Collapse All | Expand All

Volume I:
First Thirty Minutes
- Section 1
  Acute Care Algorithm/ Treatment Plans/ Acronyms
- Section 2
  Universal Approach
  - CALS Universal Approach To Emergency Advanced Life Support
- Section 3
  Steps 1-6
- Section 4
  Preliminary Impression/Focused Clinical Pathways
Volume II:
Resuscitation Procedures
Volume III:
Definitive Care

Endocrine and Metabolic 7:
Disorders of Electrolyte Concentration Portal

Hyperkalemia (an increase of serum potassium concentration above 5.5 mEq/L)

Causes of hyperkalemia

Technique/lab related falsely elevated values

Release of potassium from RBC hemolysis induced by poor blood drawing technique (narrow gauge needle; excessive shaking of sample).
Specimen drawn from an arm with IV potassium infusing.
Repeated fist clenching during phlebotomy causing release of potassium from arm muscles.
Leakage of potassium from RBCs if serum is not separated from the clot immediately (plasma potassium is normal).
Release of potassium from significant leukocytosis or thrombocytosis (plasma potassium is normal).

Shift of intracellular potassium to the extracellular fluid

Metabolic acidosis causes potassium to shift from intracellular to extracellular, with K+ being exchanged for H+ when the acidosis is due to accumulation of mineral acids such as NH4Cl or HCl. Hyperkalemia does not occur from metabolic acidosis due to organic acids such as lactic or keto acids. Rather, the hyperkalemia seen in diabetic ketoacidosis is due to insulin deficiency and the extracellular hypertonicity of hyperglycemia.
Massive release of intracellular potassium due to vigorous exercise, burns, hemolysis, GI bleeding, severe infection, rhabdomyolysis, acute tumor lysis.
Hyperkalemic periodic paralysis (usually precipitated by exercise).
Drugs: digitalis toxicity, beta blockers, succinylcholine, arginine.

Excess intake of potassium

Ingested or intravenous.

Decreased potassium excretion

Acute or chronic renal failure (especially patients on dialysis).
Other renal-related potassium disorders involving lupus, sickle cell disease, amyloidosis, interstitial nephritis, obstructive uropathy, renal transplants, and diabetic nephropathy (hyporenimic hypoaldosteronism).
Drugs along with chronic renal failure: NSAIDS, K-sparing diuretics, beta blockers, ACE inhibitors.
Heparin, lithium, trimethoprim, cyclosporine.
Hypoaldosteronism present in some AIDS patients.

Clinical findings of hyperkalemia
K+ is the major intracellular cation, a major determinant of intracellular osmolality, and a strong influence on cell membrane polarization, nerve conduction, and muscle contraction.

Cardiac toxicity is usually the first clinical sign – ECG changes, see below
Progressive muscle weakness > flaccid paralysis
Diminished reflexes
Abdominal distention
Diarrhea

ECG changes of hyperkalemia¹
In general, ECG changes worsen as the potassium level rises. However, lethal arrhythmias can occur at any elevated level, and not all patients with hyperkalemia have ECG changes, even at significant levels. Multiple rhythm disturbances are seen: bradycardia, PEA, VT, VF.
Morphologic ECG changes:

Early changes: peaked T waves, shortened QT interval, ST segment depression
Later changes: bundle branch block with widening of the QRS complex, increased PR interval, decreased P waves
Late changes: P wave disappearance and further QRS widening into a sine wave

Treatment of hyperkalemia
Treat the patient, not just the level. Be sure that the lab value is accurate. ECG and continuous cardiac monitoring is essential. Watch for over-correction.

Emergent treatment. Emergency methods are indicated if the patient has severe hyperkalemia (serum potassium > 6.5), cardiac toxicity, or muscle paralysis. The following methods (except calcium, which has a direct membrane stabilizing effect on the myocardium) rapidly decrease serum potassium levels by driving potassium intracellularly; they do not remove the potassium from the body. Give rapidly in this sequence:
- Use calcium IV first to address cardiac problems. (Calcium IV probably is not needed if the only ECG change is peaked T waves.) Calcium comes in two forms, calcium chloride (more concentrated, more irritating to tissue) and calcium gluconate. Effects are seen within 5 minutes, and last about 30 to 60 minutes. Calcium IV, acting as an antagonist, counteracts cardiac conduction abnormalities caused by hyperkalemia. Note that calcium is contraindicated in digitalis toxicity since it may worsen the arrhythmia. Monitor potassium levels as calcium IV can produce hypokalemic dysrhythmias in the non-digitalis toxic patient. Using continuous ECG monitoring, titrate doses. Stop the infusion if bradycardia develops. May repeat dose every 10 minutes if serious ECG changes do not normalize.

In hyperkalemic cardiac arrest: 10 cc of 10% calcium chloride rapid IV.
PEDS: Arrest dose unclear.

Non-arrest situations: 10% calcium chloride 5 to 10 mL IV over 5 to 10 minutes (not to exceed 1 mL/min) (10 mL = 1 g of calcium chloride = 273 mg or 13.9 mEq of elemental calcium) or 10% calcium gluconate 10 to 30 mL IV over 3 to 10 minutes (10 mL= 1 g of calcium gluconate = 98 mg of elemental calcium).
PEDS: 10% calcium chloride 0.2 mL/kg IV over 5 minutes or 10% calcium gluconate 1 mL/kg IV over 3 to 5 minutes.

Insulin IV is effective in shifting potassium into cells. Insulin IV is given with glucose to prevent hypoglycemia. The effect on potassium is seen in 15 to 30 minutes. Insulin is especially effective in uremic patients if used with nebulized albuterol.
Dose: Give 5 to 10 units of regular insulin plus 1 to 2 amps of D50 glucose IV over 5 to 10 minutes.
PEDS: 0.1 U/kg regular insulin along with 0.5 g/kg (2 mL/kg) D25 over 30 minutes. Further infusion at a ratio of 1 U regular insulin/5 g glucose (adult and PEDS) may be appropriate. Follow blood sugars closely.

Nebulized albuterol, a beta-2 agonist, helps to shift potassium into the cells. Give larger doses—up to 10 to 20 mg in 4 cc NS over 10 minutes. PEDS: Pediatric doses are adjusted according to patient’s age and weight. Onset of action is within 30 minutes with a duration of 2 to 4 hours. Serum potassium can be reduced by 0.5 to 1.0 mEq/L. Albuterol is especially effective for uremic patients. Note: The normal dose of nebulized albuterol is 2.5 mg per dose. Thus, if a nebulized dose of 10 to 20 mg is given, the patient must be closely observed for side effects such as hypertension, tachycardia, angina, or tremor.

Sodium bicarbonate IV used to be a mainstay in emergency hyperkalemia treatment. Its use is now controversial, with concerns of no efficacy and a serious side effect/complication profile.² Treatment of proven severe metabolic acidosis with hyperkalemia, especially arrest states, may be an indication.³ Dose: 1 mEq/kg of 8.4% bicarb solution, not to exceed 100 mEq, continuous IV drip (or slow IV push in arrest). PEDS: (Use the 4.2% bicarb solution): infants 0.5 mEq/kg over 5 to 10 min; children 1 to 2 mEq/kg over 5 to 10 min.

Continue with the appropriate potassium removal methods.

Less emergent methods. These methods remove excess potassium from the body, and therefore take longer to reduce serum potassium. They are used as necessary following critical emergent therapy or they may be added to emergent therapy or used by themselves if the need to reduce potassium is urgent but not emergent.
- Furosemide (a loop diuretic) acts by increasing potassium excretion by the kidney. Give furosemide 40 mg IV if the patient is not on the drug (if the patient is, double the daily PO dose and give IV). The effect starts within 30 minutes. PEDS: 0.5 to 2 mg/kg/dose.
- Sodium polystyrene sulfonate (Kayexalate) is a cation exchange resin. Administer aqueous Kayexalate 25 g to 50 g PO or PR. (PEDS: In smaller children and infants, give lower doses by using a rate of 1 mEq of potassium per gram of resin as a guide for calculation. Do not give PO in neonates.) This removes about 0.5 to 1.0 mEq of potassium per gram of Kayexalate given. Sodium overload may occur.
- Peritoneal or hemodialysis. These methods can remove 200 to 300 mEq of potassium in 48 hours.

Hypokalemia (a decrease in serum potassium below 3.5 mEq/L)

Causes of hypokalemia:

Inadequate potassium intake.
Increased shift of potassium into the cells caused by alkalosis, insulin, hypokalemic thyrotoxic periodic paralysis, familial periodic paralysis, beta agonists.
GI potassium loss caused by: vomiting, gastric suctioning, diarrhea, villous adenoma, or laxative abuse.
Renal potassium loss due to increased flow through the distal nephrons caused by: diuretic use (furosemide, thiazides, osmotic diuretics), or salt-losing nephropathy.
Renal potassium loss due to increased aldosterone effect caused by primary aldosteronism (Conn’s syndrome), secondary aldosteronism (heart failure or dehydration), excess licorice intake, renovascular hypertension, malignant hypertension, and various genetic mutations.
Renal potassium loss caused by various renal tubular diseases.
Renal potassium loss associated with hypomagnesemia from carbenicillin or penicillin use.
Other drug effects: steroids, aminoglycosides, theophylline.

Clinical findings of hypokalemia

Fatigue, muscle cramps, fasciculations, muscle weakness.
Constipation, cramping, or ileus due to the decrease in smooth muscle activity.
Altered mental status: depression, lethargy, psychosis, delirium, hallucinations are possible.
If the potassium is < 2.5 mEq/L: hyporeflexia, flaccid paralysis, respiratory failure (hypercapnia), and tetany may occur.
Variety of dysrhythmias. Note that hypokalemia can potentiate digitalis-induced arrhythmias.

ECG changes associated with hypokalemia

Prominent U waves (can appear as QT prolongation)
Flattened and broadened T waves
ST segment depression
Widening of the QRS
Prolongation of the QT interval
PACs, PVCs, atrial and ventricular tachyarrhythmias, 2nd and 3rd degree heart block

Treatment of hypokalemia

Therapy is begun after lab confirmation. Make sure the patient is making urine. In general, a 1 mEq/L serum drop in potassium represents a 100 to 200 mEq loss. Patients with periodic hypokalemia paralysis do not have a true deficit but rather a transcellular maldistribution; do not overcorrect them.
For mild hypokalemia and/or minimal symptoms or signs, numerous oral preparations are available.
For symptomatic and/or severe hypokalemia, potassium IV is needed. Avoid dextrose-containing solutions if possible (insulin stimulation). Never give potassium IV push. When potassium is given by peripheral IV line, the IV solution should not contain more than 40 mEq/L of potassium and should not be given faster than 40 mEq/h. Continuous ECG monitoring is needed when severe hypokalemia is treated with potassium IV. Monitor potassium levels.
PEDS: 0.5 to 1 mEq/kg/dose over 1 hour, not to exceed adult maximum dose of 40 mEq. Note: Oral/NG liquid K+ replacement can often supplement IV replacement therapy in severe cases of hypokalemia.
Refractory hypokalemia may be caused by hypomagnesemia and may require concomitant magnesium replacement to correct the low potassium.

Hypercalcemia
The definition varies depending on the type of calcium measured: total plasma Ca > 10.4 mg/dL; total serum Ca > 14 mg/dL; or ionized Ca > the lab’s reference value. (Ionized calcium is the best if the lab has the ion-specific technology to measure it. ‘Free’ Ca is physiologically active.) Note that a large part of Ca is bound with protein: to evaluate Ca properly, one must know the albumin level. Ca measurement should be corrected for changes in the patient’s albumin levels: Corrected total calcium = (measured total calcium) + 0.8 (4.4 – measured albumin).

Causes of hypercalcemia

Neoplastic disorders (several mechanisms): lung, kidney, ovary, breast, renal, multiple myeloma, and (rarely) lymphoma.
Primary hyperparathyroidism or secondary hyperparathyroidism (malabsorption, renal insufficiency).
Other endocrinopathies: hyperthyroidism, adrenal insufficiency, pheochromocytoma.
Other causes include: thiazide diuretic-induced hypercalcemia; sarcoidosis and other granulomatous diseases (TB, leprosy, histoplasmosis, others); immobilization; complications of renal transplantation; familial hypocalciuric hypercalcemia; Paget's disease of the bone; hypophosphatasia; increased intake or absorption of calcium as seen with milk-alkali syndrome, excess vitamin D intake, or excess vitamin A intake.

Clinical findings of hypercalcemia
Symptoms depend on the underlying cause, the health of the patient, and the chronicity of the hypercalcemia. They are nonspecific, and may include:

General: dehydration, weakness, polydipsia, fatigue, aches
GI: constipation, anorexia, nausea, vomiting, abdominal pain, ileus
Renal: polyuria, nocturia, kidney stones, azotemia
Neuro: depression, lethargy, psychosis; stupor or coma in severe cases
Cardiac: hypertension, arrhythmias

ECG changes associated with hypercalcemia

Shortened QT interval
Short and depressed ST segments
Widened or inverted T waves
In severe hypercalcemia, bundle branch blocks, heart block, and cardiac arrest may develop.

Treatment of hypercalcemia
Treatment goals include reduction and stabilization of high levels, adequate hydration, and identifying and treating the underlying cause. Monitor calcium, potassium, phosphate, and magnesium levels. Temporizing emergency treatment is discussed here:

Saline diuresis. Increasing sodium excretion increases calcium excretion. The NS bolus amount is large (1 to 2 liters) depending on the patient’s hemodynamic status. See Vol II—CIRC SKILLS 2 Central Venous Access, CIRC SKILLS 3 Central Venous Pressure Measurement. Follow with a rate of 200 to 500 mL/h. Dialysis is necessary in patients with renal failure.
Furosemide 20 to 40 mg IV every 2 h to enhance renal excretion of calcium by maintaining urine output at 200 to 300 mL/h. Also helps to prevent volume overload. PEDS: 1 mg/kg IV twice daily or more frequent prn.
Add synthetic salmon calcitonin if the patient has severe levels and symptoms. This works rapidly but is short lived. It may be synergistic with pamidronate. The usual dose is 2 to 8 U/kg IM/ SQ every 6 to 12 hours. PEDS: not established.
Bisphosphonates are potent inhibitors of osteoclast bone resorption. Pamidronate disodium (Aredia): 60 mg IV over 4 hours or 90 mg over 24 hours, along with adequate IV fluids. PEDS: not labeled for use; anecdotal use exists.
In refractory hypercalcemia, plicamycin IV 25 µg/kg/d given over 4 to 6 hours. PEDS: dose unknown. Monitor for renal, bone marrow, and hepatic toxicity.
Hydrocortisone 200 to 300 mg IV may be helpful in some cases. PEDS: 10 mg/kg/day divided twice daily.

Hypocalcemia
The definition varies depending on the type of calcium measured: total plasma Ca < 8.8 mg/dL; total serum Ca < 8.5 mg/dL; or ionized Ca < the lab’s reference value. (Ionized calcium is the best if the lab has the ion-specific technology to measure it. ‘Free’ Ca is physiologically active.) Note that part of Ca is bound with protein: to evaluate Ca properly, one must know the albumin level. Ca measurement should be corrected for changes in the patient’s albumin levels: Corrected total calcium = (measured total calcium) + 0.8 (4.4 – measured albumin)

Causes of hypocalcemia

Decreased absorption of calcium as occurs with vitamin D deficiency, malabsorption, hepatobiliary disease, short bowel syndrome.
Endocrine diseases such as hypoparathyroidism, pseudohypoparathyroidism, calcitonin secretion from medullary carcinoma of the thyroid, familial hypocalcemia.
Increased loss of calcium as occurs in renal and hepatic insufficiency and renal failure.
Physiologic causes of hypocalcemia include: hyperphosphatemia, magnesium depletion, anion chelation (eg, citrate in blood transfusions), enhanced protein binding, severe alkalosis (eg, acute anxiety causing hyperventilation can decrease ionized Ca without marked hypocalcemia).
Multifactorial causes: acute pancreatitis, rhabdomyolysis, sepsis, alcoholism.
Medication effects (multiple mechanisms): phenytoin, phenobarbital, rifampin, foscarnet, ethylene glycol, aminoglycosides, diuretic use, fluoride, cimetidine, cisplatin, glucagon, steroids, heparin, magnesium, theophylline, phosphates, norepinephrine, and drugs used in the treatment for hypercalcemia.
Factitious hypocalcemia: decreased serum albumin (free Ca concentration is normal).

Clinical findings of hypocalcemia
Hypocalcemic patients are often asymptomatic. Symptoms are due to disturbances in the cellular membrane potentials and are primarily manifestations of neuromuscular irritability:

Chvostek's sign: contraction of the facial muscles in response to tapping the facial nerve anterior to the ear
Trousseau's sign: carpal spasm that occurs after the brachial artery is occluded for 3 minutes with a BP cuff
Paresthesias of the extremities and lips
Abdominal pain
Muscle cramps
Depression, dementia, psychosis
Severe hypocalcemia: tetany, convulsions, laryngospasm severe enough to cause airway obstruction

ECG changes associated with hypocalcemia

Prolonged QT interval due to the lengthening of the ST segment
Bradycardia
Other arrhythmias: VT or torsades de pointes

Treatment of hypocalcemia
Only temporizing emergency treatment is discussed here. Severe hypocalcemia often occurs with other life threats that need concomitant treatment. Underlying causes of hypocalcemia need investigation and treatment. Monitor ionized Ca levels frequently (lab permitting) in severe hypocalcemia via arterial access. See Vol II—CIRC SKILLS 1 Arterial and Venous Catheter Insertion.

Calcium products:

10% (100 mg/mL) calcium chloride has 272 mg of elemental calcium in a 10 cc amp. It is more irritating and may affect pH. Calcium is the drug of choice in hypocalcemic arrest.
10% (100 mg/mL) calcium gluconate has 98 mg of elemental calcium in a 10 cc amp. PEDS: drug of choice in non-arrest conditions.

For hypocalcemic cardiac arrest, give 10 mL of 10% calcium chloride IV rapidly. PEDS: arrest dose unclear.
If the patient has seizures, tetany, or arrhythmias, put 100 to 300 mg of elemental calcium in 100 mL of D₅W and give IV over 5 to 10 minutes. Results may be dramatic but short lived (several hours). Consider the need for a calcium infusion: 200 to 1200 mg elemental Ca over 24 h. Monitor calcium levels at least every 4 h and adjust the infusion rate as needed. PEDS: 10 to 20 mg/kg elemental calcium over 5 to 10 minutes; if infusion is necessary, continue with 50 to 75 mg/kg/d over 24 hours with close monitoring of levels.
Normalizing serum magnesium helps to correct hypocalcemia. If tetany is due to hypomagnesemia, the response to Ca will be transient if any. Check mg level and, if low, give magnesium IV.

Hypernatremia (serum sodium > 145 mEq/L)
Na+ is the major determinant of plasma osmolality. Plasma osmolality is about equal to intracellular osmolality. Therefore, hypernatremia indicates plasma and intracellular hypertonicity/dehydration. Cellular membrane potentials are altered, and neurons are shrunken in hypernatremia. If the shrinkage is severe, intra-cranial bridging veins can stretch and tear, leading to subarachnoid hemorrhage.

Causes of hypernatremia
In general, hypernatremia is due to too much salt, too little water, or a combination of the two as a result of input or output problems. The thirst drive (input) usually takes care of increased tonicity, which is why those who depend on caretakers (the young and the old) for access to water tend to be the ones with hypernatremia.

It is helpful to clinically categorize hypernatremia by the patient’s volume status:

Euvolemic hypernatremia
Extrarenal losses: increased insensible losses (hyperventilation, sweating, etc.)
Renal losses: central (lack of anti-diuretic hormone production) and nephrogenic (lack of response to anti-diuretic hormone) diabetes insipidus.
Hypovolemic hypernatremia: (water deficit > sodium deficit)
Extrarenal losses: vomiting, diarrhea, large burns, fistulas.
Renal losses: diuretics, osmotic diuretics (mannitol), post-obstructive diuresis, renal disease.
Adipsic (decreased thirst): usually behavioral; rarely but possibly due to damage to the thirst center (hypothalamus).
Hypervolemic hypernatremia (sodium gains > water gains):
Hypertonic saline, sodium bicarb, salt ingestion, mineralocorticoid excess.

Clinical findings of hypernatremia

CNS effects: lethargy, irritability, coma, seizures
Musculoskeletal: spasticity, hyperreflexia, ataxia, tremors
Doughy skin
Dehydration, oliguria, and orthostatic hypotension are often delayed findings.

Treatment of hypernatremia
The initial tasks are restoring normal serum tonicity without complications, determining whether or not the increased tonicity did any damage (generally a head CT is indicated in severe hypernatremia), and finding and treating the underlying cause of hypernatremia.
Over vigorous rehydration/reduction of the serum sodium that is too rapid can cause cerebral edema, seizures, or coma. Correct it slowly over 48 to 72 hours. Serum sodium generally should not be reduced faster than 1 to 2 mEq/L/h. Correcting serum sodium slower if the hypernatremia is chronic. When possible, restore free water orally. Monitor inputs and outputs. Check serum Na+ frequently. Perform frequent neuro exams.

Euvolemic hypernatremia: water PO or hypotonic fluids IV (D₅W; D₅W ¼ NS).
Hypovolemic hypernatremia: stabilize vital signs/correct hemodynamics with isotonic saline (if necessary); then, replace the remaining free water deficit orally or with hypotonic saline.
Hypervolemic hypernatremia: excess sodium needs removal: use D5W and Lasix IV. Patients with acute renal failure need dialysis.

Traditional IV Fluid Management: calculate free water deficit, add insensible and ongoing losses, and give this volume over 48 hours, checking Na+ frequently.
Free water deficit = body weight in kilograms x % of total body water (TBW) x ([serum Na+/140] –1).

For % of TBW use these numbers: infants= 0.7; young men = 0.6; women and older men = 0.5; older women = 0.4.
Example: 50 kg elderly woman with a serum sodium of 168: 50 x 0.4 x [(168/140) – 1] = 4L. Add her estimated insensible losses of 400 mL in 48 h. 4.4 L/48 h = about 90 mL of free water/h over the next 48 hours.

Calculating the change in serum Na+ that occurs with one liter of IV fluid allows for estimation of sodium concentration change:⁴

change in serum sodium from 1 L IV fluid = ([Na] infused – [Na] serum)/ [TBW + 1])
Example: giving 1 L of D5W to a young man weighing 70 kg with serum Na of 160 would result in a reduction of serum sodium of: (0 – 160)/([60 x 0.6 ] + 1) = -4.32 mEq/L. Assuming no other losses during the next several hours, giving a liter of D₅W will bring the serum sodium down –4.32 mEq/L. Correcting at a rate no faster than 1 to 2 mEq/L/h will dictate giving the liter over 4 hours, or 250 mL/h: -4.32 mEq/L divided by 4 h will lower serum sodium 1.08 mEq/L/h.

Hyponatremia (serum sodium less than 130 mEq/L; an excess of water relative to solute)
Hyponatremia is significant when extracellular hypo-osmolarity promotes a shift of free water into the cells, causing cellular edema. This causes a problem when cells cannot expand as much as they are forced to, such as brain tissue in its un-giving bony box. Consequently, hyponatremic symptoms are primarily related to cerebral edema.
To determine the cause of hyponatremia, obtain serum and urine sodium, osmolality, creatinine, and urine specific gravity (SG). Fractional excretion (FE) of sodium is calculated: FE_Na = 100 x (urine Na/serum Na) ÷ (urine creatinine/serum creatinine). The patient’s values of these tests are compared to various patterns of known disease categories associated with hyponatremia.
The serum osmolality may be used to quickly assess how to approach and begin to treat your patient’s hyponatremia: is it isotonic, hypertonic, or hypotonic?

Causes of hyponatremia

Isotonic (serum osmolality of 280 to 295 mOsm/kg) hyponatremia is a pseudohyponatremia due to a marked increase in proteins or lipids in the blood that causes the sodium concentration in the total plasma volume to be decreased. The sodium concentration in the plasma water is normal (as determined by ion-specific electrodes) so the condition requires no treatment of the patient's sodium status

Hypertonic (serum osmolality > 295 mOsm/kg) hyponatremia occurs when water is osmotically drawn from the cells into the extracellular space, thus diluting the serum sodium. This is most commonly observed with hyperglycemia or after the infusion of an osmotically active substance like mannitol. This is true dilutional hyponatremia. The plasma sodium falls 1.6 mEq/L for every 100 mg/dL rise in glucose concentration from 200 to 400 mg/dL. The plasma sodium then falls 4 mEq/L for every 100 mg/dL rise in glucose concentration above 400 mg/dL. The treatment consists of treating the underlying condition(s) rather than treating the low sodium value per se.

Hypotonic (serum osmolality < 280 mOsm/kg) hyponatremia. This category is the one in which the low Na itself will be treated in one fashion or another, depending on which of the underlying disease states is causing the hyponatremia. In this category, it is useful to further categorize the hyponatremia by the patient’s clinical volume status: hypovolemic, hypervolemic, or euvolemic.

Hypovolemic hypotonic hyponatremia occurs when the loss of sodium is greater than the loss of body water, resulting in a decrease in extracellular fluid volume and a total body sodium deficiency. The body's attempt to maintain intravascular volume in the face of the forces depleting it results in a non-osmotic release of anti-diuretic hormone, which causes water retention by the kidneys but not enough in relation to the sodium lost. Causes of hypovolemic hypotonic hyponatremia are broken into two categories: renal and extrarenal losses of sodium and water.
- Conditions that cause renal salt loss (urine sodium greater than 20 mEq/L, increased FE_Na, decreased SG, variable U_osm): use of diuretics or ACE inhibitors, mineralocorticoid deficiency, ketonuria, osmotic diuresis, salt losing nephritis.
- Conditions that result in extrarenal salt loss (urine sodium less than 10 mEq/L, decreased FE_Na, increased SG, U_osm> 800): diarrhea, vomiting, third spacing of fluids, pancreatitis, traumatized muscles, burns
Hypervolemic hypotonic hyponatremia occurs with disorders associated with clinical edema. In these conditions, total body water and sodium are increased but the circulating plasma volume is sensed as being deficient by the baroreceptors so anti-diuretic hormone and angiotensin II are released, resulting in further retention of water and sodium, with the excess TBW > excess sodium, causing a dilutional hyponatremia.
- CHF, cirrhosis, and (rarely) the nephrotic syndrome are associated with urine sodium < 10 mEq/L, decreased FE_Na, increased SG, and highU_osm.
- Acute and chronic renal failure are associated with urine sodium > 20 mEq/L, increased FE_Na, decreased SG, and variable U_osm.
Euvolemic (normal volume) hypotonic hyponatremia is observed in many clinical situations. These include:
- Glucocorticoid deficiency/Addison’s disease
- Post-operative hyponatremia (non-osmotic anti-diuretic hormone release along with the patient receiving an excess of hypotonic IV fluids)
- Psychogenic polydipsia
- Hypothyroidism
- Endurance exercise hyponatremia (increased anti-diuretic hormone secretion along with a large amount of fluid ingestion)
- Drugs such as tricyclic antidepressants, SSRIs, haldol, carbamazepine, NSAIDs, cyclophosphamide, clofibrate, oxytocin, chlorpropamide
- Stress
- Syndrome of inappropriate anti-diuretic hormone secretion (SIADH). SIADH is defined as less than maximally dilute urine in the face of hyponatremia and hypo-osmolality. The diagnosis also relies on (1) euvolemia; (2) normal cardiac, liver, renal, thyroid, and adrenal function; and (3) absence of pain, emotional stress, or drugs that stimulate anti-diuretic hormone release. This abnormal anti-diuretic hormone release is seen in a myriad of disease states.
- CNS disorders: head trauma, strokes, psychosis, abscess, encephalitis, meningitis, brain tumors
- Pulmonary disorders: pneumonia, TB, abscess, positive pressure ventilation
- Malignancies: lung, duodenum, CNS, lymphoma, pancreas pain
- Lab findings include urine sodium > 20 mEq/L, normal FE_Na, increased SG, and variable U_osm. In SIADH, the U_osm is usually inappropriately high in relation to S_osm.

Clinical findings of hyponatremia
These usually do not occur until the serum sodium level is < 120 mEq/L, although the rate of decrease may be important also. Symptoms include a clouding of the sensorium with progression to frank coma and seizures. The cause of these symptoms can be cerebral edema, cerebellar tonsil herniation, or demyelinating lesions.

Treatment of hyponatremia:

General treatment considerations
Chronicity of the hyponatremia. Acute hyponatremia is less common than chronic, is associated with a history of free water ‘loading,’ and is an insult to which the brain in its skull has less time to compensate, leaving these patients at risk for herniation at relatively higher sodium levels such as just below 120 mEq/L. (If there are signs of herniation, see Vol I—STEP 3 Initial Survey.)

Chronic hyponatremic patients are more common, lack a history of free water ‘loading,’ and have had the time to initiate compensatory mechanisms that allow them to tolerate lower sodium levels before becoming symptomatic. However, they may be more susceptible to cerebral pontine myelinolysis and need their hyponatremia corrected more cautiously.

Rate and amount of serum sodium increase. A potentially serious complication with hyponatremia therapy can occur if the rate of correction is too rapid. An osmotically induced demyelination of CNS tissue can occur, leaving the patient with a permanent CNS injury called central pontine myelinolysis.
To avoid this complication, the initial goal is to bring the serum sodium up at a safe rate that abolishes the acute CNS problem(s); the goal is not to correct sodium to its normal range. Aggressive treatment is usually not indicated once the serum sodium concentration reaches this level. General treatment principles follow:

Initially, raise the sodium level enough to get out of danger. Usually this means either about a 4 to 6 mEq/L rise in serum sodium or reaching about the 120 to 125 mEq/L level.
Correct at a rate to relieve immediate danger(s). A suggested rate of serum sodium rise (note: this is not the IV rate) for asymptomatic patients is 0.5 mEq/L/h with a total rise of 10 to 12 mEq/L/day. A suggested rate of serum sodium rise for symptomatic patients is 1 to 2 mEq/L/h until symptoms abate, at which time the rate of increase in serum sodium can be reduced to 0.5 to 1 mEq/L/h with a total rise of < 12 mEq/L/day. The acutely hyponatremic patient who is actively seizing or has increased ICP/herniation is treated more rapidly until the life-threat abates, after which treatment rates are lowered.⁵

Asymptomatic versus symptomatic treatment. (See following page.)
Identify and treat the underlying clinical condition. Refer to appropriate resources once the patient is stable.

Treatment of asymptomatic hyponatremia

Hypovolemic hypotonic hyponatremia treatment: replace the lost volume with isotonic saline while carefully monitoring sodium levels to ensure correcting no faster than 0.5 mEq/L/h with replacement. Identify and treat the underlying condition.
Hypervolemic hypotonic hyponatremia treatment: restrict water to < 1 L per 24 hours, restrict sodium, and identify and treat the underlying condition. The careful use of diuretics may be indicated.
Evolemic hypotonic hyponatremia treatment: free water restriction (which can be quite restrictive in SIADH) along with identifying and treating the underlying clinical condition.

A middle therapeutic ground for patients who are asymptomatic but have significantly low level (serum sodium < 120 mEq/L) and are not responding to the listed therapies may be judicious use of 0.9% saline plus furosemide while attending to the rate of correction. Sodium and potassium losses are replaced as indicated in the following example.

Treatment of symptomatic hyponatremia
In cases where the sodium is depressed (acute < 120, chronic usually < 115) and the patient has serious CNS manifestations, IV hypertonic saline (3% NS, 513 mEq/L) is indicated along with furosemide IV. There are numerous ways to approach this. One protocol for giving saline plus furosemide for symptomatic but non-herniating/seizing hyponatremic patients is as follows:⁶

Estimate the patient’s total body water (TBW): weight in kilos x % body water. For % of TBW use these numbers: infants= 0.7, young men = 0.6, women and older men = 0.5, older women = 0.4.
Calculate the ‘therapeutic’ Na deficit (the deficit to the desired level of correction, not the physiologic/normal level): TBW x (desired Na - known Na)
For an IV infusion rate of 3% saline that will raise the serum Na about 1 mEq/L/h: (Na deficit)/(513 mEq/L) divided by 48 h.
Decide on initial starting rate for the patient using this calculation as baseline.
Use an infusion pump. Measure serum sodium at least every 2 hours to check rate of increase, and adjust IV rate accordingly. Give furosemide 0.5 to 1 mg/kg IV every 4 h. (PEDS: same)
Endpoints of using 3% NS: patient becomes asymptomatic, the serum level has reached the serum target of 120 mEq/L, or the serum level has been raised a total of 20 mEq/L.
For seizures/herniating: Raise the serum level about 4 to 6 mEq/L acutely over 1 hour to end the life threat. Calculate TBW and multiply it by 4 mEq/L to derive the correct mEq to give over 1 hour under close monitoring. Switch to the 1 mEq/L/h infusion rate when seizure/herniaton subsides.

Example: obtunded 70 kg elderly male with a serum sodium of 110.

TBW = 70 x 0.5 = 35 L
Na deficit = 35 x (120-110) = 350 mEq
1 mEq/L/h serum increase infusion rate of 3% saline: (350 mEq/513 mEq/L)/48 h = 0.014L/h = 14 mL/h.
Add furosemide 35 to 70 mg IV.

Example: seizing 70 kg elderly male with a serum sodium level of 110.

TBW = 70 x 0.5 = 35 L
35 L x 4mEq/L = 140 mEq over the first hour (which is roughly 250 cc of 3% saline [ie, 140 mEq/513 mEq/L = 0.273 L or 273 mL]) until seizure/herniation stops; then, lower the IV rate back to the amount that will give a 1 mEq/L/h rise in serum sodium.

Hypermagnesemia (serum level > 2.2 mEq/L; plasma > 2.1)

Causes of hypermagnesemia

Usually renal failure or renal failure with magnesium ingestion
Iatrogenic
Other: intestinal hypomotility, tumor lysis, rabdomyolysis, adrenal insufficiency, hypothyroidism, hypoparathyroidism, lithium intoxication, extracellular fluid contraction (DKA), milk-alkali syndrome

Clinical findings of hypermagnesemia

Nausea, vomiting, flushing
Decreased deep tendon reflexes, muscle weakness, flaccid paralysis, confusion/ mental obtundation with high levels
Note: hypermagnesmia is usually seen with other electrolyte abnormalities such as hyperkalemia or hypercalcemia.

ECG changes associated with hypermagnesemia

PR interval and QRS complexes are prolonged.
Peaked T waves, usually associated with concomitant hyperkalemia.

Treatment of hypermagnesemia

Dilution/excretion with IV fluid/diuretic therapy if kidney status is good: isotonic fluid 1 L with Lasix 20 to 80 mg IV. PEDS: 20 mL/kg isotonic fluid with Lasix 1 mg/kg.
Calcium is reserved for life-threatening symptoms/signs, such as respiratory depression or arrhythmias. Give elemental calcium 100 to 200 mg over 10 to 60 minutes. PEDS: 2 mg/kg elemental calcium over 10 to 60 minutes.
Patients with renal failure need hemodialysis or peritoneal dialysis.

Hypomagnesemia (serum level < 1.8 mEq/L; plasma < 1.4)

Causes of hypomagnesemia

Renal losses: associated with diuretic therapy (thiazide or loop diuretics), renal transplant, uncontrolled diabetes, hypercalcemia, cisplatin, primary aldosteronism, hyperthyroidism, hypoparathyroidism.
GI losses: decreased intake or absorption of magnesium associated with alcoholism, malnutrition, malabsorption syndromes, gastric suction, laxative abuse, chronic diarrhea.
Miscellaneous: increased lactation, certain pregnancies, extracellular fluid expansion, insulin.

Clinical findings of hypomagnesemia

Neuromuscular irritability: muscle cramps, tremors, jerks, weakness, hyperactive deep tendon reflexes, Trousseau and Chvostek signs, esophageal dysmotility.
Cardiac hyperexcitability: atrial and ventricular arrhythmias.
CNS hyperexcitability: irritability, depression, confusion, ataxia, vertigo, seizures.
Note: Hypomagnesemia also contributes to hypokalemia and hypocalcemia.

ECG changes associated with hypomagnesemia (nonspecific)

Prolonged QT interval with a long ST segment
Prolonged PR interval
Wide QRS complexes
Broad, flat T waves with precordial T wave inversion

Treatment of hypomagnesemia

PO treatment in mild cases without symptoms
Magnesium sulfate IV in severe and/or symptomatic cases: 1 to 4 g diluted in IV fluids over 30 to 60 minutes; IV push in life-threatening arrhythmias. PEDS: 25 to 50 mg/kg (up to 2 g) over 1 hour.
Hypomagnesemia associated with low potassium or calcium must be corrected to result in correction of the deficient potassium or calcium.

References

DuBose T Jr. Hyperkalemic hyperchloremic metabolic acidosis: Pathophysiologic insights. Kidney Int. 1997;51:591.
Halperin ML, Kamel KS. Potassium. Lancet. 1998;352:135.
Mandal AK. Hypokalemia and hyperkalemia. Med Clin North Am. 1997;81:611.
Gennari FJ. Hypokalemia. N Engl J Med. 1998;339:451.
Acker CG, et al. Hypokalemia in hospitalized patients: Causes, adequacy of treatment, and results of an attempt to improve physician compliance with published therapy guidelines. Arch Intern Med. 1998;158:917.
Palevaky PM, Bhagrath R, Greenberg A. Hypernatremia in hospitalized patients. Ann Intern Med. 1996;124.
Androgue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342:1493-1499.
Oster JR, Singer I. Hyponatremia, hyposmolality, and hypotonicity: tables and fables. Arch Intern Med. 1999;159:333-336.
Bushinsky DA, Monk RD. Electrolyte quintet: Calcium. Lancet. 1998;352:306-311.
Ziegler R. Hypercalcemic crisis. J Am Soc Nephrol. 2001;12 (suppl 17):S3-S9.
Reber P, Heath H. Hypocalcemic emergencies. Med Clin North Am. 1995;79:93-106.
Hamill-Ruth RJ, McGory R. Magnesium repletion and its effect on potassium homeostasis in critically ill adults: results of a double-blind, randomized, controlled trial. Crit Care Med. 1996;24:38.
Quamme GA. Renal magnesium handling: new insights into understanding old problems. Kidney Int. 1997;52.
Tosiello L. Hypomagnesemia and diabetes mellitus: a view of clinical implications. Arch Intern Med. 156:1143.
Sacchetti A, et al. ED hemodialysis for treatment of renal failure emergencies. Am J Emerg Med. 1999 May;17(3):305-307.
Commerford PJ, Lloyd EA. Arrhythmias in patients with drug toxicity, electrolyte, and endocrine disturbances. Med Clin North Am. 1984;68:1051-78.
Elkinton JR, Squires RD, Klingensmith WC Jr. Cation exchange resin in the treatment of congestive heart failure. I. Electrolyte exchanges during initial periods of resin therapy. Circulation. 1952;5:747-753.
McGowan CE, Saha S, Chu G, Resnick MB, Moss SF. Intestinal necrosis due to sodium polystyrene sulfonate (Kayexalate) in sorbitol. South Med J. 2009;102:493-497.

Endocrine and Metabolic 7:Disorders of Electrolyte Concentration Portal

References

Edition 13-October 2011

Endocrine and Metabolic 7:
Disorders of Electrolyte Concentration Portal