Basics
Description
- Defined as a serum potassium level <3.5 mEq/L:
- Mild: 3-3.5 mEq/L
- Moderate: 2.5-3 mEq/L
- Severe: <2.5 mEq/L
- Frequency:
- Up to 20% of inpatients have documented hypokalemia (5% have levels <3 mEq/L).
- Up to 14% of outpatients are mildly hypokalemic (most are related to diuretics or GI loss).
- 5% of geriatric patients have K <3 mEq/L.
- Potassium is the major intracellular cation:
- Gradient is maintained by Na-K ATPase activity (enhanced by insulin and β-agonists) and mineralocorticoids.
- Total body potassium is ~55 mEq/kg of body weight (98% ICF, 2% ECF).
- Electrophysiologic effects of hypokalemia:
- Increase in the normal intracellular to extracellular potassium gradient:
- Alters the depolarization threshold for muscles and nerves
- Inhibits the termination of action potentials
- Alterations in intracellular potassium directly affect cellular function.
Etiology
Renal Losses
- Diuretics (thiazides, loop diuretics, carbonic anhydrase inhibitors), usually associated with loss of other cations (Mg2+, Ca2+, P3+, Na+)
- Renal tubular damage:
- Primary renal tubular disorders (RTA type I and II)
- Interstitial nephritis, analgesic nephropathy, drug toxicity (amphotericin, gentamicin, toluene, cisplatin), myeloma kidney
- Overdose toxicity: Acetaminophen, NSAIDs, hydroxychloroquine
- Hyperaldosteronism:
- Primary (primary hyperaldosteronism, Cushing, pituitary tumor-producing ACTH, congenital adrenal hyperplasia)
- Secondary (volume depletion, CHF, cirrhosis, nephrotic)
- Exogenous (steroids; fludrocortisone, glycyrrhizic acid [licorice]) hyperrenin state in renal artery stenosis
- Hypomagnesemia (increased secretion)
- Polyuria:
- Osmotic diuresis (mannitol, hyperglycemia)
- Psychogenic polydipsia
- Congenital disorders:
- Bartter and Gitelman syndromes-hypokalemic metabolic alkalosis and low BP
- Liddle syndrome is the same but with hypertension.
- Delivery of nonreabsorbable anions such that sodium is reabsorbed and potassium is exchanged out and excreted:
- Bicarbonate in metabolic alkalosis
- β-hydroxybutyrate in DKA
- Hippurate in toluene abuse
- Penicillins-high dose IV therapy
GI Losses
- Diarrhea:
- Proportional to volume and duration
- Villous adenomas
- Laxative abuse
- Vomiting and nasogastric suction result in volume depletion and metabolic alkalosis, which increases renal losses of potassium from bicarbonaturia and hyperaldosteronism.
- Ureterosigmoidostomy
- Intestinal fistulae, ileostomy
- Cystic fibrosis
Intracellular Shift of Potassium
- Alkalosis (metabolic or respiratory)
- Insulin:
- Insulin administration
- Stimulation of insulin release by IV glucose or massive sweetened beverage intake
- Refeeding in prolonged starvation
- Adrenergic excess:
- Severe stress (trauma, MI, sepsis)
- Treatment of asthma (frequent β-agonists and theophylline toxicity)
- Cocaine, amphetamines, caffeine excess
- Dobutamine, dopamine, pseudoephedrine
- Hypokalemic periodic paralysis:
- B12 administration in severely deficient patient
- Hypothermia
- Drugs: GM-CSF, quetiapine, risperidone
Poor Intake (Rare as a Sole Cause)
- Nutritional (poverty, pica, dementia)
- Eating disorders
- Dental problems/oral lesions
- Esophageal disease
Diagnosis
Signs and Symptoms
History
- Neuromuscular:
- Severe weakness (K <2.5 mEq/L):
- Begins in the lower extremities and progresses cephalad
- May progress to paralysis if K <2 mEq/L and rapid development
- Muscle cramps, tetany, and tenderness
- Rhabdomyolysis
- Paresthesias
- Generalized fatigue and malaise
- GI:
- Cardiovascular (heart disease increases risk):
- Ventricular and atrial premature beats
- AV block, atrial or junctional tachycardias
- Ventricular tachycardia (VT) or fibrillation
- Potentiation of digoxin toxicity
- Renal:
- Impaired urinary concentrating ability resistant to ADH (polyuria, polydipsia)
- Increased renal bicarbonate reabsorption and ammonia production (worsens alkalosis)
Physical Exam
- HTN-renal artery stenosis, primary hyperaldosteronism, licorice, congenital adrenal hyperplasia, Liddle syndrome, glucocorticoid use
- Hypotension-GI losses, diuretic use, Bartter and Gitelman syndromes
- Neuromuscular-muscle weakness, decreased reflexes, muscle tenderness
Diagnosis Tests & Interpretation
Lab
- Electrolytes, BUN, creatinine, glucose:
- High HCO3 suggests diuretic abuse, vomiting, mineralocorticoid excess, Bartter, Gitelman.
- Low HCO3 suggests renal tubular disease or diarrhea
- Low serum sodium suggests diuretic use or marked volume depletion from GI losses
- High serum sodium suggests nephrogenic diabetes insipidus or primary hyperaldosteronism
- Urine K (spot sample):
- <20 mEq/L suggests GI loss, potassium shift into cells, poor intake.
- >20 mEq/L suggests renal loss.
- Urine K to creatinine ratio is more precise
- <13 mEq/g or 1.5 mEq/mmol (nonrenal)
- >13 mEq/g or >1.5 mEq/mmol (renal loss)
- Urine Na:
- <20 mEq/L with elevated urine K suggests secondary hyperaldosteronism.
- Plasma renin if hypertensive:
- High renin: Secondary hyperaldosteronism, renal artery stenosis
- Low renin: Primary hyperaldosteronism
- TSH and free T4 if Asian male
ECG Findings
- Low-voltage T-waves
- Sagging of the ST segments
- U-waves:
- In severe hypokalemia, the T disappears and the U-wave predominates, giving the illusion of dramatic QT prolongation.
- Diminutive P-waves (appears nodal)
- Dysrhythmias (very prevalent if underlying cardiomyopathy or digoxin toxic):
- Atrial: Premature atrial contractions (PACs), atrial fibrillation (Afib)
- Ventricular: Premature ventricular contractions (PVCs), VT, torsade
Differential Diagnosis
- Intrinsic cardiac disease with dysrhythmias
- Causes of muscular weakness:
- Neuromuscular junction disease (myasthenia gravis, organophosphate poisoning, botulism)
- Spinal cord disease
- Polyneuropathies
- Primary acute myopathies
- Cataplexy
Treatment
Initial Stabilization/Therapy
- Establish IV access/volume resuscitation
- ABCs
- Cardiac monitoring
Ed Treatment/Procedures
- Total body deficit is 200-300 mEq per 1 mEq/L decrement in serum potassium level.
- Rate of replacement and route dependent on presence of symptoms, severity of hypokalemia, and comorbidities.
- Complete replacement over several days
- Oral potassium preferable to IV therapy whenever possible
- Identify and prevent ongoing K losses:
- Hold diuretics or laxatives
- Treat vomiting or diarrhea
- Minimize nasogastric suction losses by administering H2 blockers or PPIs
- Avoid glucose-containing fluids
Medication
- Oral potassium chloride:
- Preferred replacement in almost all cases
- Liquid (or powder dissolved in water or juice) is more bioavailable, but nausea may occur:
- 10-40 mEq per dose
- Rapid rise in K, but will drop after 4 hr from transcellular shift
- Tablets (wax matrix and microencapsulated):
- More palatable, more sustained effect
- Slowly absorbed
- Potential for small bowel ulceration.
- Dosage for hypokalemia:
- Mild to moderate: 10-20 mEq q6-12h
- Moderate to severe: 40-60 mEq q8-12h
- Continue until K remains 3-3.5 mEq/L
- Oral potassium gluconate or citrate:
- Use in acidotic patients (e.g., RTA)
- Ineffective if accompanying metabolic alkalosis
- Less effective than KCl
- Can be used as prophylaxis of calcium oxalate renal stones or may dissolve uric acid stones
- IV potassium:
- Recommended if neuromuscular symptoms, cardiac arrhythmias, ongoing GI losses, or severe hypokalemia
- Potassium chloride is the preferred replacement:
- Potassium phosphate is used only if accompanying severe hypophosphatemia.
- Administration:
- A potassium rider at 10 mEq/h piggybacked into maintenance 0.9 NS is safest and best tolerated (peds: 0.1-0.2 mEq/kg/h)
- 15-20 mEq/h are feasible by peripheral vein but not recommended due to risk of phlebitis and pain
- If K is added to maintenance fluids, the concentration should not be >40 mEq/L and dextrose solutions should be avoided
- If sustained life-threatening dysrhythmias, 20-40 mEq/h by central line or 2 peripheral lines can be considered.
- If cardiac arrest occurs in a patient with known severe hypokalemia, 20 mEq could be given IV over 2-3 min
- Monitor serum potassium after every 40 mEq IV
- Hypokalemic periodic paralysis and other situations in which there is significant transcellular K shifts (adrenergic excess):
- Small amounts of K are effective (20 mEq IV).
- More zealous administration may lead to rebound hyperkalemia.
- Electrolyte corrections:
- Magnesium:
- Consider if hypokalemia is resistant to K replacement.
- Magnesium sulfate 2 g slow IV infusion
- Chloride:
- Hypokalemia with alkalosis is resistant to replacement unless volume depletion and hypochloremia is corrected by saline administration.
Follow-Up
Disposition
Admission Criteria
- Need of IV potassium repletion
- Cardiac dysrhythmias
- Profound muscle weakness
- Ongoing K losses
- Serum potassium <2.5 mEq/L
- Associated with significant hypotension or severe HTN
- Significant comorbidities or geriatric
Discharge Criteria
- Asymptomatic
- Able to replete deficiency with oral potassium
- Early follow-up available and reliable patient
- Repeat electrolyte determination in 2-3 days with the primary care doctor.
- Nephrology referral or consult if suspicion of renal wasting.
- Continue K replacement for 2-3 days if acute, self-limited loss, but ongoing therapy if the cause is not corrected (e.g., diuretic therapy, chronic diarrhea).
Pearls and Pitfalls
- If hypokalemia is accompanied by acidosis, correct hypokalemia 1st before treating the acidosis so as to avoid life-threatening hypokalemia from transcellular shifts.
- Minimize glucose administration when treating hypokalemia, since glucose will stimulate insulin release, which will lead to K movement into cells.
- Large doses of oral potassium can be given safely in patients with normal renal function, limited only by GI tolerance.
- Check for hypomagnesemia if hypokalemia is severe or resistant to replacement therapy.
- Relatively small amounts of IV potassium are required to reverse hypokalemia in periodic paralysis and states of adrenergic excess since transcellular shifts are transient.
Additional Reading
- Alkaabi JM, Mushtaq A, Al-Maskari FN, et al. Hypokalemic periodic paralysis: A case series, review of the literature and update of management. Eur J Emerg Med. 2010;17(1):45-47.
- Ben Salem C, Himouda H, Bouraoui K. Drug-induced hypokalaemia. Curr Drug Saf. 2009;4(1):55-61.
- Grenniee M, Wingo CS, McDonough AA, et al. Narrative review: Evolving concepts in potassium homeostasis and hypokalemia. Ann Intern Med. 2009;150:619-625.
- Palmer BF. A physiologic based approach to the evaluation of a patient with hypokalemia. Am J Kidney Dis. 2010;56(6):1184-1190.
- Pepin J, Shields C. Advances in diagnosis and management of hypokalemic and hyperkalemic emergencies. Emerg Med Pract. 2012;14(2):1-18.
- Philips DA, Bauch TD. Rapid correction of hypokalemia in a patient with an implantable cardioverter-defibrillator and recurrent ventricular tachycardia. J Emerg Med. 2010;38(3):308-316.
- Schaefer TJ, Wolford RW. Disorders of potassium. Emerg Med Clin North Am. 2005;23(3):723-747.
See Also (Topic, Algorithm, Electronic Media Element)
Hyperkalemia
Codes
ICD9
- 255.13 Bartters syndrome
- 276.3 Alkalosis
- 276.8 Hypopotassemia
ICD10
- E26.81 Bartters syndrome
- E87.3 Alkalosis
- E87.6 Hypokalemia
SNOMED
- 43339004 hypokalemia (disorder)
- 22774003 Hypokalemic alkalosis (disorder)
- 236465009 Bartters syndrome with hypercalciuria and nephrocalcinosis (disorder)
- 38495009 hypokalemia, excessive renal losses (disorder)