Hypokalemia

Aka: Hypokalemia, Hypokalemia Related EKG Changes

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II. Epidemiology

  1. Prevalence
    1. General Population: 1.9%
    2. Emergency Department: 5.5%
    3. Inpatient: 2.9 to 7.4%
    4. Brookes (2021) Intern Med J 51(11): 1906-18 [PubMed]
    5. Kovesdy (2018) Eur Heart J 39(17): 1535-42 [PubMed]
    6. Singer (2017) Clin Exp Emerg Med 4(2): 73-9 [PubMed]

III. Pathophysiology

  1. See Potassium Homeostasis
  2. Approximate Total body Potassium = 55 meq/kg
  3. Serum Potassium decreased 0.3 mEq/L: 100 mEq K+ total body deficit
  4. Serum Potassium decreased 1 mEq/L: 350 mEq K+ total body deficit
  5. Serum Potassium less than 2 mEq/L: 1000 mEq K+ total body deficit
  6. Images
    1. potassiumHomeostasis.png

IV. Causes

  1. Hypokalemia due to Transcellular Potassium Shift
    1. See Transcellular Potassium Shift
    2. Medications (Beta-Agonists, Insulin excess, Caffeine, Theophylline)
    3. Metabolic Alkalosis
    4. Hypokalemic Periodic Paralysis
    5. Thyrotoxicosis
    6. Hypothermia
    7. Refeeding Syndrome
  2. Hypokalemia due to Renal Potassium Loss
    1. See Renal Potassium Loss (Hyperkaluria)
    2. Hypertension: Obtain Plasma Renin and Aldosterone
      1. Renin high
        1. Renovascular disease
        2. Renin Secreting tumor
        3. Malignant Hypertension
      2. Renin normal
        1. Liddle Syndrome
      3. Renin low
        1. Aldosterone High
          1. Primary Hyperaldosteronism
          2. Bilateral adrenal hyperplasia
        2. Aldosterone Low
          1. Congenital Adrenal Hyperplasia
          2. Cushing's Syndrome
          3. Ectopic ACTH
          4. Exogenous Corticosteroids (e.g. Prednisone)
    3. Normotensive: Obtain Serum Magnesium, serum bicarbonate and Urine Chloride
      1. Hypomagnesemia
        1. See Hypomagnesemia Causes
      2. Serum Bicarbonate Low
        1. Renal Tubular Acidosis (Types 1 and 2)
      3. Serum Bicarbonate High
        1. Urine Chloride Low: Vomiting
        2. Urine Chloride High
          1. Intrinsic renal transport defect (Bartter Syndrome, Gitelman Syndrome)
          2. Normotensive primary Hyperaldosteronism
          3. Diuretic use (Loop Diuretics, Thiazide Diuretics)
  3. Hypokalemia due to Extrarenal Potassium Loss
    1. See Extrarenal Potassium Loss
    2. Normal Acid-Base Status or Metabolic Alkalosis
      1. Gastrointestinal or skin losses
      2. Hypomagnesemia
      3. Medications (e.g. Penicillin or Aminoglycosides, Sodium Polystyrene Sulfonate)
      4. Acute Leukemia
    3. Metabolic Acidosis
      1. Diabetic Ketoacidosis
      2. Diarrhea
      3. Laxatives
  4. Other causes
    1. See Drug-Induced Hypokalemia
    2. Inadequate Potassium intake (typically in hospitalized patients)
      1. Total Parenteral Nutrition
      2. Anorexia or Starvation
      3. Dementia
    3. Pseudohypokalemia
      1. Delayed lab analysis of sample
      2. Severe Leukocytosis (>75,000 to 100,000/mm3)
      3. Recent Insulin administration

V. Findings: Symptoms and Signs (when Serum Potassium < 2.5 mEq/L or with rapid drop in Serum Potassium)

  1. General
    1. Malaise
    2. Fatigue
  2. Neurologic
    1. Weakness
    2. Decreased Deep Tendon Reflexes
    3. Paresthesia
    4. Cramps
    5. Restless Legs Syndrome
    6. Rhabdomyolysis
    7. Paralysis
  3. Gastrointestinal
    1. Constipation
    2. Ileus
    3. Exacerbated Hepatic Encephalopathy in Cirrhosis
      1. Kidney retains Potassium in exchange for Hydrogen Ion, resulting in increased ammonia synthesis
  4. Cardiovascular
    1. Orthostatic Hypotension
    2. Hypertension
    3. Arrhythmias (rare in otherwise healthy patients)
      1. Acute or recent Myocardial Infarction (5 fold increased risk of Ventricular Fibrillation if K+ <3.9 mEq/L)
      2. Digoxin use and Hypokalemia predisposes to Arrhythmia
  5. Renal
    1. Metabolic Alkalosis
    2. Polyuria, Polydipsia
    3. Decreased GFR
    4. Glucose Intolerance

VI. Labs

  1. Serum Potassium <3.5 mEq/L
  2. Serum Magnesium
    1. Confirm no Hypomagnesemia (Hypokalemia cause)
  3. Complete Blood Count
    1. Confirm no severe Leukocytosis (pseudohypokalemia)
  4. 24 hour Urine Potassium and Urine Sodium
    1. Most accurate evaluation of Urine Potassium excretion
    2. However, Urine Potassium-to-Creatinine ratio is typically obtained instead
    3. Sample should have total Urine Sodium > 100 meq
    4. Urine Potassium <20-30 meq/day
      1. See Extrarenal Potassium Loss
    5. Urine Potassium >20-30 meq/day
      1. See Renal Potassium Loss
  5. Urine Potassium-to-Creatinine ratio
    1. Ratio <=1.5 mEq/mmol: Hypokalemia due to Extrarenal Potassium Loss
      1. Manage underlying losses
    2. Ratio >1.5 mEq/mmol: Hypokalemia due to Renal Potassium Loss
      1. Elevated Blood Pressure or hypervolemia (mineralcorticoid excess)
        1. Hyperaldosteronism
        2. Renal Artery Stenosis
        3. Cushing Syndrome
        4. Congenital Adrenal Hyperplasia
      2. Metabolic Acidosis
        1. Type I and II Renal Tubular Acidosis
      3. Metabolic Alkalosis
        1. Diuretics
        2. Renal Tubular transport disorders (e.g. Bartter Syndrome)

VII. Diagnostics: Electrocardiogram

  1. Early changes
    1. T Waves decreased amplitude to flattened
  2. Later changes
    1. Prominent U Waves
    2. ST depression (esp. mid-precordial leads, V2, V3)
      1. ST may appear to sag downwards from a normal J Point
      2. May give rise to a biphasic appearing T Wave
      3. May end in an upright U Wave
    3. T Wave Inversion
    4. Biphasic T Wave (mid-precordial leads, V1-V3)
      1. Mattu (2017) Crit Dec Emerg Med 31(3): 11
    5. PR prolongation (first degree AV Block)
    6. QTc Prolongation
  3. Arrhythmias associated with Hypokalemia
    1. Sinus Bradycardia
    2. Ventricular Tachycardia or Ventricular Fibrillation
    3. Torsade de pointes
  4. References
    1. Mattu (2021) Crit Dec Emerg Med 35(3):14

VIII. Management: General

  1. Potassium Replacement
    1. Goal Serum Potassium >3.5 mEq/L (>4.0 in CAD, CHF)
    2. Expect 0.1 mEq increase in Serum Potassium for every 10 mEq Potassium administered
    3. Total body Potassium deficit
      1. Serum Potassium: <3.5 mEq/L = 100 meq total Potassium deficit
      2. Serum Potassium: 3.2 mEq/L = 200 meq total Potassium deficit
      3. Serum Potassium: 2.9 mEq/L= 300 meq total Potassium deficit
      4. Serum Potassium: 2.6 mEq/L = 400 meq total Potassium deficit
    4. Avoid rebound Hyperkalemia (over-shooting replacement)
      1. Hyperkalemia with replacement is unlikely if normal Renal Function, adequate fluid intake
    5. Dietary Potassium (Potassium phosphate) is less efficient replacement than Potassium chloride
      1. Most Hypokalemia is associated with concurrent chloride depletion
      2. However Potassium chloride compliance is poor (Dyspepsia, Dietary Potassium tastes better)
    6. Half of Potassium Replacement is typically excreted by the Kidneys
      1. Aside from Renal Failure and Dehydration, at least half of Potassium Replacement (esp. oral) is excreted
    7. Approximate oral Potassium Replacement
      1. Start intravenous Potassium Replacement if Serum Potassium <2.5 mEq
      2. Serum Potassium 2.5 mEq to 3.0 mEq/L (total body deficit 200-300 meq)
        1. Start with KCl 20 meq orally every 2 hours for 4 doses and consider recheck level at 4 hours
        2. Typically continue Potassium Replacement at 20 meq twice daily for 4-5 days
      3. Serum Potassium: 3.0 to 3.5 mEq/L(total body deficit 100-200 meq)
        1. Give KCl 20 mEq orally every 2 hours for 2 doses OR KCl 40 mEq once
        2. Typically continue Potassium Replacement at 20 meq twice daily for 2-3 days
    8. Other Potassium Replacement
      1. See Potassium Replacement
      2. Intravenous Potassium Replacement
        1. See emergent replacement indications below
      3. Oral replacement other than with Potassium chloride (which is typically preferred)
        1. Potassium bicarbonate (or oral preparations with citrate or gluconate, or IV Potassium acetate)
          1. Consider in Metabolic Acidosis with Hypokalemia
        2. Potassium phosphate (IV)
          1. Indicated in Hypokalemia with Hypophosphatemia (e.g. Refeeding Syndrome, RTA 2, Fanconi Syndrome)
  2. Magnesium Replacement (empirically or based on lab demonstrated Hypomagnesemia)
    1. Especially consider empiric Magnesium Replacement in refractory Hypokalemia
    2. Take oral Magnesium Supplement 400-500 mg tabs 1-2 daily along with Potassium supplement
  3. Emergent replacement (IV Potassium chloride Replacement) indicated for serious findings or risks
    1. EKG changes (esp. QTc Prolongation, see above)
    2. Severe Hypokalemia (Serum Potassium <2.5 mEq/L)
    3. Rapid onset Hypokalemia
    4. Serious comorbidity (heart disease, Cirrhosis)
  4. Consider pseudohypokalemia
    1. Consider re-drawing lab for confirmation if delayed analysis
    2. Confirm no severe Leukocytosis (WBC >75,000/mm3)
  5. Consider Transcellular Potassium Shift
    1. See Transcellular Potassium Shift
    2. Hypokalemia from transcellular shift is typically transient

IX. Management: Hospital Replacement Criteria

  1. Hypokalemia with Serum Potassium <3.0 mEq/L AND QTc Prolongation >500 ms
  2. Severe Hypokalemia with Serum Potassium <2.5 mEq/L

X. Prevention

  1. Modify antihypertensive regimen
    1. Decrease or eliminate Diuretics
    2. Add ACE Inhibitor or Angiotensin Receptor Blocker (ARB)
  2. Dietary Changes
    1. Follow Low salt diet
    2. Increase Dietary Potassium (may be insufficient to replace Potassium chloride losses)
  3. Potassium Supplementation
    1. Potassium chloride 50 to 75 meq per day increases Serum Potassium 0.14 mEq/L

XI. References

  1. Orman and Slovis in Herbert (2018) EM:Rap 18(8): 4-5
  2. Kim (2023) Am Fam Physician 107(1): 59-70 [PubMed]
  3. Viera (2015) Am Fam Physician 92(6): 487-95 [PubMed]

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