What is A 75 years female patient with fracture neck of femur 1 month hack, presents with 2 days history of altered sensorium & decreased urine output. Urea is 140 mg/dl, creatinine is 2 mg/dl, Ca is 15.5 mg/dl. All of will be useful in immediate treatment except and explain in detail?
Furosemide Initial therapy of severe hypercalcemia includes the simultaneous administration of saline, calcitonin and a biphosphonate. Isotonic saline Isotonic saline corrects possible volume depletion due to hypercal- cemia induced urinary salt wasting and in some cases vomiting. Hypovolemia exacerbates hypercalcemia by impairing the renal clearance of calcium. - The rate of saline infusion depends upon several factors including the severity of hypercalcemia, the age of the patient and the presence of comorhid conditions paicularly underlying cardiac or renal disease. - A reasonable regimen in the absence of edema is the administration of isotonic saline at an initial rate of 200-300 ml/h that is then adjusted to maintain the urine output at 100-150 ml/h, - Saline therapy requires careful monitoring since it can lead to fluid overload in patients who cannot excrete the administered salt because of impaired renal function which can be induced by hypercalcemia or hea failure. - The saline infusion should be stopped in patients who develop edema and a loop diuretic may be necessary. Saline therapy rarely normalizes the serum calcium concentration in patients with more than mild hypercalcemia. Saline therapy beyond that necessary to restore euvolemia has fallen out of our for two reasons: - The availability of drugs such as biphosphonates and calcitonin that inhibit bone resorption which is primarily responsible .for hypercalcemia. - The requirement for careful monitoring because of potential fluid and electrolyte complications resulting .from a massive saline infusion and furosemide induced diuresis such as hypokalemia, hypomagnesemia and volume depletion if the diuretic induced losses are not replaced. Furosemide in hypercalcemia In the past administration of loop diuretic was initiated routinely once fluid repletion had been achieved to fuher increase urinary calcium excretion. - However this practice was based upon an approach that involved intensive administration of furosemide (80-100 mg every one to two hours) with aggressive fluid hydration. - In the patients with hypercalcemia receiving saline hydration, routinely using a loop diuretic is not suggested. However in individuals with renal insufficiency or hea failure, careful monitoring and judicious use of loop diuretics may be required to prevent. fluid overload. - In the absence of renal failure or hea failure, loop diuretic therapy to directly increase calcium excretion is not recommended because of potential complications and the availability of drugs that inhibit bone resorption. William's Endocrinology on I.V. furosemide in hypercalcemia Use of furosemide or other potent loop diuretics to promote calciuresis can exacerbate extracellular volume depletion if used too early in the course of treatment. In the light of availability of highly effective alternatives for the therapy of hypercalcemia such drugs probably are best avoided except in circumstances in which rigorous hydration fails to improve severe hypercalcemia or might ppt precipitase C.H. F.. In any case prolonged use of saline induced dieresis without early introduction of an effective antiresorptive agent is ill advised and ultimately futile. Concurrent treatment with biphosphonates with or without calcitonin is typically required to treat moderate to severe hypercalcemia. Calcitonin Pharmacological doses of serum calcitonin reduce the serum calcium concentration by increasing renal calcium excretion and, more impoantly by decreasing bone resorption interference with osteoclast maturation. - Calcitonin is relatively safe and nontoxic although a relatively weak agent, it works rapidly, lowering the serum calciwn concentration by maximum of 1-2 mg/dl beginning within, four to six hours. Thus it is useful in combination with hydration .for the initial management of severe hypercalcemia. The efficacy of calcitonin is limited to the first 48 hours even with repeated doses, indicating the development of tachyphylaxis, perhaps due to receptor downregulation. - Because of its limited duration of effect, calcitonin is most beneficial in symptomatic patients with calcium >14 mg/L when combined with hydration and biphosphonates. Calcitonin and hydration provide a rapid reduction in serum calcium concentration while a biphosphonate provides a more sustained effo. Biphosphonates - The biphosphonates are nonhydrolyzable analogues of inorganic pyrophosphate that adsorb to the surface of bone hydroxyapatite and inhibits calcium release by interfering with osteoclast mediated bone resorption. They are effective in treating the hypercalcemia resulting ,from excess of any cause. All of the biphosphonates are relatively nontoxic compounds and they are more potent than calcitonin and saline .for patients with moderate or severe hypercalcemia. As a result, they have became the preferred agents for management of hypercalcemia due to excessive bone resorption from a variety of causes. -Their maximum effifct occurs in two to four days so that they are usually given in conjunction with saline / calcitonin which reduce serum calcium concentration more rapidly. Biphosphonates in renal impairment "Biphosphonates have potential nephrotoxicity. But this does not mean that they are completely avoided in patients with renal failure" In clinical trials of zolindronate for the treatment of hypercalcemia, patients with serum creatinine concentration as high as 4.5 mg/d1 were eligibile for paicipation. In addition there are case repos of successful use of ibandronate and pamidronate in patients with renal failure and multiple myeloma, renal insufficiency (creatinine 2 1.5 mg/dl) and in hemodialysis patients with severe hypercalcemia. - However caution is suggested when using intravenous to treat hypercalcemia in patients with impaired renal function (creatinine > 4.5 mg/dl). - Adequate hydration with saline and t/t with a reduced dosage and/or slower infusion rate (4 mg Z4 over 30-60 minutes, 30-45 mg pamidronate over 4 hours, 2 mg ibandronate over one hour / ?nay minimize risk). Dialysis -Hemodialysis with little or no calcium in the dialysis fluid and peritoneal dialysis (though it is slower) are both effective therapies for hypercalcemia and are considered tit of last reso. - Dialysis may be indicated in patients with severe malignancy associated hypercalcemia and renal insufficiency or hea, failure, in whom hydration cannot be safely administered. - The use of hypercalcemia in patients with without renal failure may require alterations in the composition of conventional dialysis solutions in order to avoid an exacerbation or induction of other metabolic abnormalities, paicularly hypophosphatemia.