Circulation Atmegiso tmO Learn and live JOURNAL OF THE AMERICAN HEART ASSOCIATION Part 10.1: Life-Threatening Electrolyte Abnormalities Circulation 2005: 1 12: 121-125; originally published online Nov 28, 2005 DOI: 10.1161/CIRCULATIONAHA. 105.166563 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, Tx 72514 Copyright o 2005 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online ISSN:15244539 The online version of this article, along with updated information and services, is located on the world wide web at http://circ.ahajournals.org/cgi/content/full/112/24suppl/iv-121 Subscriptions: Information about subscribing to Circulation is online at http://circ.ahajournals.org/subsriptions/ Permissions: Permissions Rights Desk, Lippincott Williams Wilkins, 351 West Cam Street. Baltimore MD 21202-2436 Phone 410-5280-4050. Fax: 410-528-8550 En journalpermissions@lww.com Reprints: Information about reprints can be found online at http://www.Iww.com/static/html/reprints.html Downloaded from circ. ahajournals. org by on February 21, 2006
ISSN: 1524-4539 Copyright © 2005 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX DOI: 10.1161/CIRCULATIONAHA.105.166563 Circulation 2005;112;121-125; originally published online Nov 28, 2005; Part 10.1: Life-Threatening Electrolyte Abnormalities http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-121 located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/static/html/reprints.html Reprints: Information about reprints can be found online at journalpermissions@lww.com Street, Baltimore, MD 21202-2436. Phone 410-5280-4050. Fax: 410-528-8550. Email: Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, 351 West Camden http://circ.ahajournals.org/subsriptions/ Subscriptions: Information about subscribing to Circulation is online at Downloaded from circ.ahajournals.org by on February 21, 2006
Part 10.1: Life-Threatening Electrolyte Abnormalities E lectrolyte abnormalities are commonly associated with inflammatory agents). Additional treatment is based on the cardiovascular emergencies. These abnormalities may everity of the hyperkalemia and its clinical consequences cause or contribute to cardiac arrest and may hinder resusci- The following sequences list the treatments for hyperkalemi ative efforts. In some cases therapy for life-threatening in order of priority electrolyte disorders should be initiated before laboratory For mild elevation(5 to 6 mEq/L), remove potassium from results become available Potassium(K) 1. Diuretics: furosemide 40 to 80 mg Iy The magnitude of the potassium gradient across cell membranes 2. Resins: Kayexalate 15 to 30 g in 50 to 100 mL of 20% determines excitability of nerve and muscle cells, including the sorbitol either orally or by retention enema myocardium. Rapid or significant changes in the serum potas- sium concentration can have life-threatening consequen Evaluation of serum potassium must consider the effects of For moderate elevation (6 to 7 mEq/L), shift potassium intracellularly with changes in serum pH. When serum pH falls, serum potassium rises because potassium shifts from the cellular to the 1. Glucose plus insulin: mix 25 g(50 mL of Dso)glucose and 10 U regular insulin and give IV over 15 to 30 minutes because potassium shifts from the vascular space into the 2. Sodium bicarbonate: 50 mEq IV over 5 minutes(sodium cells. Effects of pH changes on serum potassium should be bicarbonate alone is less effective than glucose plus anticipated during therapy for hyperkalemia or hypokalemia insulin or nebulized albuterol, particularly for treatment of and during any therapy that may cause changes in serum pH tients with renal failure; it is best used in conjunction (eg, treatment of diabetic ketoacidosis) with these medications. 5) 3. Nebulized albuterol: 10 to 20 mg nebulized over 15 minutes hyperkalemia Although hyperkale defined as a serum potassium For severe elevation(7 mEq/L with toxic ECG changes), concentration >5 mEq/L, it is moderate(6 to 7 mEq/L)and severe(7 mEq/L) hyperkalemia that are life-threatening potassium from the body. Therapies that shift potassium will and require immediate therapy. Hyperkalemia is most com- act rapidly but they are temporary; if the serum potassium monly seen in patients with end-stage renal disease. Other rebounds you may need to repeat those therapies. In order of causes are listed in the Table. Many medications can contrib- priority, treatment includes the following ute to the development of hyperkalemia. Identification of potential causes of hyperkalemia will contribute to rapid identification and treatment TABLE. Common Causes of Hyperkalemia Signs and symptoms of hyperkalemia include weakness, endogenous Causes of ● Chronic renal failure electrocardiographic(ECG) changes suggest hyperkalemia Early findings include peaked T waves(tenting). As the Metabolic acidosis(eg, diabetic ketoacidosis) serum potassium rises further, flattened P waves, prolonged Pseudohypoaldosteronism type ll (also known as Gordons PR interval (first-degree heart block), widened QRS complex, syndrome; familial hyperkalemia and hypertension) deepened S waves, and merging of S and T waves can be seen Chemotherapy causing tumor lysis If hyperkalemia is left untreated, a sine-wave pattern, idio Muscle breakdown(rhabdomyolysis tricular rhythms, and asystolic cardiac arrest may develop Renal tubular acidosis Treatment of Hyperkalemia The treatment of hyperkalemia is determined by its severity Hypoaldosteronism(Addison's disease, hyporeninemia and the patients clinical condition. Stop sources of exoge- perkalemic periodic paralysis nous potassium administration(eg, consider supplements and ogenous Causes maintenance Iv fluids) and evaluate drugs that can increase Medications: K+-sparing diuretics, ACE inhibitors, nonsteroidal serum potassium(eg, potassium-sparing diuretics, angioten Iti-inflammatory drugs, potassium supplements, penicillin sin-converting enzyme [ACE] inhibitors, nonsteroidal anti- derivatives, succinylcholine, heparin therapy(especially in patients with other risk factors), B-blockers (Circulation. 2005: 112: IV-121-IV-125. ood administration (particularly with large transfusions of o 2005 American Heart Association This special supplement to Circulation is freely available at Diet(rarely the sole cause ), salt substitutes http://www.circulationaha.org udohyperkalemia(due to blood sar DOI: 10.1161/CIRCULATIONAHA. 105.166563 ite blood cell count, high platelets. 4 tumor osis syndrome, ⅣV12l
Part 10.1: Life-Threatening Electrolyte Abnormalities Electrolyte abnormalities are commonly associated with cardiovascular emergencies. These abnormalities may cause or contribute to cardiac arrest and may hinder resuscitative efforts. In some cases therapy for life-threatening electrolyte disorders should be initiated before laboratory results become available. Potassium (K) The magnitude of the potassium gradient across cell membranes determines excitability of nerve and muscle cells, including the myocardium. Rapid or significant changes in the serum potassium concentration can have life-threatening consequences. Evaluation of serum potassium must consider the effects of changes in serum pH. When serum pH falls, serum potassium rises because potassium shifts from the cellular to the vascular space. When serum pH rises, serum potassium falls because potassium shifts from the vascular space into the cells. Effects of pH changes on serum potassium should be anticipated during therapy for hyperkalemia or hypokalemia and during any therapy that may cause changes in serum pH (eg, treatment of diabetic ketoacidosis). Hyperkalemia Although hyperkalemia is defined as a serum potassium concentration 5 mEq/L, it is moderate (6 to 7 mEq/L) and severe (7 mEq/L) hyperkalemia that are life-threatening and require immediate therapy. Hyperkalemia is most commonly seen in patients with end-stage renal disease. Other causes are listed in the Table. Many medications can contribute to the development of hyperkalemia. Identification of potential causes of hyperkalemia will contribute to rapid identification and treatment.1–3 Signs and symptoms of hyperkalemia include weakness, ascending paralysis, and respiratory failure. A variety of electrocardiographic (ECG) changes suggest hyperkalemia. Early findings include peaked T waves (tenting). As the serum potassium rises further, flattened P waves, prolonged PR interval (first-degree heart block), widened QRS complex, deepened S waves, and merging of S and T waves can be seen. If hyperkalemia is left untreated, a sine-wave pattern, idioventricular rhythms, and asystolic cardiac arrest may develop. Treatment of Hyperkalemia The treatment of hyperkalemia is determined by its severity and the patient’s clinical condition. Stop sources of exogenous potassium administration (eg, consider supplements and maintenance IV fluids) and evaluate drugs that can increase serum potassium (eg, potassium-sparing diuretics, angiotensin-converting enzyme [ACE] inhibitors, nonsteroidal antiinflammatory agents). Additional treatment is based on the severity of the hyperkalemia and its clinical consequences. The following sequences list the treatments for hyperkalemia in order of priority. For mild elevation (5 to 6 mEq/L), remove potassium from the body with 1. Diuretics: furosemide 40 to 80 mg IV 2. Resins: Kayexalate 15 to 30 g in 50 to 100 mL of 20% sorbitol either orally or by retention enema For moderate elevation (6 to 7 mEq/L), shift potassium intracellularly with 1. Glucose plus insulin: mix 25 g (50 mL of D50) glucose and 10 U regular insulin and give IV over 15 to 30 minutes 2. Sodium bicarbonate: 50 mEq IV over 5 minutes (sodium bicarbonate alone is less effective than glucose plus insulin or nebulized albuterol, particularly for treatment of patients with renal failure; it is best used in conjunction with these medications4,5) 3. Nebulized albuterol: 10 to 20 mg nebulized over 15 minutes For severe elevation (7 mEq/L with toxic ECG changes), you need to shift potassium into the cells and eliminate potassium from the body. Therapies that shift potassium will act rapidly but they are temporary; if the serum potassium rebounds you may need to repeat those therapies. In order of priority, treatment includes the following: (Circulation. 2005;112:IV-121-IV-125.) © 2005 American Heart Association. This special supplement to Circulation is freely available at http://www.circulationaha.org DOI: 10.1161/CIRCULATIONAHA.105.166563 TABLE. Common Causes of Hyperkalemia Endogenous Causes ● Chronic renal failure ● Metabolic acidosis (eg, diabetic ketoacidosis) ● Pseudohypoaldosteronism type II (also known as Gordon’s syndrome; familial hyperkalemia and hypertension) ● Chemotherapy causing tumor lysis ● Muscle breakdown (rhabdomyolysis) ● Renal tubular acidosis ● Hemolysis ● Hypoaldosteronism (Addison’s disease, hyporeninemia) ● Hyperkalemic periodic paralysis Exogenous Causes ● Medications: K-sparing diuretics, ACE inhibitors, nonsteroidal anti-inflammatory drugs, potassium supplements, penicillin derivatives, succinylcholine, heparin therapy (especially in patients with other risk factors), -blockers ● Blood administration (particularly with large transfusions of older “bank” blood) ● Diet (rarely the sole cause), salt substitutes ● Pseudohyperkalemia (due to blood sampling or hemolysis, high white blood cell count, high platelets, tumor lysis syndrome) IV-121
lV-122 Circulation December 13. 2005 Shift potassium into cells patient's chart that rapid infusion is intentional in respons to life-threatening hypokalemia 1. Calcium chloride(10%): 500 to 1000 mg(5 to 10 mL)IV over 2 to 5 minutes to reduce the effects of potassium at the myocardial cell membrane (lowers risk of ventricular Sodium(Na) fibrillation [VFD) Sodium is the major intravascular ion that influences 2. Sodium bicarbonate: 50 mEq IV over 5 minutes(may be serum osmolality. An acute increase in serum sodium will less effective for patients with end-stage renal disease) produce an acute increase in serum osmolality: an acute 3. Glucose plus insulin: mix 25 g(50 mL of Dso) glucose and decrease in serum sodium will produce an acute fall in 10 U regular insulin and give IV over 15 to 30 minutes serum osmolality Nebulized albuterol: 10 to 20 nebulized over 15 Sodium concentration and osmolality in the intravascular and interstitial spaces equilibrate across the vascular mem- brane. Acute changes in serum sodium will produce free water shifts into and out of the vascular space until osmolality 5. Diuresis: furosemide 40 to 80 mg Iv 6. Kayexalate enema: 15 to 50 g plus sorbitol PO or per sodium will produce an acute shift of free water from the rectum vascular into the interstitial space and may cause cerebral edema. 8.9 An acute rise in serum sodium will produce an Hypokalemia acute shift of free water from the interstitial to the vascular Hypokalemia is defined as a serum potassium level 145 to 150 mEq/L. It may be caused by a primary gain in Symptoms of mild hypokalemia are weakness, fatigue, Na* or excess loss of water. Gains in sodium can result from paralysis, respiratory difficulty, constipation, paralytic il- hyperaldosteronism (excess mineralocorticoid), Cushings eus, and leg cramps; more severe hypokalemia will alter syndrome (excess glucocorticoid), or excessive hypertonic cardiac tissue excitability and conduction. Hypokalemia saline or sodium bicarbonate administration loss of free can produce ECG changes such as U waves, T-wave water can result from gastrointestinal losses or renal excretion flattening, and arrhythmias (especially if the patient is (eg, osmotic diuresis or diabetes insipidus) taking digoxin), particularly ventricular arrhythmia Hypernatremia may cause neurologic symptoms such as Pulseless electrical activity or asystole may develop altered mental status, weakness, irritability, focal neurologic Treatment of hypokalemia deficits, and even coma or seizures. The severity of symp- The treatment of hypokalemia consists of minimizing toms is determined by the speed and magnitude of the change further potassium loss and providing potassium replace- in serum sodium concentration. ment. IV administration of potassium is indicated when arrhythmia uas are present or hypokalemia is severe(potas- Treatment of Hypernatremia sium level of <2.5 mEq/L). Gradual correction of hypo- Treatment of hypernatremia includes reduction of ongoing kalemia is preferable to rapid correction unless the patient water losses(by treating the underlying cause) and correction is clinically unstable. of the water deficit. For stable, asymptomatic patients Administration of potassium may be empirical in emergent replacement of fluid by mouth or through a nasogastric tube onditions. When indicated. the maximum amount of Iv is effective and safe potassium replacement should be 10 to 20 mEg/h with In hypovolemic patients the extracellular fluid(ECF) continuous ECG monitoring during infusion. A more concen- volume is typically restored with normal saline or a 59 trated solution of potassium may be infused if a central line is dextrose in half-normal saline solution to prevent a rapid fall used, but the tip of the catheter used for the infusion should in the serum sodium concentration. Avoid Ds w because it not extend into the right atrium will reduce the serum sodium too rapidly. During rehydra- If cardiac arrest from hypokalemia is imminent(ie, mal ion, monitor serum sodium closely to ensure a gradual fall nant ventricular arrhythmias are present), rapid replacement (and prevent rapid fall) in serum sodium of potassium is required. Give an initial infusion of 10 mEq The quantity of water needed to correct hypernatremia can IV over 5 minutes; repeat once if needed. Document in the be calculated by using the following equation:
● Shift potassium into cells: 1. Calcium chloride (10%): 500 to 1000 mg (5 to 10 mL) IV over 2 to 5 minutes to reduce the effects of potassium at the myocardial cell membrane (lowers risk of ventricular fibrillation [VF]) 2. Sodium bicarbonate: 50 mEq IV over 5 minutes (may be less effective for patients with end-stage renal disease) 3. Glucose plus insulin: mix 25 g (50 mL of D50) glucose and 10 U regular insulin and give IV over 15 to 30 minutes 4. Nebulized albuterol: 10 to 20 mg nebulized over 15 minutes5–7 ● Promote potassium excretion: 5. Diuresis: furosemide 40 to 80 mg IV 6. Kayexalate enema: 15 to 50 g plus sorbitol PO or per rectum 7. Dialysis Hypokalemia Hypokalemia is defined as a serum potassium level 3.5 mEq/L. The most common causes of low serum potassium are gastrointestinal loss (diarrhea, laxatives), renal loss (hyperaldosteronism, severe hyperglycemia, potassiumdepleting diuretics, carbenicillin, sodium penicillin, amphotericin B), intracellular shift (alkalosis or a rise in pH), and malnutrition. The major consequences of severe hypokalemia result from its effects on nerves and muscles (including the heart). The myocardium is extremely sensitive to the effects of hypokalemia, particularly if the patient has coronary artery disease or is taking a digitalis derivative. Symptoms of mild hypokalemia are weakness, fatigue, paralysis, respiratory difficulty, constipation, paralytic ileus, and leg cramps; more severe hypokalemia will alter cardiac tissue excitability and conduction. Hypokalemia can produce ECG changes such as U waves, T-wave flattening, and arrhythmias (especially if the patient is taking digoxin), particularly ventricular arrhythmias. Pulseless electrical activity or asystole may develop. Treatment of Hypokalemia The treatment of hypokalemia consists of minimizing further potassium loss and providing potassium replacement. IV administration of potassium is indicated when arrhythmias are present or hypokalemia is severe (potassium level of 2.5 mEq/L). Gradual correction of hypokalemia is preferable to rapid correction unless the patient is clinically unstable. Administration of potassium may be empirical in emergent conditions. When indicated, the maximum amount of IV potassium replacement should be 10 to 20 mEq/h with continuous ECG monitoring during infusion. A more concentrated solution of potassium may be infused if a central line is used, but the tip of the catheter used for the infusion should not extend into the right atrium. If cardiac arrest from hypokalemia is imminent (ie, malignant ventricular arrhythmias are present), rapid replacement of potassium is required. Give an initial infusion of 10 mEq IV over 5 minutes; repeat once if needed. Document in the patient’s chart that rapid infusion is intentional in response to life-threatening hypokalemia. Sodium (Na) Sodium is the major intravascular ion that influences serum osmolality. An acute increase in serum sodium will produce an acute increase in serum osmolality; an acute decrease in serum sodium will produce an acute fall in serum osmolality. Sodium concentration and osmolality in the intravascular and interstitial spaces equilibrate across the vascular membrane. Acute changes in serum sodium will produce free water shifts into and out of the vascular space until osmolality equilibrates in these compartments. An acute fall in serum sodium will produce an acute shift of free water from the vascular into the interstitial space and may cause cerebral edema.8,9 An acute rise in serum sodium will produce an acute shift of free water from the interstitial to the vascular space. Rapid correction of hyponatremia has been associated with development of pontine myelinolysis and cerebral bleeding.10 –12 For these reasons, monitor neurologic function closely in the patient with hypernatremia or hyponatremia, particularly during correction of these conditions. Whenever possible, correct serum sodium slowly, carefully controlling the total change in serum sodium over 48 hours and avoiding overcorrection.13,14 Hypernatremia Hypernatremia is defined as a serum sodium concentration 145 to 150 mEq/L. It may be caused by a primary gain in Na or excess loss of water. Gains in sodium can result from hyperaldosteronism (excess mineralocorticoid), Cushing’s syndrome (excess glucocorticoid), or excessive hypertonic saline or sodium bicarbonate administration. Loss of free water can result from gastrointestinal losses or renal excretion (eg, osmotic diuresis or diabetes insipidus). Hypernatremia may cause neurologic symptoms such as altered mental status, weakness, irritability, focal neurologic deficits, and even coma or seizures. The severity of symptoms is determined by the speed and magnitude of the change in serum sodium concentration. Treatment of Hypernatremia Treatment of hypernatremia includes reduction of ongoing water losses (by treating the underlying cause) and correction of the water deficit. For stable, asymptomatic patients, replacement of fluid by mouth or through a nasogastric tube is effective and safe. In hypovolemic patients the extracellular fluid (ECF) volume is typically restored with normal saline or a 5% dextrose in half-normal saline solution to prevent a rapid fall in the serum sodium concentration. Avoid D5W because it will reduce the serum sodium too rapidly. During rehydration, monitor serum sodium closely to ensure a gradual fall (and prevent rapid fall) in serum sodium. The quantity of water needed to correct hypernatremia can be calculated by using the following equation: IV-122 Circulation December 13, 2005
Part 10.1: Life-Threatening Electrolyte Abnormalities IV-123 Water deficit(in liters)Plasma Na* concentration-140 X total body water Total body water is approximately 50%0 of lean body If the patient develops neurologic compromise, weight in men and 40% of lean body weight in women. For 3% saline IV immediately to correct(raise)the serum sodium example, if a 70-kg man had a serum Na level of 160 at a rate of l mEq/L per hour until neurologic symptoms are mEq/L, the estimated free water deficit would be controlled. Some experts recommend a faster rate of correc- 160-140 tion(ie, increase concentration 2 to 4 mEq/L per hour) when (0.5×70)=5L seizures are present. After neurologic symptoms are con- trolled, provide 3% saline I to correct(raise) the serum Once the free water deficit is calculated, administer fluid to sodium at a rate of 0.5 mEq/L per hour ower serum sodium at a rate of 0.5 to I mEq/h with a To determine the amount of sodium (eg, 3% saline decrease of no more than approximately 12 mEq/L in the first required to correct the deficit, calculate the total body sodium 24 hours and the remainder over the next 48 to 72 hours deficit. The following formula may be used Na* deficit=(desired [Na*]-current [Na DX0.6* xbody Hyponatremia is defined as a serum sodium concentration wt(kg)(use 0.6 for men and 0.5 for women). 2.2 mEq/L(normal: 1.3 to 2.2 mEq/L). The most Treatment of Hyponatremia mon cause of hypermagnesemia is renal fail Treatment of hyponatremia involves administration of so- pre-eclampsia in pregnant women is treated with magnesium dium and elimination of intravascular free water, If SIAdh is administration, often titrated to maintain the serum magne- present, the treatment is restriction of fluid intake to 50%to sium near the maximum normal concentration, without com- 6% of estimated maintenance fluid requirement Correction plications of hypermagnesemia. of asymptomatic hyponatremia should be gradual: typically Neurologic symptoms of hypermagnesemia are muscular increase the Na* by 0.5 mEq/L per hour to a maximum weakness, paralysis, ataxia, drowsiness, and confusion. Mod- change of about 12 mEq/L in the first 24 hours. Rapid erate hypermagnesemia can produce vasodilation; severe orrection of hyponatremia can cause coma, which may be hypermagnesemia can produce hypotension. Extremely high associated with osmotic demyelination syndrome or central serum magnesium levels may produce a depressed level of pontine myelinolysis, lethal disorders thought to be caused by consciousness, bradycardia, cardiac arrhythmias, hypover apid fluid shifts into and out of brain tissue. 10. lation, and cardiorespiratory arrest. 5
Water deficit (in liters) plasma Na concentration140 140 total body water Total body water is approximately 50% of lean body weight in men and 40% of lean body weight in women. For example, if a 70-kg man had a serum Na level of 160 mEq/L, the estimated free water deficit would be 160140 140 (0.570)5 L Once the free water deficit is calculated, administer fluid to lower serum sodium at a rate of 0.5 to 1 mEq/h with a decrease of no more than approximately 12 mEq/L in the first 24 hours and the remainder over the next 48 to 72 hours. Hyponatremia Hyponatremia is defined as a serum sodium concentration 130 to 135 mEq/L. It is caused by an excess of water relative to sodium. Most cases of hyponatremia are caused by reduced renal excretion of water with continued water intake or by loss of sodium in the urine. Impairment of renal water excretion may be caused by ● Use of thiazide diuretics ● Renal failure ● ECF depletion (eg, vomiting with continued water intake) ● Syndrome of inappropriate antidiuretic hormone (SIADH) secretion ● Edematous states (eg, congestive heart failure, cirrhosis with ascites) ● Hypothyroidism ● Adrenal insufficiency Most cases of hyponatremia are associated with low serum osmolality (so-called hypo-osmolar hyponatremia). The one common exception to this is in uncontrolled diabetes, in which hyperglycemia leads to a hyperosmolar state despite a serum sodium that is below normal (hyperosmolar hyponatremia). Hyponatremia is usually asymptomatic unless it is acute or severe (120 mEq/L). An abrupt fall in serum sodium produces a free water shift from the vascular to the interstitial space that can cause cerebral edema. In this case the patient may present with nausea, vomiting, headache, irritability, lethargy, seizures, coma, or even death. Treatment of Hyponatremia Treatment of hyponatremia involves administration of sodium and elimination of intravascular free water. If SIADH is present, the treatment is restriction of fluid intake to 50% to 66% of estimated maintenance fluid requirement. Correction of asymptomatic hyponatremia should be gradual: typically increase the Na by 0.5 mEq/L per hour to a maximum change of about 12 mEq/L in the first 24 hours. Rapid correction of hyponatremia can cause coma, which may be associated with osmotic demyelination syndrome or central pontine myelinolysis, lethal disorders thought to be caused by rapid fluid shifts into and out of brain tissue.10 –12 If the patient develops neurologic compromise, administer 3% saline IV immediately to correct (raise) the serum sodium at a rate of 1 mEq/L per hour until neurologic symptoms are controlled. Some experts recommend a faster rate of correction (ie, increase concentration 2 to 4 mEq/L per hour) when seizures are present. After neurologic symptoms are controlled, provide 3% saline IV to correct (raise) the serum sodium at a rate of 0.5 mEq/L per hour. To determine the amount of sodium (eg, 3% saline) required to correct the deficit, calculate the total body sodium deficit. The following formula may be used: Na deficit(desired [Na]current [Na])0.6*body wt (kg) (*use 0.6 for men and 0.5 for women). Once the deficit is estimated, determine the volume of 3% saline (513 mEq/L Na) necessary to correct the deficit (divide the deficit by 513 mEq/L). Plan to increase the sodium by 1 mEq/L per hour over 4 hours (or until neurologic symptoms improve); then increase the sodium by 0.5 mEq/L per hour. To calculate this amount, use the amount you wish to correct the sodium in an hour (eg, 0.5 mEq/L) and multiply by 0.6 (or 0.5 in women) and then multiply by the body weight; that will calculate the amount of sodium to administer that hour. Check serum sodium frequently and monitor neurologic status. Magnesium (Mg) Magnesium is the fourth most common mineral and the second most abundant intracellular cation (after potassium) in the human body. Because extracellular magnesium is bound to serum albumin, magnesium levels do not reliably reflect total body magnesium stores. Magnesium is necessary for the movement of sodium, potassium, and calcium into and out of cells, and magnesium plays an important role in stabilizing excitable membranes. Low potassium in combination with low magnesium is a risk factor for severe arrhythmias. Thus, magnesium balance is closely tied to sodium, calcium, and potassium balance. Hypermagnesemia Hypermagnesemia is defined as a serum magnesium concentration 2.2 mEq/L (normal: 1.3 to 2.2 mEq/L). The most common cause of hypermagnesemia is renal failure. Note that pre-eclampsia in pregnant women is treated with magnesium administration, often titrated to maintain the serum magnesium near the maximum normal concentration, without complications of hypermagnesemia. Neurologic symptoms of hypermagnesemia are muscular weakness, paralysis, ataxia, drowsiness, and confusion. Moderate hypermagnesemia can produce vasodilation; severe hypermagnesemia can produce hypotension. Extremely high serum magnesium levels may produce a depressed level of consciousness, bradycardia, cardiac arrhythmias, hypoventilation, and cardiorespiratory arrest.15 Part 10.1: Life-Threatening Electrolyte Abnormalities IV-123
IV-124 Circulation December 13. 2005 Treatment of hypermagnesemia Although total serum albumin is directly related to total Hypermagnesemia is treated with administration of calcium, erum calcium, the ionized calcium is inversely related to which removes magnesium from serum. It is important serum albumin. The lower the serum albumin. the higher the eliminate sources of ongoing magnesium intake. Cardiorespi- portion of the total calcium that is present in ionized form.In ratory support may be needed until magnesium levels are the presence of hypoalbuminemia, although total calcium reduced. Administration of 10% solution of calcium chloride level may be low, the ionized calcium level may be normal (5 to 10 mL [500 to 1000 mg Iv) will often correct lethal Calcium antagonizes the effects of both potassium and arrhythmias. This dose may be repeated if needed. magnesium at the cell membrane. For this reason it is Dialysis is the treatment of choice for severe hypermag- extremely useful for treating the effects of hyperkalemia and nesemia. If renal function is normal and cardiovascular function adequate, IV saline diuresis(administration of IV normal saline and furosemide [1 mg/kgl) can be used to Hypercalcemia increase renal excretion of magnesium until dialysis can be Hypercalcemia is defined as a total serum calcium concen- performed Diuresis can also increase calcium excretion; the tration >10.5 mEq/L(or an elevation in ionized calcium development of hypocalcemia will make signs and symptoms >4.8 mg/dL). Primary hyperparathyroidism and malignancy of hypermagnesemia wor account for >90% of reported cases. 7 In these and most forms of hypercalcemia, release of calcium from the bones Hy hypomagneseMia and intestines is increased, and renal clearance may be Hypomagnesemia, defined as a serum magnesium concentra compromised tion 15 mg/dL. Above this level myocardial depression occurs. Automaticity is decreased and ventricular de pointes (multifocal ventricular tachycardia). Other possi- systole is shortened. Arrhythmias occur because the refrac- ble symptoms are ataxia, vertigo, seizures, and dysphagia. toxicity and may cause hypertension. In addition, many Treatment of hypomagnesemia patients with hypercalcemia develop hypokalemia. Both of The treatment of hypomagnesemia is determined by its these conditions contribute to cardiac arrhythmias. 8 The QT severity and the patient's clinical status. For severe or interval typically shortens when the serum calcium is >13 ymptomatic hypomagnesemia, give I to 2 g of IV MgSO4 mg/dL, and the PR and QRS intervals are prolonged. Atrio- over 5 to 60 minutes. For torsades de pointes with cardiac ventricular block may develop and progress to complete heart arrest, give I to 2 g of MgSO IV push over 5 to 20 minutes. block and even cardiac arrest when the total serum calcium i If torsades de pointes is intermittent and not associated with >15 to 20 mg/dL. arrest, administer the magnesium over 5 to 60 minutes Iv. If Gastrointestinal symptoms of hypercalcemia include dys izures are present, give 2 g IV MgSO, over 10 minutes. phagia, constipation, peptic ulcers, and pancreatitis. Effects Administration of calcium is usually appropriate because on the kidney include diminished ability to concentrate urine most patients with hypomagnesemia are also hypocalcemic. 16 diuresis, leading to loss of sodium, potassium, magnesium, and phosphate; and a vicious cycle of calcium absorption in Calcium(Catt) the intestines and calcium release from the bones that Calcium is the most abundant mineral in the body. Many worsens hypercalcemia. processes depend on intracellular calcium, such as enzymatic Treatment of hypercalcemia reactions,receptor activation, muscle contraction, cardiac Treatment for hypercalcemia is required if the patient is contractility,and platelet aggregation. Calcium is essential symptomatic( typically a total serum concentration of appl for bone strength and neuromuscular function. Half of all imately >12 mg/dL) or if the calcium level is >15 mg/dL calcium in the ECF is bound to albumin; the other half is in Immediate therapy is directed at restoring intravascular vol- the biologically active, ionized form. Calcium concentration ume and promoting calcium excretion in the urine In patients is normally regulated by parathyroid hormone and vitamin D with adequate cardiovascular and renal function this is Total serum calcium is directly related to the serum accomplished with infusion of 0.9% saline at 300 to 500 albumin concentration. The total serum calcium will increase mL/h(saline diuresis) until any fluid deficit is replaced and 0.8 mg/dL for every I g/dL rise in serum albumin and will fall diuresis occurs (urine output >200 to 300 mL/h). Once 0.8 mg/dL for every I g/dL fall in serum albumin. adequate rehydration has occurred, the saline infusion rate is
Treatment of Hypermagnesemia Hypermagnesemia is treated with administration of calcium, which removes magnesium from serum. It is important to eliminate sources of ongoing magnesium intake. Cardiorespiratory support may be needed until magnesium levels are reduced. Administration of 10% solution of calcium chloride (5 to 10 mL [500 to 1000 mg] IV) will often correct lethal arrhythmias. This dose may be repeated if needed. Dialysis is the treatment of choice for severe hypermagnesemia. If renal function is normal and cardiovascular function adequate, IV saline diuresis (administration of IV normal saline and furosemide [1 mg/kg]) can be used to increase renal excretion of magnesium until dialysis can be performed. Diuresis can also increase calcium excretion; the development of hypocalcemia will make signs and symptoms of hypermagnesemia worse. Hypomagnesemia Hypomagnesemia, defined as a serum magnesium concentration 1.3 mEq/L, is far more common than hypermagnesemia. Hypomagnesemia usually results from decreased absorption or increased loss of magnesium from either the kidneys or intestines (diarrhea). Alterations in thyroid hormone function and certain medications (eg, pentamidine, diuretics, alcohol) can also induce hypomagnesemia. Hypomagnesemia interferes with the effects of parathyroid hormone, resulting in hypocalcemia. It may also cause hypokalemia. Symptoms of low serum magnesium are muscular tremors and fasciculations, ocular nystagmus, tetany, altered mental state, and cardiac arrhythmias such as torsades de pointes (multifocal ventricular tachycardia). Other possible symptoms are ataxia, vertigo, seizures, and dysphagia. Treatment of Hypomagnesemia The treatment of hypomagnesemia is determined by its severity and the patient’s clinical status. For severe or symptomatic hypomagnesemia, give 1 to 2 g of IV MgSO4 over 5 to 60 minutes. For torsades de pointes with cardiac arrest, give 1 to 2 g of MgSO4 IV push over 5 to 20 minutes. If torsades de pointes is intermittent and not associated with arrest, administer the magnesium over 5 to 60 minutes IV. If seizures are present, give 2 g IV MgSO4 over 10 minutes. Administration of calcium is usually appropriate because most patients with hypomagnesemia are also hypocalcemic.16 Calcium (Ca) Calcium is the most abundant mineral in the body. Many processes depend on intracellular calcium, such as enzymatic reactions, receptor activation, muscle contraction, cardiac contractility, and platelet aggregation. Calcium is essential for bone strength and neuromuscular function. Half of all calcium in the ECF is bound to albumin; the other half is in the biologically active, ionized form. Calcium concentration is normally regulated by parathyroid hormone and vitamin D. Total serum calcium is directly related to the serum albumin concentration. The total serum calcium will increase 0.8 mg/dL for every 1 g/dL rise in serum albumin and will fall 0.8 mg/dL for every 1 g/dL fall in serum albumin. Although total serum albumin is directly related to total serum calcium, the ionized calcium is inversely related to serum albumin. The lower the serum albumin, the higher the portion of the total calcium that is present in ionized form. In the presence of hypoalbuminemia, although total calcium level may be low, the ionized calcium level may be normal. Calcium antagonizes the effects of both potassium and magnesium at the cell membrane. For this reason it is extremely useful for treating the effects of hyperkalemia and hypermagnesemia. Hypercalcemia Hypercalcemia is defined as a total serum calcium concentration 10.5 mEq/L (or an elevation in ionized calcium 4.8 mg/dL). Primary hyperparathyroidism and malignancy account for 90% of reported cases.17 In these and most forms of hypercalcemia, release of calcium from the bones and intestines is increased, and renal clearance may be compromised. Symptoms of hypercalcemia usually develop when the total serum calcium concentration is 12 to 15 mg/dL. Neurologic symptoms are depression, weakness, fatigue, and confusion at lower levels. At higher levels patients may experience hallucinations, disorientation, hypotonicity, seizures, and coma. Hypercalcemia interferes with renal concentration of urine; the diuresis can cause dehydration. Cardiovascular symptoms of hypercalcemia are variable. Myocardial contractility may initially increase until the calcium level reaches 15 mg/dL. Above this level myocardial depression occurs. Automaticity is decreased and ventricular systole is shortened. Arrhythmias occur because the refractory period is shortened. Hypercalcemia can worsen digitalis toxicity and may cause hypertension. In addition, many patients with hypercalcemia develop hypokalemia. Both of these conditions contribute to cardiac arrhythmias.18 The QT interval typically shortens when the serum calcium is 13 mg/dL, and the PR and QRS intervals are prolonged. Atrioventricular block may develop and progress to complete heart block and even cardiac arrest when the total serum calcium is 15 to 20 mg/dL. Gastrointestinal symptoms of hypercalcemia include dysphagia, constipation, peptic ulcers, and pancreatitis. Effects on the kidney include diminished ability to concentrate urine; diuresis, leading to loss of sodium, potassium, magnesium, and phosphate; and a vicious cycle of calcium absorption in the intestines and calcium release from the bones that worsens hypercalcemia. Treatment of Hypercalcemia Treatment for hypercalcemia is required if the patient is symptomatic (typically a total serum concentration of approximately 12 mg/dL) or if the calcium level is 15 mg/dL. Immediate therapy is directed at restoring intravascular volume and promoting calcium excretion in the urine. In patients with adequate cardiovascular and renal function this is accomplished with infusion of 0.9% saline at 300 to 500 mL/h (saline diuresis) until any fluid deficit is replaced and diuresis occurs (urine output 200 to 300 mL/h). Once adequate rehydration has occurred, the saline infusion rate is IV-124 Circulation December 13, 2005
Part 10.1: Life-Threatening Electrolyte Abnormalities IV-125 reduced to 100 to 200 mL/h. During this therapy, monitor and S umma maintain potassium and magnesium concentrations closely Electrolyte abnormalities are among the most common causes because the diuresis can reduce potassium and magnesium of cardiac arrhythmias, and they can cause or complicate attempted resuscitation and postresuscitation care. A high Hemodialysis is the treatment of choice to rapidly decrea egress serum calcium in patients with heart failure or renal insuffi- underlying electrolyte abnormalities can prevent these abnor- ciency 19 Chelating agents(eg, 50 mmol POa over 8 to 12 malities from progressing to cardiac arrest. hours or EDTA 10 to 50 mg/kg over 4 hours)may be used for extreme conditions References Use of furosemide (I mg/kg IV) for treatment of hyper SG. Hyperkalaemic cardiac calcemia is controversial. In the presence of heart failure, successfully treated with peritoneal dialysis. BMJ. 1996: 312: 1289-1290 administration of furosemide is required, but it can actually 2. Voelckel w, Kroesen G. Unexpected return of cardiac action after ter foster release of calcium from bone, thus worsening mination of cardiopulmonary resuscitation. Resuscitation. 1996; 32 27-29 3. Niemann JT, Cairns CB Hyperkalemia and ionized hypocalcemia during cardiac arrest and resuscitation: possible culprits for postcountershoc Hypocalcemia arrhythmias? Ann Emerg Med. 1999; 34: 1 Hypocalcemia is defined as a serum calcium concentration 4. Ngugi NN, McLigeyo so, Kayima JK. Treatment of hyperkalaemia by 8.5 mg/dL(or ionized calcium <4.2 mg/dL). Hypocalce altering the transcellular gradient in patients with renal failure: effect of mia may develop with toxic shock syndrome, with abnormal- various therapeutic approaches. East Afr Med J. 1997: 74: 503-509 ities in serum magnesium, after thyroid surgery, with fluoride 5. Allon M, Shanklin N. Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol. sonn and with tumor lysis syndrome(rapid cell turnover Am J Kidney Dis. 1996: 28: 508-514. with resultant hyperkalemia, hyperphosphatemia, and 6. Lin JL. Lim PS, Leu ML, Huang CC. Outcomes of severe hyperkalemia hypocalcemia) n cardiopulmonary resuscitation with concomitant hemodialysis. Symptoms of hypocalcemia usually occur when ionized Intensive Care Med 1994: 20: 287-290 7. Allon M. Hyperkalemia in end-stage renal disease: mechanisms and levels fall to <2.5 mg/dL. Symptoms include paresthesias of nagement [editorial]. J Am Soc Nephrol. 1995: 6: 1134-1142 the extremities and face, followed by muscle cramps, carpo- 8. Adrogue H, Madias NE. Aiding fluid prescription for the dysnatremias pedal spasm, stridor, tetany, and seizures. Hypocalcemic Intensive Care Med. 1997: 23: 309-316 patients show hyperreflexia and positive Chvostek and Trous- 9. Fraser CL, Arieff AL. Epidemiology, pathophysiology, and management seau signs. Cardiac effects include decreased myocardial 10. Laureno R. Karp BL Myelinolysis after correction of hyponatremia. An contractility and heart failure. Hypocalcemia can exacerbate Intern med.1997;126:57-62. Il. Gross P, Reimann D, Neidel J, Doke C, Prospert F, Decaux G, verbalis Schrier RW. The treatment of severe hyponatremia. Kidney Int Suppl Treatment of hypocalcemia 998:64:S6-SI1. Treatment of hypocalcemia requires administration of cal- 12. Soupart A, Decaux G. Therapeutic recom ons for management of cium. Treat acute, symptomatic hypocalcemia with 10% calcium gluconate, 93 to 186 mg of elemental calcium(10 to 13. Brunner JE, Redmond JM, Haggar AM. Kruger DF. Elias SB. Central 20 mL)IV over 10 minutes. Follow this with an IV infusion pontine myelinolysis and pontine lesions after rapid correction of hypo- of 540 to 720 mg of elemental calcium (58 to 77 mL of 10% natremia: a prospective magnetic resonance imaging study. Ann Neurol. calcium gluconate)in 500 to 1000 mL D5 at 0.5 to 2 mg/kg per hour (10 to 15 mg/kg). Alternatively, administer 10% 14. Ayus JC, Krothapalli RK, Arieff Al. Treatment of symptomatic hypona- 5 mL (136.5 mg of eleme calcium) over 10 minutes, followed by 36.6 mL (I g)over the 15. Higham PD, Adams PC, Murray A, Campbell Rw. Plasma potassium, next 6 to 12 hours IV Measure serum calcium every 4 to 6 serum magnesium and ventricular fibrillation: a prospective study. Q hours. Aim to maintain the total serum calcium concentration JMed.1993:86:609-61 at 7 to 9 mg/dL. Correct abnormalities in magnesium 16. al-Ghamdi SM. Cameron EC, Sutton RA. Magnesium de and clinical overview. Am J Kidney Dis. 1994: 24: 737-752 potassium, and pH simultaneously. Note that untreated hypo- 17. Barri YM, Knochel JP. Hypercalcemia and electrolyte disturbances in magnesemia will often make hypocalcemia refractory to malignancy. Hematol Oncol Clin North Am. 1996: 10:775-790. therapy. Therefore, evaluate serum magnesium when hy 18. Aldinger KA, Samaan NA Hypokalemia with hypercalcemia: prevalence pocalcemia is present and particularly if hypocalcemia is 19. Edelson GW Kleerekoper M Hypercalcemic crisis. Med Clin North Am refractory to initial calcium therapy 1995:79:79-92
reduced to 100 to 200 mL/h. During this therapy, monitor and maintain potassium and magnesium concentrations closely because the diuresis can reduce potassium and magnesium concentrations. Hemodialysis is the treatment of choice to rapidly decrease serum calcium in patients with heart failure or renal insufficiency.19 Chelating agents (eg, 50 mmol PO4 over 8 to 12 hours or EDTA 10 to 50 mg/kg over 4 hours) may be used for extreme conditions. Use of furosemide (1 mg/kg IV) for treatment of hypercalcemia is controversial. In the presence of heart failure, administration of furosemide is required, but it can actually foster release of calcium from bone, thus worsening hypercalcemia. Hypocalcemia Hypocalcemia is defined as a serum calcium concentration 8.5 mg/dL (or ionized calcium 4.2 mg/dL). Hypocalcemia may develop with toxic shock syndrome, with abnormalities in serum magnesium, after thyroid surgery, with fluoride poisoning, and with tumor lysis syndrome (rapid cell turnover with resultant hyperkalemia, hyperphosphatemia, and hypocalcemia). Symptoms of hypocalcemia usually occur when ionized levels fall to 2.5 mg/dL. Symptoms include paresthesias of the extremities and face, followed by muscle cramps, carpopedal spasm, stridor, tetany, and seizures. Hypocalcemic patients show hyperreflexia and positive Chvostek and Trousseau signs. Cardiac effects include decreased myocardial contractility and heart failure. Hypocalcemia can exacerbate digitalis toxicity. Treatment of Hypocalcemia Treatment of hypocalcemia requires administration of calcium. Treat acute, symptomatic hypocalcemia with 10% calcium gluconate, 93 to 186 mg of elemental calcium (10 to 20 mL) IV over 10 minutes. Follow this with an IV infusion of 540 to 720 mg of elemental calcium (58 to 77 mL of 10% calcium gluconate) in 500 to 1000 mL D5W at 0.5 to 2 mg/kg per hour (10 to 15 mg/kg). Alternatively, administer 10% calcium chloride, giving 5 mL (136.5 mg of elemental calcium) over 10 minutes, followed by 36.6 mL (1 g) over the next 6 to 12 hours IV. Measure serum calcium every 4 to 6 hours. Aim to maintain the total serum calcium concentration at 7 to 9 mg/dL. Correct abnormalities in magnesium, potassium, and pH simultaneously. Note that untreated hypomagnesemia will often make hypocalcemia refractory to therapy. Therefore, evaluate serum magnesium when hypocalcemia is present and particularly if hypocalcemia is refractory to initial calcium therapy. Summary Electrolyte abnormalities are among the most common causes of cardiac arrhythmias, and they can cause or complicate attempted resuscitation and postresuscitation care. A high degree of clinical suspicion and aggressive treatment of underlying electrolyte abnormalities can prevent these abnormalities from progressing to cardiac arrest. References 1. Jackson MA, Lodwick R, Hutchinson SG. Hyperkalaemic cardiac arrest successfully treated with peritoneal dialysis. BMJ. 1996;312:1289 –1290. 2. Voelckel W, Kroesen G. Unexpected return of cardiac action after termination of cardiopulmonary resuscitation. Resuscitation. 1996;32: 27–29. 3. Niemann JT, Cairns CB. Hyperkalemia and ionized hypocalcemia during cardiac arrest and resuscitation: possible culprits for postcountershock arrhythmias? Ann Emerg Med. 1999;34:1–7. 4. Ngugi NN, McLigeyo SO, Kayima JK. Treatment of hyperkalaemia by altering the transcellular gradient in patients with renal failure: effect of various therapeutic approaches. East Afr Med J. 1997;74:503–509. 5. Allon M, Shanklin N. Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol. Am J Kidney Dis. 1996;28:508 –514. 6. Lin JL, Lim PS, Leu ML, Huang CC. Outcomes of severe hyperkalemia in cardiopulmonary resuscitation with concomitant hemodialysis. Intensive Care Med. 1994;20:287–290. 7. Allon M. Hyperkalemia in end-stage renal disease: mechanisms and management [editorial]. J Am Soc Nephrol. 1995;6:1134 –1142. 8. Adrogue HJ, Madias NE. Aiding fluid prescription for the dysnatremias. Intensive Care Med. 1997;23:309 –316. 9. Fraser CL, Arieff AI. Epidemiology, pathophysiology, and management of hyponatremic encephalopathy. Am J Med. 1997;102:67–77. 10. Laureno R, Karp BI. Myelinolysis after correction of hyponatremia. Ann Intern Med. 1997;126:57– 62. 11. Gross P, Reimann D, Neidel J, Doke C, Prospert F, Decaux G, Verbalis J, Schrier RW. The treatment of severe hyponatremia. Kidney Int Suppl. 1998;64:S6 –S11. 12. Soupart A, Decaux G. Therapeutic recommendations for management of severe hyponatremia: current concepts on pathogenesis and prevention of neurologic complications. Clin Nephrol. 1996;46:149 –169. 13. Brunner JE, Redmond JM, Haggar AM, Kruger DF, Elias SB. Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: a prospective magnetic resonance imaging study. Ann Neurol. 1990;27:61– 66. 14. Ayus JC, Krothapalli RK, Arieff AI. Treatment of symptomatic hyponatremia and its relation to brain damage: a prospective study. N Engl J Med. 1987;317:1190 –1195. 15. Higham PD, Adams PC, Murray A, Campbell RW. Plasma potassium, serum magnesium and ventricular fibrillation: a prospective study. Q J Med. 1993;86:609 – 617. 16. al-Ghamdi SM, Cameron EC, Sutton RA. Magnesium deficiency: pathophysiologic and clinical overview. Am J Kidney Dis. 1994;24:737–752. 17. Barri YM, Knochel JP. Hypercalcemia and electrolyte disturbances in malignancy. Hematol Oncol Clin North Am. 1996;10:775–790. 18. Aldinger KA, Samaan NA. Hypokalemia with hypercalcemia: prevalence and significance in treatment. Ann Intern Med. 1977;87:571–573. 19. Edelson GW, Kleerekoper M. Hypercalcemic crisis. Med Clin North Am. 1995;79:79 –92. Part 10.1: Life-Threatening Electrolyte Abnormalities IV-125
