Tromethamine (THAM) is a specialized medication administered in hospital settings for the treatment of severe metabolic acidosis. Classified as an organic amine buffer, this chemical agent neutralizes acid in the bloodstream. It is reserved for critically ill patients whose acid-base balance is dangerously low (typically pH 7.20 or lower) and often unresponsive to standard treatments like sodium bicarbonate. THAM acts to restore the body’s internal pH, which is necessary for normal organ function. Its primary function is to stabilize life-threatening conditions, allowing time to treat the underlying cause of the acidosis.
How THAM Corrects Acidosis
THAM is a weak base that functions as a proton acceptor in the bloodstream, actively binding to free hydrogen ions (H+) to correct the acidic environment. When it accepts a proton, it generates bicarbonate (HCO3-), effectively supplementing the blood’s existing buffering capacity. Unlike conventional sodium bicarbonate treatment, THAM does not produce carbon dioxide (CO2) during this buffering process. Sodium bicarbonate reacts with hydrogen ions to form carbonic acid, which then breaks down into water and CO2, requiring sufficient lung function to exhale the CO2 load.
The mechanism of THAM offers a significant advantage in patients with limited ventilatory capacity or respiratory failure, as it improves pH without increasing the CO2 burden. THAM has a higher pKa of 7.8 at body temperature, making it a more effective buffer than bicarbonate (pKa 6.1) within the physiological range of blood pH. The drug is available as a 0.3 M solution, adjusted to a pH of approximately 8.6.
Once administered, THAM distributes quickly through the extracellular fluid and slowly penetrates the intracellular space, allowing for partial buffering inside the cells. The non-ionized fraction enables it to cross cell membranes and neutralize acidic ions within the intracellular fluid. This ability to buffer both outside and inside the cells distinguishes it from bicarbonate, which primarily buffers extracellularly. THAM is not metabolized; it is rapidly eliminated by the kidneys in its protonated form, though elimination half-life is dependent upon the patient’s renal function.
Specific Conditions Treated with THAM
THAM is typically reserved for severe metabolic acidosis that is refractory to standard therapy. A common application is correcting acidosis occurring during or immediately following cardiac bypass surgery. The drug can also be added directly to the blood used to prime the pump-oxygenator, correcting the acidity of stored blood and sparing the patient an initial acid load.
In respiratory distress, THAM facilitates permissive hypercapnia, a ventilation strategy used in patients with Acute Respiratory Distress Syndrome (ARDS). Permissive hypercapnia allows CO2 levels to rise to protect the lungs from mechanical ventilation injury. THAM prevents severe acid buildup without worsening CO2 retention. It is also used in cases of severe hypercapnic or mixed acidosis where bicarbonate use would be detrimental.
Specialized Indications
Other indications include managing increased intracranial pressure (ICP) associated with cerebral trauma, as THAM rapidly reduces brain extracellular CO2. It is also employed during liver transplantation to correct acidosis during the anhepatic phase. In neonates and infants with hypernatremia and metabolic acidosis, THAM may be chosen over sodium bicarbonate to avoid administering additional sodium.
Administration, Monitoring, and Risks
THAM solution must be administered slowly via intravenous (IV) infusion, and central venous access is recommended. The solution is a vesicant, meaning it can cause tissue inflammation, sloughing, and necrosis if it leaks into surrounding tissue (extravasation). To minimize local adverse effects like venospasm or venous thrombosis, care must be taken to ensure the needle is positioned correctly within the largest available vein.
Close monitoring of the patient’s physiological status is mandatory during infusion. Healthcare providers must regularly analyze arterial blood gas results to track acid-base status and adjust the dosage. This ensures the blood pH does not rise above the normal range, which could lead to alkalosis. Since THAM is substantially excreted by the kidneys, patients with impaired renal function, uremia, or anuria are at a higher risk of toxic reactions and drug accumulation.
Potential Adverse Effects
A significant adverse effect is the risk of hypoglycemia, particularly with rapid administration or large doses. Frequent monitoring of blood glucose levels is necessary, and glucose administration may be required to counteract this effect. Caution is exercised in patients with reduced urinary output due to the potential for hyperkalemia, necessitating frequent serum potassium and electrocardiographic monitoring. Large doses of THAM may also cause respiratory depression as the blood pH rises and the body’s drive to breathe decreases, often requiring mechanical ventilation.