Diabetic ketoacidosis:
electrolytes abnormality
Ji Yeon Lee
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(-)
• 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
18.13
14.4
47.4
371
134 102
3.1 <10
25
1.4
1632
anion gap >22
ABG: 6.99 / 10.1 / 144 / 2.4 / 96.4 / -27 RA
UA: gluc >1000, ketone>80, (-)protein, (-)blood
• EKG: sinus tachycardia
• CXR: clear
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 lifethreatening illnesses.
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
Pathogenesis
• Insulin deficiency and/or resistance.
• increased levels of counter-regulatory hormones
(glucagon, catecholamines, cortisol, and growth
hormone).
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
Pathophysiology
Insulin deficiency
Glucose
uptake
Proteolysis
Amino acids
Hyperglycemia
Gluconeogenesis
+ Glycogenolysis
Lipolysis
Nitrogen
loss
Glycerol
Free
fatty acids
ketogenesis
ketonemia
Osmotic
diuresis
Electrolyte depletion
Dehydration
Hypotonic losses
Acidosis
ketonuria
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
Symptoms and signs
• Early: Polyuria, polydipsia, weight loss
• Later: neurologic symptoms including lethargy, obtundation,
coma(plasma osm> 320-330 mosm/kg)
– calculated Osm=367.6mmol/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
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->
decreased GFR
• Hyponatremia
• U/A: glucosuria, ketonuria
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.
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)
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
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
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.
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 β-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.
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)
Treatment
1. Frequent Monitoring:The plasma glucose Q1-2hours,
plasma electrolytes, phosphate, and venous pH Q26hours
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
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.
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.
Back to our case
• In ER
– Insulin drip started in ER
VT
–Istat: K <2.0
Insulin
• Hypokalemia (K+ <3.3 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.
Back to our case- electrolytes
• HD#1
– Fluid and potassium
– Intubated
– NaHCO3 given
– Empiric IV zosyn started b/c elevated WBC and fever
– Labs:
18.13
13.13
14.4
47.4
11.7
32.8
371
134 102
3.1 <10
25
1.4
1632
231
155 121
2.2 <10
23
0.9
684
Mg 1.9
Phos 1.1
167 123
3.8 14
24
0.8
734
Mg 1.7
Phos <1.0
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
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 >3.3 mEq/L to avoid
arrhythmias or cardiac arrest and respiratory muscle
weakness.
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 <7.0; no
bicarbonate is necessary if pH is >7.0
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 <7.0), 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.
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
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.
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.
Prevention
• early detection
• the education of patients, healthcare professionals,
and the general public
• diabetes education programs
• improved follow-up care
• access to medical advice