Hypocalcemia: Author: Christopher B Beach, MD, FACEP, FAAEM, Associate Professor and Vice

Hypocalcemia
Author: Christopher B Beach, MD, FACEP, FAAEM, Associate Professor and Vice
Chair of Emergency Medicine, Department of Emergency Medicine, Associate Professor
of Institute for Healthcare Studies, Institute for Patient Safety, Feinberg School of
Medicine, Northwestern University
Contributor Information and Disclosures
Updated: Mar 29, 2010
• Print This
• Email This
• Overview
• Differential Diagnoses & Workup
• Treatment & Medication
• Follow-up
• References
• Keywords
Information from Industry
View efficacy data in the bacterial RTIs you see most Clinical success > 90% was
demonstrated in acute bacterial sinusitis, acute bacterial exacerbation of chronic
bronchitis, and in community-acquired pneumonia Learn more
Introduction
Background
Calcium regulation is critical for normal cell function, neural transmission, membrane
stability, bone structure, blood coagulation, and intracellular signaling. The essential
functions of this divalent cation continue to be elucidated, particularly in head
injury/stroke and cardiopulmonary effects. Depending on the cause, unrecognized or
poorly treated hypocalcemic emergencies can lead to significant morbidity or death.
Pathophysiology
Metabolic and endocrine emergencies require an understanding of normal physiology.
Calcium regulation is maintained by parathyroid hormone (PTH), vitamin D, and

calcitonin through complex feedback loops. These compounds act primarily at bone,
renal, and GI sites. Calcium also is affected by magnesium and phosphorus.1
Distribution
Approximately 99% of calcium is found in bone, and 1% is found in extracellular fluid.

Of this 1%, 50% is in the free (active) ionized form (1-1.15 mmol/L), 40% is bound to
protein (predominantly albumin), and 10% is complexed with anions (eg, citrate).
Homeostasis is maintained by an extracellular to intracellular gradient, which is largely

due to abundant high-energy phosphates intracellularly.
Intracellular calcium regulates cAMP-mediated messenger systems and most cell

organelle functions. Ion pumps control levels.
Extracellular calcium levels are maintained at 8.7-10.4 mg/dL. Variations depend upon
serum pH, protein and anion levels, and calcium-regulating hormone function.
Total body levels of calcium are controlled by a complex feedback system. PTH directly
targets the bone and the kidneys to increase serum calcium levels. Indirectly, through
vitamin D, it causes intestinal calcium absorption. Vitamin D directly targets GI
absorption of calcium to increase calcium levels. Calcitonin lowers calcium by targeting
bone, renal, and GI losses.
Frequency
United States
Epidemiology of hypocalcemia versus other electrolyte abnormalities has not been

performed. During the last 20 years, laboratory tests have quantified serum and ionized
calcium and PTH levels, enabling easier diagnosis. The incidence of ionized
hypocalcemia is difficult to quantify, but it has been reported to be 15-50% for ICU
patients. In a series of 500 postsurgical patients operated on for hyperparathyroidism, 2%
had permanent hypocalcemia.2
International
Similar standards exist in other industrialized nations throughout the world.
Mortality/Morbidity
Severe, symptomatic hypocalcemia may result in cardiovascular collapse, hypotension

unresponsive to fluids and vasopressors, and dysrhythmias. Clinically evident
hypocalcemia generally presents in milder forms and is usually the result of a chronic
disease state. Chronic or subacute complaints secondary to mild or moderate
hypocalcemia are more likely to be a chief complaint in the ED than severe symptomatic
hypocalcemia.
• Neurologic sequelae (eg, tetany, seizures) may occur.

• Death is rare but has been reported.
• The disease causing hypocalcemia may have greater impact on morbidity than
hypocalcemia itself.
Sex
The incidence in males and females is equal.
Age
Hypocalcemia spans all ages. The differential diagnosis varies depending on the age of
the patient and the coexistent medical illnesses.
Clinical
History
• The patient may complain of muscle cramping, shortness of breath secondary to

bronchospasm, tetanic contractions, distal extremity numbness, and tingling
sensations.
• Chronic manifestations include cataracts, dry skin, coarse hair, brittle nails,
psoriasis, chronic pruritus, and poor dentition.
• Acute hypocalcemia may lead to syncope, congestive heart failure (CHF), and
angina due to the multiple cardiovascular effects.3
• The patient's past medical history should be explored for pancreatitis, anxiety
disorders, renal or liver failure, gastrointestinal disorders, and hyperthyroidism or
hyperparathyroidism.
• The patient may have a recent history of thyroid, parathyroid, or bowel surgeries
or recent neck trauma.
• Inquire about recent radiocontrast, estrogen, loop diuretics, bisphosphonates,
calcium supplements, antibiotics, and antiepileptics.
• Evaluate for appropriate dietary intake.
Physical
Neuromuscular and cardiovascular findings predominate. Neural hyperexcitability due to

acute hypocalcemia causes smooth and skeletal muscle contractions. The patient should
be examined for the following:
• Dry skin and psoriasis (if long-term hypocalcemia)

• Perioral anesthesia, cataracts, papilledema, and laryngeal stridor
• Scars over thyroid region
• Recent trauma or surgery to the neck
• Cardiopulmonary effects
o Wheezing, dysphagia, stridor, bradycardia, rales, and S3 may be noted.4
o Acute hypocalcemia causes prolongation of the QT interval, which may
lead to ventricular dysrhythmias. It also causes decreased myocardial
contractility, leading to CHF, hypotension, and angina. Cardiomyopathy
and ventricular tachycardia may be reversible with treatment.
o Smooth muscle contraction may lead to laryngeal stridor, dysphagia, and
bronchospasm.
• Smooth muscle contraction causes biliary colic, intestinal colic, and dysphagia.
• Diarrhea and/or gluten intolerance (celiac sprue) may result in significant
malabsorption and electrolyte abnormalities.
• Preterm labor or detrusor dysfunction may result from smooth muscle contraction.
• Peripheral nervous system findings include tetany, focal numbness, and muscle
spasms.
• Classic peripheral neurologic findings include the Chvostek sign and Trousseau
sign.
o Chvostek sign: Tap over the facial nerve about 2 cm anterior to the tragus
of the ear. Depending on the calcium level, a graded response will occur:
twitching first at the angle of the mouth, then by the nose, the eye, and the
facial muscles.
o Trousseau sign: Inflation of a blood pressure cuff above the systolic
pressure causes local ulnar and median nerve ischemia, resulting in carpal
spasm.
• Irritability, confusion, hallucinations, dementia, extrapyramidal manifestations,
and seizures may occur.
o Calcification of basal ganglia, cerebellum, and cerebrum may occur.
o Seizures often occur in individuals with preexistent epileptic foci when the
excitation threshold is lowered.
Causes
The causes of hypocalcemia include hypoalbuminemia, hypomagnesemia,

hyperphosphatemia, multifactorial enhanced protein binding and anion chelation,
medication effects, surgical effects, PTH deficiency or resistance, and vitamin D
deficiency or resistance.
• Hypoalbuminemia is the most common cause of hypocalcemia and is due to

cirrhosis, nephrosis, malnutrition, burns, chronic illness, and sepsis.
o Calcium level should be corrected in hypoalbuminemic states and often is
found to be normal.
o Calcium level is corrected as follows: Corrected calcium (mg/dL) =
measured total Ca (mg/dL) + 0.8 (4.4 - serum albumin [g/dL]), where 4.4
represents the average albumin level.
o Note: For unknown reasons, calcium correction based on the above
calculation may be inaccurate in geriatric patients. Ionized calcium levels
should be obtained if hypocalcemia is considered to be clinically
significant in a geriatric patient.
• Hypomagnesemia causes end-organ resistance to PTH and inhibits the
hypocalcemic feedback loop through uncertain mechanisms. Causes of
hypomagnesemia include pancreatitis, aminoglycoside treatment, amphotericin B,
loop diuretics, alcoholism, and malnutrition.
• Hyperphosphatemia may be seen in critical illness and in patients who have
ingested phosphate-containing enemas. Phosphate binds calcium avidly, causing
acute hypocalcemia.
• Multifactorial causes are probably the most clinically relevant hypocalcemic
emergencies in the ED and include the following:
o Acute pancreatitis: Free fatty acids chelate calcium, causing saponification
in the retroperitoneum.
o Rhabdomyolysis: Increased phosphates from creatine phosphokinase
(CPK) and other anions (ie, lactate, bicarbonate) chelate calcium.
o Sepsis can cause hypocalcemia through many mechanisms.
o Toxic shock syndrome can cause hypocalcemia.
o High calcitonin levels cause low calcium.
o Malignancy: Osteoblastic metastases (eg, breast cancer, prostate cancer)
and tumor lysis syndrome may cause hypocalcemia (by differing
mechanisms).
o Hepatic or renal insufficiency: Calciuresis, hypomagnesemia,
hypoalbuminemia, and low active vitamin D levels may contribute to poor
calcium homeostasis.
o Infiltrative disease: Sarcoidosis, tuberculosis, and hemochromatosis may
infiltrate the parathyroids, causing dysfunction.
o Toxicologic causes include hydrofluoric acid burn or ingestion.
o Trauma patients with massive transfusion will have hemostasis
impairment as one effect of hypocalcemia.5
• Enhanced protein binding and anion chelation
o Protein binding is enhanced by elevated pH and free fatty acid release in
high catecholamine states.
o Anion chelation is seen in high phosphate states (eg, renal failure,
rhabdomyolysis, mesenteric ischemia, oral administration of phosphate-
containing enemas); high citrate states (eg, massive blood transfusion,
radiocontrast dyes); and high bicarbonate, lactate, and oxalate levels.
• Medication effects
o Proton pump inhibitors (PPIs) reduce gastric acid production resulting in
reduced calcium absorption. An association with these medicines and an
increased risk for hip fractures in elderly patients has been made due to
decreased calcium absorption.
o Selective serotonin inhibitors can have a calcium antagonistic effect on
smooth muscle, particularly vascular endothelium.
o Calcitonin and bisphosphonates cause chelation and end-organ inhibition.
o Phenobarbital and phenytoin enhance vitamin D catabolism and decrease
calcium resorption in the gut.
o Foscarnet complexes with calcium.
o Fluoride, particularly hydrofluoric acid, chelates calcium avidly and
causes profound hypocalcemia.
o Ethylene glycol complexes with calcium.
o Estrogen inhibits bone resorption.
o Cimetidine decreases gastric pH, slowing fat breakdown, which is
necessary to complex calcium for gut absorption.
o Aluminum and alcohol suppress PTH.
o Gadolinium-based contrast material can falsely lower serum calcium
levels and should be considered if levels are drawn shortly after magnetic
resonance imaging.
• Postsurgical effects
o Parathyroid adenoma resection causes a transient hypocalcemia due to
end-organ PTH resistance in the first postoperative day.
o Vascular/parathyroid injury may occur during trauma or as an operative
mishap.
o Pancreatectomy prevents calcium absorption in the duodenum and the
jejunum by eliminating necessary enzymes.
o Small bowel syndrome causes hypocalcemia by reducing the surface
available to absorb fatty acids and calcium.
• PTH deficiency/resistance
o Childhood/congenital causes are rare but include DiGeorge syndrome.
o Idiopathic hypoparathyroidism interferes with calcium regulation.
o Infiltrative diseases include Wilson disease and metastatic cancer.
o Pseudohypoparathyroidism is due to PTH resistance and has many forms,
most notably Albright disease.
o Renal failure can result in a variety of endocrine disorders, occasionally
including hypocalcemia.
• Vitamin D deficiency/resistance
o Rickets may be due to lack of vitamin D or end-organ receptor resistance.
o Hepatorenal disease: The liver and the kidney provide intermediary
enzymes to form active 1,25(OH)2 D.
Laboratory Studies
• Symptomatic patients with classic clinical findings of acute hypocalcemia require

immediate resuscitation and evaluation. However, most cases of hypocalcemia are
discovered by clinical suspicion and appropriate laboratory testing.
• Calcium levels
o A serum calcium level less than 8.5 mg/dL or an ionized calcium level less
than 1.0 mmol/L is considered hypocalcemia.
o Analysis for ionized level must be performed rapidly with whole blood to
avoid changes in pH and anion chelation. Blood should be drawn in an
unheparinized syringe for best results.
o Falsely elevated calcium levels may be seen with elevated acetaminophen
levels, alcohol, hydralazine, and hemolysis.
o Falsely depressed levels can be seen with heparin, oxalate, citrate, or
hyperbilirubinemia.
• Magnesium, phosphate, and other electrolyte levels should be obtained.
• Elevated BUN and creatinine levels may indicate renal dysfunction.
• Albumin, liver function studies, and coagulation parameters should be obtained to
assess liver dysfunction and hypoalbuminemia.
• The PTH level (an antibody-mediated radioimmunoassay) should be checked as
early as possible.
Imaging Studies
• Depending on the patient's clinical status and the suspected etiology of

hypocalcemia, imaging studies may or may not be indicated in the ED.
Other Tests
• ECG and electrocardiographic monitoring should be obtained to rule out

dysrhythmias and a prolonged QT interval.
Treatment
Prehospital Care
Standard advanced cardiac life support (ACLS) procedures should be initiated in the
patient whose condition is unstable. No specific therapy, other than supportive care, is
recommended.
Emergency Department Care
Most hypocalcemic emergencies are mild and require only supportive treatment and
further laboratory evaluation. On occasion, severe hypocalcemia may result in seizures,
tetany, refractory hypotension, or arrhythmias that require a more aggressive approach.
• Mild hypocalcemia (when symptoms are not life threatening)

o Confirm ionized hypocalcemia and check other pertinent laboratory tests.
o If the cause is not obvious, send for a PTH level.
o Depending on the PTH level, the endocrinologist may do further
laboratory workup, particularly an evaluation of vitamin D levels.
o Oral repletion may be indicated for outpatient treatment; patients requiring
intravenous (IV) repletion should be admitted. (Recommended dose of
elemental calcium in healthy adults is 1-3 g/d.)
• Severe hypocalcemia (life-threatening symptoms)
o Supportive treatment often is required prior to directed treatment of
hypocalcemia (ie, IV replacement, oxygen, monitoring). Be aware that
severe hypocalcemia often is associated with other life-threatening
conditions.
o Check ionized calcium and other pertinent screening laboratory tests.
o IV replacement is recommended in severe cases. Doses of 100-300 mg of
elemental calcium (calcium gluconate – 10 mL contains 90 mg elemental
calcium; calcium chloride – 10 mL contains 272 mg elemental calcium)
should be given over 5-10 minutes. This dosage raises the ionized level to
0.5-1.5 mmol and should last 1-2 hours. Caution should be used when
giving CaCl intravenously (see Medication).
o Calcium infusion drips should be started at 0.5 mg/kg/h and increased to 2
mg/kg/h as needed, with an arterial line placed for frequent measurement
of ionized calcium.
Consultations
Depending on the clinical situation, multiple consultations may be necessary, including

internist, endocrinologist, intensivist, surgeon, oncologist, nephrologist, dietitian, and/or
toxicologist.6
Medication
In the ED, magnesium and calcium (in their many different forms) are the only
medications necessary to treat hypocalcemic emergencies. The consulting
endocrinologist may choose to prescribe any of the various vitamin D supplements
depending on laboratory workup findings and oral calcium supplementation for
outpatient therapy.
Electrolyte supplements
These agents are used to increase blood calcium levels.
Calcium citrate (Citracal)
Oral formulation usually used as supplementation to IV calcium therapy. Moderates

nerve and muscle performance by regulating action potential excitation threshold and
facilitating normal cardiac function. Give amount needed to supplement diet to reach
recommended daily amounts. Amount of elemental calcium in calcium citrate is 200 mg.
• Dosing
• Interactions
• Contraindications
• Precautions
Adult
1-2 g PO divided bid/qid
Pediatric
45-65 mg/kg/d PO divided qid
• Dosing
• Interactions
• Precautions
May increase effect of quinidine; may decrease effects of tetracyclines, atenolol,

salicylates, iron salts, and fluoroquinolones; large intakes of dietary fiber may decrease
absorption and levels
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; hypercalcemia; hypophosphatemia; renal calculi; renal or

cardiac disease; digitalis toxicity
• Dosing
• Interactions
• Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans;
may use if benefits outweigh risk to fetus
Precautions
Hypercalcemia or hypercalcuria may occur when therapeutic amounts are given; caution
in digitalized patients and respiratory failure or acidosis
Calcium chloride
Moderates nerve and muscle performance by regulating action potential excitation

threshold. Used when ventricular fibrillation is not associated with hyperkalemia,
digitalis toxicity, hypercalcemia, renal insufficiency, or cardiac disease. Preferred when
patient is in cardiac arrest and in other serious cases. The 10% IV solution provides 100
mg/mL of calcium chloride that equals 27.2 mg/mL (1.4 mEq/mL) of elemental calcium
(10 mL of calcium chloride 10% contain 272 mg of elemental calcium).
DOC for patients in cardiac arrest.
• Dosing
• Interactions
• Precautions
Adult
100-300 mg elemental calcium IV diluted in 150 mL D5W over 5-10 min; initial rate of
infusion is 0.3-2 mg of elemental calcium/kg/h
Pediatric
0.2 mL/kg/dose IV for patients in cardiac arrest
• Dosing
• Interactions
• Precautions
Coadministration with digoxin may cause arrhythmias; with thiazides, may induce
hypercalcemia; may antagonize effects of calcium channel blockers, atenolol, and sodium
polystyrene sulfonate
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; ventricular fibrillation not associated with hyperkalemia;

digitalis toxicity; hypercalcemia; renal insufficiency; cardiac disease
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Administer slowly (not to exceed 0.5-1 mL/min) to avoid extravasation; hypercalcemia

may occur in renal failure
Calcium carbonate (Oystercal)
Used orally as supplementation to IV calcium therapy. Moderates nerve and muscle

performance by regulating action potential excitation threshold.
Amounts of elemental calcium in calcium carbonate are as follows: Tums - 200 mg;
Rolaids - 220 mg; Os-Cal - 500 mg.
• Dosing
• Interactions
• Precautions
Adult
1-2 g PO divided bid/qid
Pediatric
45-65 mg/kg/d PO divided qid
• Dosing
• Interactions
• Precautions
May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and

fluoroquinolones; large intakes of dietary fiber may decrease absorption and levels
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; renal calculi; hypercalcemia; hypophosphatemia; renal or

• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Caution in digitalized patients and respiratory failure or acidosis
Calcium gluconate (Kalcinate)
Useful in treating hypocalcemia. Moderate nerve and muscle performance by regulating

action potential excitation threshold.
DOC for patients not in cardiac arrest (90 mg of elemental calcium in 10 mL of 10%
solution). Oral formulation usually used as supplementation to IV calcium therapy.
Amounts of elemental calcium in calcium gluconate are as follows: 500-mg tablet - 45
mg; 650-mg tablet - 58.5 mg; 975-mg tablet - 87.75 mg; 1-g tablet - 90 mg.
• Dosing
• Interactions
• Precautions
Adult
Parenteral: 100-300 mg elemental calcium IV diluted in 150 mL D5W over 5-10 min;
initial rate of infusion is 0.3-2 mg of elemental calcium/kg/h
Oral: 1-2 g PO divided bid/qid
Pediatric
Parenteral: 1 mL (100 mg)/kg/dose IV continuous infusion over 24 h for patients not in

cardiac arrest
10-20 mg/kg of elemental calcium IV over 5-10 min
Oral: 45-65 mg/kg/d PO divided qid
• Dosing
• Interactions
• Precautions
fluoroquinolones; IV administration antagonizes effects of verapamil; large intakes of
dietary fiber may decrease absorption and levels
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; renal calculi; hypercalcemia; hypophosphatemia; renal or

• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Adverse effects include hypertension, nausea, vomiting, flushing, and bradycardia;

caution when administering to digitalized patients and to patients with respiratory failure,
acidosis, or severe hyperphosphatemia
Follow-up
Further Inpatient Care
• Care is determined by the probable underlying etiology of hypocalcemia.

• Many patients require ICU or ward admission for inpatient workup and repeat
laboratory testing.
• If a patient is given intravenous calcium in the ED, admit for further evaluation
and observation.
Further Outpatient Care
• Although uncommon, outpatient evaluation by an endocrinologist or an internist

is appropriate in some cases.
• Oral repletion should be initiated in the ED, with a clear plan for timely follow-up
care.
Transfer
• Transfer should be considered when the etiology of hypocalcemia requires a

subspecialty that is not available at the initial hospital.
Deterrence/Prevention
• Patients with diseases that predispose them to the development of hypocalcemia

should have scheduled appointments with an outpatient provider.
Prognosis
• Prognosis is dependent on the etiology of hypocalcemia but is generally good.
Patient Education
• For excellent patient education resources, visit eMedicine's Bone Health Center;
Esophagus, Stomach, and Intestine Center; and Kidneys and Urinary System
Center. Also, see eMedicine's patient education articles Osteoporosis, Celiac
Sprue, and Kidney Stones.
Hypercalcemia
Author: Robin R Hemphill, MD, MPH, Associate Professor, Director, Quality and
Safety, Department of Emergency Medicine, Emory University
Updated: Sep 1, 2010
• Print This
• Email This
• Overview
• Follow-up
• References
• Keywords
• Further Reading
Postmenopausal osteoporosis treatment

Get the facts about an FDA approved treatment.
Learn more
Introduction
Background
Hypercalcemia is a disorder that most commonly results from malignancy or primary

hyperparathyroidism.1,2,3 Other causes of elevated calcium are less common and usually
are not considered until malignancy and parathyroid disease are ruled out.
Hypercalcemic crisis does not have an exact definition, although marked elevation of
serum calcium, usually more than 14 mg/dL, is associated with acute signs and symptoms
of hypercalcemia. Treatment of the elevated calcium level may resolve the crisis.
The reference range of serum calcium levels is 8.7-10.4 mg/dL, with somewhat higher
levels present in children. Approximately 40% of the calcium is bound to protein,
primarily albumin, while 50% is ionized and is in physiologic active form. The remaining
10% is complexed to anions.
Pathophysiology
Plasma calcium is maintained within the reference range by a complex interplay of 3

major hormones, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (ie, calcitriol),
and calcitonin. These 3 hormones act primarily at bone, kidney, and small intestine sites
to maintain appropriate calcium levels.
Calcium enters the body through the small intestine and eventually is excreted via the
kidney. Bone can act as a storage depot. This entire system is controlled through a
feedback loop; individual hormones respond as needed to increase or decrease the serum
calcium concentration.
For hypercalcemia to develop, the normal calcium regulation system must be

overwhelmed by an excess of PTH, calcitriol, some other serum factor that can mimic
these hormones, or a huge calcium load.
Hypercalcemia can result from a multitude of disorders. The causes are divided into
PTH-mediated hypercalcemia and non–PTH-mediated hypercalcemia.
PTH-mediated hypercalcemia
Primary hyperparathyroidism originally was the disease of "stones, bones, and abdominal
groans." In most primary hyperparathyroidism cases, the calcium elevation is caused by
increased intestinal calcium absorption. This is mediated by the PTH-induced calcitriol
synthesis that enhances calcium absorption. The increase in serum calcium results in an
increase in calcium filtration at the kidney. Because of PTH-mediated absorption of
calcium at the distal tubule, less calcium is excreted than might be expected. In PTH-
mediated hypercalcemia, bones do not play an active role because most of the PTH-
mediated osteoclast activity that breaks down bone is offset by hypercalcemic-induced
bone deposition. Hypercalcemia of this disorder may remain mild for long periods
because some parathyroid adenomas respond to the feedback generated by the elevated
calcium levels.
Non–PTH-mediated hypercalcemia
Hypercalcemia associated with malignancy commonly is the result of multiple myeloma,

breast cancer, or lung cancer and is caused by increased osteoclastic activity within the
bone.4 The ED physician should be concerned about any patient with a history of cancer
who presents with lethargy or altered mental status. Granulomatous disorders with high
levels of calcitriol may be found in patients with sarcoidosis, berylliosis, tuberculosis,
leprosy, coccidioidomycosis, and histoplasmosis. Iatrogenic disorders of calcium levels
may increase secondary to the ingestion of many medications.3
Frequency
United States
Hypercalcemia is a fairly common metabolic emergency. Between 20 and 40% of

patients with cancer develop hypercalcemia at some point in their disease (this may be
decreasing with the use of bisphosphates, but data are lacking), and it is the most
common serious electrolyte presenting in adults with malignancies.5
Primary hyperparathyroidism occurs in 25 per 100,000 persons in the general population

and in 75 per 100,000 hospitalized patients. This condition is the most common cause of
mild hypercalcemia, which can be treated on an outpatient basis. In the United States,
more than 50,000 new cases occur each year.
Mortality/Morbidity
• Prognosis of hypercalcemia associated with malignancy is poor; the 1-year

survival rate is 10-30%. In one study, 50% of patients died within 30 days of
beginning treatment; 75% died within 3 months.
• Prognosis related to many of the other causes of hypercalcemia can be excellent
once the underlying disease is addressed.
Sex
• The incidence of primary hyperparathyroidism is considerably higher in women.

The annual incidence in women older than 65 years is 250 per 100,000.
• Elevations in calcium levels related to cancer have no sex predominance.
Age
• The incidence of primary hyperparathyroidism increases with age.

• The rate of malignancy and, thus, of malignancy-associated hypercalcemia
increases with age.
Clinical
History
• Symptoms of hypercalcemia depend on the underlying cause of the disease, the

time over which it develops (rapid increases in calcium cause more severe
symptoms), and the overall physical health of the patient.
• Mild elevations in calcium levels usually have few or no symptoms.
• Increased calcium levels may cause the following:
o Nausea
o Vomiting
o Alterations of mental status
o Abdominal or flank pain (The workup of patients with a new kidney stone
occasionally reveals an elevated calcium level.)
o Constipation
o Lethargy
o Depression
o Weakness and vague muscle/joint aches
o Polyuria, polydipsia, nocturia
o Headache
o Confusion
• Severe elevations in calcium levels may cause coma.
• Elderly patients are more likely to be symptomatic from only moderate elevations
of calcium levels.
• Hypercalcemia of malignancy may lack many of the features commonly
associated with hypercalcemia caused by hyperparathyroidism. In addition, the
symptoms of elevated calcium level may overlap with the symptoms of the
patient's malignancy.
• Hypercalcemia associated with renal calculi, joint complaints, and ulcer disease is
more likely to be caused by hyperparathyroidism.
Physical
Hypercalcemia has few physical examination findings specific to its diagnosis.
• Often it is the symptoms or signs of underlying malignancy that bring the patient
with hypercalcemia to seek medical attention.
• The primary malignancy may be suggested by lung findings, skin changes,
lymphadenopathy, or liver or spleen enlargement.
• Hypercalcemia can produce a number of nonspecific findings, as follows:
o Hypertension and bradycardia may be noted in patients with
hypercalcemia, but this is nonspecific.
o Abdominal examination may suggest pancreatitis or the possibility of an
ulcer.
o Patients with long-standing elevation of serum calcium may have
proximal muscle weakness that is more prominent in the lower
extremities; they also may have bony tenderness to palpation.
o Hyperreflexia and tongue fasciculations may be present.
o Anorexia or nausea may occur.
o Polyuria and dehydration are common.
o Lethargy, stupor, or even coma may be observed.
• Long-standing hypercalcemia may cause band keratopathy, but this is rarely
recognized in the ED.
• If hypercalcemia is caused by sarcoidosis, vitamin D intoxication, or
hyperthyroidism, patients may have physical examination findings suggestive of
those diseases.
Causes
Hypercalcemia is divided into PTH-mediated hypercalcemia (primary

hyperparathyroidism) and non–PTH-mediated hypercalcemia.
• PTH-mediated hypercalcemia is related to increased calcium absorption from the

intestine.
• Non–PTH-mediated hypercalcemia includes the following:
o Hypercalcemia associated with malignancy: Unlike PTH-mediated
hypercalcemia, the elevation of calcium that results from malignancy
generally worsens until therapy is provided. Hypercalcemia caused by
malignancy is the result of increased osteoclastic activity within the bone.
This results from one or both of the mechanisms that follow:
 Extensive localized bone destruction may result from osteolytic
metastasis of solid tumors. Evidence indicates that many malignant
cells may release local osteoclastic activating factors.
 Increased calcium levels resulting from malignancy caused by a
PTH-related protein is a second mechanism. This protein is a
humeral factor that acts on the skeleton to increase bone
reabsorption; it acts on the kidney to decrease excretion of
calcium. The gene that produces this protein is present in many
malignant tissues.
o Granulomatous disorders: High levels of calcitriol may be found in
patients with sarcoidosis and other granulomatous diseases. In these
disorders, the increased level of calcitriol results from production within
the macrophages, which constitute a large portion of some granulomas.
o Iatrogenic: In some cases, elevation of calcium is a known adverse effect
of appropriate dosage. In other cases, large ingestions must be taken to
induce the increase in calcium levels. Obtain a complete review of current
medications for patients presenting with hypercalcemia. Record any
vitamin use.
• Other causes of hypercalcemia
o Neoplasms (nonparathyroid) - Metastasis to the bone from breast, multiple
myeloma, and hematologic malignancies (Breast cancer is one of the most
common malignancies responsible for hypercalcemia.)
o Nonmetastatic (humoral-induced) - Ovary, kidney, lung, head and neck,
esophagus, cervix, lymphoproliferative disease, multiple endocrine
neoplasia, pheochromocytoma, and hepatoma
o Pharmacologic agents - Thiazide, calcium carbonate (antacid),
hypervitaminosis D, hypervitaminosis A, lithium, milk-alkali syndrome,
and theophylline toxicity
o Endocrinopathies (nonparathyroid) -Hyperthyroidism, adrenal
insufficiency, and pheochromocytoma
o Familial hypocalciuric hypercalcemia
o Tertiary hyperparathyroidism -Postrenal transplant and initiation of
chronic hemodialysis
o Miscellaneous - Immobilization, hypophosphatasia, primary infantile
hyperparathyroidism, AIDS, and advanced chronic liver disease
Differential Diagnoses
HIV Infection and AIDSToxicity, Theophylline
Hyperparathyroidism Toxicity, Thyroid
Hormone
Malignancy Toxicity, Vitamin
Sarcoidosis Tuberculosis
Toxicity, Lithium
Toxicity, Salicylate
Other Problems to Be Considered
Pheochromocytoma
Immobilization
Addison disease
Inflammatory disorders
Rhabdomyolysis
Paget disease
Parenteral nutrition
Workup
Laboratory Studies
• Confirmatory tests: Changes in serum protein concentrations alter the total serum
calcium level but do not affect the unbound fraction. Calcium level reported by
the laboratory usually represents the bound and unbound calcium. When calcium
levels are reported as high or low, the physician must be able to calculate the
actual level of calcium. A common formula is as follows:
Corrected total calcium (mg/dL) = (measured total calcium mg/dL) + 0.8

(4.4 - measured albumin g/dL)
The average normal albumin level is 4.4. The reference range for corrected value
of calcium is approximately 9-10.6 mg/dL.
o The corrected calcium value is useful in most situations, but individual

variation can occur.
o If the corrected serum calcium level still is not accurate, it is possible to
measure the free calcium ion activity (ie, ionized calcium level).
• Other nonspecific laboratory abnormalities commonly found in patients with
hypercalcemia result from disordered renal function. Patients commonly have
significant azotemia at presentation.
• Hypercalcemia may produce ECG abnormalities related to altered trans-
membrane potentials that affect conduction time. QT interval shortening is
common, and, in some cases, the PR interval is prolonged. At very high levels,
the QRS interval may lengthen, T waves may flatten or invert, and a variable
degree of heart block may develop. Digoxin effects are amplified.
• After a diagnosis of hypercalcemia is established, the next step is to determine the
cause. Initial testing is directed at malignancy, hyperparathyroidism, and
hyperthyroidism, the most common causes of hypercalcemia.
o The measurement of circulating PTH in the serum is the most direct and
sensitive measure of parathyroid function. A reference range is 2-6 mol/L.
A nonsuppressed PTH level in the presence of hypercalcemia suggests a
diagnosis of primary hyperparathyroidism. If the PTH level is suppressed
in the face of an elevated calcium level, hyperparathyroidism is unlikely.
o Parathyroid hormone-related peptide (PTHrP) is thought to mediate the
hypercalcemia that develops with many malignancies. Assays to measure
this peptide are available.6
o Measurement of calcitriol is difficult but can be accomplished. This
laboratory value is useful in diagnosing hypercalcemia secondary to a
granulomatous disease such as sarcoidosis.
o Other electrolytes also may be disturbed in hypercalcemia. Serum
phosphate levels tend to be low or normal in primary hyperparathyroidism
and hypercalcemia of malignancy. Phospate levels are elevated in
hypercalcemia secondary to vitamin D–related disorders or thyrotoxicosis.
Serum chloride levels usually are higher than 102 mEq/L in
hyperparathyroidism and less than this value in other forms of
hypercalcemia.
Imaging Studies
• No imaging studies definitively diagnose hypercalcemia.

• Consider hypercalcemia in patients with multiple nonspecific complaints and an
associated lung mass.
• If laboratory evidence of primary hyperparathyroidism is present, CT scan of the
head, MRI, ultrasound, or nuclear parathyroid scans may be helpful. Preoperative
diagnostic imaging is essential in patients with previous neck surgery.
Treatment
Prehospital Care
Prehospital care is primarily supportive with management of the ABCs. If a patient has a
history of hypercalcemia and displays evidence of acute hypercalcemia, immediately
begin IV hydration.
The treatment of hypercalcemia depends on the level, the chronicity, and the underlying
cause of the problem. In mild-to-moderate elevations of calcium, few treatment options
may be available in the ED. A physical evaluation to help delineate the source of the
elevation is always appropriate, as is a subsequent timely follow-up visit.
• Initial goals of treatment

o Stabilization and reduction of the calcium level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Discontinuation of pharmacologic agents associated with hypercalcemia
o Treatment of the underlying cause (when possible)
• The initial step in the care of severely hypercalcemic patients is hydration with
saline. Most of these patients are profoundly dehydrated. Hydration helps
decrease the calcium level through dilution. The expansion of extracellular
volume also increases the renal calcium clearance. The rate of fluid therapy is
based upon the following:
o Degree of hypercalcemia
o Severity of dehydration
o Ability of the patient to tolerate rehydration - Vigilance to prevent volume
overload is critical.
o Hydration is ineffective in patients with kidney failure because diuresis is
impossible. Dialysis is necessary to correct hypercalcemia in patients with
renal failure.
• Loop diuretics
o A loop diuretic (eg, furosemide) may be used with hydration to increase
calcium excretion. This may also prevent volume overload during therapy.
o In contrast to loop diuretics, avoid thiazide diuretics because they increase
the reabsorption of calcium.
• Bisphosphates - These agents will inhibit osteoclast activity for up to a month.
Consultations
• Patients with renal failure or heart failure may not be able to tolerate fluid
hydration or some of the other medications. Patients in this group who present
with severe elevations of calcium may require urgent dialysis. Consult a
nephrologist immediately in such cases.
• Patients with primary hyperparathyroidism may require surgery to eliminate the
condition,7 but surgery usually does not need to be performed on an urgent basis.
• Patients with malignancy may require surgery, chemotherapy, or radiation
treatment. Appropriate consultation should be undertaken.
Medication
Several classifications of medications are used to treat elevations of serum calcium. Some
can be used in acute life-threatening elevations, while others are used to help control
calcium elevations after the acute event has been treated. Agents that help treat
hypercalcemia include plicamycin (also known as Mithracin), calcitonin, gallium nitrate,
intravenous phosphate, bisphosphates, and glucocorticoids.
Bisphosphonates
These compounds are analogs of pyrophosphate that act by binding to hydroxyapatite in

bone matrix, thereby inhibiting the dissolution of crystals. These agents prevent
osteoclast attachment to bone matrix and interfere with osteoclast recruitment and
viability.
Pamidronate (Aredia)
Mechanism of action is inhibition of normal and abnormal bone resorption; appears to

inhibit bone resorption without inhibiting bone formation and mineralization. Potent
agent that has several regimens for administration. Adverse effects of IV administration
include mild transient increases in temperature, leukopenia, and mild reduction in serum
phosphate levels. PO maintenance therapy is available after acute event has resolved, but
this therapy is experimental. With acute hypercalcemia, all of these agents are effective;
pamidronate may be preferable because of its potency and efficacy.
• Dosing
• Interactions
• Precautions
Adult
Moderate hypercalcemia: 60 mg IV infusion over 4 h initial; alternatively, 90 mg IV

infusion over 24 h initial
Severe hypercalcemia: 90 mg IV infusion over 24 h initial
Pediatric
Not established
• Dosing
• Interactions
• Precautions
None reported
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; hypocalcemia
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Monitor hypercalcemia-related parameters, such as serum levels of calcium, phosphate,

magnesium, and potassium once treatment begins; adequate intake of calcium and
vitamin D is necessary to prevent severe hypocalcemia; caution when administering
bisphosphonates in active upper GI problems; do not coadminister with alendronate for
osteoporosis in postmenopausal women
Zoledronic acid (Zometa)
Inhibits bone resorption, possibly by acting on osteoclasts or osteoclast precursors.

Median duration of complete response (maintaining normalized calcium levels) and time
to relapse reported as 32 and 30 d, respectively. Indicated for hypercalcemia of
malignancy.
• Dosing
• Interactions
• Precautions
Adult
4 mg IV over at least 15 min once qmo; hydrate patient before infusion; may retreat
following 7 d if desired response not observed
Pediatric
Not established
• Dosing
• Interactions
• Precautions
Concurrent administration with loop diuretics may increase risk of hypocalcemia,

nephrotoxic agents; valacyclovir levels may be increased
• Dosing
• Interactions
• Precautions
Documented hypersensitivity
• Dosing
• Interactions
• Precautions
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal insufficiency; risk of renal deterioration increased with <15 min IV
infusion; flulike syndrome (fever, arthralgias, myalgias, skeletal pain), gastrointestinal
reactions, anemia, neutropenia, pancytopenia, insomnia, dyspnea, electrolyte and mineral
disturbances, such as low serum phosphate, calcium, magnesium, and potassium may
occur
Etidronate (Didronel)
Reduces bone formation; does not appear to alter renal tubular reabsorption of calcium.
Does not affect hypercalcemia in patients with hyperparathyroidism where increased
calcium reabsorption may increase blood calcium levels. Response generally observed
within first 48 h; more effective if patient is well hydrated before initial dose. If patient
responds well before 7 d, therapy can be discontinued. Generally well tolerated; most
common adverse effect is a transient elevation of serum creatinine and phosphorous. PO
therapy is experimental and not always effective.
• Dosing
• Interactions
• Precautions
Adult
7.5 mg/kg IV over 4 h for 3-7 d; dilute in at least 250 mL of sterile saline; use beyond 3 d
may increase risk of hypocalcemia; full initial doses may be used in repeat dosing
situations if etidronate has not been used in previous 7 d
Pediatric
Not established
• Dosing
• Interactions
• Precautions
Coadministration with calcium-containing products and other multivalent cations

decrease absorption
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; hypocalcemia; renal impairment
• Dosing
• Interactions
• Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in
animals
Precautions
Monitor hypercalcemia-related parameters (eg, serum levels of calcium, phosphate,

magnesium and potassium); maintain adequate intake of calcium and vitamin D to
prevent severe hypocalcemia; caution in active upper GI problems; do not administer
with alendronate for osteoporosis in postmenopausal women
Antidote, Hypercalcemia
Inhibit RNA synthesis in osteoclasts and effective in treatment of hypercalcemia.
Calcitonin (Miacalcin, Cibacalcin, Calcimar)
A naturally occurring hormone that inhibits bone reabsorption and increases excretion of
calcium. Most rapid onset of action of anticalcemic agents. Effects may be observed
within a few hours with peak response at 12-24 h; because of short duration of action,
other more potent but slower-acting agents should be started in patients with severe
hypercalcemia. Salmon calcitonin is used most often and is more potent than human
calcitonin. Action of this agent is short-lived. If elevation of calcium is severe,
coadminister 1-2 doses with fluids and Lasix to provide a rapid, although limited,
reduction of the calcium level.
• Dosing
• Interactions
• Precautions
Adult
2-8 U/kg IM/SC q6-12h
Pediatric
Not established
• Dosing
• Interactions
• Precautions
None reported
• Dosing
• Interactions
• Precautions
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Hypocalcemia may occur; examine urine sediment during prolonged therapy

Effective in only 60-70% of patients and tachyphylaxis will usually develop in 48-72 h
Gallium nitrate (Ganite)
Works by inhibiting bone reabsorption and altering structure of bone crystals.

Exerts hypocalcemic effect, possibly by reducing bone resorption; performs well against
other anticalcium agents but has slow onset of action.
• Dosing
• Interactions
• Precautions
Adult
Severe hypercalcemia: 200 mg/m2/d IV for 5 d in 1 L of NS or D5W

Mild hypercalcemia: 100 mg/m2/d IV for 5 d in 1 L of NS or D5W
Pediatric
Not established
• Dosing
• Interactions
• Precautions
Nephrotoxic effects increase when administered with amphotericin B or aminoglycosides
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; renal failure
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Caution in renal failure
Plicamycin
No longer manufactured and distributed in the United States. Inhibits cellular ribonucleic
acid (RNA) and enzymatic RNA synthesis. Possibly blocks hypercalcemic action of
pharmacologic doses of vitamin D and may act on osteoclasts or block action of
parathyroid hormone. Effect in lowering calcium is not related to tumoricidal activity.
• Dosing
• Interactions
• Precautions
Adult
25 mcg/kg/d IV for 3-4 d

Alternatively, 25 mcg/kg IV once and repeat in 48 h if no response
Alternatively, 25-50 mcg/kg/dose IV qod for 3-8 doses
Pediatric
Not established
• Dosing
• Interactions
• Precautions
Coadministration with glucagon, calcitonin, and etidronate, may increase toxicity
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; thrombocytopenia, coagulation disorders, impairment of

bone marrow function
• Dosing
• Interactions
• Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor platelets, prothrombin and bleeding times periodically during therapy and for
several days after last dose; discontinue therapy if significant prolongation of bleeding
times occurs and thrombocytopenia is observed; correct any electrolyte imbalance
(especially hypokalemia, hypocalcemia, and hypophosphatemia) prior to treatment
Phosphate salts
Use of IV phosphate is very effective in lowering serum calcium levels most likely
because of a precipitation phenomenon. Significant risk exists with use of this agent. This
agent is reserved for hypercalcemia unresponsive to other agents.
Potassium phosphate
IV preparations are available as sodium or potassium phosphate (K2 PO4). Response to IV

serum phosphorus supplementation is highly variable and is associated with
hyperphosphatemia.
• Dosing
• Interactions
• Precautions
Adult
Initial: 8 mmol IV q6h (32 mmol/24 h)

Aggressive: 15 mmol IV over 6 h
Pediatric
0.25-0.5 mmol/kg IV over 4-6 h; repeat prn
• Dosing
• Interactions
• Precautions
Magnesium and aluminum-containing antacids or sucralfate can act as phosphate binders

and decrease serum phosphate levels; potassium-sparing diuretics, ACE inhibitors, and
salt substitutes may increase serum phosphate levels
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; hyperphosphatemia; hypocalcemia; hypomagnesemia;
hyperkalemia; renal failure
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Caution in patients with renal insufficiency, and metabolic alkalosis; admixture of

phosphate and calcium in IV fluids can result in calcium phosphate precipitation
Corticosteroids
While these agents do not treat hypercalcemia directly, they are useful for treating
hypercalcemia caused by vitamin D toxicity, certain malignancies (eg, multiple myeloma,
lymphoma), sarcoidosis, and other granulomatous diseases. These agents generally are
not effective in patients with solid tumors or primary hyperparathyroidism. Several
different glucocorticoids may be used.
Hydrocortisone (Cortef)
Mineralocorticoid activity and glucocorticoid effects; onset of activity is rapid.

Significant number of adverse reactions for those on long-term steroids. In acute phase,
few severe reactions present.
• Dosing
• Interactions
• Precautions
Adult
200-300 mg IV for 3 d
Pediatric
10 mg/kg/d IV divided qid

• Dosing
• Interactions
• Precautions
Corticosteroid clearance may decrease with estrogens; may increase digitalis toxicity
secondary to hypokalemia
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; viral, fungal, or tubercular skin infections
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative

colitis, diabetes, and myasthenia gravis
Calcimimetic Agent
Binds to and modulates the parathyroid calcium-sensing receptor, increases sensitivity to

extracellular calcium, and reduces parathyroid hormone secretion.
Cinacalcet (Sensipar)
Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium

sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results
in concomitant serum calcium decrease. Indicated for hypercalcemia with parathyroid
carcinoma.
• Dosing
• Interactions
• Precautions
Adult
30 mg PO qd initially; titrate q2-4wk as needed to normalize calcium levels by sequential

doses of 30 mg bid, 60 mg bid, 90 mg bid, and 90 mg tid/qid
Take with meals or immediately following; do not crush, chew, or cut tabs
Pediatric
Not established
Follow-up
• Serum calcium level generally responds to fluids and Lasix; however, this therapy
has no effect on the principle pathologic process causing hypercalcemia.
Additional therapy must be added to the temporizing treatment described above.
• Treatment of the underlying disease must be addressed.
• Patients with primary hyperparathyroidism who present with symptoms of severe

or moderate elevations of calcium levels should be referred for
parathyroidectomy. This referral may be urgent, depending on the severity of the
hypercalcemia.
• Patients with mild-to-moderate elevations of calcium who have no symptoms may
be evaluated on an outpatient basis and usually are treated medically. For those
patients with malignancy as the cause of their hypercalcemia, a cure may not be
possible.
• The ideal scenario finds a treatable underlying cause for hypercalcemia and
allows the physician to attend to this primary process. If this is accomplished, the
patient may not need therapy for the hypercalcemia itself.
• The drug regimen most appropriate for each individual depends on the cause of
the elevation and usually is not managed by the ED physician.
• Patients may require ongoing treatment for calcium elevation.
• This type of treatment can be frustrating and difficult, and it is not always
successful.
Transfer
• Transfer may be considered in a number of situations.

o If a patient presents with severe hypercalcemia and renal failure,
emergency dialysis is necessary. Consider transfer if this is unavailable at
the initial treatment center.
o If no intensivist or physician familiar with the inpatient treatment of
hypercalcemia is available, consider transferring patients with normal
kidney function who are being treated for severe hypercalcemia.
• Avoid prolonged bedrest for patients known to have rapid bone turnover.
• Consider elective surgical procedures for patients with Paget disease after therapy
has been initiated for calcium elevation. Mobilize patients as quickly as possible
to minimize bone loss.
• Worsening hypercalcemia is common in patients with known metastatic disease
who are too ill to ambulate. This should be anticipated and treated before the
patient becomes symptomatic.
• Patients at risk for hypercalcemia should have scheduled appointments with
ongoing evaluation to monitor for development or progression of the disease.
• Avoid salt restriction, diuretics, and other causes of volume depletion and
dehydration in patients with active or potential hypercalcemia.
Prognosis
• The prognosis of patients with hypercalcemia depends upon the etiology of the
elevation.
o Prognosis is very poor with malignancy that has progressed into
development of hypercalcemia.
o Prognosis is excellent when the underlying cause is treatable and treatment
is initiated promptly.
Hyperkalemia
Author: David Garth, MD, Attending Physician, Department of Emergency Medicine,
Mary Washington Hospital
Updated: Jul 16, 2010
• Print This
• Email This
• Overview
• Follow-up
• Multimedia
• References
• Keywords
Significant BMD increases at the spine and hip

Postmenopausal osteoporosis treatment showed significant BMD increases.
Learn more
Introduction
Background
Hyperkalemia is a potentially life-threatening illness that can be difficult to diagnose

because of a paucity of distinctive signs and symptoms. The physician must be quick to
consider hyperkalemia in patients who are at risk for this disease process. Because
hyperkalemia can lead to sudden death from cardiac arrhythmias, any suggestion of
hyperkalemia requires an immediate ECG to ascertain whether electrocardiographic signs
of electrolyte imbalance are present.
Pathophysiology
Potassium is a major ion of the body. Nearly 98% of potassium is intracellular, with the
concentration gradient maintained by the sodium- and potassium-activated adenosine
triphosphatase (Na+/K+ –ATPase) pump. The ratio of intracellular to extracellular
potassium is important in determining the cellular membrane potential. Small changes in
the extracellular potassium level can have profound effects on the function of the
cardiovascular and neuromuscular systems. The normal potassium level is 3.5-5.0
mEq/L, and total body potassium stores are approximately 50 mEq/kg (3500 mEq in a
70-kg person).
Minute-to-minute levels of potassium are controlled by intracellular to extracellular

exchange, mostly by the sodium-potassium pump that is controlled by insulin and beta2
receptors. A balance of GI intake and renal potassium excretion achieves long-term
potassium balance.
Hyperkalemia is defined as a potassium level greater than 5.5 mEq/L.1 Ranges are as
follows:
• 5.5-6.0 mEq/L - Mild

• 6.1-7.0 mEq/L - Moderate
• 7.0 mEq/L and greater - Severe
Hyperkalemia results from the following:
• Decreased or impaired potassium excretion - As observed with acute or chronic

renal failure2 (most common), potassium-sparing diuretics, urinary obstruction,
sickle cell disease, Addison disease, and systemic lupus erythematosus (SLE)
• Additions of potassium into extracellular space - As observed with potassium
supplements (eg, PO/IV potassium, salt substitutes), rhabdomyolysis, and
hemolysis (eg, blood transfusions, burns, tumor lysis)
• Transmembrane shifts (ie, shifting potassium from the intracellular to
extracellular space) - As observed with acidosis and medication effects (eg, acute
digitalis toxicity, beta-blockers, succinylcholine)
• Factitious or pseudohyperkalemia - As observed with improper blood collection
(eg, ischemic blood draw from venipuncture technique), laboratory error,
leukocytosis, and thrombocytosis
Frequency
United States
Hyperkalemia is diagnosed in up to 8% of hospitalized patients.
Mortality/Morbidity
• The primary cause of morbidity and death is potassium's effect on cardiac

function.3
• The mortality rate can be as high as 67% if severe hyperkalemia is not treated
rapidly.4
Sex
The male-to-female ratio is 1:1.
Clinical
History
• Hyperkalemia can be difficult to diagnose clinically because complaints may be

vague. The history is most valuable in identifying conditions that may predispose
to hyperkalemia.
• Hyperkalemia frequently is discovered as an incidental laboratory finding.
• Cardiac and neurologic symptoms predominate.
• Patients may be asymptomatic or report the following:
o Generalized fatigue
o Weakness
o Paresthesias
o Paralysis
o Palpitations
• Hyperkalemia is suggested in any patient with a predisposition toward elevated
potassium level. Potential potassium level elevation is observed in the following:
o Acute or chronic renal failure, especially in patients who are on dialysis
o Trauma, including crush injuries (rhabdomyolysis), or burns
o Ingestion of foods high in potassium (eg, bananas, oranges, high-protein
diets, tomatoes, salt substitutes). This alone is not likely to cause clinically
significant hyperkalemia in most people; it is often a contributing factor to
an acute potassium elevation.
o Medications - Potassium supplements, potassium-sparing diuretics,
nonsteroidal anti-inflammatory drugs (NSAIDs), beta-blockers, digoxin,
succinylcholine, and digitalis glycoside
o Medication combinations (ie, spironolactone, ACE inhibitors)5
o Redistribution - Metabolic acidosis (diabetic ketoacidosis [DKA]),
catabolic states
Physical
• Evaluation of vital signs is essential to determine hemodynamic stability and

presence of cardiac arrhythmias related to the hyperkalemia.1
• Cardiac examination may reveal extrasystoles, pauses, or bradycardia.
• Neurologic examination may reveal diminished deep tendon reflexes or decreased
motor strength.
• In rare cases, muscular paralysis and hypoventilation may be observed.
• Search for the stigmata of renal failure, such as edema, skin changes, and dialysis
sites.
• Look for signs of trauma that could put the patient at risk for rhabdomyolysis.
Causes
• Pseudohyperkalemia
o Hemolysis (in laboratory tube) most common
o Thrombocytosis
o Leukocytosis
o Venipuncture technique (ie, ischemic blood draw from prolonged
tourniquet application)
• Redistribution
o Acidosis
o Insulin deficiency
o Beta-blocker drugs
o Acute digoxin intoxication or overdose
o Succinylcholine6
o Arginine hydrochloride
o Hyperkalemic familial periodic paralysis
• Excessive endogenous potassium load
o Hemolysis
o Rhabdomyolysis
o Internal hemorrhage
• Excessive exogenous potassium load
o Parenteral administration
o Excess in diet
o Potassium supplements
o Salt substitutes
• Diminished potassium excretion
o Decreased glomerular filtration rate (eg, acute or end-stage chronic renal
failure)
o Decreased mineral corticoid activity
o Defect in tubular secretion (eg, renal tubular acidosis II and IV)
o Drugs (eg, NSAIDs, cyclosporine, potassium-sparing diuretics)
• Laboratory error7
Hypocalcemia
Cardiac arrhythmias
Workup
Laboratory Studies
• Potassium level - The relationship between the serum potassium level and
symptoms is not consistent. For example, patients with a chronically elevated
potassium level may be asymptomatic at much higher levels than other patients.
The rapidity of change in the potassium level influences the symptoms observed
at various potassium levels.
• BUN and creatinine level - For evaluation of renal status
• Calcium level - If patient has renal failure (because hypocalcemia can exacerbate
cardiac rhythm disturbances)
• Glucose level - In patients with diabetes mellitus
• Digoxin level - If patient is on a digitalis medication
• Arterial or venous blood gas - If acidosis is suspected
• Urinalysis - If signs of renal insufficiency without an already known cause are
present (to look for evidence of glomerulonephritis)
Other Tests
• Continuous cardiac monitoring - Indicated for evaluation of rhythm disturbances

• ECG is essential and may be instrumental in diagnosing hyperkalemia in the
appropriate clinical setting. ECG changes have a sequential progression of effects,
which roughly correlate with the potassium level.
• ECG findings may be observed as follows:
o Early changes of hyperkalemia include peaked T waves, shortened QT
interval, and ST-segment depression (see Media files 1-2).
Peaked T waves in hyperkalemia.
[ CLOSE WINDOW ]

[ CLOSE WINDOW ]
o These changes are followed by bundle-branch blocks causing a widening

of the QRS complex, increases in the PR interval, and decreased
amplitude of the P wave (see Media files 3-4).
Widened QRS complexes in hyperkalemia.
[ CLOSE WINDOW ]
Widened QRS complexes in hyperkalemia.
Widened QRS complexes in a patient whose serum potassium level

was 7.8 mEq/L.
[ CLOSE WINDOW ]
Widened QRS complexes in a patient whose serum potassium level
was 7.8 mEq/L.
o These changes reverse with appropriate treatment (see Media file 5).
ECG of a patient with pretreatment potassium level of 7.8 mEq/L and

widened QRS complexes after receiving 1 ampule of calcium chloride.
Notice narrowing of QRS complexes and reduction of T waves.
[ CLOSE WINDOW ]
ECG of a patient with pretreatment potassium level of 7.8 mEq/L and
widened QRS complexes after receiving 1 ampule of calcium chloride.
Notice narrowing of QRS complexes and reduction of T waves.
o Without treatment, the P wave eventually disappears and the QRS

morphology widens to resemble a sine wave. Ventricular fibrillation or
asystole follows.
o ECG findings generally correlate with the potassium level, but potentially
life-threatening arrhythmias can occur without warning at almost any level
of hyperkalemia.
• Cortisol and aldosterone levels - To check for mineralocorticoid deficiency when
other causes are eliminated
Treatment
Prehospital Care
A patient with known hyperkalemia or a patient with renal failure with suspected
hyperkalemia should have intravenous access established and should be placed on a
cardiac monitor.8 In the presence of hypotension or marked QRS widening, intravenous
bicarbonate, calcium, and insulin given together with 50% dextrose may be appropriate
as discussed in Medication. Avoid calcium if digoxin toxicity is suspected. Magnesium
sulfate (2 g over 5 min) may be used alternatively in the face of digoxin-toxic cardiac
arrhythmias.

• Perform continuous ECG monitoring with frequent vital sign checks when
hyperkalemia is suspected or when laboratory values indicative of hyperkalemia
are received.
• Initial management includes assessment of the ABCs and prompt evaluation of
the patient's cardiac status with an ECG.
• Discontinue any potassium-sparing drugs or dietary potassium.
• If the hyperkalemia is severe (potassium >7.0 mEq/L) or if the patient is
symptomatic, begin treatment before diagnostic investigation of the underlying
cause.
o Individualize treatment based upon the patient's presentation, potassium
level, and ECG.
o Not all patients should receive every medication listed in Medication s.
Patients with mild hyperkalemia, for example, may need only excretion
enhancement.
• Some studies are emerging that suggest sodium polystyrene sulfonate (SPS), also
known as Kayexalate, may be unhelpful in hyperkalemia and may increase the
chance of colonic necrosis (especially when used with sorbitol).9
Consultations
Consult a nephrologist or the dialysis team for patients with either severe symptomatic
hyperkalemia or renal failure. Admit these patients to an ICU.
Medication
Direct treatment is aimed at stabilizing the myocardium, shifting potassium from the
extracellular environment to the intracellular compartment, and promoting the renal
excretion and GI loss of potassium.
These agents are used to treat hyperkalemia and to reduce the risk of ventricular
fibrillation caused by hyperkalemia. They act quickly and can be lifesaving, thus they are
the first-line treatment for severe hyperkalemia when the ECG shows significant
abnormalities (eg, widening of QRS interval, loss of P wave, cardiac arrhythmias).
Calcium usually is not indicated when the ECG shows only peaked T waves.
Calcium chloride or calcium gluconate (Kalcinate)
Calcium increases threshold potential, thus restoring normal gradient between threshold
potential and resting membrane potential, which is elevated abnormally in hyperkalemia.
One ampule of calcium chloride has approximately 3 times more calcium than calcium
gluconate. Onset of action is <5 min and lasts about 30-60 min. Doses should be titrated
with constant monitoring of ECG changes during administration; repeat dose if ECG
changes do not normalize within 3-5 min.
• Dosing
• Interactions
• Precautions
Adult
Calcium chloride: 5 mL of 10% sol IV over 2 min (stop infusion if bradycardia develops)
Calcium gluconate: 10 mL of 10% sol IV over 2 min (stop infusion if bradycardia
develops)
Pediatric
Calcium chloride: 0.2 mL/kg/dose of 10% sol IV over 5 min; not to exceed 5 mL (stop
infusion if bradycardia develops)
Calcium gluconate: 100 mg/kg (1 mL/kg) of 10% sol IV over 3-5 min; not to exceed 10
mL (stop infusion if bradycardia develops)
• Dosing
• Interactions
• Precautions

fluoroquinolones; antagonizes effects of verapamil; large intakes of dietary fiber may
decrease absorption and levels
• Dosing
• Interactions
• Precautions
Renal calculi; hypercalcemia; hypophosphatemia; renal or cardiac disease; digitalis

toxicity
• Dosing
• Interactions
• Precautions
Pregnancy
animals
Precautions
Caution in digitalized patients, respiratory failure, acidosis, or severe hyperphosphatemia
Antidotes
Insulin is administered with glucose to facilitate the uptake of glucose into the cell,
bringing potassium with it.
Dextrose (D-Glucose)
Glucose and insulin temporarily shift K+ into cells; effects occur within first 30 min of
administration.
• Dosing
• Interactions
• Precautions
Adult
1-2 amps D50W and 5-10 U regular insulin IV
Pediatric
0.5 g/kg (2 mL/kg) 25% dextrose solution with 0.1 U/kg regular insulin (1 U regular
insulin/5 g glucose) IV over 30 min
• Dosing
• Interactions
• Precautions
Caution when administering parenteral fluids to patients receiving corticosteroids or

corticotropin, especially if solution contains Na+ ions
• Dosing
• Interactions
• Precautions
Diabetic coma if blood glucose levels extremely high
Avoid in severely dehydrated patients, especially those with delirium tremens, hepatic
coma, or glucose-galactose malabsorption syndrome
Do not administer concentrated solution if intraspinal or intracranial hemorrhage is
present
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
May cause nausea, which also may occur with hypoglycemia; IV dextrose solutions may
result in dilution of serum electrolyte concentrations or overhydration when patient is
fluid overloaded; caution in patients suffering from congested states or pulmonary
edema; hypertonic dextrose given peripherally may cause thrombosis (administer instead
through central venous catheter); caution in subclinical diabetes mellitus or carbohydrate
intolerance; increased risk of inducing significant hyperglycemia or hyperosmolar
syndrome if solution administered rapidly, especially in patients with chronic uremia or
carbohydrate intolerance; concentrated solutions should not be administered SC or IM;
rates of dextrose infusion higher than 0.5 g/kg/h may produce glycosuria; at infusion rates
of 0.8 g/kg/h, incidence of glycosuria is 5%; monitor fluid balance, electrolyte
concentrations, and acid-base balance closely; dextrose administration may produce
vitamin B complex deficiency
Insulin (Humulin, Humalog, Novolin)
Stimulates cellular uptake of K+ within 20-30 min; administer glucose along with insulin
to prevent hypoglycemia (monitor blood glucose levels closely).
• Dosing
• Interactions
• Precautions
Adult
5-10 U regular insulin and 1-2 amps D50W IV bolus

Pediatric
0.5 g/kg (2 mL/kg) 25% dextrose solution with 0.1 U/kg regular insulin (1 U regular
insulin/5 g glucose) IV over 30 min
• Dosing
• Interactions
• Precautions
Medications that may decrease hypoglycemic effects of insulin include acetazolamide,

AIDS antivirals, asparaginase, phenytoin, nicotine, isoniazid, diltiazem, diuretics,
corticosteroids, thiazide diuretics, thyroid, estrogens, ethacrynic acid, calcitonin, oral
contraceptives, diazoxide, dobutamine phenothiazines, cyclophosphamide,
dextrothyroxine, lithium carbonate, epinephrine, morphine sulfate, and niacin
Medications that may increase hypoglycemic effects of insulin include calcium, ACE
inhibitors, alcohol, tetracyclines, beta-blockers, lithium carbonate, anabolic steroids,
pyridoxine, salicylates, MAOIs, mebendazole, sulfonamides, phenylbutazone,
chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and
sulfinpyrazone
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; hypoglycemia
• Dosing
• Interactions
• Precautions
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Hyperthyroidism may increase renal clearance of insulin and may increase dose of insulin
needed to treat hyperkalemia; hypothyroidism may delay insulin turnover, requiring less
insulin to treat hyperkalemia; monitor glucose levels carefully; dose adjustments may be
necessary in patients with renal and hepatic dysfunction
Alkalinizing agents
These agents increase the pH, which results in a temporary potassium shift from the
extracellular to the intracellular environment. These agents enhance the effectiveness of
insulin in patients with acidemia.
Sodium bicarbonate (Neut)
Bicarbonate ion neutralizes hydrogen ions and raises urinary and blood pH. Onset of
action within minutes, lasts approximately 15-30 min. Only likely to be efficacious if
underlying acidosis present. Monitor blood pH to avoid excess alkalosis.
Use 8.4% solution in adults and children, 4.2% solution in infants.
• Dosing
• Interactions
• Precautions
Adult
1 mEq/kg slow IV push or continuous IV drip; not to exceed 50-100 mEq
Pediatric
Infants: 0.5 mEq/kg IV over 5-10 min; repeat in 10 min prn (only use 4.2% sol, not 8.4%
sol used in older children and adults)
Children: 1-2 mEq/kg IV over 5-10 min; repeat in 10 min prn; monitor ABGs to avoid
arterial pH >7.55
• Dosing
• Interactions
• Precautions
Urinary alkalinization induced by increased sodium bicarbonate concentrations may

cause decreased levels of lithium, tetracyclines, chlorpropamide, methotrexate, and
salicylates; increases levels of amphetamines, pseudoephedrine, flecainide, anorexiants,
mecamylamine, ephedrine, quinidine, and quinine
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; alkalosis; hypernatremia; hypocalcemia; severe pulmonary

edema
• Dosing
• Interactions
• Precautions
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Use only to treat documented metabolic acidosis and hyperkalemia-induced cardiac

arrest; can cause alkalosis, decreased plasma potassium, hypocalcemia, and
hypernatremia; caution in electrolyte imbalances such as those seen in patients with CHF,
cirrhosis, edema, corticosteroid use, or renal failure; avoid extravasation since can cause
tissue necrosis
Beta2-adrenergic agonists
These agents promote cellular reuptake of potassium, possibly via the cyclic gAMP
receptor cascade.
Albuterol (Ventolin, Proventil)
Adrenergic agonist that increases plasma insulin concentration, which may in turn help
shift K+ into intracellular space. Lowers K+ level by 0.5-1.5 mEq/L. Can be very
beneficial in patients with renal failure when fluid overload is concern. Onset of action is
30 min; duration of action is 2-3 h.
• Dosing
• Interactions
• Precautions
Adult
5 mg mixed with 3 mL isotonic saline via high-flow nebulizer q20min as tolerated
Pediatric
<1 year: 0.05-0.15 mg/kg/dose with 3 mL isotonic saline nebulized

1-5 years: 1.25-2.5 mg/dose with 3 mL isotonic saline nebulized
5-12 years: 2.5 mg/dose with 3 mL isotonic saline nebulized
>12 years: 2.5-5 mg/dose with 3 mL isotonic saline nebulized
• Dosing
• Interactions
• Precautions
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration

of bronchodilatation by albuterol; MAOIs, inhaled anesthetics, tricyclic antidepressants,
and sympathomimetic agents may increase cardiovascular effects
• Dosing
• Interactions
• Precautions
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders
Diuretics
These agents cause the loss of potassium through the kidney.
Furosemide (Lasix)
Effects are slow and frequently take an hour to begin. Lowers potassium level by
inconsistent amount. Large doses may be needed in renal failure.
• Dosing
• Interactions
• Precautions
Adult
20-40 mg IV push in patients not already on this drug

Double daily PO dose as IV slow push in patients already taking this drug
Pediatric
Neonates: 0.5-2 mg/kg/dose IV; not to exceed 2 mg/kg/dose

Infants and children: 0.5-2 mg/kg/dose IV; if response unsatisfactory, may increase by 1-
2 mg/kg q6-8h; not to exceed 6 mg/kg/dose
• Dosing
• Interactions
• Precautions
Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic

agents and antagonizes muscle-relaxing effect of tubocurarine; may increase auditory
toxicity of aminoglycosides, and hearing loss of varying degrees may occur; may
enhance anticoagulant activity of warfarin; may increase plasma levels and toxicity of
lithium
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; hepatic coma; anuria; severe electrolyte depletion
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Perform frequent serum electrolyte, CO2, glucose, creatinine, uric acid, calcium, and
BUN determinations during first few months of therapy and periodically thereafter
Ethacrynic acid (Edecrin)
Increases excretion of water by interfering with chloride-binding cotransport system,

which in turn inhibits sodium and chloride reabsorption in ascending loop of Henle and
distal renal tubule.
• Dosing
• Interactions
• Precautions
Adult
Oral: 25-400 mg qd or divided bid

Intravenous: 0.5-1 mg/kg/dose, may repeat q8-12h; not to exceed 100 mg/dose
Pediatric
Oral: 1 mg/kg qd, may increase gradually (q3d), not to exceed 3 mg/kg/d
Intravenous: 1 mg/kg/dose, may repeat q8-12h
• Dosing
• Interactions
• Precautions
May cause additive ototoxicity with aminoglycosides or cisplatin; increases hypotensive

effects of other diuretics or antihypertensives; may cause hypokalemia and increase
toxicity of digoxin; may increase anticoagulant effect of warfarin; increases lithium
serum levels
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion
• Dosing
• Interactions
• Precautions
Pregnancy
animals
Precautions
Caution with blood dyscrasias, liver, or kidney; monitor electrolytes, calcium, glucose,
uric acid, CO2, creatinine, and BUN levels
Binding resins
These agents promote exchange of potassium for sodium in GI system.
Sodium polystyrene sulfonate (Kayexalate)
Exchanges Na+ for K+ and binds it in gut, primarily in large intestine, decreasing total
body potassium. Onset of action after PO ranges from 2-12 h (longer when administered
rectally). Lowers K+ over 1-2 h with duration of action of 4-6 h. Potassium level drops by
approximately 0.5-1 mEq/L.
Multiple doses usually necessary.
• Dosing
• Interactions
• Precautions
Adult
25-50 g mixed with 100 mL of 20% sorbitol PO/PR
Pediatric
1 g/kg/dose PO/PR
• Dosing
• Interactions
• Precautions
Magnesium hydroxide, aluminum carbonate, or similar antacids or laxatives may cause

systemic alkalosis
• Dosing
• Interactions
• Precautions
Documented hypersensitivity; hypernatremia
• Dosing
• Interactions
• Precautions
Pregnancy
Precautions
Caution in patients who can be affected adversely by small increases in sodium loads,
such as those with severe hypertension, severe congestive heart failure, or marked edema;
constipation may occur, with possibility of fecal impaction—treat with 10-20 mL of 70%
sorbitol every 2 h or as necessary to produce at least 1-2 watery stools daily
Electrolytes
These agents have been successfully used in the treatment of acute SLOW released oral
potassium overdose.
Magnesium sulfate
Nutritional supplement in hyperalimentation; cofactor in enzyme systems involved in

neurochemical transmission and muscular excitability. In adults, 60-180 mEq of
potassium, 10-30 mEq of magnesium, and 10-40 mmol of phosphate per day may be
necessary for optimum metabolic response. Give IV for acute suppression of torsade.
Repeat doses are dependent upon continuing presence of patellar reflex and adequate
respiratory function.
• Dosing
• Interactions
• Precautions
Adult
1-2 g IV over 30-60 s, repeat in 5-15 min if necessary; alternatively, 3-10 mg/min IV
infusion
Pediatric
Not established
Follow-up
• Order continuous cardiac monitoring for patients who are hyperkalemic.

• Definitive therapy is dialysis in patients with renal failure or when pharmacologic
therapy is not sufficient. Any patient with significantly elevated potassium levels
should undergo dialysis, as pharmacologic therapy alone is not likely to
adequately bring down the potassium levels in a timely fashion.
• Monitor serial potassium levels.
• Resolve acid-base problems.
• Correct coexistent electrolyte disturbances.
• Treat digoxin toxicity, if present.
• Adjust diet to decrease potassium dietary load.

• Adjust medications that predispose to or exacerbate hyperkalemia.
• Repeat potassium level tests in 2-3 days.
• Reevaluate renal function if signs of renal insufficiency are present.
Transfer
• If unable to correct hyperkalemia with pharmacologic therapy and dialysis is

unavailable, stabilize the patient and transfer to a center where dialysis can be
performed.
• Avoid foods high in potassium.

• Avoid medications that predispose to hyperkalemia.
Complications
• Life-threatening cardiac arrhythmias may ensue.

• Hypokalemia may result from the treatment of hyperkalemia.
Prognosis
• Expect full resolution with correction of the underlying etiology.

• Reduction of plasma potassium should begin within the first hour of initiation of
treatment.
Patient Education
• Pursue diet modification.

• Discontinue use of medications that may worsen hyperkalemia.
• Encourage adherence to dialysis schedule if patient is noncompliant.
Miscellaneous
Medicolegal Pitfalls
• Ascertain whether the elevated potassium level is real or factitious. In a patient

who does not have a predisposition to hyperkalemia, repeat the blood test before
any actions are taken to bring down the potassium levels unless ECG changes are
present.
• Continuous ECG monitoring is essential if the patient is found to be
hyperkalemic.
• An ECG is essential to assess for cardiac conduction disturbances related to
hyperkalemia.
• Liability is associated with failure to order the ECG quickly or failure to
recognize and treat the condition based on the ECG. Severe hyperkalemia with
ECG changes is a life-threatening emergency. Intravenous calcium is the initial
treatment of choice to stabilize the cardiac membrane.
• Liability also can result from a delay in instituting definitive therapy after initial
successful stabilization of the patient's condition. Medications, such as calcium,
insulin, glucose, and sodium bicarbonate, are temporizing measures. Definitive
loss of excess potassium can be achieved only with resin-binding agents, dialysis,
or increased renal excretion. Begin administration of a resin-binding agent soon
after the other drugs have been administered.
• Watch for overcorrection of potassium level.
• Liability may result from failure to adjust therapy for concurrent conditions. For
example, in diabetic ketoacidosis (DKA) and in many other types of metabolic
acidosis, the extracellular potassium level is elevated, yet the patient may have a
total body deficit of potassium. Once the clinician initiates therapy for DKA, the
extracellular potassium level decreases spontaneously.
• If the patient is taking digoxin, look for evidence of digitalis toxicity.
Hypokalemia
Author: David Garth, MD, Attending Physician, Department of Emergency Medicine,
Mary Washington Hospital
Updated: Apr 2, 2010
• Print This
• Email This
• Overview
• Follow-up
• Multimedia
• References
• Keywords
A smart choice for bacterial RTIs and a strong position on the formularies Detailed
reimbursement information customized to your locality. Learn more
Introduction
Background
Potassium is one of the body's major ions. Nearly 98% of the body's potassium is
intracellular. The ratio of intracellular to extracellular potassium is important in
determining the cellular membrane potential. Small changes in the extracellular
potassium level can have profound effects on the function of the cardiovascular and
neuromuscular systems.1,2,3
The kidney determines potassium homeostasis, and excess potassium is excreted in the
urine.
The reference range for serum potassium level is 3.5-5 mEq/L, with total body potassium
stores of approximately 50 mEq/kg (ie, approximately 3500 mEq in a 70-kg person).
Hypokalemia is defined as a potassium level less than 3.5 mEq/L.
Moderate hypokalemia is a serum level of 2.5-3 mEq/L.
Severe hypokalemia is defined as a level less than 2.5 mEq/L.
Pathophysiology
Hypokalemia may result from conditions as varied as renal or GI losses, inadequate diet,
transcellular shift (movement of potassium from serum into cells), and medications.
Frequency
United States
As many as 20% of hospitalized patients are hypokalemic; however, hypokalemia is

clinically significant in only about 4-5% of these patients. Severe hypokalemia is
relatively uncommon.
Up to 14% of outpatients who undergo laboratory testing are found to be mildly

hypokalemic.
Approximately 80% of patients who are receiving diuretics become hypokalemic.
Sex
Incidence is equal in males and females.
Clinical
History
The history may be vague. Patients are often asymptomatic, particularly with mild
hypokalemia. Symptoms are often due to the underlying cause of the hypokalemia rather
than the hypokalemia itself. Hypokalemia should be suggested by a constellation of
symptoms that involve the GI, renal, musculoskeletal, cardiac, and nervous systems. The
patient's medications should be reviewed to ascertain whether any of them could cause
hypokalemia.
Common symptoms include the following:
• Palpitations
• Skeletal muscle weakness or cramping
• Paralysis, paresthesias
• Constipation4
• Nausea or vomiting
• Abdominal cramping
• Polyuria, nocturia, or polydipsia
• Psychosis, delirium, or hallucinations
• Depression
Physical
Findings that are consistent with severe hypokalemia may include the following:
• Signs of ileus
• Hypotension
• Ventricular arrhythmias5
• Cardiac arrest
• Bradycardia or tachycardia
• Premature atrial or ventricular beats
• Hypoventilation, respiratory distress
• Respiratory failure
• Lethargy or other mental status changes
• Decreased muscle strength, fasciculations, or tetany
• Decreased tendon reflexes
• Cushingoid appearance (eg, edema)
Causes
• Renal losses
o Renal tubular acidosis
o Hyperaldosteronism
o Magnesium depletion
o Leukemia (mechanism uncertain)
• GI losses (source may be medical or psychiatric6 , ie, anorexia or bulimia)
o Vomiting or nasogastric suctioning
o Diarrhea
o Enemas or laxative use
o Ileal loop
• Medication effects
o Diuretics (most common cause)
o Beta-adrenergic agonists
o Steroids
o Theophylline
o Aminoglycosides
• Transcellular shift
o Insulin
o Alkalosis
• Malnutrition or decreased dietary intake, parenteral nutrition
Cushing Syndrome
Hypocalcemia
Hypomagnesemia

Medication side effect
Renal tubular acidosis
Thyrotoxic hypokalemic periodic paralysis7
Workup
Laboratory Studies
• Serum potassium level <3.5 mEq/L (3.5 mmol/L)8

• BUN and creatinine level
• Glucose, calcium, and/or phosphorus level if coexistent electrolyte disturbances
are suspected.
• Magnesium levels are unreliable and typically do not change management, since
patients with hypokalemia almost always have coincident hypomagnesemia and
should be treated empirically.
• Consider digoxin level if the patient is on a digitalis preparation; hypokalemia can
potentiate digitalis-induced arrhythmias.
• Consider arterial blood gas (ABG): Alkalosis can cause potassium to shift from
extracellular to intracellular.
Imaging Studies
• CT scan of the adrenal glands is indicated if mineralocorticoid excess is evident

(rarely needed emergently).
Other Tests
• Electrocardiography
o T-wave flattening or inverted T waves
o Prominent U wave that appears as QT prolongation (see Media file 1)
o
Prominent U waves after T waves in hypokalemia.
[ CLOSE WINDOW ]
Prominent U waves after T waves in hypokalemia.
o ST-segment depression
o Ventricular arrhythmias (eg, premature ventricular contractions [PVCs],
torsade de pointes, ventricular fibrillation)5
o Atrial arrhythmias (eg, premature atrial contractions [PACs], atrial
fibrillation)
• Thyroid screening studies - Thyroid-stimulating hormone (TSH), free T3, and free
T4 in patients with tachycardia, especially Asian patients7
Treatment
Prehospital Care
• Be attentive to the ABCs.

• If the patient is severely bradycardic or manifesting cardiac arrhythmias,
appropriate pharmacologic therapy or cardiac pacing should be considered.
• Patients in whom severe hypokalemia is suspected should be placed on a cardiac

monitor; establish intravenous access and assess respiratory status.
• Direct potassium replacement therapy by the symptomatology and the potassium
level. Begin therapy after laboratory confirmation of the diagnosis.
• Patients who have mild or moderate hypokalemia (potassium level of 2.5-3.5
mEq/L) are usually asymptomatic; if these patients have only minor symptoms,
they may need only oral potassium replacement therapy. Patients with mild
hypokalemia whose underlying cause of hypokalemia can be corrected may not
need any potassium replacement, such as those with vomiting successfully treated
with antiemetics. If cardiac arrhythmias or significant symptoms are present, then
more aggressive therapy is warranted. This treatment is similar to the treatment of
severe hypokalemia.
• If the potassium level is less than 2.5 mEq/L, intravenous potassium should be
given. Admission or ED observation is indicated; replacement therapy takes more
than a few hours.
• The serum potassium level is difficult to replenish if the serum magnesium level
is also low. Look to replace both.
Consultations
An internist or a nephrologist should be consulted for admission or follow-up care.
Consider psychiatric consultation in laxative abuse, anorexia, or bulimia cases.9
Medication
Oral is the preferred route for potassium repletion because it is easy to administer, safe,
inexpensive, and readily absorbed from the GI tract. For patients with mild hypokalemia
and minimal symptoms, oral replacement is sufficient. For patients who have severe
hypokalemia and are symptomatic, both intravenous and oral replacement are necessary.
While intravenous potassium dosages of up to 40 mEq/h have been advocated, patients
should receive no more than 20 mEq/h IV to avoid potential deleterious effects on the
cardiac conduction system. Potassium solutions should never be given as an intravenous
push and should be administered as a dilute solution. Higher concentrations of
intravenous potassium are damaging to the smaller peripheral veins.
Potassium is essential for transmission of nerve impulses, contraction of cardiac muscle,

maintenance of intracellular tonicity, skeletal and smooth muscles, and maintenance of
normal renal function. These agents increase the body's potassium level. In general, 1
mEq/L drop in potassium correlates to a loss of 100-200 mEq of total body potassium.
Hypokalemia may result from the movement of potassium into cells without loss of
potassium from the body.
Potassium chloride (Klor-Con, K-Dur)
Potassium depletion sufficient to cause 1 mEq/L drop in serum potassium requires a loss
of about 100-200 mEq of potassium from total body store.
Available in liquid, powder, or tablet form. Any form may irritate the stomach and cause
vomiting. Should be taken with food or after meals to minimize GI discomfort.
Oral potassium preparations include 8 mEq KCI slow-release tablets, 20 mEq KCI elixir,
20 mEq KCI powder, 25 mEq KCI tablet.
In the symptomatic patient with severe hypokalemia, administer up to 40 mEq/h of the IV
preparation. Maintain close follow-up care, provide continuous ECG monitoring, and
check serial potassium levels.
Higher dosages may increase risk of cardiac complications. Many institutions have
policies that limit maximum amount of potassium that can be given per hour.
• Dosing
• Interactions
• Precautions
Adult
20-40 mEq PO bid/qid; not to exceed 40 mEq PO/dose

Alternatively, 10-20 mEq/h IV via peripheral or central line
Pediatric
1-4 mEq/kg/24 h PO divided bid/qid

Alternatively, 0.5-1 mEq/kg/dose over 1 h; not to exceed adult maximum dose
Follow-up
• Continue intravenous replacement of potassium as needed.

• Continue cardiac monitoring in severe hypokalemia.
• Repeat potassium level measurement every 1-3 hours.
• Identify the etiology of the hypokalemia.
• Repeat potassium level in 2-3 days.
Inpatient & Outpatient Medications
• Consider switching to potassium-sparing diuretic if diuretic therapy is needed.

• Take 40 mEq KCI daily for 2-3 days and repeat the potassium level.
Transfer
• Patients should be transferred only after any cardiac arrhythmias have been
treated and the condition has been stabilized.
• Depending on the level of hypokalemia, an advanced cardiac life support (ACLS)
ambulance should be used to allow continuous cardiac monitoring during
transport.
Complications
• Replacing potassium too quickly can cause a rapid rise in the blood potassium
level, leading to a relative hyperkalemia with subsequent cardiac complications.
• If hypokalemia is not corrected easily with replacement therapy, search for other
coexistent metabolic abnormalities (eg, hypomagnesemia). Hypokalemia may be
refractory to treatment until hypomagnesemia is corrected.
• Hypokalemia can potentiate digitalis toxicity in patients who are taking digoxin.
Prognosis
• Hypokalemia usually resolves with appropriate therapy.
Patient Education
• Diet modification is recommended for those patients who are predisposed to

hypokalemia. Increase intake of bananas, tomatoes, oranges, and peaches because
they are high in potassium.
• For excellent patient education resources, visit eMedicine's Endocrine System
Center. Also, see eMedicine's patient education article Low Potassium.
Miscellaneous
Medicolegal Pitfalls
• If potassium is replaced too quickly, the rapid rise of the serum potassium level
can induce symptomatic hyperkalemia; however, the total body reserves of
potassium might still be less than normal.
• Failure to monitor and repeat potassium levels during replacement therapy
• Failure to recognize and correct other coexistent metabolic disorders (eg,
hypomagnesemia)
Special Concerns
• Do not overcorrect potassium in patients with periodic hypokalemic paralysis.

This condition is a transcellular maldistribution, not a true deficit.
• Diuretic therapy, diarrhea, and chronic laxative abuse are the most common
causes of hypokalemia in elderly patients.
• In patients with hypokalemia and diabetic ketoacidosis, part of the serum
potassium should be administered as potassium phosphate.

Hypocalcemia: Author: Christopher B Beach, MD, FACEP, FAAEM, Associate Professor and Vice

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Hypocalcemia: Author: Christopher B Beach, MD, FACEP, FAAEM, Associate Professor and Vice

Uploaded by

Copyright:

Available Formats

Hypocalcemia

Updated: Mar 29, 2010

Information from Industry

Metabolic and endocrine emergencies require an understanding of normal physiology.

Calcium regulation is maintained by parathyroid hormone (PTH), vitamin D, and

Approximately 99% of calcium is found in bone, and 1% is found in extracellular fluid.

Homeostasis is maintained by an extracellular to intracellular gradient, which is largely

Intracellular calcium regulates cAMP-mediated messenger systems and most cell

Epidemiology of hypocalcemia versus other electrolyte abnormalities has not been

Similar standards exist in other industrialized nations throughout the world.

Severe, symptomatic hypocalcemia may result in cardiovascular collapse, hypotension

• Neurologic sequelae (eg, tetany, seizures) may occur.

The incidence in males and females is equal.

• The patient may complain of muscle cramping, shortness of breath secondary to

Neuromuscular and cardiovascular findings predominate. Neural hyperexcitability due to

• Dry skin and psoriasis (if long-term hypocalcemia)

The causes of hypocalcemia include hypoalbuminemia, hypomagnesemia,

• Hypoalbuminemia is the most common cause of hypocalcemia and is due to

• Symptomatic patients with classic clinical findings of acute hypocalcemia require

• Depending on the patient's clinical status and the suspected etiology of

• ECG and electrocardiographic monitoring should be obtained to rule out

Emergency Department Care

• Mild hypocalcemia (when symptoms are not life threatening)

Depending on the clinical situation, multiple consultations may be necessary, including

These agents are used to increase blood calcium levels.

Calcium citrate (Citracal)

Oral formulation usually used as supplementation to IV calcium therapy. Moderates

1-2 g PO divided bid/qid

45-65 mg/kg/d PO divided qid

May increase effect of quinidine; may decrease effects of tetracyclines, atenolol,

Documented hypersensitivity; hypercalcemia; hypophosphatemia; renal calculi; renal or

Moderates nerve and muscle performance by regulating action potential excitation

0.2 mL/kg/dose IV for patients in cardiac arrest

Documented hypersensitivity; ventricular fibrillation not associated with hyperkalemia;

Administer slowly (not to exceed 0.5-1 mL/min) to avoid extravasation; hypercalcemia

Calcium carbonate (Oystercal)

Used orally as supplementation to IV calcium therapy. Moderates nerve and muscle

1-2 g PO divided bid/qid

45-65 mg/kg/d PO divided qid

May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and

Documented hypersensitivity; renal calculi; hypercalcemia; hypophosphatemia; renal or

Caution in digitalized patients and respiratory failure or acidosis

Calcium gluconate (Kalcinate)

Useful in treating hypocalcemia. Moderate nerve and muscle performance by regulating

Parenteral: 1 mL (100 mg)/kg/dose IV continuous infusion over 24 h for patients not in

Documented hypersensitivity; renal calculi; hypercalcemia; hypophosphatemia; renal or

Adverse effects include hypertension, nausea, vomiting, flushing, and bradycardia;

• Care is determined by the probable underlying etiology of hypocalcemia.

Further Outpatient Care

• Although uncommon, outpatient evaluation by an endocrinologist or an internist

• Transfer should be considered when the etiology of hypocalcemia requires a

• Patients with diseases that predispose them to the development of hypocalcemia

• Prognosis is dependent on the etiology of hypocalcemia but is generally good.

Updated: Sep 1, 2010

Postmenopausal osteoporosis treatment

Hypercalcemia is a disorder that most commonly results from malignancy or primary

Plasma calcium is maintained within the reference range by a complex interplay of 3

For hypercalcemia to develop, the normal calcium regulation system must be

Hypercalcemia associated with malignancy commonly is the result of multiple myeloma,

Hypercalcemia is a fairly common metabolic emergency. Between 20 and 40% of

Primary hyperparathyroidism occurs in 25 per 100,000 persons in the general population

• Prognosis of hypercalcemia associated with malignancy is poor; the 1-year