Tromethamine

Description

DESCRIPTION Tham Solution (tromethamine injection) is a sterile, non-pyrogenic 0.3 M solution of tromethamine, adjusted to a pH of approximately 8.6 with glacial acetic acid. It is administered by intravenous injection, by addition to ACD blood for priming cardiac bypass equipment and by injection into the ventricular cavity during cardiac arrest. Each 100 mL contains tromethamine 3.6 g (30 mEq) in water for injection. The solution is hypertonic 389 mOsmol/L (calc.). pH 8.6 (8.4-8.7). The solution contains no bacteriostat, antimicrobial agent or added buffer (except acetic acid for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded. Tham solution is a parenteral systemic alkalizer and fluid replenisher. Tromethamine, USP (sometimes called “tris” or “tris buffer”) is chemically designated 2-amino-2-(hydroxymethyl)-1, 3-propanediol, a solid readily soluble in water, also classified as an organic amine buffer. It has the following structural formula: Water for Injection, USP is chemically designated H 2 0. structural formula tromethamine

What Is Tromethamine Used For?

INDICATIONS AND USAGE Tham Solution (tromethamine injection) is indicated for the prevention and correction of metabolic acidosis. In the following conditions it may help to sustain vital functions and thus provide time for treatment of the primary disease: Metabolic Acidosis Associated with Cardiac Bypass Surgery. Tham Solution has been found to be primarily beneficial in correcting metabolic acidosis which may occur during or immediately following cardiac bypass surgical procedures. Correction of Acidity of ACD Blood in Cardiac Bypass Surgery. It is well known that ACD blood is acidic and becomes more acidic on storage. Tromethamine effectively corrects this acidity. Tham Solution may be added directly to the blood used to prime the pump-oxygenator. When ACD blood is brought to a normal pH range the patient is spared an initial acid load. Additional tromethamine may be indicated during cardiac bypass surgery should metabolic acidosis appear. Metabolic Acidosis Associated with Cardiac Arrest. Acidosis is nearly always one of the consequences of cardiac arrest and, in some instances, may even be a causative factor in arrest. It is important therefore, that the correction of acidosis should be started promptly with other resuscitative efforts. By correcting acidosis, Tham Solution (tromethamine injection) has caused the arrested heart to respond to resuscitative efforts after standard methods alone had failed. In these cases, tromethamine was given intraventricularly. It is to be noted, however, that such precariously ill patients often have died subsequently of causes unrelated to the administration of tromethamine. With administration by the peripheral venous route, metabolic acidosis has been corrected in a majority of patients. The success in reinstitution of cardiac rhythm by this means probably has not been of the same order of magnitude as with the intraventricular route.

Dosage and Administration

DOSAGE AND ADMINISTRATION Tham Solution (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). Pretreatment and subsequent determinations of blood values (e.g. pH, PCO 2 , PO 2 , glucose and electrolytes) and urinary output should be made as necessary to monitor dosage and progress of treatment. In general, dosage should be limited to an amount sufficient to increase blood pH to normal limits (7.35 to 7.45) 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 Tham Solution (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. The following formula is intended as a general guide: Tham Solution (mL of 0.3 M) Required = Body Weight (kg) X Base Deficit (mEq/liter) X 1.1* Thus, a 70 kg patient with a buffer base deficit (“negative base excess”) of 5 mEq/liter would require 70 x 5 x 1.1 = 385 mL of Tham Solution containing 13.9 g (115 mEq) of tromethamine. The need for administration of additional Tham Solution is determined by serial determinations of the existing base deficit. * Factor of 1.1 accounts for an approximate reduction of 10% in buffering capacity due to the presence of sufficient acetic acid to lower pH of the 0.3 M solution to approximately 8.6. Correction of Metabolic Acidosis Associated with Cardiac Bypass Surgery: An adverse dose of approximately 9.0 mL/kg (324 mg/kg) has been used in clinical studies with Tham Solution (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. Thus, for a 70 kg (154 pound) patient the dose should not exceed a maximum of 35 g per hour (1078 mL of a 0.3 M solution). Repeated determinations of pH and other clinical observations should be used as a guide to the need for repeat doses. Correction of Acidity of ACD Blood in Cardiac Bypass Surgery: The pH of stored blood ranges from 6.80 to 6.22 depending upon the...

Side Effects (Adverse Reactions)

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.

Contraindications

CONTRAINDICATIONS Tham Solution (tromethamine injection) is contraindicated in uremia and anuria. In neonates it is also contraindicated in chronic respiratory acidosis and salicylate intoxication.

Pregnancy and Breastfeeding

Pregnancy: Animal reproduction studies have not been conducted with tromethamine. It is also not known whether tromethamine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Tromethamine should be given to a pregnant woman only if clearly needed.

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when THAM Solution is administered to a nursing mother.

Overdosage

OVERDOSAGE Too rapid administration and/or excessive amounts of tromethamine may cause alkalosis, hypoglycemia, overhydration or solute overload. In the event of overdosage, discontinue the infusion, evaluate the patient and institute appropriate countermeasures (see WARNINGS , PRECAUTIONS and ADVERSE REACTIONS ). The LD 50 values for the acute intravenous toxicity of THAM are influenced by the rate of infusion of the dose administered. Intravenous LD 50 Mice = 3,500 mg/kg Intravenous LD 50 Rats = 2,300 mg/kg

How Supplied

HOW SUPPLIED Tham Solution (tromethamine injection) is available as: Unit of Sale Concentration NDC-0409-1593-04 Case of 6 Single-dose 500 mL large volume glass containers 500 mL (150 mEq) Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.] Protect from freezing.