Guidelines for the Treatment of Acidaemia with THAM

Abstract

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37 degrees C, the pK (the pH at which the 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 physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia. THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at the 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 is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration. The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated 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 disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH< or = 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 assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated 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 concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.

Treatment options for lactic acidosis and metabolic crisis in children with mitochondrial disease

“…THAM (Tris-hydroxymethyl-amino-methane) buffering THAM is a Na + -free buffer solution that can be used in conditions of respiratory or metabolic acidosis (Nahas et al 1998). Importantly, THAM does not generate increased CO 2 levels, which is ideal in situations where CO 2 elimination is impaired (Nahas et al 1998).…”

“…Importantly, THAM does not generate increased CO 2 levels, which is ideal in situations where CO 2 elimination is impaired (Nahas et al 1998). During lactic acidosis, THAM reacts according to the following chemical equation: R-NH 2 + H + + Lactate − = > R-NH 3 + + Lactate − .…”

Carbon Dioxide in the Critically Ill: Too Much or Too Little of a Good Thing?

“…3,54,55 Alternatively, there may be a role for using tris-hydroxymethyl aminomethane (THAM) to buffer hypercapnic acidosis, as it can easily enter cells to buffer pH and simultaneously reduce carbon dioxide levels. 56 Through more effectively correcting pH, THAM can also mitigate the adverse effects of acidosis on the cardiovascular system and restore hemodynamic stability. 57 …”

Anions and the anaesthetist

“…All these agents are anions. Guidelines for the administration of THAM have been reviewed [57]. The main advantages are regeneration of bicarbonate with a lowering of P a co 2 , slow penetration of the intracellular space, maintenance of buffering power in hypothermia and effectiveness in a closed or semiclosed system.…”