Diabetic ketoacidosis: electrolytes abnormality

Ji Yeon Lee

case• CC: altered mental status• HPI: 31yo Hispanic woman without significant medical history br

ought 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

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

1343.1

102 251.4<10

163214.4

47.437118.13

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.

Normal glucose control• the extracellular supply of glucose is primarily regulat

ed 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 b

oth 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 i

nhibition 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 (glu

cagon, catecholamines, cortisol, and growth hormone).

Precipitating factors• Stressful settings that increases secretion of catecholamines, co

rtisol, 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 Proteolysis Lipolysis

uptake

Amino acids Nitrogenloss

Gluconeogenesis+ Glycogenolysis

Hyperglycemia

Osmotic diuresis

Hypotonic losses

Electrolyte depletion

Dehydration

Acidosis

Glycerol Free fatty acids

ketogenesis

ketonemia

ketonuria

ketoacidosis• 3 ketones: Acetoacetic acid beta-hydroxybutyric aci

d 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, co

ma(plasma osm> 320-330 mosm/kg)– calculated Osm=367.6mmol/kg

• Nausea, vomiting • Abdominal pain: associated with the severity of the metabolic ac

idosis

-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, abd

ominal 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-> de

creased GFR• Hyponatremia• U/A: glucosuria, ketonuria

sodium

• dilutional hyponatremia: Hyperglycemia increased plasma osmosmotic water movement out of the cells – Correction factor: a 2.4meq/L decrease in Na per 100mg/dL i

ncrease 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 hyp

erglycemia 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 ac

idosis– Unmasked after insulin treatment

amylase and lipase

• Standard tests to diagnose acute pancreatitis• Often elevated in DKA patient who do not hav

e pancreatitis• Mechanism unknown• Rise in amylase correlates with pH and plasm

a 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. S

erum 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 ma

in caloric source for days to weeks. – even higher ratio of β-hydroxybutyrate to acetoacetate than

DKA– Respiratory alkalosis associated with delirium tremens, agit

ation, 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 hyperchloremi

c acidosis)

Treatment1. Frequent Monitoring:The plasma glucose Q1-2hours,

plasma electrolytes, phosphate, and venous pH Q2-6hours

2. Fluid replacement3. Insulin: lowers the plasma glucose concentration prim

arily by decreasing hepatic glucose production rather than enhancing peripheral utilization – The antilipolytic action of insulin requires a much l

ower dose than that required to reduce the plasma glucose concentration

4. Electrolytes replacement– Bicarb therapy?

5. Careful search for the precipitating cause

• 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 sta

te • 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

Fluid replacement

– switched to half-isotonic saline• When? depends on the state of hydration, seru

m electrolyte levels, and urinary output• This decision will be influenced in part by the de

gree 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 continuou

s 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 ga

p). ketonemia and ketonuria may remain detectable for more than 36 hours due to the slower removal of acetone.

• HD#1– Fluid and potassium– Intubated– NaHCO3 given– Empiric IV zosyn started b/c elevated WBC and fever– Labs:

1552.2

121 230.9<10

68411.7

32.823113.13 Mg 1.9

Phos 1.1

1673.8

123 240.8 14

734 Mg 1.7Phos <1.0

1343.1

102 251.4<10

163214.4

47.437118.13

Back to our case- electrolytes

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 insulinlower the plasma osmolalitywater move into the cells raise the plasma sodium concentration

• 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- Potassium

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 aci

dosis during treatment. • bicarbonate may be beneficial in patients with a pH <7.0; no bic

arbonate 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 act

s by increasing hepatic ketogenesis – a posttreatment metabolic alkalosis

•  Indications:–  severe acidemia (arterial pH <7.0), in whom decreased cardia

c 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 phosph

ate 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.

• 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 sol

ution once blood glucose reaches 250 mg/dL.

Complication

Prevention

• early detection• the education of patients, healthcare

professionals, and the general public• diabetes education programs• improved follow-up care • access to medical advice