Saline infusion

Primary therapy is based on disease severity and type of hemorrhage.7 Most patients with mild to moderate disease and a minor bleeding episode can be treated with l-desamino-8-D-arginine vasopressin [desmopressin acetate (DDAVP)], a synthetic analog of the antidiuretic hormone vasopressin. DDAVP causes release of von Willebrand factor (vWF) and factor VIII from endogenous storage sites. This formulation increases plasma factor VIII levels by three- to fivefold within 30 minutes. The recommended dose is 0.3 mcg/kg intravenously (in 50 mL normal saline infused over 15 to 30 minutes) or subcutaneously or 300 meg intranasally via concentrated nasal spray every 12 hours. Peak effect with intranasal administration occurs 60 to 90 minutes after administration, which is somewhat later than with intravenous administration. Desmopressin infusion may be administered daily for up to 2 to 3 days. Tachyphylaxis, an attenuated response with repeated administration, may occur after several doses.8... 

Most patients with type 1 vWD (functionally normal vWF) and a minor bleeding episode can be treated successfully with desmopressin, which induces secretion of autologous factor VIII and vWF into plasma. The recommended dose is the same as that used to treat mild factor VIII deficiency (0.3 mcg/kg intravenously in 50 mL of normal saline infused over 15 to 30 minutes). This therapy generally is ineffective in type 2A patients who secrete qualitatively abnormal vWF and is controversial in type 2B patients because it may increase the risk of postinfusion thrombocytopenia. Type 3 vWD patients who lack releasable stores of vWF do not respond to DDAVP therapy.18... 

Many animal species excrete more calcium if fed an acid or acidforming compounds. In the calf, Steenbock and coworkers (13) observed hypercalciuria and acidic urine after feeding hydrochloric acid to the calf. Stehle (14) pointed out that calcium represented the main long-term fixed base to be lost in the urine of the dog loaded with excessive amounts of hydrochloric acid. Walzer and Browder (15) demonstrated that when infused with a sulfate containing solution, the dog excreted several fold more acid and calcium than saline-infused controls the increased calcium loss returned to normal upon removal of the sulfate. Marone, et al. (16) demonstrated increased excretion of calcium in the acidotic dog. Correction of the acidosis reduced the excessive fractional calcium excretion rate, but did not alter sodium excretion. 

Loading 15 mg/kg in 250 mL normal saline infused over 4 hours followed by Maintenance beginning 24 hours after the beginning of the loading dose, 7.5 mg/kg infused over 4 hours, every 8 hours for 7 days or until oral therapy can be instituted. 

This is a medical emergency, and must be treated with intravenous hydrocortisone (50-100 mg 6-hourly) as intramuscular absorption may be unreliable. Patients are usually hypovolaemic and shocked, so mineralocorticoid deficiency must also be treated by using intravenous saline infusion, often requiring several liters of fluid, until the patient is well enough to take oral fludrocortisone. 

Hypercalcemia can be a medical emergency. Because loop diuretics reduce Ca2+ reabsorption significantly, they can be quite effective in promoting Ca2+ diuresis. However, loop diuretics alone can cause marked volume contraction. If this occurs, loop diuretics are ineffective (and potentially counterproductive) because Ca2+ reabsorption in the proximal tubule would be enhanced. Thus, saline must be administered simultaneously with loop diuretics if an effective Ca2+ diuresis is to be maintained. The usual approach is to infuse normal saline and furosemide (80-120 mg) intravenously. Once the diuresis begins, the rate of saline infusion can be matched with the urine flow rate to avoid volume depletion. Potassium chloride may be added to the saline infusion as needed. 

Etidronate, 7.5 mg/kg in 250-500 mL saline, infused over several hours each day for 3 days, has proved quite useful in treating hypercalcemia of malignancy. More recently, pamidronate, 60-90 mg, infused over 2-4 hours, and zoledronate, 4 mg, infused over 15 minutes, have been approved for the same indication and appear to be more effective. This form of treatment is remarkably free of toxicity. The effects generally persist for weeks, but treatment can be repeated after a 7-day interval if necessary and if renal function is not impaired. 

The irreversible form of amphotericin nephrotoxicity usually occurs in the setting of prolonged administration (> 4 g cumulative dose). Renal toxicity commonly presents with renal tubular acidosis and severe potassium and magnesium wasting. There is some evidence that the prerenal component can be attenuated with sodium loading, and it is common practice to administer normal saline infusions with the daily doses of amphotericin B. 

The platinum complexes appear to synergize with certain other anticancer drugs. Aggressive hydration with intravenous saline infusion alone or with saline and mannitol or other diuretics appears to significantly reduce the incidence of nephrotoxicity. 

The photodegradation of pyridoxine is noticeable in sugar and saline infusion solutions, but much less in amino acid infusion solutions. The presence of tyrosine and tryptophan inhibits photodecomposition, whereas flavine mononucleotide accelerates it (84). 

Small doses of heparin are used for the prophylaxis of infusion-related thrombophlebitis (23). Low molecular weight heparin is added to recombinant factor Vila to prevent a 50% loss of activity of factor VII within 4 hours of storage (9). In one case, however, there was co-preci-pitation of reconstituted factor Vila and low molecular weight heparin in syringes (24). The authors therefore suggested that a parallel saline infusion be used instead of heparin to prevent thrombophlebitis. 

Tune BM, Hsu C-Y, Fravert D. Mechanisms of bacterial endotoxin-cephaloridine toxic synergy and the protective effects of saline infusion in the rabbit kidney. J Pharmacol Exp Ther 1988 244(2) 520-525. 

Hydration with isotonic saline beginning several hours before cisplatin infusion and continuous infusion of saline infusion several days after cisplatin... 

Another study in rabbits has compared the efficacy and safety of pamidronate (1 mg/kg in 20 ml saline infused over 2 hours) and zoledronic acid (0.1 mg/kg in 20 ml saline infused over 20 minutes). Renal toxicity was identified histologically in 14 of 20 kidneys of pamidronate-treated rabbits but was not detected in the 20 kidneys of rabbits infused with zoledronic acid [49]. Because zoledronic acid is a much more potent inhibitor of bone resorption, this agent could be administered at one tenth of the pamidronate dose and yet still achieve superior therapeutic efficacy without... 

Carraro M, Stacul E, Collar P,Toson D, Zucconi E,Torre R, Eaccini E, Dalla Palma E. Contrast media nephrotoxicity urinary protein and enzyme pattern in patients with or without saline infusion during digital subtracting angiography. Contrib Nephrol 1993 101 251-254. 

Hypomagnesemia occurs when the serum magnesium level is less than 1.5 mEq/L caused by long-term administration of saline infusions, diuretics, antibiotics, laxatives, and steroids. Hypomagnesemia increases the action of digitalis, resulting in digitalis toxicity. 

Document polyuria (urine volume >2.5L/day) and exclude glycosuria. If desired, creatinine excretion can be measured as an estimate of completeness of urine collections snbstances that inflnence ADH secretion should be avoided (e.g., nicotine, alcohol, and caffeine). If plasma osmolality is >295 mOsm/kg or if serum sodium concentration >145mmol/L, primary polydipsia is unlikely proceed with the overnight water deprivation test (Box 50-9) or the hypertonic saline infusion test (Box 50-10). 

Hypertonic saline infusion test (Box 50-10) Plot plasma osmolality versus plasma ADH concentration. 

BOX 50- i 0 Protocol for the Saline Infusion Test for. Diabetes Insipidus... 

Procedure An intravenous infiision of 3% saline is begun at a minimum rate to maintain flow two baseline blood specimens are drawn 15 minutes apart for plasma osmolality and ADH determination. The rate of saline infusion is then adjusted to 0.1 mL/kg/min and maintained with an infusion pump for 2 hours. Blood specimens are collected for plasma osmolality and ADH measurement every 15 minutes during this 2-hour period. 

Interpretation Normal subjects show a plasma aldosterone concentration of 5 ng/dL (140pmol/L) or less after saline infusion. Concentrations >10 ng/dL are usually seen in patients with autonomously functioning aldosterone-secreting tumors. 

---