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.
Total extracorporeal lung assist (ECLA) requires a bypass flow approaching cardiac output. Recirculation of venous blood through the oxygenator is minimized with a veno-right ventricular cannulation technique which separates venous drainage from returned oxygenated blood. A case of posttraumatic ARDS was treated with surface-heparinized veno-right ventricular ECLA for 35 days. Cardiac output was stabilized by means of sedation, hypothermia (35 degrees C) and beta blockers (pulse rate less than 90) in order to match the maximal venous drainage achieved (5.5 l/min). A bypass flow around 85% of cardiac output resulted in mean arterial PO2 values between 9-13.6 kPa without any contribution from the lungs. Low platelet counts and a marked bleeding tendency complicated treatment, even though no heparin was used during the last 24 days of ECLA. Weaning from the ventilator was accomplished 2 months after ECLA. Lung function tests show constant improvement.
A 20-year-old male, recovering from post-traumatic ARDS, subsequently developed pneumonia with extreme hypercapnia (PaCO2 max 19.4 kPa) and hypoxemia (PaO2 min 5.1 kPa), in spite of maximal mechanical ventilation. Hypothermia was induced by surface cooling, reducing the body temperature from 40 degrees C to a mean of 33.3 degrees C. Buffer infusion (1375 mmol) during the first 2 days increased base excess from 3 to 22 mmol/l and pH from 7.16 to a median value of 7.30. Active cooling was discontinued on day 11. Weaning from the ventilator was possible 9 days later and the patient subsequently recovered fully. Combined use of hypothermia and buffering might offer an alternative to extracorporeal lung assist (ECLA) and facilitate a reduction of barotrauma and oxygen toxicity during mechanical ventilation.
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