Hypokalemia, Emergency Medicine

Basics

Description

- 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

- 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

- Diarrhea: - Proportional to volume and duration - Villous adenomas - Laxative abuse

- Alkalosis (metabolic or respiratory) - Insulin: - Insulin administration - Stimulation of insulin release by IV glucose or massive sweetened beverage intake - Refeeding in prolonged starvation

- 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

- 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

- 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

- 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.

- 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

Defined as a serum potassium level <3.5 mEq/L:Mild: 3-3.5 mEq/LModerate: 2.5-3 mEq/LSevere: <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 nervesInhibits the termination of action potentialsAlterations 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 kidneyOverdose 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 BPLiddle 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 alkalosisβ-hydroxybutyrate in DKAHippurate in toluene abusePenicillins-high dose IV therapy

GI Losses

Diarrhea:Proportional to volume and durationVillous adenomasLaxative 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 administrationStimulation of insulin release by IV glucose or massive sweetened beverage intakeRefeeding in prolonged starvation
Adrenergic excess:Severe stress (trauma, MI, sepsis)Treatment of asthma (frequent β-agonists and theophylline toxicity)Cocaine, amphetamines, caffeine excessDobutamine, 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 cephaladMay progress to paralysis if K <2 mEq/L and rapid developmentMuscle cramps, tetany, and tendernessRhabdomyolysisParesthesiasGeneralized fatigue and malaise
GI:
Cardiovascular (heart disease increases risk):Ventricular and atrial premature beatsAV block, atrial or junctional tachycardiasVentricular tachycardia (VT) or fibrillationPotentiation 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 diarrheaLow serum sodium suggests diuretic use or marked volume depletion from GI lossesHigh 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 stenosisLow 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 diseasePolyneuropathiesPrimary acute myopathiesCataplexy

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 laxativesTreat vomiting or diarrheaMinimize nasogastric suction losses by administering H2 blockers or PPIsAvoid glucose-containing fluids

Medication

Oral potassium chloride:Preferred replacement in almost all casesLiquid (or powder dissolved in water or juice) is more bioavailable, but nausea may occur:10-40 mEq per doseRapid rise in K, but will drop after 4 hr from transcellular shiftTablets (wax matrix and microencapsulated):More palatable, more sustained effectSlowly absorbedPotential for small bowel ulceration.Dosage for hypokalemia:Mild to moderate: 10-20 mEq q6-12hModerate to severe: 40-60 mEq q8-12hContinue until K remains 3-3.5 mEq/L
Oral potassium gluconate or citrate:Use in acidotic patients (e.g., RTA)Ineffective if accompanying metabolic alkalosisLess effective than KClCan 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 hypokalemiaPotassium 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 painIf K is added to maintenance fluids, the concentration should not be >40 mEq/L and dextrose solutions should be avoidedIf 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 minMonitor serum potassium after every 40 mEq IVHypokalemic 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 infusionChloride: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.

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)