Long-term extracorporeal membrane oxygenation in acute respiratory distress syndrome

Intensive Car

Role of bone and kidney in tumor-induced hypercalcemia and its treatment with bisphosphonate and sodium chloride

The efficacy of intravenous aminohydroxypropylidene bisphosphonate as treatment for the hypercalcemia of malignancy was examined in a phase II multicenter study in 132 patients with a large variety of primary tumors. This provided an opportunity for an analysis of the separate influences of bone resorption and renal calcium handling on the genesis and maintenance of hypercalcemia. The results demonstrated that increased bone resorption is the major contributory factor and that inhibition with bisphosphonate normalizes the serum calcium concentration within five days in more than 90 percent of patients. Hypercalcemia is sustained by an inability of the kidney to deal efficiently with a chronically increased calcium load. This is influenced by the requirements of volume regulation in the presence of a sodium diuretic effect of hypercalcemia and is very sensitive to induced variations of sodium load. In addition, in a minority of patients, direct renal actions of tumor-derived humoral factors adversely reduce the ability to excrete calcium. For optimal treatment of tumor-induced hypercalcemia, bisphosphonate treatment should be combined with intravenous administration of saline solution

Reduces morbidity from skeletal metastases in breast cancer patients during long-term bisphosphonate (apd) treatment

131 patients with osteolytic metastases from breast cancer were randomised to receive long-term oral treatment with aminohydroxy-propylidene-bisphosphonate (APD), 300 mg daily (n = 70), or to act as controls (n = 61) in a multicentre trial. Specific antitumour therapy was at the discretion of the clinician and variable. An interim analysis was made after a median follow-up of 13 months in the APD group and 14 months in the controls. There was a significant reduction in pathological fractures and severe bone pain in the APD group, and hypercalcaemia was prevented. Consequently the necessity for radiotherapy for skeletal complications was more than halved; the number of systemic therapy changes was also reduced. Gastrointestinal side-effects of APD led to a drop-out of 8% of patients. Oral supportive APD therapy is simple and convenient, and significantly reduces skeletal morbidity in advanced breast cancer

Immobilization hypercalcaemia responding to intravenous pamidronate sodium therapy.

A 16 year old male developed symptomatic hypercalcaemia of immobilization on day 47 following a diving accident which had resulted in incomplete C4 tetraplegia. Following initial reduction in serum calcium with salmon calcitonin 100 U/day, symptomatic hypercalcaemia recurred. A single dose of 30 mg pamidronate sodium, given intravenously, caused serum calcium to fall within 48 hours. Initial mild, asymptomatic hypocalcaemia was followed by a return to sustained normocalcaemia. No major adverse reaction was encountered, and if further clinical experience confirms its efficacy, pamidronate sodium will warrant consideration as first-line therapy for immobilization hypercalcaemia

Infusion rate and pharmacokinetics of intravenous pamidronate in the treatment of tumour-induced hypercalcaemia.

We report the results of two consecutive randomized studies in the treatment of malignant hypercalcaemia with intravenous pamidronate. Overall normocalcaemia was achieved in greater than 90% of patients and a single infusion of 60 mg pamidronate given over 2 hours was as effective in restoring normocalcaemia as infusions given over 4, 8 or 24 hours. Similarly duration of normocalcemia after treatment with pamidronate and the control of the symptoms of hypercalcaemia were independent of infusion rate. Study of the pharmacokinetics of pamidronate in the treatment of hypercalcaemia show this drug to have a very high clearance due to calcified tissue retention and renal excretion. The initial half life of the drug in plasma is very short and most of the drug is cleared before distribution equilibrium is achieved. Short infusions of pamidronate are as safe and effective as infusions given over a longer time and are therefore to be preferred because of their greater convenience