Diabetic ketoacidosis: electrolytes abnormality

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Diabetic ketoacidosis electrolytes abnormality

• Ji Yeon Lee

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case

• CC altered mental status
• HPI 31yo Hispanic woman without significant
  medical history brought to ER for AMS. Per
  family, she has been vomiting for the past 5 days
  and could not eat anything. She could only drink
  lots of water and juice. She also complained
  abdominal pain for the last 2days. Her weakness
  has been gradually worsening, and the family
  found her unresponsive on the day of admission,
  so they brought her to ER. No fever, no recent
  URI. She lost 25lbs for the past 6months.
• PMH none
• Allergy nkda
• Meds none
• FHx no DM, HTN, CAD
• SHx cig(-), ETOH(-), illicit drug(-)

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• PEx Gen WDWN female minimally responsive to
  sternal rub
• VS BP 116/71 PR 140 RR36 Temp 97.2
  Sat 98 RA
• HEENT PERLA
• Chest tachycardic, RRR no MRG, CTA
  bilaterally
• Abd soft, non distended, BS
  present
• Ext no edema
• Labs
• 
  anion gap gt22
• ABG 6.99 / 10.1 / 144 / 2.4 /
  96.4 / -27 RA
• UA gluc gt1000, ketonegt80,
  (-)protein, (-)blood
• EKG sinus tachycardia
• CXR clear

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Epidemiology

• DKA is responsible for more than 100,000 hospital
  admissions per year in the US
• accounts for 4-9 of all admissions among
  patients with diabetes.
• Mortality a mortality rate of less than 5 using
  standardized written guidelines for therapy.
• higher mortality rates observed in elderly
  patients and those with concomitant
  life-threatening illnesses.

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Normal glucose control

• the extracellular supply of glucose is primarily
  regulated by two hormones insulin and glucagon
• Normal response to hyperglycemia glucose enters
  the pancreatic beta cells? initiating a sequence
  of events leading to insulin release.
• Action of Insulin major anabolic hormone
• 1) diminishes hepatic glucose production, via
  reductions in both glycogenolysis and
  gluconeogenesis
• 2) increases glucose uptake by skeletal muscle
  and adipose tissue, increases glycogen synthesis.
• 3) Insulin-induced inhibition of glucagon
  secretion by direct inhibition of glucagon
  secretion and of the glucagon gene in the
  pancreatic alpha cells

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Pathogenesis

•  
• Insulin deficiency and/or resistance.
• increased levels of counter-regulatory hormones
  (glucagon, catecholamines, cortisol, and growth
  hormone).

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Precipitating factors

• Stressful settings that increases secretion of
  catecholamines, cortisol, and glucagon.
• Infection(30-50) most commonly pneumonia, UTI
• Surgery
• Alcohol and drug abuse
• Silent myocardial infarction
• Stroke
• Pancreatitis
• Trauma
• Drugs corticosteroid, higher dose thiazide
  diuretics, AAP
• Psychological stress
• Noncompliance with insulin therapy

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Pathophysiology

• 
  Insulin deficiency
• Glucose
  Proteolysis Lipolysis
• uptake

Free fatty acids
Amino acids
Nitrogen loss
Glycerol
ketogenesis
Hyperglycemia
Gluconeogenesis Glycogenolysis
ketonemia
Osmotic diuresis
Electrolyte depletion
ketonuria
Dehydration
Hypotonic losses
Acidosis
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ketoacidosis

• 3 ketones Acetoacetic acid? beta-hydroxybutyric
  acid or acetone
• Severity of metabolic acidosis
• rate of ketoacid production
• Duration of increased ketoacid production
• Rate of acid secretion in urine renal function

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Symptoms and signs

• Early Polyuria, polydipsia, weight loss
• Later neurologic symptoms including lethargy,
  obtundation, coma(plasma osmgt 320-330 mosm/kg)
• calculated Osm367.6mmol/kg
• Nausea, vomiting
• Abdominal pain associated with the severity of
  the metabolic acidosis
• -Etiology of abdominal pain should be
  investigated in patients without severe metabolic
  acidosis.
• Signs of volume depletion decreased skin turgor,
  dry axillae and oral mucosa, low JVP, hypotension
• fruity odor
• Kussmaul respirations

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Laboratory findings

• Hyperglycemia
• Generally below 800 mg/dL
• early presentation to hospital due to short of
  breath, abdominal pain
• GFR usually maintained normal and capacity to
  excrete glucose into urine
• Hyperosmolarity
• High anion gap acidosis usually above 20
• Elevations in BUN, Cr volume depletion-gt
  decreased GFR
• Hyponatremia
• U/A glucosuria, ketonuria

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sodium

• dilutional hyponatremia Hyperglycemia? increased
  plasma osm?osmotic water movement out of the
  cells
• Correction factor a 2.4meq/L decrease in Na per
  100mg/dL increase in glucose
• In our case, 134 2.4 x 15 170 meq/L
• Marked osmotic diuresis may have normal or even
  hypernatremia extreme hyperosmolar, develop
  neurologic symptoms (seizure, coma)
• In Impaired renal function hyponatremia, marked
  hyperglycemia without neurologic sx.

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potassium

• Potassium deficit averages 3 to 5mg/kg
• osmotic diuresis
• the need to maintain electroneutrality as
  ketoacid anions are excreted
• GI loss due to vomiting
• Loss from cells due to glycogenolysis,
  proteolysis
• Usually normal or elevated, paradoxically
• translocation of potassium out of cells due to
  acidosis
• Hyperosmolarity, insulin deficiency 1) rise in
  cell potassium concentration induced by water
  loss favors passive potassium exit through
  potassium channels. 2) frictional forces between
  water and solute can result in potassium being
  carried out through the water pores in the cell
  membrane. (solvent drag)

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phosphate

• Typically negative phosphate balance decreased
  PO intake and phosphaturia
• Despite depletion, plasma phosphate concentration
  at presentation is usually normal or even high
• Insulin deficiency
• Shift of phosphate out of the cells b/c metabolic
  acidosis
• Unmasked after insulin treatment

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amylase and lipase

• Standard tests to diagnose acute pancreatitis
• Often elevated in DKA patient who do not have
  pancreatitis
• Mechanism unknown
• Rise in amylase correlates with pH and plasma
  osmolality, rise in lipase correlates only with
  plasma osmolality
• Amylase peak 20 to 24hours after presentation

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Diagnosis

• Suspected from clinical history
• Hyperglycemia, high anion gap metabolic acidosis,
  ketouria and ketonemia
• Primarily in type 1 diabetes
• But it may occur in type 2 diabetes, particularly
  in African-American.

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Differential Diagnosis

• Starvation ketosis
• The blood glucose is usually normal. can have
  ketonuria. Serum ketone usually normal. Arterial
  pH is normal, and the anion gap is at most mildly
  elevated.
• alcoholic ketoacidosis
• a more severe form of starvation ketosis
• long-standing alcoholics for whom ethanol has
  been the main caloric source for days to weeks.
• even higher ratio of ß-hydroxybutyrate to
  acetoacetate than DKA
• Respiratory alkalosis associated with delirium
  tremens, agitation, or pulmonary processes often
  normalizes the pH
• Treatment thiamine, carbohydrates, fluids, and
  electrolytes with special attention to the more
  severe consequences of alcohol toxicity, alcohol
  withdrawal, and chronic malnutrition.

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Differential Diagnosis

• other causes of high-anion gap metabolic acidosis
• lactic acidosis
• Ingestion of salicylate, methanol, ethylene
  glycol, and paraldehyde
• chronic renal failure (more typically
  hyperchloremic acidosis)

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Treatment

• 1. Frequent MonitoringThe plasma glucose
  Q1-2hours, plasma electrolytes, phosphate, and
  venous pH Q2-6hours
• 2. Fluid replacement
• 3. Insulin lowers the plasma glucose
  concentration primarily by decreasing hepatic
  glucose production rather than enhancing
  peripheral utilization
• The antilipolytic action of insulin requires a
  much lower dose than that required to reduce the
  plasma glucose concentration
• 4. Electrolytes replacement
• Bicarb therapy?
• 5. Careful search for the precipitating cause

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Fluid replacement

• The average fluid loss is 3 to 6 liters in DKA
  due largely to the glucose osmotic diuresis
• generally begin with isotonic saline.
• For adequate circulation and to maintain a brisk
  diuresis.
• Water deficit 0.5x 52kg X(170-140)/140 5.57L
• The optimal rate of administration depend on the
  clinical state
• as quickly as possible in patients in shock. At a
  rate of 15 to 20 mL/kg body weight per hour or
  greater during the 1st hour (approximately 1 to
  1.5 liters in the average adult)
• patients who do not have an extreme volume
  deficit at a rate of 500 mL/h for the first four
  hours followed by 250 mL/h for the next four
  hours.

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Fluid replacement

• switched to half-isotonic saline
• When? depends on the state of hydration, serum
  electrolyte levels, and urinary output
• This decision will be influenced in part by the
  degree of the associated potassium deficit. the
  addition of potassium to isotonic saline results
  in the generation of a hypertonic fluid that will
  not correct the hyperosmolality in these
  patients.

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Back to our case

• In ER
• Insulin drip started in ER

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VT

• Istat K lt2.0

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Insulin

• Hypokalemia (K lt3.3 mEq/L) should be excluded
  first!
• IV bolus of regular insulin at 0.15 units/kg,
  followed by a continuous infusion at 0.1 unit/kg
  per hour (5 to 7 units per hour in adults)-This
  low dose of insulin usually decreases plasma
  glucose concentration at a rate of 50 to 75 mg/dL
  per hour
• When the plasma glucose reaches 250 mg/dL in DKA,
  it may be possible to decrease the insulin
  infusion rate to 0.05 to 0.1 unit/kg per hour (3
  to 6 units per hour), and dextrose (5 to 10) may
  be added to the intravenous fluids.
• With resolution of ketosis, the rate of infusion
  approaches the physiologic range of 0.3 to 0.5
  U/kg per day.
• Stop insulin infusion when two goals are reached
•    The plasma glucose falls below 250 mg/dL (13.9
  mmol/L) to minimize the risk of cerebral edema.
•    The ketoacidosis has resolved(normalization of
  the anion gap). ketonemia and ketonuria may
  remain detectable for more than 36 hours due to
  the slower removal of acetone.

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Back to our case- electrolytes

• HD1
• Fluid and potassium
• Intubated
• NaHCO3 given
• Empiric IV zosyn started b/c elevated WBC and
  fever
• Labs

Mg 1.9 Phos 1.1
Mg 1.7 Phos lt1.0
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Treatment- sodium

• a patient with a normal initial plasma sodium
  concentration will probably become hypernatremic
  during therapy with insulin and isotonic saline.
• The degree can be estimated at presentation by
  calculation of the "corrected" plasma sodium
  concentration
• Reversing the hyperglycemia with insulin?lower
  the plasma osmolality?water move into the cells?
  raise the plasma sodium concentration

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Treatment- Potassium

• Potassium replacement is initiated after serum
  levels fall below 5.5 mEq/L, assuming the
  presence of adequate urine output. Generally, 20
  to 30 mEq potassium (2/3 potassium chloride and
  1/3 potassium phosphate) in each liter of
  infusion fluid is sufficient .
• Patients with massive deficits who are
  hypokalemic prior to therapy urgent KCl therapy
  with 40 to 60 mEq being added to each liter
• insulin treatment should be delayed until
  potassium concentration is restored to gt3.3 mEq/L
  to avoid arrhythmias or cardiac arrest and
  respiratory muscle weakness.

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Treatment- Metabolic acidosis

•  Ketoacid anions potential bicarbonate," since
  the administration of insulin results in the
  generation of bicarbonate and reversal of the
  acidosis.
•  30 percent of the ketoacids produced in DKA are
  excreted in the urine the conversion of
  acetoacetic acid to acetone can neutralize
  another 15 to 25 percent of the acid load.
•  The excretion of ketoacid anions equivalent to
  bicarbonate loss.
• almost all patients with DKA develop a normal
  anion gap acidosis during treatment.
• bicarbonate may be beneficial in patients with a
  pH lt7.0 no bicarbonate is necessary if pH is
  gt7.0

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Bicarb therapy

• Concerns
• a paradoxical fall in cerebral pH
• slower rate of recovery of the ketosis
  bicarbonate therapy acts by increasing hepatic
  ketogenesis
• a posttreatment metabolic alkalosis
•  Indications
•  severe acidemia (arterial pH lt7.0), in whom
  decreased cardiac contractility and
  vasodilatation can further impair tissue
  perfusion.
•  potentially life-threatening hyperkalemia.
•  Patients with a relatively normal anion gap in
  whom ketoacid anions are not available in the
  circulation to generate bicarbonate.
• the aim of therapy to raise the arterial pH
  above 7.15 to 7.20, a level at which the patient
  should be out of danger.

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Treatment- Phosphate

• the phosphate depletion is rapidly unmasked
  following the institution of insulin therapy,
  frequently leading to hypophosphatemia.
• Most patients remain asymptomatic and
  prophylactic phosphate administration is more
  likely to be harmful than beneficial.
• Prospective randomized studies have failed to
  show any beneficial effect of phosphate
  replacement on the clinical outcome in DKA, and
  overzealous phosphate therapy can cause
  hypocalcemia with no evidence of tetany.
• careful phosphate replacement may sometimes be
  indicated in patients with cardiac dysfunction,
  anemia, or respiratory depression and in those
  with serum phosphate concentration less than 1.0
  mg/dL

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Search for underlying causes

• Fever? can be absent in a significant proportion
  of patients with diabetic emergencies.
• WBC? not uncommonly elevated in the range of
  20,000 or higher even in the absence of
  infection.
• cultures should be performed for most patients,
  and if there is significant concern about
  infection, empirical broad antibiotic coverage
  should be considered.

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Complication

• Cerebral edema complication of therapy in
  uncontrolled diabetes mellitus that occurs within
  24 hours after treatment has been initiated.
• Headache is the earliest clinical manifestation
• marked neurologic dysfunction can occur more
  than one-half of patients either die or have
  permanent neurologic sequelae.
• Subclinical brain swelling, as evidenced by CT
  scanning and an increase in cerebrospinal fluid
  pressure, is more common.
• Almost all affected patients are below the age of
  20 years.
• Prevention gradual replacement of sodium and
  water deficits in patients who are hyperosmolar
  (maximal reduction in osmolality 3 mOsm/kg H2O
  per hour) and the addition of dextrose to the
  hydrating solution once blood glucose reaches 250
  mg/dL.

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Prevention

• early detection
• the education of patients, healthcare
  professionals, and the general public
• diabetes education programs
• improved follow-up care
• access to medical advice