Fluids, Electrolytes, and Nutrition PDF

Fluids, Electrolytes, and Nutrition IV. HYPOTONIC INTRAVENOUS FLUIDS A. Hypotonic fluids administered intravenously can cause cell hemolysis and patient death. 1. Albumin 25% diluted with sterile water to make albumin 5% has an osmolarity of about 60 mOsm/L, which can cause hemolysis. 2. “Quarter...

Fluids, Electrolytes, and Nutrition IV. HYPOTONIC INTRAVENOUS FLUIDS A. Hypotonic fluids administered intravenously can cause cell hemolysis and patient death. 1. Albumin 25% diluted with sterile water to make albumin 5% has an osmolarity of about 60 mOsm/L, which can cause hemolysis. 2. “Quarter normal saline,” or 0.225% sodium chloride, has an osmolarity of 77 mOsm/L and can cause hemolysis. B. Avoid using intravenous fluid with an osmolarity less than 150 mOsm/L. 1. Sterile water alone should never be administered intravenously. 2. Some prescribers use hypotonic saline for a patient with hypernatremia. a. In reality, a patient with mild hypernatremia generally needs water, not additional Na+. b. Therefore, for patients with hypernatremia, enteral administration of water is preferable. c. If the enteral route is unavailable, recommend D5W administered intravenously. C. P  revent a potentially dangerous error by recommending one of the following alternatives to 0.225% sodium chloride: 1. Recommend changing 0.225% sodium chloride to D5W alone or a combination of D5W and 0.225% sodium chloride. 2. Alternatively, if there are concerns related to hyperglycemia with using D5W (50 g of dextrose or 170 kcal/L), recommend using 2.5% dextrose and 0.225% sodium chloride. 3. Alternatively, potassium chloride can be added to increase osmolarity. 4. Recommend administering water enterally (by mouth or feeding tube). 5. If 0.225% sodium chloride is used, recommend use by central venous line. V. HYPONATREMIA AND HYPO-OSMOLALITY STATES A. S  odium salts are the primary determinants of plasma osmolality (and subsequent fluid shifts between the IC and EC compartments). 1. A reduction in serum sodium to less than 136 mEq/L usually correlates with a reduction in plasma osmolality. 2. Hyponatremia with subsequent hypo-osmolality causes fluid to shift into cells (cellular overhydration). Hypotonic hyponatremia can be divided into three types according to volume status (Table 6). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-370 Fluids, Electrolytes, and Nutrition Table 6. Classification of Hypoosmolar Hyponatremia Description Example Diagnosis Treatment Hypovolemic Hyponatremia Deficit of both Na+ and fluid, but total Na+ is decreased more than total body water Fluid loss (e.g., emesis, diarrhea, fever), third spacing, renal loss (diuretics), cerebral salt wasting Urine Na+ < 25 mEq/L indicates nonrenal loss of Na+ (e.g., emesis, diarrhea); urine Na+ > 40 mEq/L indicates renal loss of Na+a Euvolemic Hyponatremia Normal total body Na+ with excess fluid volume (i.e., dilutional) SIADH, medications Urine osmolality > 100 mOsm/kg (indicates impaired water excretion in presence of plasma osmolality < 275 mOsm/kg); urine sodium > 40 mEq/La Fluid resuscitation (see above); If drug-induced SIADH, in patients with cerebral salt remove offending agent; fluid wasting because of a neurologic restriction; demeclocycline; injury or tumor, hyponatremia vasopressin receptor can be prevented with antagonists (e.g., conivaptan, sodium chloride tablets or tolvaptan), some institutions fludrocortisone use urea Hypervolemic Hyponatremia Excess Na+ and fluid, but fluid excess predominates Heart failure, cirrhosis, nephrotic syndrome Urine Na+ < 25 mEq/L indicates edematous disorders (i.e., heart failure, cirrhosis, nephrotic syndrome); urine Na+ > 25 mEq/L indicates acute or chronic renal failurea Sodium and water restriction; treat underlying cause; vasopressin receptor antagonists (e.g., conivaptan, tolvaptan), diuretics Na+ = sodium; SIADH = syndrome of inappropriate secretion of antidiuretic hormone. a Urine Na+ measurement may be inaccurate if a patient is receiving diuresis. 3. In select cases, hyponatremia is associated with either a normal or an elevated plasma osmolality. a. This is known as pseudohyponatremia because Na+ content in the body is not actually reduced. Instead, Na+ shifts from the EC compartment into the cells in an attempt to maintain plasma osmolality in a normal range. Another adaptation to increased plasma osmolality is the shift of water from inside cells to the EC compartment, which further dilutes the Na+ concentration. i. Severe hyperlipidemia can be associated with a normal or elevated plasma osmolality. ii. Severe hyperglycemia (i.e., during diabetic ketoacidosis) is associated with an elevated plasma osmolality. b. Once the underlying condition is corrected, Na+ will shift out of the cells, and hyponatremia will resolve. B. Causes of hyponatremia 1. Replacement of lost solute with water a. Loss of solute (e.g., vomiting, diarrhea) usually involves the loss of isotonic fluid; therefore, alone, it will not cause hyponatremia. b. After the loss of isotonic fluid, hyponatremia can develop when the lost fluid is replaced with water. c. A common cause of hyponatremia in hospitals is the postoperative administration of hypotonic fluid. 2. Volume depletion and organ hypoperfusion stimulate ADH secretion to increase water reabsorption in the collecting tubules, potentially causing hyponatremia. 3. SIADH and cortisol deficiency are both related to the excessive release of ADH. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-371 Fluids, Electrolytes, and Nutrition 4. 5. Medications, including thiazide diuretics, antiepileptic drugs (e.g., carbamazepine, oxcarbazepine), and antidepressants (especially selective serotonin reuptake inhibitors, but also tricyclic antidepressants), can cause hyponatremia. Drug-induced hyponatremia is more likely to occur in older adults and in those who drink large volumes of water. Renal failure impairs the ability to excrete dilute urine, predisposing to hyponatremia. C. Symptoms of hyponatremia (Table 7) Table 7. Symptoms of Hyponatremia Serum Sodium (mEq/L) 120–125 115–120 < 115 1. 2. 3. 4. Clinical Manifestations Nausea, malaise Headache, lethargy, obtundation, unsteadiness, confusion Delirium, seizure, coma, respiratory arrest, death  ymptoms are generally attributable to hypo-osmolality, with subsequent water movement into brain S cells causing cerebral edema. If hyponatremia occurs chronically, cerebral cell swelling is prevented by osmotic adaptation. a. Solutes move out of brain cells to prevent the osmotic shift of water into brain cells. b. For this reason, patients with chronic hyponatremia may show less severe or no symptoms. Neurologic symptoms are related to the rate and degree of change in serum sodium. Acute hyponatremia occurs over 1–3 days. D. Treatment of hyponatremia 1. Treat underlying cause. 2. Raise serum sodium at a safe rate, defined as a change no greater than 10–12 mEq/L in 24 hours (some recommend a change of no more than 8 mEq/L in 24 hours). 3. Treatment depends on volume status, the presence and severity of symptoms, and the onset of hyponatremia. a. If the patient is euvolemic or edematous, there are typically two treatment options: i. Fluid restriction (to less than 1000 mL/day) is the typical first-line recommendation for asymptomatic patients. Note that sodium administration is not recommended for asymptomatic patients because it can worsen edema. ii. Vasopressin antagonists (e.g., intravenous conivaptan, oral tolvaptan) can be used in euvolemic (i.e., SIADH) or hypervolemic (i.e., heart failure) patients to promote aquaresis, increase serum sodium, alleviate symptoms, and reduce weight; however, this approach is costly and has not been shown to improve clinical outcomes (i.e., fall prevention, hospitalization, hospital length of stay, quality of life, mortality) in prospective randomized controlled trials. Vasopressin antagonists are substrates and inhibitors of cytochrome P450 3A4 isoenzymes. Monitor for drug interactions with other 3A4 inhibitors that could increase effect and lead to a rapid increase in serum sodium. Fluid restriction in combination with a vasopressin antagonist during the first 24 hours can also increase the risk of overly rapid correction of serum sodium. If needed, fluid restriction can be used after 24 hours. Tolvaptan should not be administered for more than 30 days to minimize risk of liver injury. Monitor for recurrence of hyponatremia once treatment is discontinued. In hypervolemic hyponatremia, diuretics can also be used cautiously. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-372 Fluids, Electrolytes, and Nutrition b. If the patient has intravascular volume depletion, volume must be replaced first with intravenous crystalloids (e.g., 0.9% sodium chloride). i. Until intravascular volume is restored, the patient will continue to secrete ADH, causing water reabsorption and subsequent hyponatremia. ii. Once intravascular volume is restored, ADH secretion will decrease, causing water to be excreted. This can lead to a rapid correction of serum sodium; careful monitoring is necessary to prevent overly rapid correction. iii. Volume status can be assessed by skin turgor, jugular venous pressure, and urine sodium. c. Once intravascular volume is restored, patients who experienced volume depletion, diureticinduced hyponatremia, or adrenal insufficiency may still need Na+. i.  The amount of Na+ (in milliequivalents) needed to raise the serum sodium to a safe concentration of about 120 mEq/L (if the serum sodium is less than this) is estimated using LBW as follows: 0.5 (LBW) × (120 − Na+) for women (multiply LBW by 0.6 for men). LBW has been estimated using weight in kilograms and height in centimeters for men as LBW = [(0.3)(kg) + (0.3)(cm) − 29] or for women as LBW= [(0.3)(kg) + (0.4)(cm) − 43] (J Clin Pathol 1966;19:389-91.) ii. Alternatively, this equation can be modified to estimate the Na+ deficit in the following manner: 0.5 (LBW) × (140 − Na+) for women (multiply LBW by 0.6 for men). If calculating the Na+ deficit, it is recommended to administer 25%–50% of the deficit during the first 24 hours to prevent the overly rapid correction of serum sodium. iii. Regardless of the method used to estimate Na+ replacement, the amount of Na+ administered should be guided by serial serum sodium concentrations (e.g., every 4 hours). d. Patients with symptomatic hyponatremia should be treated with hypertonic saline (see Hypertonic Saline section). 4. Correct hypokalemia, if present, with hyponatremia. a. Hypokalemia will cause a reduction in serum sodium because Na+ enters cells to account for the reduction in IC K+ to maintain cellular electroneutrality. b. Administration of K+ will help correct hyponatremia. c. Use caution when giving K+ to prevent overly rapid correction of serum sodium. Patient Case Questions 3–5 pertain to the following case. A 72-year-old woman (weight 60 kg) with a history of hypertension has developed hyponatremia after starting hydrochlorothiazide 3 weeks earlier. She experiences dizziness, fatigue, and nausea. Her serum sodium is 116 mEq/L. Her blood pressure is 86/50 mm Hg, and heart rate is 122 beats/minute. 3. In addition to discontinuing hydrochlorothiazide, which initial treatment regimen is best? A. Administer 0.9% sodium chloride infused at 100 mL/hour. B. Administer 0.9% sodium chloride 500-mL bolus. C. Administer 3% sodium chloride infused at 60 mL/hour. D. Administer 23.4% sodium chloride 30-mL bolus as needed. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-373 Fluids, Electrolytes, and Nutrition Patient Case (Cont’d) 4. W hich is the best treatment goal for the first 24 hours in correcting the patient’s serum sodium from her initial value of 116 mEq/L? A. Increase Na+ concentration to 140 mEq/L. B. Increase Na+ concentration to 132 mEq/L. C. Increase Na+ concentration to 126 mEq/L. D. Maintain serum sodium of 116–120 mEq/L. 5.  ne day later, the patient has somewhat improved. Her blood pressure is 122/80 mm Hg, and heart rate is O 80 beats/minute. Her serum sodium is 120 mEq/L, and K+ is 3.2 mEq/L; she still feels tired. She is eating a regular diet. Her ECG is normal. Which is the best recommendation? A. D5W/0.9% sodium chloride plus potassium chloride 40 mEq/L to infuse at 100 mL/hour. B. 0.9% sodium chloride infused at 100 mL/hour. C. 3% sodium chloride infused at 60 mL/hour. D. Potassium chloride 20 mEq by mouth every 6 hours for 4 doses. VI. HYPERNATREMIA AND HYPEROSMOLAL STATES A. Hyperosmolality with serum sodium greater than 145 mEq/L 1. The osmotic gradient associated with hypernatremia causes water movement out of cells and into the EC space. 2. Symptoms are related primarily to the dehydration of brain cells. B. Causes of hypernatremia 1. Loss of water because of fever, burns, infection, renal loss (e.g., diabetes insipidus), gastrointestinal (GI) loss 2. Retention of Na+ because of the administration of hypertonic saline or any form of Na+ 3. Certain neurologic injuries receive hypertonic saline to target a higher sodium goal C. Prevention of hypernatremia through osmoregulation 1. Plasma osmolality is maintained at 275–290 mOsm/kg, despite changes in water and Na+ intake. 2. Hypernatremia is prevented first by the release of ADH, causing water reabsorption. 3. Hypernatremia is also prevented by thirst. a. Hypernatremia occurs primarily in adults with altered mental status who have an impaired thirst response or do not have access to or the ability to ask for water. b. Hypernatremia can also occur in infants. D. Cerebral osmotic adaptation 1. Similar to patients with hyponatremia, patients with chronic hypernatremia can have cerebral osmotic adaptation. a. Brain cells take up solutes, Na+, and K+, thus limiting the osmotic gradient between the IC and EC fluid compartments. b. This prevents cellular dehydration, and it will increase the brain volume toward a normal value, despite hypernatremia. 2. Because of osmotic adaptation, patients with chronic hypernatremia may be asymptomatic. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-374 Fluids, Electrolytes, and Nutrition E. Symptoms of hypernatremia are primarily neurologic. 1. Similar to hyponatremia, the symptoms of hypernatremia are related to the rate of increase in plasma osmolality and the degree of increase in plasma osmolality. 2. Earlier symptoms include lethargy, weakness, and irritability. 3. Symptoms can progress to twitching, seizures, coma, and death if serum sodium is greater than 158 mEq/L. However, some neurologic injuries may have higher serum sodium targets. 4. Cerebral dehydration can cause cerebral vein rupture with subsequent intracerebral or subarachnoid hemorrhage. F. Treatment of hypernatremia 1. Rapid correction of chronic hypernatremia can result in cerebral edema, seizure, permanent neurologic damage, and death. a. With osmotic adaptation, the brain volume is raised toward normal despite an elevated serum osmolality. b. Osmotic adaptation combined with a rapid reduction in plasma osmolality can cause an osmotic gradient, causing water to move into brain cells with subsequent cerebral edema. 2. In patients with symptomatic hypernatremia, serum sodium should be reduced slowly by no more than 0.5 mEq/L/hour or 12 mEq/L/day. 3. Treat hypernatremia by replacing water deficit slowly over several days to prevent overly rapid correction of serum sodium. a. Using LBW, the estimated water deficit (in liters) is (0.4 × LBW) × [(Serum sodium/140) − 1] in women (multiply LBW by 0.5 in men). b. Note that in women and men, total body water is typically about 50% and 60%, respectively, of LBW. Thus, some sources recommend a variation on the earlier equation as follows: Water deficit = (0.5 × LBW) × [(Serum sodium/140) − 1] in women (multiply LBW by 0.6 in men). However, patients with hypernatremia are generally water depleted; thus, the equation using the lower values above (i.e., 40% or 0.4 and 50% or 0.5) is reasonable. 4. Administer free water orally or intravenously as D5W. 5. If concurrent Na+ and water depletion occur (e.g., vomiting, diarrhea, diuretic-induced depletion), use a combination of D5W and 0.225% sodium chloride. 6. If the patient is hypotensive because of volume depletion, first restore intravascular volume with 0.9% sodium chloride to restore tissue perfusion. Normal saline is the preferred crystalloid for fluid resuscitation, and it is still relatively hypotonic in the patient with hypernatremia. 7. Patients with severe central diabetes insipidus may require desmopressin (DDAVP) (a synthetic analog of ADH) to replace insufficient or absent endogenous ADH. Diabetes insipidus is marked by increased urine output and decreased urine specific gravity. Patient Case 6. A 74-year-old woman (weight 50 kg) has been receiving isotonic tube feedings at 60 mL/hour for the past 8 days through her gastrostomy feeding tube. She recently had an ischemic stroke; she is responsive but is not able to communicate. Her serum sodium was 142 mg/dL on the day the isotonic formula was initiated, and it has risen steadily to 149, 156, and 159 mg/dL on days 3, 4, and 8, respectively, after the start of the tube feedings. What is the best treatment for her hypernatremia? A. Administer sterile water intravenously at 80 mL/hour. B. Administer D5W intravenously at 80 mL/hour. C. Administer D5W/0.225% sodium chloride intravenously at 80 mL/hour. D. Administer water by enteral feeding tube 200 mL every 6 hours. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-375 Fluids, Electrolytes, and Nutrition VII. DISORDERS OF K+ A. Normal plasma potassium concentrations are 3.5–5 mEq/L. B. K+ is the primary IC cation (maintains electroneutrality with Na, the primary EC cation). C. K+ balance is maintained between the IC and EC compartments by several factors, including the following: 1. β2-Adrenergic stimulation (caused by epinephrine) promotes cellular uptake of K+. 2. Insulin promotes cellular uptake of K+. 3. Plasma potassium concentration directly correlates with movement of K+ in and out of cells because of passive shifts based on the concentration gradient across the cell membrane. (A normal response to diarrhea-induced hypokalemia is for K+ to shift out of the cells passively, minimizing the reduction in plasma potassium concentration.) D. Normal plasma concentrations of K+ are maintained by renal excretion. E. Hypokalemia (K+ concentration less than 3.5 mEq/L) 1. Causes of hypokalemia a. Reduced intake seldom causes hypokalemia because renal excretion is minimized as a result of increased renal tubular absorption. b. Increased shift of K+ into cells can occur with the following: i. Alkalosis ii. Insulin or a carbohydrate load iii. β2-Receptor stimulation caused by stress-induced epinephrine release or administration of a β-agonist (e.g., albuterol, dobutamine) iv. Hypothermia c. Increased GI losses of K+ can occur with vomiting, diarrhea, intestinal fistula, or enteral tube drainage, and chronic laxative abuse. d. Increased urinary losses can occur with mineralocorticoid excess (e.g., aldosterone) and diuretic use (e.g., loops and thiazides). e. Hypomagnesemia is commonly associated with hypokalemia caused by increased renal loss of K+; correction of plasma potassium requires simultaneous correction of serum magnesium. 2. Symptoms of hypokalemia generally occur when plasma potassium is less than 3 mEq/L and can include the following: a. Muscle weakness occurs most commonly in the lower extremities, but it can progress to the trunk, upper extremities, and respiratory muscles. Muscle weakness in the GI tract can manifest as paralytic ileus, abdominal distention, nausea, vomiting, and constipation. b. ECG changes (flattened T waves or elevated U wave) occur. c. Cardiac arrhythmias (bradycardia, heart block, ventricular tachycardia, ventricular fibrillation) occur. d. Digoxin toxicity can occur despite normal serum digoxin concentrations in the presence of hypokalemia. e. Rhabdomyolysis can occur because hypokalemia can cause reduced blood flow to skeletal muscle. 3. Treatment of hypokalemia a.  K+ deficit can be estimated as 200–400 mEq of K+ for every 1 mEq/L reduction in plasma potassium (assuming a normal distribution of K+ between EC and IC compartments). b. Although the K+ deficit can be estimated, K+ replacement is guided by K+ concentrations; recheck every 2–4 hours if K+ is less than 3 mEq/L. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-376 Fluids, Electrolytes, and Nutrition c. Potassium chloride is the preferred salt in patients with concurrent metabolic alkalosis because these patients typically lose Cl– through diuretics or GI loss. This is the most common presentation of hypokalemia. d. Potassium acetate can be administered intravenously, or potassium bicarbonate can be administered orally for patients with a metabolic acidosis that requires frequent K+ supplementation. e. Guidelines for administering K+ (Table 8) Table 8. K+ Replacement Plasma K+ Treatmenta (mEq/L) 3–3.5 Oral KCl 40–80 mEq/day if no signs or symptoms (doses > 60 mEq should be divided to avoid GI adverse effects) 2.5–3 Oral KCl 120 mEq/day (in divided doses) or IV 60–80 mEq administered at 10–20 mEq/hr if signs or symptoms 2–2.5 IV KCl 10–20 mEq/hr until normalized <2 IV KCl 20–40 mEq/hr until normalized Comments Recheck K+ daily Monitor K+ closely (i.e., 2 hr after infusion) Consider continuous ECG monitoring Requires continuous ECG monitoring Treatment doses are for patients with normal kidney function and should be reduced for patients with kidney dysfunction or older adults. ECG = electrocardiogram; GI = gastrointestinal; IV = intravenous; KCl = potassium chloride; K+ = potassium. a i. Patients without ECG changes or symptoms of hypokalemia can be treated with oral supplementation. ii. Avoid mixing K+ in dextrose, which can cause insulin release with a subsequent IC shift of K+. iii. To avoid irritation, no more than about 60–80 mEq/L should be administered through a peripheral vein. iv. Recommended infusion rate is 10–20 mEq/hour to a maximum of 40 mEq/hour. v.  Patients who receive K+ at rates faster than 10–20 mEq/hour should be monitored using a continuous ECG. F. Hyperkalemia 1. Causes of hyperkalemia a. Increased intake b.  Shift of K+ from the IC to the EC compartment causes hyperkalemia and can occur with the following: i. Acidosis ii. Insulin deficiency iii. β-Adrenergic blockade iv. Digoxin overdose v. Rewarming after hypothermia (e.g., after cardiac surgery) vi. Succinylcholine c. Reduced urinary excretion can occur with: i. Kidney dysfunction ii. Intravascular volume depletion iii. Hypoaldosteronism iv. K+-sparing diuretics v. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers vi. Trimethoprim ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-377 Fluids, Electrolytes, and Nutrition 2. Symptoms of hyperkalemia a. Muscle weakness or paralysis is caused by changes in neuromuscular conduction; it typically occurs when plasma potassium exceeds 8 mEq/L. b. Abnormal cardiac conduction can first manifest as peaked, narrowed T waves (typically, when plasma potassium exceeds 6 mEq/L) and widening of the QRS, and it can progress to ventricular fibrillation and asystole. c. Not all patients will experience ECG changes, and the initial manifestation of hyperkalemia can be ventricular fibrillation; thus, consider emergency treatment even in patients with no ECG changes if plasma potassium exceeds 6.5 mEq/L. d. Conduction disturbances are increased by hypocalcemia, hyponatremia, acidosis, and rapid elevation in the plasma potassium concentration. 3. Pseudohyperkalemia should be considered if there is no apparent cause or symptoms of hyperkalemia. a. Can occur if K+ is released from cells while or after obtaining the blood specimen, usually because of trauma during venipuncture (hemolysis) b. Can result from measurement of the serum rather than the plasma potassium concentration; caused by K+ release during coagulation c. Contamination of blood specimen with potassium-containing intravenous fluids or parenteral nutrition 4. Treatment of hyperkalemia a. Patients with an asymptomatic elevation in the plasma potassium who do not have signs or symptoms can be treated with a cation exchange resin (e.g., sodium polystyrene sulfonate) alone. b. Urgent and immediate treatment is required for patients with the following signs or symptoms: i. Plasma potassium greater than 6.5 mEq/L ii. Severe muscle weakness iii. ECG changes c. Calcium should be administered intravenously to patients with symptomatic hyperkalemia to prevent hyperkalemia-induced arrhythmias, even if patients demonstrate normocalcemia. i. Calcium gluconate can be administered peripherally, and it is preferred to calcium chloride because of a reduced risk of tissue necrosis; dose is 10 mL (equivalent to 1 g, 90 mg elemental, or 4.65 mEq) of 10% calcium gluconate administered over 2–10 minutes. It can be repeated in 5 minutes if no improvement in ECG. Calcium chloride can be used if central intravenous access is available; however, the dose should be adjusted because 10 mL (1 g, 270 mg elemental, or 13.6 mEq) provides 3-fold the amount of elemental Ca as calcium gluconate. ii. Onset is within minutes, but duration is short (30–60 minutes). iii. It does not reduce plasma potassium, but it antagonizes the effect of K+ in cardiac conduction cells iv. Use in urgent circumstances while waiting for other measures (e.g., insulin and glucose) to lower plasma potassium. v. Use caution in patients receiving digoxin because hypercalcemia can precipitate digoxin toxicity, and there are reports of sudden death. d. The following treatment options are transient, causing a temporary shift of K+ from the EC fluid into the cells, and should be used for symptomatic hyperkalemia. i. Insulin and glucose (a) Dose is typically regular insulin 10 units intravenously plus 25–50 g of dextrose administered as a 50% dextrose intravenous push to prevent hypoglycemia. (b) Typically lowers plasma potassium by 0.5–1.5 mEq/L within 1 hour and may last for several hours (c) If patients have hyperglycemia, insulin alone can be administered. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-378 Fluids, Electrolytes, and Nutrition (d) M  ore predictable than sodium bicarbonate or β2-adrenergic agonists in patients with kidney failure (e) Caution with increased risk of insulin errors when used in emergencies (e.g., incorrectly preparing insulin syringes). Errors involving calculations (100 units/mL) and use of 5- or 10-mL syringes instead of an insulin syringe are possible. (f) Monitor for signs and symptoms of hypoglycemia even if dextrose is given ii. Sodium bicarbonate (a) Dose is 50 mEq of intravenous sodium bicarbonate administered slowly over 5 minutes; it can be repeated after 30 minutes if needed. (b) It can lower plasma potassium within 30–60 minutes and persist for several hours. (c) The efficacy of bicarbonate is disputed, and it seems least effective in patients with advanced kidney disease; it may be effective in patients with underlying metabolic acidosis. Sodium bicarbonate use has recently been limited by shortages. Its use should be reserved for other conditions during shortages. iii. β2-Adrenergic agonists (e.g., albuterol) (a) Dose is albuterol 10–20 mg nebulized over 10 minutes or 0.5 mg intravenously (not available in the United States). (b) The dose will lower plasma potassium by 0.5–1.5 mEq/L. (c) Onset is within 30 minutes with inhalation. (d) Avoid use in patients with coronary ischemia because of the risk of tachycardia. (e) Up to 40% of patients do not respond to inhaled albuterol (especially patients taking β-blockers); therefore, it is not recommended as a single agent for urgent treatment of hyperkalemia. Consider use in combination with insulin. e. The previous treatment options should be followed by one of the following agents to remove excess K+ from the body. i. Diuretics (a) Loop or thiazide-type diuretics increase K+ renal excretion. (b) Ineffective in patients with advanced kidney disease ii. Cation exchange resins (a) Sodium polystyrene sulfonate exchanges Na+ for K+, resulting in GI excretion of K+. Exercise caution in patients with kidney disease or heart failure caused by Na+ (and subsequent fluid) retention. (b) Because of its slow onset (2 hours) and unpredictable efficacy, sodium polystyrene sulfonate is not indicated for emergency treatment of hyperkalemia. (c) It was approved by the U.S. Food and Drug Administration in 1958, before demonstrated efficacy was required. No controlled trials show efficacy. (d) Oral dose of sodium polystyrene sulfonate is 15 g repeated every 6 hours as needed. This can be mixed in 20–100 mL of water or syrup, but it is no longer recommended to mix in 70% sorbitol because of the risk of intestinal necrosis (there are also reports with the premixed 33% sorbitol suspension, but 70% sorbitol appears to have a stronger correlation with intestinal necrosis). Bowel injury is linked to the deposition of drug crystals in the GI tract. Oral sorbitol can prevent constipation associated with the resin; however, the highest risk of intestinal necrosis occurs when administered to patients within 1 week of surgery (occurs in about 1.8% of patients). (e) Although the oral route is more effective, 30–50 g can also be given as a retention enema mixed in 100–200 mL of an aqueous vehicle (e.g., water, 10% dextrose) that has been warmed to body temperature and kept in the colon for 30–60 minutes, or up to 3 hours. Irrigate the colon afterward. Sorbitol is not recommended as a vehicle for rectal use because of the risk of intestinal necrosis and other serious GI adverse events. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-379 AL GRAWANY Fluids, Electrolytes, and Nutrition (f) A systematic review found that GI injury is also associated with sodium polystyrene preparations without sorbitol (Am J Med 2013;126:264). (g) Two potassium binders have largely supplanted sodium polystyrene sulfonate in the treatment of hyperkalemia. As opposed to sodium polystyrene sulfonate, patiromer exchanges Ca2+ for K+, resulting in GI excretion of K+. As with other binders, caution should be used if patiromer is administered with other medications because it may reduce their absorption. Like sodium polystyrene sulfonate, patiromer should not be used for life-threatening hyperkalemia, because it has a slower onset of action. The other potassium-binding agent, sodium zirconium cyclosilicate, works by exchanging potassium for hydrogen and sodium. Sodium zirconium cyclosilicate has a faster onset of action than patiromer. iii. Dialysis (a) It is used when other measures are ineffective or when severe hyperkalemia is present. (b) Plasma potassium falls by more than 1 mEq/L in the first hour of dialysis and by about 2 mEq/L after 3 hours of dialysis. (c) Hemodialysis removes K+ faster than peritoneal dialysis. (d) Monitor for rebound increase in K+ after dialysis. (e) It is used in patients with advanced kidney disease Patient Case 7. A 61-year-old man comes to the emergency department with shortness of breath and bilateral lower leg edema. Pertinent vital signs and laboratory values include heart rate 30 beats/minute, blood pressure 102/57 mm Hg, K+ 7.9 mEq/L, Na+ 139 mEq/L, glucose 278 mg/dL, Ca2+ 8.8 mg/dL, digoxin 2.2 ng/mL, BUN 49 mg/dL, and SCr 2.4 mg/dL. His ECG shows wide QRS and peaked T waves. His medical history includes heart failure, atrial fibrillation, coronary artery disease, peripheral arterial disease, and diabetes. The patient has peripheral intravenous access and an external pacemaker. Which treatment is most appropriate? A. Calcium gluconate 10 mL intravenously over 2 minutes. B. Insulin 10 units intravenously. C. Sodium bicarbonate 50 mEq intravenously over 10 minutes. D. Albuterol 10 mg nebulized over 10 minutes. VIII. DISORDERS OF MAGNESIUM HOMEOSTASIS A. Normal serum magnesium concentration is 1.7–2.3 mg/dL (1.4–1.8 mEq/L or 0.85–1.15 mmol/L). B. Hypomagnesemia (serum magnesium concentration less than 1.7 mg/dL) 1. Usually associated with impaired intestinal absorption (e.g., ulcerative colitis, diarrhea, pancreatitis, chronic laxative abuse), inadequate intake, hypokalemia, or increased renal excretion (e.g., diuretic use) a. Common in hospitalized patients b. Often associated with alcoholism and delirium tremens 2. Often occurs concurrently with hypokalemia and hypocalcemia 3. Signs and symptoms a. Neuromuscular symptoms include tetany, twitching, and seizures. b. Cardiovascular symptoms include arrhythmias, sudden cardiac death, and hypertension. 4. Treatment a. Oral supplements (e.g., magnesium oxide, magnesium-containing antacids, or laxatives) can be used for asymptomatic patients; however, treatment is limited by the high frequency of diarrhea. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-380 Fluids, Electrolytes, and Nutrition b. c. d. e. Symptomatic patients should initially be treated with 1–4 g (8–32 mEq) of magnesium sulfate by slow intravenous infusion (about 1 g/hour to avoid hypotension or increased renal excretion because of rapid administration). Initial boluses can be followed by about 0.5 mEq/kg/day added to intravenous fluid and administered as a continuous infusion. For emergency treatment (e.g., torsades), magnesium can be administered by intravenous push. Asymptomatic patients with mild to moderate hypomagnesemia should also be treated with 1–4 g of magnesium sulfate by slow intravenous infusion. Reduce the dose by half in patients with kidney insufficiency. About half of administered magnesium is excreted in the urine; therefore, magnesium replacement can occur over 3–5 days. Intravenous magnesium has also been affected by shortages. Reserve use for symptomatic patients. C. Hypermagnesemia (serum magnesium greater than 2.3 mg/dL) 1. Rarely occurs and is generally associated with chronic kidney disease 2. Signs and symptoms include nausea, vomiting, bradycardia, hypotension, heart block, asystole, respiratory failure, and death; signs and symptoms rarely occur unless magnesium concentration is greater than 4–5 mg/dL. 3. Treatment a. Discontinue all magnesium-containing medications. b. Asymptomatic patients with normal kidney function can be treated with 0.9% sodium chloride and loop diuretics. c. Symptomatic patients should be treated with 100–200 mg of elemental Ca2+ administered intravenously over 5–10 minutes for cardiac stability. d. Hemodialysis may be needed for patients with kidney disease. IX. DISORDERS OF PHOSPHORUS HOMEOSTASIS A. Normal serum phosphorus concentration is 2.5–4.5 mg/dL. B. Hypophosphatemia (serum phosphorus concentration less than 2.5 mg/dL) 1. Causes of hypophosphatemia a. Increased renal elimination (e.g., diuretics, glucocorticoids, sodium bicarbonate) b. Rapidly feeding patients with chronic malnutrition (see “refeeding syndrome” in Parenteral Nutrition section) c. Respiratory alkalosis d. Treatment of diabetic ketoacidosis; phosphorus shifts into the IC compartment as diabetic ketoacidosis is corrected 2. Signs and symptoms a. Tissue hypoxia can occur because of a decrease in oxygen release to peripheral tissues. b. Neurologic manifestations include confusion, delirium, seizures, and coma. c. Pulmonary and cardiac symptoms can include respiratory failure, difficulty weaning from mechanical ventilation, heart failure, and arrhythmias. d. Other organ systems affected include muscle, hematologic, bone, and kidney. 3. Prevention and treatment a. Prevent hypophosphatemia by supplementing intravenous fluid with 10–30 mmol/L intravenous phosphorus in patients at risk of hypophosphatemia (e.g., malnourished, alcoholism, diabetic ketoacidosis). ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 1-381