Page 1389 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

962 PART 8: Renal and Metabolic Disorders

TABLE 99-12 Treatment of Hypercalcemia
Drugs Dose Onset Effectiveness Duration Concerns
Saline and Infuse saline at a rate high enough to 24-48 h 0.5-2.0 mg/dL; frequent 3 d Volume overload, electrolyte
furosemide achieve urine output of 250-300 mL/h treatment failures abnormalities
Calcitonin 4-8 IU/kg SC or IV bid-qid for 1-2 d 4 h 2-3 mg/dL 1-4 d Tachyphylaxis, nausea, rash, flushing,
malaise
Hemodialysis 3 h with low-calcium dialysate Significant decrease 4-6 mg/dL in 3 h Variable; may be repeated as Cardiovascular instability from rapid
(0-1 mmol/L) in calcium after 1 h needed decrease in calcium
Plicamycin 25 µg/kg IV over 4-6 h, repeat qd 12-72 h 1-2 mg/dL per dose 2-14 d Hepatic, renal, bone marrow toxicity;
( mithramycin) thrombocytopenia
Pamidronate a Single infusion over 2, 4, or 24 h; 48 h with 30 mg lowered Ca by 2.2 mg/dL; 10-30 d; dosing every 2 weeks Limit to 30 mg in patients with renal
30 mg for Ca <12 mg/dL; 60 mg for Ca normocalcemia 60 mg lowered Ca by 3.3 mg/ increased maintenance of failure; fever in 20%; hypocalcemia
12-13.5 mg/dL at 96 h dL; 90 mg lowered Ca by normocalcemia (asymptomatic)
90 mg for Ca >13.5 mg/dL 3.9 mg/dL
Zoledronate b 4 mg given over 5 min; 8 mg for relapse 96 h; calcium was not 50% remission at 4 d; 88% 32 d for 4 mg; 43 d for 8 mg Fever; rare (1-2%) renal insufficiency
or refractory hypercalcemia assessed prior to 96 h at 7 d
Chloroquine c 250 mg bid 1-3 d Able to normalize serum Maintenance chloroquine Only used in patients with increased
calcium in sarcoidosis 1,25 dihydroxyvitamin D; ineffective
in hypercalcemia of malignancy
Corticosteroids Hydrocortisone 200-400 mg/d for 3-5 d 4-7 d 0.5-3 mg/dL 3-4 d Hyperglycemia, immunosuppression,
electrolyte abnormalities
Data from these references:
209 b
211 c
a Nussbaum et al ; Major et al ; Adams and Kantorovich. 339

Dialysis Dialysis should be considered in patients with severe symptom- phosphate (eg, organic phospholipids and phosphorylated proteins,
atic hypercalcemia that is unresponsive to drug therapy. Low-calcium which represent two-thirds of all phosphorus located in the serum, are
hemodialysis (dialysate calcium of 0-0.5 mmol/L) has repeatedly been not measured in the lab assay). The normal range of phosphorus is 3
shown to rapidly correct hypercalcemia. Calcium clearance for hemo- to 4.5 mg/dL. The molecular weight is 31 so the normal concentration
dialysis ranges from 270 to 680 mg/h. While there is a risk of rebound in SI units is 1 to 1.5 mmol/L (1.7 to 2.6 mEq/L). Normal values of
hypercalcemia, many patients are able to maintain normocalcemia with phosphorus vary with age (higher levels in younger people). The upper
medical management following a single dialysis session. Continuous limit of normal in infants is 6.5 mg/dL and adult ranges are not found
212
renal replacement therapy (CRRT) has been used in cases in which until late adolescence. The majority (80%) of phosphorus is mineral-
rebound hypercalcemia has been a problem. CRRT can be paired with ized in bone with almost all of the remainder in the intracellular com-
citrate regional anticoagulation, which chelates free calcium, allowing partment. Only 0.1% of total body phosphorus is in the extracellular
rapid and durable control of hypercalcemia. 213 compartment.
Initially calcium and vitamin D preparations should be stopped. The ■ RENAL HANDLING OF PHOSPHORUS
Overview Treatment of hypercalcemia may utilize multiple modalities.
next action should be to administer saline to restore euvolemia. In the Ninety percent of serum phosphorus is filtered at the glomerulus and 75%
absence of evidence of volume overload, addition of a loop diuretic is no to 99% is subsequently resorbed. Na-P cotransporters in the proximal
longer recommended. In severe hypercalcemia a bisphosphonate should tubule resorb 70% of the filtered phosphorus. PTH and metabolic acidosis
be administered concurrently. As their onset of action can be delayed both decrease phosphate resorption by the Na-P transporters, increasing
up to 48 hours, calcitonin may be used as a bridge. In hypercalcemia of the renal excretion of phosphorus. Since phosphorus is resorbed con-
214
malignancy, bisphosphonates are the standard of care. In cases of endog- comitantly with sodium, any factor that decreases sodium resorption will
enous calcitriol excess, steroids are an effective acute treatment and decrease the tubular resorption of phosphorus (see Fig. 99-13).
chloroquine/hydroxychloroquine or ketoconazole may be used as long- Normal phosphorus concentrations are maintained by adjusting
term therapies. In patients with hyperparathyroidism, surgical treatment intestinal absorption and renal excretion. Hypophosphatemia stimu-
is the definitive therapy and seldom is additional therapy required. lates production of calcitriol, which increases intestinal phosphorus
Using bisphosphonates prior to surgery may result in severe hypocalce- and calcium absorption. The increased calcium suppresses PTH, and
mia postoperatively (hungry bone syndrome). In recalcitrant cases, or if decreased PTH will increase resorption of phosphorus in the proximal
patients are severely symptomatic, dialysis should be initiated. tubule (see Fig. 99-12).
215
PHOSPHORUS ■ HYPOPHOSPHATEMIA
■ METABOLISM Modest degrees of hypophosphatemia are common and of little conse-
quence. Severe hypophosphatemia, however, is rare. In a retrospective
In medicine phosphate and phosphorus are often used interchangeably, review of 55,000 serum phosphorus measurements, persistent phospho-
though using strict nomenclature, phosphorus refers to the element and rus levels less than 1.5 mg/dL were found in only 0.2%. The incidence
216
phosphate to the PO anion. Inorganic phosphorus exists as a weak is higher in selected patient series, being found in 10% to 30% of patients
2−
4
acid with three protons that can dissociate: H PO , H PO , HPO , with COPD exacerbations or those admitted to the ICU. 217-219 A higher
−
2−
2
4
3
4
4
PO . At a pH of 7.4, the ratio of HPO to H PO is 4 : 1 and the other incidence still has been reported in those with severe sepsis or major
3−
2−
−
4
2
4
4
forms are essentially nonexistent. Clinical labs report the concentration trauma. Because only a tiny proportion of the total body phosphorus
220
of elemental inorganic phosphorus which exists almost exclusively as is found in the vascular space, the serum phosphorus is not a reliable
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