2. OUT LINE
• Objectives
• Diabetic Ketoacidosis
• Epidemiology
• Pathophysiology
• Clinical features
• Diagnostic testing
• Management
• Complications
• Disposition and follow-up
• Ketoacidotic syndromes
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3. Objectives
• Understanding the definition and pathophysiology of
DKA and other ketoacidotic syndromes
• Understanding Clinical features and Diagnostic testing in
DKA
• Understand Management of DKA and its complications
• Understanding the disposition and follow-up of DKA
patient
• Understanding Ketoacidotic syndromes and their
management
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4. Diabetic Ketoacidosis
• Acute, life-threatening complication of
diabetes mellitus.
• Characterized by hyperglycemia, ketoacidosis
and ketonuria
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5. Epidemiology
• Predominant in type 1 diabetes mellitus
• Increasing in non insulin dependent diabetics
• Incidence of ~ 10,000 cases/year in US
• Mortality decreased to <1% (prior to insulin
was 100%)
• Mortality is up to 5%, in patients with
significant comorbidity & advanced age
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9. Pathophysiology …
–Lipolysis
• Serum FFA
– Acetone, hydroxybutyrate,acetoacetic
acid
–Increased ketone production with
decreased ketone use leads to
ketoacidosis
–Vomiting ,anion gap metabolic
acidosis
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10. • Dehydration and electrolyte loss
–Increased glucose load in kidney leads
to increased glucose in urine and
osmotic diuresis
• Osmotic diuresis + poor intake and vomiting,
produces profound dehydration and
electrolyte imbalance
• Volume depletion leads to impaired GFR
• RAAS activation
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11. Causes
• An acute insult leads to decompensation of a
chronic disease
• Inadequate insulin therapy and infection are
the most common precipitants
• New onset diabetes (particularly in children)
• Myocardial ischemia or infarction
• Alcohol or drug related problem
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12. CLINICAL FEATURES
• Clinical manifestations of DKA are related
directly to hyperglycemia, volume depletion,
and acidosis.
• Polyuria and polydipsia are usually the only
symptoms until ketonemia and acidosis
develop
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15. Diagnosis
• Traditionally, DKA is divided into mild,
moderate, and severe states based on total-
body deficits of water and electrolytes.
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16. Diagnosis….
• Definitive diagnosis is established by
laboratory criteria (hyperglycemia, ketosis and
acidosis
• Blood glucose level >250 milligrams/dL
• Anion gap >10 to 12 mEq/L
• Bicarbonate level <15 mEq/L and a pH <7.3
with moderate ketonuria or ketonemia
• Urine ketone >=+2
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17. • EUGLYCEMIC DKA
– glucose <250mg/dl
• Patients presenting shortly after receiving insulin
• Type1diabetics who are young and vomiting
• Patients with impaired gluconeogenesis (alcohol abuse
or liver failure)
• Low caloric intake/starvation
• Pregnancy
• SGLT2inhibitors
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18. Diagnostic Testing
• Essential Diagnostic Tests
– Serum glucose
• Typically > 250 mg/dL
• Euglycemic DKA (< 250 mg/dL)
– Blood gas
• Patients will exhibit an anion gap metabolic
• Electrolytes: hypo/hyper/normokalemia,hyponatremia
• Arterial or venous blood gas can be used
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19. – Urinalysis
• Glucosuria
• Ketonuria
– Electrocardiogram (EKG)
• Typically will exhibit non-specific changes including
sinus tachycardia
• Can see changes associated with hyperkalemia or
hypokalemia
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20. Diagnostic Testing…cont.
• Serum potassium
– Patients with DKA are total body K+ depleted
• Osmotic diuresis + vomiting lead to potassium loss
• Often depleted by 100’s of mEq
– Initial serum K+ can be elevated, normal or low
• Potassium elevation 2ry to acidemia + hyperglycemia
• 4-6% of patients will present with hypokalemia
• Serum K+ correction: subtract 0.6 mEq/L from the
laboratory K+ value for every 0.1 decrease in pH
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21. • Sodium and Other Electrolytes
– Osmotic diuresis leads -> excessive renal losses of
NaCl
– Hyperglycemia artificially lowers serum sodium l
– Correction factor: Add 1.6 mEq Na for every 100
mg/dL the glucose is >100mg/dl
– Osmotic diuresis -> urinary losses and total-body
depletion of phosphorous, calcium, and magnesium
– Hemoconcentration ->
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22. ?
• If the potassium is reported as 5 mEq/L and
the pH is 6.94, the corrected potassium value
would be ?
• IF RBS is 400mg/dl , and measured Na is 130
what is the corrected Na measurenment?
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23. Diagnostic Testing…cont.
• BUN/Cr
– Patients will often exhibit prerenal acute kidney
injury
– BUN/Cr ratio will be elevated reflecting
intravascular volume depletion
• Serum ketones are typically unnecessary in the
Emergency Department
• Blood cultures and other laboratory tests should be
done as clinically indicated
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24. Management
• Basics:
• ABCs, IV, Cardiac Monitor and 12-lead EKG
• Establish at least 2 peripheral IVs as patients typically
require multiple medication and infusions
• Diagnosis should be suspected at triage
• Begin aggressive fluid therapy before receiving
laboratory results
• Diligently search for the underlying cause
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25. Management…
• The goals of therapy are
– volume repletion
– reversal of the metabolic consequences of insulin
insufficiency
– correction of electrolyte and acid-base imbalances
– recognition and treatment of precipitating causes
– avoidance of complications
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26. Management…
• VOLUME REPLETION
– Role
• Replenish intravascular depletion resulting from
osmotic diuresis
• Correct decreased GFR
• The average adult patient has a water deficit of 100
mL/ kg (5 to 10 L)
• sodium deficit of 7 to 10 mEq/kg
•
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27. Management…
• VOLUME REPLETION
– ADA: 1000-1500 mL of 0.9% NS during the first hour
– After the 1st hr: maintain between 250 and 500mL/h
• Adjust to hemodynamic and electrolyte status
• ADA:Patients with eu or hypernatremia
0.45%NS
• UK: 9% NS continued throughout the
management
– Blood glucose <250 mg/dL -> add 5% dextrose
– Patient in hypovolemic shock ?
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28. Management…
• 9% NaCl (Normal Saline)
• Large volume infusions can cause hyperchloremic
metabolic acidosis (unclear impact on patient)
• In profoundly acidemic patients, avoidance of NS may be
beneficial
• Lactated Ringers
– Closer to physiologic solution
– Does not cause hyperchloremic metabolic acidosis
– Other options: balanced solutions (i.e. Plasma-Lyte)
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29. Management…
• Electrolyte Disorder Correction
–Potassium – most important lab value in DKA
–Aggressive repletion frequently necessary
–Patients often 100s of mEq depleted
–DKA treatments (i.e. fluids, insulin) will
decrease serum potassium level
–Insulin infusion shifts potassium intracellularly
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30. Management…
• •
POTASSIUM REPLACEMENT
– Replace after adequate renal function (urine
output) is assessed
– K+ >5.2 initiate regular insulin & check K+ in 2 hrs
– K+ >3.3 <5.2 add 20-30 meq of K+ to each L of
fluid and continue insulin drip
– K+ <3.3 hold insulin drip and give K+ @20-30
meq/hr until K+ is >3.3 then initiate insulin drip
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31. Management…
• Bicarbonate for acidosis
– Hypothetically prevent cardiorespiratory compromise
– Potential deleterious effects
• Worsening hypokalemia and intracellular acidosis
• Inhibition of RBC oxygen release at tissue level
• Delay in improvement of ketosis
– If pH <6.9 give 100 mmol NaHCO3 in 400ml of water with
20 meq KCL at 200 ml/hr
– Repeat q 2 hours until pH >7 + Check K+ q 2 hrs
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32. Management…
• Sodium
– Typically dilutional hyponatremia
– Will correct without specific treatment
• Magnesium
– Hypokalemia = Hypomagnesaemia
• Both electrolytes lost during osmotic diuresis
• Cannot replete intracellular K+ without Mg
• Serum Mg level may not correlate with total body stores
• Add 0.35 mEq/kg of Mg in the fluids of the first 3 to 4 hrs
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33. Management…
• Insulin therapy
–Ultimately, patients will require insulin
repletion in order to reverse pathophysiology
in DKA and stop ketosis
–Don’t give insulin if K+ is <3.3, replace K+ and
fluid deficit first
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34. Management…
• Dose
– Continuous Regular infusion 0.14 units/kg
– Bolus 0.1units/kg then 0.1/kg/hr continuous infusion
– If serum glucose doesn’t fall by 50-70mg/dl in the first
hour double rate of infusion
– When serum glucose reaches 200 mg/dl decrease
infusion rate by 0.02-0.05 units/kg/hr
– Continue insulin infusion until ketoacidosis is resolved,
blood glucose <200, subcutaneous insulin is begun
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35. Management…
• Transition from IV Insulin After DKA Correction
– It is important to overlap the IV and SC insulin for
2 to 4 hours to avoid potential relapse to
hyperglycemia or DKA
– New-onset diabetics can be started on a total daily
dose of 0.5 to 0.8 unit/kg/dL,
– previously treated diabetic patients can be
restarted on their previous insulin dosage.
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36. Continued Management
• Continuous Monitoring
– Vital Signs
– Urine output
– Serum glucose, K+, Cl–, HCO3
–, pH q1 hour until
stable
• Insulin Infusion
– Continue until anion gap normalizes
– When serum glucose < 250 mg/dL add
D5W/0.45%NS solution to avoid hypoglycemia
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38. Complications…
• COMPLICATIONS RELATED TO THERAPY
– Hypokalemia from inadequate K+ replacement
– Hypoglycemia
– Alkalosis from overaggressive bicarbonate
replacement
– pulmonary edema from overaggressive hydration
– Cerebral edema
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39. Complications…
• Cerebral Edema
• Excess accumulation of intracellular and extracellular
fluid in the brain
• Rare (< 1%) complication but high mortality (> 30%)
• More common in patients with newly diagnosed
diabetes presenting with DKA
• Cause: it is unclear what causes patients to develop
cerebral edema
• usually develops within 4 to 12 hours but can present
up to 24 to 48 hours after starting treatment
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40. Complications…
• Signs + Symptoms
– potential neurologic deterioration
• New onset or intensifying headache
• Decline in level of consciousness, Lethargy
• Focal neurologic deficits (CN III, IV or VI palsy common)
– recurrent vomiting, incontinence, irritability,
– abnormal respirations,
– delayed rise in serum sodium with treatment,
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41. Complications…
• Management
– Prompt administration of mannitol help to abort
further neurologic deterioration
– Elevate head of bed to 30 degrees
– Decrease IV fluid infusion
– Mannitol: 1 gm/kg over 20 minutes
– 3% Hypertonic saline: 5-10 ml/kg
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42. Complications…
• Best Practice to Prevent Cerebral Edema
– Slow reduction of osmolality during treatment
– Avoid large volumes of hypotonic fluid
– Drop blood glucose slowly during treatment
– Do not allow plasma Na+ to fall during treatment
– Avoid unnecessary bicarbonate during treatment
– Avoid hypoxia, hypo-K+,PO4, Mg
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43. Complications…
• LATER COMPLICATIONS
– Metabolic acidosis refractory to routine therapy
• Unrecognized infection (lactic acidosis)
• Rarely insulin antibodies
• Improper preparation or administration of the insulin
drip
– Shock that is unresponsive to aggressive fluid
therapy
– Hyperchloremic non–anion gap metabolic acidosis
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44. Complications…
• Late vascular thrombosis
– Cerebral vessels appear to be most susceptible
– Volume depletion, low CO, increased blood
viscosity, and underlying atherosclerosis may
predispose the elderly to this complication
– Thrombosis may occur
• Several hrs or days after institution of therapy
• After resolution of ketoacidosis
– No studies support prophylactic anticoagulant use
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45. DISPOSITION AND FOLLOW-UP
• Experienced nursing staff trained in
monitoring and management of DKA
• Written guidelines for DKA management
• Access to a laboratory
• presenting early in the course of their illness
who can tolerate oral liquids may be managed
safely in the ED or observation unit and
discharged after 6 to 12 hours of therapy
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47. SPECIAL POPULATIONS
• RECURRENT DKA PATIENTS
• PATIENTS WITH INSULIN PUMPS
• DKA IN PREGNANCY
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48. • DKA IN PREGNANCY
– fetal mortality rate of approximately 30%
– Lower maternal fasting glucose relative insulin
deficiency
– increased levels of counter regulatory hormones
– vomiting and urinary tract infections are increased
– Maternal hyperglycemia, acidosis, hypokalemia
also happen in the fetus
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49. Ketoacidotic Syndromes
• Several conditions result in excessive
production of ketoacids
• The challenge is to differentiate excessive,
uncontrolled ketoacidosis from
• Physiologic ketonemia
• States where excessive ketones may be
produced
• Toxin altering normal metabolism
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51. PATHOPHYSIOLOGY
• Ketones are produced through metabolism of
long-chain fatty acids
• Serum ketones are also used as an energy
source for the brain
• The normal blood ketone level is about 1
milligram/dL
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52. PATHOPHYSIOLOGY
• Ketone production is typically tightly regulated
– prevent excessive ketoacid production and
metabolic acidosis
– Ketones are metabolized as rapidly as they are
formed
• low levels of insulin are not found in
ketoacidotic syndromes except DKA
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53. PATHOPHYSIOLOGY
• Pathologic states arise when production
exceeds metabolism or consumption, resulting
in metabolic acidosis.
• Acetyl coenzyme A, an energy source that can
enter the citric acid cycle for metabolism, is
produced in the liver and then converted to
the ketones β-hydroxybutyrate and
acetoacetate.
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54. COMMON KETOACIDOTIC
SYNDROMES
• •
ALCOHOLIC KETOACIDOSIS
– Occur in alcoholic patients who enter a period of
fasting after a dramatic period of ethanol binging
– results in metabolic acidosis and dehydration,
with variable levels of serum glucose
– Nausea, vomiting, abdominal pain
– Elevated ratio of β-hydroxybutyrate to
acetoacetate(10:1)
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55. • •
STARVATION KETOSIS
– During periods of fasting (overnight) or increased
energy demands (exercise), local ketone
production increases
– As the duration of carbohydrate fasting increases
• hepatic ketone production and Intracerebral ketone
utilization increase
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56. • STARVATION KETOSIS
– Fasts of 14 days are well tolerated in those with
• Adequate endogenous insulin and no other
• No coexisting condition that alters the serum
hormonal milieu
– Pregnancy induced 24 to 48 hours of vomiting
and inadequate oral intake can lead to
• ketone production with metabolic acidosis, ketonuria,
and dehydration
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57. • NUTRITIONAL KETOSIS
– athletic performance enhancement
• KETOGENIC DIET
– weight control and seizures
• TOXIC INGESTIONS
– primary result of the toxin
– acetone, aspirin, isoniazid, isopropanol ,methanol,
and propylene glycol
• INBORN ERRORS OF METABOLISM
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58. TREATMENT
• Treatment of ketoacidosis is supportive
• Reestablish intravascular volume
• Monitor and correct electrolyte abnormalities
• Administer supplemental dextrose
• Acidosis should clear within 12 to 24 hours
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59. DISPOSITION AND FOLLOW-UP
• Adults with an uncomplicated ED course can
be discharged home
– resolution of acidosis
– the patient is able to tolerate oral fluids
• When caring for complicated conditions
coordinate care with the primary team
treating the underlying disorder
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60. Reference
• ROSEN’S EMERGENCY MEDICINE:CONCEPTS
AND CLINICAL PRACTICE, 8th edition
• Tintinalli’s Emergency Medicine A
Comprehensive Study Guide, 9th edition
• Uptodate
• DKA protocol for Emergency and critical unit
of Tikur Anbessa Specialized Hospital
• ADA/UK guidelines
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