Tromethamine

Clinical summary

Indications and usage INDICATIONS AND USAGE 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. Tromethamine Injection 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. Tromethamine Injection 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, 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 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 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: Tromethamine Injection (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 Tromethamine Injection containing 13.9 g (115 mEq) of tromethamine. The need for administration of additional Tromethamine Injection 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 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 duration of storage. The amount of Tromethamine Injection used to correct th