicarbonate <5mmol/l
• Venous pH<7.0 (H+ >100nmol/l)
• Glasgow Coma Score of <12
• O2 saturation <92% on air
• Systolic BP <90 mmHg
• heat rate >100 b.p.m. or <60 b.p.m.
• Anion gap >16mmol/l

Principles of Treatment
Average loss of fluid and electrolytes in adult diabetic ketoacidosis of
moderate severity.
Water loss is about 6L, sodium 500mmol, chloride 400mmol and
potassium 350mmol.
The principles of treatment of DKA Includes;
• Fluid therapy
• Insulin therapy
• Potassium replacement
• Treat underlying precipitant

What to do immediately?
1. Assess
2. Send bloods to laboratory
3. Set up i.v. infusion
Blood glucose
– measure baseline and hourly initially
– aim for fall of 3–6 mmol/L (55–110 mg/dL) per hour
Urea and electrolytes – do at baseline and hourly until 6 hours, then at 12 hours and 24
hours
– Potassium – add when K+ <3.5 mmol/L. Give 20 mmol/h in infusion. 10 mmol/h when K+
= 3.5–5 mmol
Full blood count
Blood gases – at 0, 2 hours, 6 hours
Creatinine – at 0, 6, 12, 24 hours
Bicarbonate – at 0, 1, 2, 3, 6, 12, 24 hours.

Phase 1
• Admit patient
• INSULIN: soluble insulin i.v. 0.1 U/kg/h by infusion, or 20 units i.m. stat. followed
by 6 units i.m. hourly.
• FLUID AND ELECTROLYTE REPLACEMENT: i.v. 0.9% sodium chloride with 20 mmol
KCl/L.
• – 1 L in 30 min, then
• – 1 L in 1 h
• – 1 L in 2 h
• – 1 L in 4 h
• – 1 L in 8 h.
• Adjust KCl concentration depending on results of regular blood K+ measurement.

• IF:
• Blood pressure below 80 mmHg, give 500 mL 0.9% sodium chloride over
15 min; if no response, give plasma expander
• pH below 7.0 give 500 mL of sodium bicarbonate 1.26% plus 10 mmol KCl.
Repeat if necessary to bring pH up to 7.0.

Phase 2
• INSULIN AND GLUCOSE: When blood glucose falls to 10–12 mmol/L,
change infusion fluid to 1L 5% glucose plus 20 mmol KCl 6-hourly.
• Continue insulin with dose adjusted according to hourly blood glucose
test results (e.g. i.v. 3 U/h glucose 15 mmol/L; 2 U/h when glucose 10
mmol/L).

Phase 3
• Once stable and able to eat and drink normally, transfer patient to
four times daily subcutaneous insulin regimen (based on previous 24
hours’ insulin consumption and trend in consumption).
• Do not discontinue IV insulin until 30 mins after SC short-acting insulin
injection

Special measures
• Broad-spectrum antibiotic if infection likely
• Bladder catheter if no urine passed in 2 hours
• Nasogastric tube if drowsy
• Consider CVP pressure monitoring if in shocked or if previous cardiac or renal impairment
• Measure arterial blood gases and repeat chest X-ray if O2 saturation < 92%
• ECG monitoring in severe cases (to exclude myocardial infarction)
• Thromboprophylaxis with low molecular weight heparin.
Subsequent management
• Monitor glucose hourly for 8 hours.
• Monitor electrolytes 2-hourly for 8 hours.
• Adjust K replacement according to results.

COMPLICATIONS
• Acute kidney Injury
• Thrombotic events
• Hypoglycemia
• Hypokalemia
• Hypotension
• Hypomagnesemia
• Cerebral edema
• Aspiration pneumonia
• Hypophophatemia

DKA vs HHS
• Hyperglycaemic hyperosmolar state (HHS) is characterized by severe
hyperglycaemia (> 30 mmol/L (600 mg/ dL)), hyperosmolality (serum
osmolality > 320 mOsm/ kg), and dehydration in the absence of
significant hyperketonaemia (< 3 mmol/L) or acidosis (pH > 7.3,
bicarbonate > 15 mmol/L).
• It was previously referred to as hyperosmolar non-ketotic (HONK) coma
but, as in DKA, coma is not invariable.
• As with DKA, there is glycosuria, leading to an osmotic diuresis, with loss
of water, sodium, potassium and other electrolytes.

• However, in HHS, hyperglycaemia usually develops over a longer period (a
few days to weeks), causing more profound hyperglycaemia and dehydration
(fluid loss may be 10–22 litres in a person weighing 100 kg).
• The reason that patients with HHS do not develop significant ketoacidosis is
unclear, although it has been speculated that insulin levels may be too low
to stimulate glucose uptake in insulin-sensitive tissues, but still sufficient to
prevent lipolysis and subsequent ketogenesis.

Other differential diagnosis
• Alcoholic ketoacidosis
• Pancreatitis
• Myocardial infraction

Conclusion
• The majority of cases reaching hospital could have been prevented by
earlier diagnosis, better communication between patient and doctor
and better patient education.
• The most common error of management is for patients to reduce or
omit insulin because they feel unable to eat, owing to nausea or
vomiting. This is a factor in at least 25% of all hospital admissions.
• Insulin may need adjusting up or down but should never be stopped.

References
• Parveen June Kumar, Michael L. Clark, Kumar & Clark's Clinical
Medicine, 8th edition,
• Davidson’s Principle and Practice of Medicine, 24th Edition.

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