Diabetic ketoacidosis electrolytes abnormality Ji Yeon Lee case

Diabetic ketoacidosis: electrolytes abnormality Ji Yeon Lee

case • CC: altered mental status • HPI: 31 yo 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 2 days. 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 25 lbs for the past 6 months. • 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 RR 36 Temp 97. 2 Sat 98% RA HEENT PERLA Chest tachycardic, RRR no MRG, CTA bilaterally Abd soft, non distended, BS present Ext no edema 14. 4 • Labs 134 102 25 18. 13 371 1632 3. 1 <10 1. 4 47. 4 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 Proteolysis Lipolysis uptake Amino acids Hyperglycemia Gluconeogenesis + Glycogenolysis 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. 6 mmol/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/d. L • 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 osmotic water movement out of the cells – Correction factor: a 2. 4 meq/L decrease in Na per 100 mg/d. L 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 5 mg/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 p. H and plasma osmolality, rise in lipase correlates only with plasma osmolality • Amylase peak 20 to 24 hours 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 p. H 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 p. H 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 Q 1 -2 hours, plasma electrolytes, phosphate, and venous p. H Q 26 hours 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. 5 x 52 kg X(170 -140)/140= 5. 57 L – 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 m. L/kg body weight per hour or greater during the 1 st 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 m. L/h for the first four hours followed by 250 m. L/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 m. Eq/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/d. L per hour • When the plasma glucose reaches 250 mg/d. L 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/d. L (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 – Na. HCO 3 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 m. Eq/L, assuming the presence of adequate urine output. Generally, 20 to 30 m. Eq 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 m. Eq being added to each liter • insulin treatment should be delayed until potassium concentration is restored to >3. 3 m. Eq/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 p. H <7. 0; no bicarbonate is necessary if p. H is >7. 0

Bicarb therapy • Concerns – a paradoxical fall in cerebral p. H – slower rate of recovery of the ketosis: bicarbonate therapy acts by increasing hepatic ketogenesis – a posttreatment metabolic alkalosis • Indications: – severe acidemia (arterial p. H <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 p. H 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/d. L

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 m. Osm/kg H 2 O per hour) and the addition of dextrose to the hydrating solution once blood glucose reaches 250 mg/d. L.

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