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251

Also at risk are patients who receive prolonged parenteral nutrition

252 and those who

undergo prolonged nasogastric suction.

253 Hypomagnesemia may be present in

patients who have increased magnesium requirements, such as pregnant women and

infants.

254 Conditions associated with steatorrhea, such as nontropical sprue and

short-bowel syndrome, can result in reduced GI magnesium absorption. Insoluble

magnesium soaps may be formed in the GI tract because of the presence of

unabsorbed fat.

255 Hypomagnesemia can also occur in patients with a bowel

resection

256 and severe diarrhea.

257 A rare genetic disorder has also been reported in

patients with defective GI magnesium absorption.

258 An impaired carrier-mediated

magnesium transport system is believed to be responsible for the symptomatic

deficiency, which requires high oral magnesium intake to overcome the defect.

Renal magnesium wasting can be caused by a primary defect or be secondary to

systemic factors. A rare form of renal magnesium wasting is congenital.

259 Various

drugs can induce hypomagnesemia through increased renal loss: cisplatin,

260

aminoglycosides,

261 cyclosporine,

262 and amphotericin B.

263 Use of loop and thiazide

diuretics can also result in hypomagnesemia, which can be reversed with the

concurrent use of amiloride or triamterene. Magnesium depletion can be associated

with phosphate depletion,

264 calcium infusion,

265 and ketoacidosis.

266 Acute and

chronic ingestion of alcohol will result in increased renal magnesium loss.

253,267

Various endocrinologic disorders, such as SIADH,

268 hyperthyroidism,

269

hyperaldosteronism,

244 and postparathyroidectomy,

271 are also associated with

hypomagnesemia.

R.J. could be hypomagnesemic for many reasons. His long history of alcohol use,

malnutrition, and malabsorption may all have contributed to his magnesium deficit.

The vomiting and diarrhea that he experienced could have reduced GI magnesium

absorption. Use of furosemide and nasogastric suction while in the hospital could

also have exacerbated his magnesium depletion through renal and GI losses,

respectively.

CLINICAL MANIFESTATIONS

CASE 27-13, QUESTION 2: What are the clinical manifestations of hypomagnesemia in R.J.?

Magnesium depletion can result in abnormal function of the neurologic,

neuromuscular, and cardiovascular systems. Hypomagnesemia lowers the threshold

for nerve stimulation, resulting in increased irritability. Typical findings include

Chvostek and Trousseau signs, muscle fasciculation, tremors, muscle spasticity,

generalized convulsions, and possibly tetany. The patient may experience weakness,

anorexia, nausea, and vomiting, as seen in R.J. Hypokalemia, hypocalcemia, and

alkalosis may be present as well. In patients who are moderately depleted, changes

in the ECG include widening of the QRS complex and a peaking T wave.

272

In severe

depletion, a prolonged PR interval and a diminished T wave may be seen.

Ventricular arrhythmias have also been reported in some patients.

273

TREATMENT

CASE 27-13, QUESTION 3: Outline a regimen to replenish the body stores of magnesium for R.J., and

develop a monitoring plan to assess efficacy and potential adverse effects.

The specific regimen for magnesium replenishment depends on the clinical

presentation of the patient. Symptomatic patients require more aggressive parenteral

therapy, whereas oral replacement may suffice for asymptomatic hypomagnesemia.

Patients with life-threatening symptoms, such as seizures and arrhythmias, need

immediate magnesium infusion. Because serum magnesium concentrations do not

reflect total body stores, symptoms are more important determinants of the urgency

and aggressiveness of therapy.

The body stores of magnesium must be replenished slowly. Serum magnesium

concentrations may return to the normal range within the first 24 hours, but total

replenishment of body stores may take several days. Furthermore, approximately

50% of the administered IV dose of magnesium will be excreted in the urine.

273

Because the threshold for urinary magnesium excretion is low, the abrupt increase in

serum magnesium after an IV dose will result in increased urinary magnesium

excretion despite a total body magnesium deficit. Conversely, in patients with renal

insufficiency, decreased excretion of magnesium will place the patient at risk for

hypermagnesemia. A reduced rate of magnesium administration and frequent

monitoring of serum magnesium concentrations are therefore necessary in patients

with renal dysfunction.

Oral replacement of magnesium is indicated for asymptomatic patients with mild

depletion. Magnesium-containing antacids, milk of magnesia, and magnesium oxide

are effective choices for replacement. Sustained-release preparations, such as Slow

Mag

p. 594

p. 595

(magnesium chloride) or Mag-Tab SR (magnesium lactate), are preferred,

however. With 5 to 7 mEq (2.5–3.5 mmol or 60–84 mg) of magnesium per tablet, six

to eight tablets should be given daily in divided doses for severe magnesium

depletion. For mild and asymptomatic disease, two to four tablets per day may be

sufficient.

274 A diet high in magnesium (cereals, nuts, meat, fruits, fish, legumes, and

vegetables) will also help replenish body stores and prevent depletion.

275

For patients with symptomatic hypomagnesemia, such as R.J., parenteral

magnesium replacement is indicated. The magnesium deficit in patients with chronic

alcoholism is estimated to be 1 to 2 mEq/kg.

276 Because up to half of the IV

magnesium dose will be excreted in the urine during replacement, approximately 2 to

4 mEq/kg will be needed to replenish R.J.’s body store.

277 Magnesium of 1 mEq/kg ,

as magnesium sulfate 10% solution, should be administered IV in the first 24 hours.

Half of this amount is given in the first 3 hours, and the remaining half is infused over

the course of the rest of the day. This dose may be repeated to keep the serum

magnesium concentration greater than 1.0 mg/dL.

274 Later on, 0.5 mEq/kg of

magnesium may be replenished daily for up to 4 additional days.

277,278 Magnesium can

be given IM as 50% solution, but the injections are painful and potentially sclerosing,

and multiple administrations are needed. Therefore, the IV route is the preferred

mode of parenteral administration. For patients with symptomatic hypomagnesemia

who are unstable, such as those experiencing seizures or life-threatening arrhythmias,

16 mEq of magnesium sulfate may be administered as a short IV infusion over the

course of 2 minutes, followed by 16 mEq over the course of 20 minutes, then 16 to 24

mEq over the course of 2 to 4 hours.

278,279

After IV magnesium administration, the patient should remain in a supine position

to avoid hypotension. He should be monitored carefully for marked suppression of

deep tendon reflexes (magnesium, 4–7 mEq/L); ECG, BP, and respiration changes;

and high serum magnesium levels. Facial flushing, a sensation of warmth, and

sweatiness may result from vasodilation secondary to a rapid magnesium infusion.

277

Particular caution is warranted in patients with renal impairment, in whom the rate of

magnesium should be reduced. These patients should be monitored frequently to

avoid toxicities related to hypermagnesemia. IV magnesium should also be

administered cautiously in patients with severe atrioventricular heart block or

bifascicular blocks because magnesium possesses pharmacologic properties similar

to calcium channel blockers.

277,279

In patients who exhibit hypomagnesemia secondary to a thiazide or loop diuretic,

amiloride may be added to reduce renal magnesium loss by increasing reabsorption

in the cortical collecting tubule.

274

CASE 27-13, QUESTION 4: For the initial 2 days of hospitalization, R.J. received 3 mEq/kg of IV

magnesium sulfate. However, his serum magnesium concentration remained less than 1.5 mEq/L. What might

have contributed to the lack of favorable response to the magnesium therapy?

The total amount of magnesium administered to R.J. during the past 2 days was

higher than the usual recommended rate (4–5 days) of magnesium replenishment,

leading to renal excretion of a large portion of the dose.

280 Furthermore, the use of

nasogastric suction and furosemide have increased the magnesium loss during the

replacement period, and hypokalemia may have reduced the effectiveness of

magnesium replacement. In a patient whose serum magnesium concentration does not

increase after appropriate magnesium therapy, a 24-hour urine collection to assess

magnesium renal excretion can be helpful. A low urinary magnesium concentration is

consistent with magnesium depletion, whereas high urinary magnesium excretion in

the presence of hypomagnesemia suggests renal magnesium wasting.

Hypermagnesemia

ETIOLOGY

CASE 27-14

QUESTION 1: J.O., a 63-year-old man with renal insufficiency, was admitted to the hospital because of

increasing weakness during the past several days. J.O. began taking a magnesium–aluminum hydroxide antacid

several times daily 2 weeks ago when he exhibited stomach upset. Physical examination reveals hypotension

and depressed deep tendon reflexes. The ECG reveals prolonged PR and QRS intervals. The serum

magnesium concentration is 6.5 mEq/dL. What is the most likely cause of hypermagnesemia in J.O.?

Because the kidney is the primary route of magnesium elimination, renal

impairment is a virtual requisite for hypermagnesemia (see Chapter 28, Chronic

Kidney Diseases). A common cause of hypermagnesemia is the use of magnesiumcontaining medications, such as antacids and laxatives, by patients with impaired

renal function, including older adults. When a patient with renal failure, such as J.O.,

takes magnesium-containing medications, the serum magnesium concentration can

increase substantially, resulting in toxicities. Hypermagnesemia may be seen when

the creatinine clearance drops to less than 30 mL/minute; an inverse relationship is

observed between the serum magnesium concentrations and the creatinine

clearances.

281 Hypermagnesemia is also seen in patients with acute renal failure

during the oliguric phase, but not the diuretic phase.

282 Other potential causes of

hypermagnesemia include adrenal insufficiency,

232 hypothyroidism,

283

lithium,

283

magnesium citrate used as a cathartic for drug overdose,

284 and parenteral magnesium

given for preeclampsia.

285

CLINICAL MANIFESTATIONS

CASE 27-14, QUESTION 2: Describe the usual clinical presentation of a patient with hypermagnesemia.

An elevated magnesium serum concentration alters the normal function of the

neurologic, neuromuscular, and cardiovascular systems. When the serum magnesium

concentration is greater than 4 mEq/L, deep tendon reflexes are depressed; they are

usually lost at greater than 6 mEq/L. Flaccid quadriplegia can develop when the

concentration is greater than 8 to 10 mEq/L. Respiratory paralysis, hypotension, and

difficulty in talking and swallowing may also be present. Changes in the ECG may

include a prolonged PR interval and widening of the QRS complex. Complete heart

block may be seen at concentrations of approximately 15 mEq/L. In mild

hypermagnesemia, the patient may experience nausea and vomiting.

Drowsiness, lethargy, diaphoresis, and altered consciousness may be present at

higher serum magnesium concentrations. J.O.’s increasing weakness, hypotension,

depressed deep tendon reflexes, and ECG findings are consistent with

hypermagnesemia.

TREATMENT

CASE 27-14, QUESTION 3: How should J.O.’s hypermagnesemia be treated?

If magnesium-containing medications are discontinued in patients with

hypermagnesemia, the serum magnesium concentration will usually return to the

normal range through renal elimination. When potentially life-threatening

complications are present, as in J.O., 5 to 10 mEq of IV calcium should be

administered to

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p. 596

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