140

In a diabetic patient who

is both hyperkalemic and hyperglycemic, insulin alone may be insufficient. If the

patient has end-stage renal disease, the insulin–glucose combination is more

predictable in lowering plasma potassium concentrations than sodium

bicarbonate.

110,163,165

β2

-Agonists, by binding with the β2

-adrenoreceptor to activate adenylate cyclase,

have an additive effect with the insulin–dextrose combination in decreasing serum

potassium. When albuterol nebulization is used alone, the hypokalemic effect may be

inconsistent.

166 Although side effects of albuterol nebulization are minimal, these

agents can cause tachycardia and should be used cautiously in patients with

underlying coronary artery disease.

167 Although not commercially available, IV

albuterol has a faster onset of action (30 vs. 90 minutes).

168

In contrast, nebulization

is easier to set up and is less likely to be associated with tachycardia, but multiple

doses are often necessary to attain an adequate response. In conjunction with the

insulin–dextrose combination, albuterol (20 mg dissolved in 4 mL of saline) can be

administered by nebulization and inhaled over the course of 10 minutes to further

decrease serum potassium, if necessary.

169

Although sodium bicarbonate has long been recommended for the acute treatment

of hyperkalemia, its efficacy in this setting has been questioned.

110,163 The usual dose,

44 to 50 mEq, is infused slowly over the course of 5 minutes and repeated in 30

minutes when necessary. Alternatively, it can be added to dextrose and saline

solution to form an isotonic sodium bicarbonate infusion.

170 The hypokalemic effect

is variable and may be delayed up to 4 hours, and it is reportedly ineffective in

patients on maintenance hemodialysis. Although bicarbonate therapy is not a reliable

option in the acute management of hyperkalemia, it may be beneficial in patients with

severe metabolic acidosis (pH < 7.20).

110 Potential complications of sodium

bicarbonate therapy are volume overload and metabolic alkalosis.

The definitive treatment of hyperkalemia is removal of potassium from the body.

Sodium polystyrene sulfonate (SPS) with sorbitol is an ion-exchange resin that binds

potassium in the bowel and enhances its excretion in the stools.

171 Each gram of SPS

exchanges 0.5 to 1.0 mmol of potassium for an equal amount of sodium. SPS can be

administered orally or rectally; the latter route is preferred in the symptomatic

hyperkalemic patient because intestinal potassium exchange occurs mainly in the

ileum and colon. A dose of 50 g of SPS in sorbitol can be given as an enema,

retained for at least 30 to 60 minutes, at 4-hour to 6-hour intervals. For nonemergent

removal of body potassium, 15 to 60 g of SPS with sorbitol suspension can be given

orally, which can be repeated as needed. The onset of action is approximately 1 to 2

hours after administration. The major side effects are GI intolerance, including

constipation, diarrhea, and sodium overload. Potentially fatal intestinal necrosis,

though rare, have been reported with the use of SPS with sorbitol.

172

It is unclear if

intestinal injury is caused by SPS or sorbitol, but FDA has released a safety warning

against the use of SPS in individuals with impaired bowel function.

173

Hemodialysis is the most efficient way to remove potassium; potassium clearance

by peritoneal dialysis is lower than for hemodialysis.

174 The hypokalemic effect is

immediate and lasts for the duration of dialysis

163

; however, the amount of potassium

removed is variable.

175 Dialysis with a glucose-free dialysate will remove 30%

more potassium than one containing 200 mg/dL of glucose.

176 Table 27-3 summarizes

the treatment alternatives for hyperkalemia. Although V.C. is receiving chronic

maintenance hemodialysis, the severe cardiac effects of hyperkalemia she

experienced warrant immediate institution of the aforementioned measures while

awaiting preparation for dialysis. Loop diuretics, which enhance kaliuresis, are

rarely useful in managing severe hyperkalemia, especially in patients with renal

dysfunction.

Two new oral agents, patiromer and sodium zirconium cyclosilicate, currently still

under investigation, have been shown to be effective in reducing serum potassium

concentrations in patients with mild-to-moderate hyperkalemia.

177,178 As the studies

conducted thus far are short-term studies and excluded patients with severe

hyperkalemia, the long-term beneficial and adverse effects of these agents need to be

further evaluated.

After V.C.’s condition stabilized, she admitted to eating a lot of fruits in the past

few days. Because noncompliance with dietary potassium restriction is the most

common cause for acute and chronic hyperkalemia in a dialysis patient, V.C. should

be counseled to consume potassium-rich foods in moderation. Medications that

impair V.C.’s extrarenal potassium handling should be avoided. If V.C. remains

chronically hyperkalemic, SPS will then be needed, probably 3 or 4 times weekly. If

hyperkalemia is associated with metabolic acidosis, however, an alkalinizing agent

should be added to maintain a serum bicarbonate concentration of about 24 mEq/L.

CALCIUM

Homeostasis

Healthy adults have approximately 1,400 g of calcium in the body, of which greater

than 99% is stored in bone. Nonetheless, the 0.1% of the total body calcium that is in

the plasma and extravascular fluid plays a critical role in many physiologic and

metabolic processes. Calcium is important in maintaining nerve tissue excitability

and muscle contractility. It regulates the secretory activities of exocrine and

endocrine glands and serves as a cofactor for enzyme systems and the coagulation

cascade. It is also an essential component of bone metabolism.

Plasma calcium concentration is normally maintained within a relatively narrow

range: 8.5 to 10.5 mg/dL. This is accomplished through a complex interaction

between parathyroid hormone (PTH), vitamin D, and calcitonin, as well as the effect

of these hormones on calcium metabolism in bone, the GI tract, and the kidneys.

Normally, about 40% of the plasma calcium is protein-bound, primarily to

albumin, and is nondiffusible.

126 Of the 60% that is diffusible, about 13% is

complexed to various small ligands: phosphate, citrate, and sulfate. The remaining

47% is ionized, free, and physiologically active. Changes in serum protein

concentration will alter the concentrations of both protein-bound and total calcium.

Therefore, the serum albumin concentration needs to be monitored to adequately

interpret the total serum calcium concentration. Each 1-g/dL increase in serum

albumin concentration is expected to increase the protein-bound calcium by 0.8

mg/dL, thus increasing the total serum calcium concentration by the same amount. The

total serum calcium therefore can be corrected by the following equation:

p. 586

p. 587

Table 27-3

Treatment of Hyperkalemia

Drug Mechanism Dose Comment

Calcium gluconate Reverse cardiotoxicity

caused by K+

10 to 20 mL 10% calcium

gluconate IV over 1 to 3

minutes; may repeat once

Onset: 1 to 3 minutes

Duration: 30 to 60

minutes. (K+) remains

unchanged

Insulin and glucose Redistribution of K+

intracellularly

5 to 10 units regular insulin

with 50 mL 50% dextrose,

then D10W infused at 50

mL/hour

a

Onset: 15 to 30 minutes

Duration:several hours

Watch for hypoglycemia

and hypokalemia. Does

not ↓ total body K+

β2

-agonists (e.g.,

albuterol)

Redistribution of K+

intracellularly

Oral: 2 or 4 mg TID–QID

Inhalation: 20 mg in 4 mL

saline via nebulizer

Onset: 30 to 60 minutes

Duration: 2 hours

SPS Cationic binding resin. 1 g

of resin binds 0.5 to 1 mEq

K+ in exchange for Na+

Oral: 15 to 20 g with 20 to

100 mL 70% sorbitol

every 4 to 6 hours; PRN

preferred

Retention enema: 50 g in

50 mL (70% sorbitol and

150 mL H2O). Retain 30

minutes and follow with

nonsaline irrigation

Onset: Slow; 50 g will

lower (K+) by 0.5 to 1

mEq/L over 4 to 6 hours;

watch for Na+ overload

(100 mg Na+/1 g SPS)

NaHCO3 Redistribution of K+

intracellularly

50 mEq IV for 5 minutes.

Repeat PRN

Onset: variable, ≈30

minutes

May work best in acidosis

Watch for Na+ overload

and hyperosmolar state

No change in total body

K+

Dialysis Removal of K+ Use as last resort

aGlucose unnecessary in patients with high glucose concentrations.

BID, twice daily; IV, intravenous; PRN, as needed; QID, 4 times daily; SPS, sodium polystyrene sulfonate; TID, 3

times daily.

where normal albumin = 4 g/dL.

Calcium is also bound to plasma globulins at the rate of 0.16 mg of calcium for

each gram of globulin. When the total globulin concentration exceeds 6 g/dL,

moderate hypercalcemia may be seen. Changes in pH have an effect on calcium

protein-binding; acidosis decreases calcium binding, resulting in an increase in freecalcium fraction, whereas an increase in pH reduces the amount of ionized calcium.

Changes in serum phosphate and sulfate concentrations are expected to alter the

fraction of ionized calcium because of the formation of calcium complexes with these

anions. The presence of abnormal plasma proteins with a high affinity for calciumbinding, as in patients with multiple myeloma, also affects the preceding equation for

serum calcium concentration correction.

179

Serum calcium concentration is regulated by the combined effect of GI absorption

and secretion, renal reabsorption, and turnover of the skeletal calcium pool. Several

hormones, such as PTH, 1,25-dihydroxyvitamin D3

, and calcitonin, have significant

effects on these processes. Balanced diets generally contain 600 to 1,000 mg of

calcium, although the minimum daily requirement is 400 to 500 mg. Calcium is

primarily absorbed in the duodenum and jejunum via saturable and nonsaturable

processes.

180 The nonsaturable process is diffusive in nature and varies with luminal

calcium concentration. The saturable carrier-mediated component is stimulated by

1,25-dihydroxyvitamin D3

. Absorption of calcium is enhanced when the calcium

intake is low and also when the demand is increased, such as in pregnancy and when

total body calcium is depleted. Conversely, protein deficiency can reduce intestinal

calcium absorption, presumably because of the reduced amount of specific calciumbinding protein.

181 Calcium is also secreted into the bowel lumen, which may account

for the presence of a negative calcium balance when there is no oral calcium

intake.