Tromethamine

DOSAGE AND ADMINISTRATION

Tromethamine Injection is administered by slow intravenous infusion, by addition to pump-oxygenator ACD blood or other priming fluid or by injection into the ventricular cavity during cardiac arrest. For infusion by peripheral vein, a large needle should be used in the largest antecubital vein or an indwelling catheter placed in a large vein of an elevated limb to minimize chemical irritation of the alkaline solution during infusion.

Catheters are recommended. Dosage and rate of administration should be carefully supervised to avoid overtreatment (alkalosis). g. pH, PCO 2 , PO 2 , glucose and electrolytes) and urinary output should be made as necessary to monitor dosage and progress of treatment.

45) and to correct acid-base derangements. The total quantity to be administered during the period of illness will depend upon the severity and progression of the acidosis. The possibility of some retention of tromethamine, especially in patients with impaired renal function, should be kept in mind.

The intravenous dosage of Tromethamine Injection may be estimated from the buffer base deficit of the extracellular fluid in mEq/liter determined by means of the Siggaard-Andersen nomogram. 9 g (115 mEq) of tromethamine. The need for administration of additional Tromethamine Injection is determined by serial determinations of the existing base deficit.

6. 0 mL/kg (324 mg/kg) has been used in clinical studies with Tromethamine Injection. This is equivalent to a total dose of 630 mL (189 mEq) for 70 kg patient. A total single dose of 500 mL (150 mEq) is considered adequate for most adults.

Larger single doses (up to 1000 mL) may be required in unusually severe cases. It is recommended that individual doses should not exceed 500 mg/kg (227 mg/lb) over a period of not less than one hour. 3 M solution). Repeated determinations of pH and other clinical observations should be used as a guide to the need for repeat doses.

22 depending upon the duration of storage. 3 M solution) added to each 500 mL of ACD blood used for priming the pump-oxygenator. 3 M solution) added to 500 mL of ACD blood is usually adequate.

Correction of Metabolic Acidosis Associated with Cardiac Arrest:

ADVERSE REACTIONS

Generally, side effects have been infrequent.

Respiratory:

Although the incidence of ventilatory depression is low, it is important to keep in mind that such depression may occur. Respiratory depression may be more likely to occur in patients who have chronic hypoventilation or those who have been treated with drugs which depress respiration.

In patients with associated respiratory acidosis, tromethamine should be administered with mechanical assistance to ventilation.

Vascular:

Extreme care should be taken to avoid perivascular infiltration. Local tissue damage and subsequent sloughing may occur if extravasation occurs. Chemical phlebitis and venospasm also have been reported.

Hematologic:

Transient depression of blood glucose may occur.

Hepatic:

Infusion via low-lying umbilical venous catheters has been associated with hepatocellular necrosis. Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection extravasation and hypervolemia.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures and save the remainder of the fluid for examination if deemed necessary.

WARNINGS

Large doses of Tromethamine Injection may depress ventilation, as a result of increased blood pH and reduced CO 2 concentration. Thus, dosage should be adjusted so that blood pH is not allowed to increase above normal. In situations in which respiratory acidosis may be present concomitantly with metabolic acidosis, the drug may be used with mechanical assistance to ventilation.

Care must be exercised to prevent perivascular infiltration since this can cause inflammation, necrosis and sloughing of tissue. Venospasm and intravenous thrombosis, which may occur during infusion, can be minimized by insuring that the injection needle is well within the largest available vein and that solutions are slowly infused.

Intravenous catheters are recommended. If perivascular infiltration occurs, institute appropriate countermeasures (See ADVERSE REACTIONS ). Tromethamine injection should be administered slowly and in amounts sufficient only to correct the existing acidosis, and to avoid overdosage and alkalosis.

Overdosage in terms of total drug and/or too rapid administration, may cause hypoglycemia of a prolonged duration (several hours). Therefore, frequent blood glucose determinations should be made during and after therapy. Extreme care should be exercised in patients with renal disease or reduced urinary output because of potential hyperkalemia and the possibility of a decreased excretion of tromethamine.

In such patients, the drug should be used cautiously with electrocardiographic monitoring and frequent serum potassium determinations. Because clinical experience has been limited generally to short-term use, the drug should not be administered for more than a period of one day except in a life-threatening situation.

The intravenous administration of Tromethamine Injection can cause fluid and/or solute overloading resulting in dilution of serum electrolyte concentrations, overhydration, congested states or pulmonary edema. Additives may be incompatible.

CONTRAINDICATIONS

Tromethamine Injection is contraindicated in uremia and anuria. In neonates it is also contraindicated in chronic respiratory acidosis and salicylate intoxication.