GUIDELINES FOR THE TREATMENT OF ACIDEMIA WITH THAM

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically i nert amino alcohol of low toxicity, which buffers carbon dioxide and a cids in vitro and in vivo. At 37 degrees C, the pK (the pH at which th e weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the phys iological range of blood pH. THAM is a proton acceptor with a stoichio metric equivalence of titrating 1 proton per molecule. In vivo, THAM s upplements the buffering capacity of the blood bicarbonate system, acc epting a proton, generating bicarbonate and decreasing the partial pre ssure of carbon dioxide in arterial blood (paCO(2)). It rapidly distri butes through the extracellular space and slowly penetrates the intrac ellular space, except for erythrocytes and hepatocytes, and it is excr eted by the kidney in its protonated form at a rate that slightly exce eds creatinine clearance. Unlike bicarbonate, which requires an open s ystem for carbon dioxide elimination in order to exert its buffering e ffect, THAM is effective in a closed or semiclosed system, and maintai ns its buffering power in the presence of hypothermia. THAM rapidly re stores pH and acid-base regulation in acidaemia caused by carbon dioxi de retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at t he site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein; THAM acetate 0.3 mol/L (pH 8. 6) is well tolerated, does not cause tissue or venous irritation and i s the only formulation available in the US. In large doses, THAM may i nduce respiratory depression and hypoglycaemia, which will require ven tilatory assistance and glucose administration. The initial loading do se of THAM acetate 0.3 mol/L in the treatment of acidaemia may be esti mated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight ( kg) x base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient). When distur bances result in severe hypercapnic or metabolic acidaemia, which over whelms the capacity of normal pH homeostatic mechanisms (pH less than or equal to 7.20), the use of THAM within a 'therapeutic window' is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assu me their normal function. In the treatment of respiratory failure, THA M has been used in conjunction with hypothermia and controlled hyperca pnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associat ed with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi. THAM administration must follow established guidelines, along with concurr ent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.