Hypophosphatemia treatment

Barcia, J. E, Strife, C. R, and Langman, C. (1997). Infantile hypophosphatemia Treatment options to control hyperealcemip, hypcicalciuria, and chronic bone demineralization, /. Pediair 130, 825-828-... 

Parathyroidectomy is a treatment of last resort for sHPT, but should be considered in patients with persistently elevated iPTH levels above 800 pg/mL (800 ng/L) that is refractory to medical therapy to lower serum calcium and/or phosphorus levels.39 A portion or all of the parathyroid tissue may be removed, and in some cases a portion of the parathyroid tissue may be transplanted into another site, usually the forearm. Bone turnover can be disrupted in patients undergoing parathyroidectomy whereby bone production outweighs bone resorption. The syndrome, known as hungry bone syndrome, is characterized by excessive uptake of calcium, phosphorus, and magnesium for bone production, leading to hypocalcemia, hypophosphatemia, and hypomagnesemia. Serum ionized calcium levels should be monitored frequently (every 4 to 6 hours for the first 48 to 72 hours) in patients receiving a parathyroidectomy. Calcium supplementation is usually necessary, administered IV initially, then orally (with vitamin D supplementation) once normal calcium levels are attained for several weeks to months after the procedure. 

Severe (less than 1 mg/dL) or symptomatic hypophosphatemia should be treated with IV phosphorus replacement. The infusion of 15 mmol of phosphorus in 250 mL of IV fluid over 3 hours is a safe and effective treatment but the recommended dosage of IV phosphorus (5 to 45 mmol or 0.08 to 0.64 mmol/kg) and infusion recommendations (over 4 to 12 hours) are highly variable. 

Phosphate is critical to normal bone mineralization when phosphate stores are deficient, a clinical and pathologic picture resembling vitamin D-deficient rickets develops. However, such children fail to respond to the usual doses of vitamin D employed in the treatment of nutritional rickets. A defect in l,25(OH)2D production by the kidney has also been noted, because the serum l,25(OH)2D levels tend to be low relative to the degree of hypophosphatemia observed. This combination of low serum phosphate and low or low-normal serum l,25(OH)2D provides the rationale for treating such patients with oral phosphate (1-3 g daily) and calcitriol (0.25-2 Mg daily). Reports of such combination therapy are encouraging in this otherwise debilitating disease. 

A 72-year-old man was treated with ceftriaxone (2 g bd) and gentamicin (80 mg tds) for a severe urinary tract infection (75). On day 5 his serum potassium concentration was 3 mmol/1 with a normal serum creatinine and urine examination. Despite treatment with oral potassium chloride plus a high potassium diet, his serum potassium fell to 2.3 mmol/1 4 days later, accompanied by inappropriate kaliuresis, hypouricemia with inappropriate uri-cosuria, and hypophosphatemia with inappropriate phosphaturia. There was no bicarbonate wasting, but there was proteinuria 1.2 g/day, with a predominance of low molecular weight proteins in contrast, serum creatinine was normal and creatinine clearance was 78 ml/minute. The aminoglycoside was withdrawn with subsequent progressive improvement in renal proximal tubular function, which normalized 9 days later. 

Other iron compounds for intravenous use Saccharated iron oxide is strongly alkaline and hypertonic if injected outside the vein it can cause marked local reactions. Significant serum hypophosphatemia has on occasion been observed during treatment, accompanied by reduced renal tubular reabsorption of phosphate. The mechanism of these changes, which were reversible after stopping the iron injections, has not been clarified (13). 

Taylor A, Sherman NH, Norman ME. Nephrocalcinosis in X-linked hypophosphatemia effect of treatment versus disease. Pediatr Nephrol 1995 9(2) 173-5. 

Gatchalian RA, Popli A, Ejaz A A, Leehey DJ, Kjellstrand CM, Ing TS. Management of hypophosphatemia induced by high-flux hemodiafiltration for the treatment of vancomycin toxicity intravenous phosphorus therapy versus use of a phosphorus-enriched dialysate. Am J Kidney Dis 2000 36(6) 1262-6. 

Dibasic sodium phosphate is used in a wide variety of pharmaceutical formulations as a buffering agent and as a sequestering agent. Therapeutically, dibasic sodium phosphate is used as a mild laxative and in the treatment of hypophosphatemia. ... 

Phosphate occurs extensively in the body and is involved in many physiological processes since it is the principal anion of intracellular fluid. Most foods contain adequate amounts of phosphate, making hypophosphatemia (phosphate deficiency) virtually unknown except for certain disease states or in patients receiving total parenteral nutrition. Treatment is usually by the oral administration of up to 100 mmol of phosphate daily. 

The clinical manifestations and treatment of hypophosphatemia in the horse have not been reported and in humans there is no good evidence for commencing treatment in the absence of clinical signs (Bugg Jones 1998). Treatment options reported in small animals include i.v. (0.01-0.03 mmol/h per kg) and oral (0.5-2 mmol/kg daily) potassium phosphate or sodium potassium phosphate (Macintire 1997). The author has used this dose rate of phosphate in mature horses, with apparent clinical success. The potential effects of potassium phosphate on the plasma potassium concentration must be considered before commencing treatment. Glucose 1-phosphate (Bollaert et al 1995) and sodium phosphate administration i.v. have also been reported in humans. The safety of these treatments has not been evaluated in the horse. 

Intracellular phosphate may be lost in acidosis as a result of the catabolism of organic compounds within the cell. Diabetic ketoacidosis is associated initially with high-normal to increased serum phosphate. Treatment of the ketosis and acidosis with insuhn and intravenous fluids, however, results in a rapid reduction in the serum phosphate concentration. Consequently, patients being treated for diabetic ketoacidosis may have both intracellular phosphate depletion and hypophosphatemia. 

Treatment of hypophosphatemia depends on the degree of hypophosphatemia and the presence of symptoms. Patients with moderate hypophosphatemia may require only treatment of the underlying disorder or oral phosphate supplementation. In patients with marked symptoms of hypophosphatemia, particularly if respiratory muscle weakness is present, parenteral administration of phosphate may be indicated. 

R. Subramanian and R. Khardori Severe hypophosphatemia pathological implications, clinical presentations and treatment. Medicine 79,1 (2000). 

Antacids neutralize gastric acid, inactivate pepsin, and bind bile salts. Aluminum-containing antacids also suppress HP and enhance mucosal defense. ° G1 adverse effects are most common with antacids and are dose dependent. Magnesium salts cause an osmotic diarrhea, whereas aluminum salts cause constipation. Diarrhea usually predominates with magnesium/aluminum preparations. Aluminum-containing antacids (except aluminum phosphate) form insoluble salts with dietary phosphorus and interfere with phosphorus absorption. Hypophosphatemia occurs most often in patients with low dietary phosphate intake (e.g., malnutrition or alcoholism). Combined treatment with sucralfate may amplify the hypophosphatemia and the potential for aluminum toxicity (see section on sucralfate). 

H2-receptor antagonists are preferred for prophylaxis of SRMB. A large landmark study demonstrated that intravenous ranitidine was superior to oral sucralfate in preventing SRMB. Moreover, ranitidine did not increase the risk for nosocomial pneumonia, as the incidence of pneumonia was no different between the two treatment groups. In itself, critical illness places the patient at risk for nosocomial pneumonia. Also there are potential problems associated with sucralfate therapy (e.g., constipation, clogging tubes, hypophosphatemia, and drug interactions). ... 

The treatment for hypophosphatemia consists of intravenous phosphate salts in doses of 0.08 to 0.64 mmolAg for acute therapy and oral doses of 50 to 60 mmol/d for maintenance therapy. 

Finally, intravenous phosphate may rapidly reduce ionized calcium concentrations through the formation of insoluble calcium-phosphate salts. However, intravenous phosphate is extremely hazardous because extraskeletal precipitation of calcium-phosphate may result in metastatic calcification, hypotension, acute renal failure, or death. Therefore intravenous phosphates should be reserved for the extraordinary patient with severe hypercalcemia and concomitant hypophosphatemia. Oral phosphorus is not used chronically for the treatment of hypercalcemia because calcium-phosphate crystals may precipitate in the kidneys or other major organs when the calcium-phosphorus product is > 50 to 60 mg /dL . Serum calcium, phosphorus, and creatinine should be monitored closely. Oral phosphorus treatment is only indicated when there is concomitant hypophosphatemia (<2 mg/dL). 

The manifestations of hypophosphatemia depend on the chronicity and severity of the phosphate depletion. The major conditions associated with symptomatic hypophosphatemia are chronic alcoholism, intravenous hyperalimentation without adequate phosphate supplementation, and the chronic ingestion of antacids. Severe hypophosphatemia can also be seen during treatment of diabetic ketoacidosis and with prolonged hyperventilation. 

Subramanian R, Khardori R. Severe hypophosphatemia. Pathophysiologic implications, clinical presentation, and treatment. Medicine (Baltimore) 2000 79 1-78. 

Lentz RD, Brown DM, Kjellstrand CM. Treatment of severe hypophosphatemia. Ann Intern Med 1978 89 941-944. 

Clark CL, Sacks GS, Dickerson RN, et al. Treatment of hypophosphatemia in patients receiving specialized nutrition support using a graduated dosing scheme Results from a prospective clinical trial. Crit Care Med 1995 23 1504-1511. 

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