What Does Tham Do? Understanding Tromethamine in Critical Care

October 8, 2025 •

4 min read

Tromethamine, commonly known as THAM, is a parenteral systemic alkalizing agent historically used for the prevention and correction of severe metabolic acidosis in critical care settings. It has specific applications, particularly during cardiac bypass surgery and cardiac arrest, where it helps sustain vital functions by neutralizing excess acid.

Quick Summary

Tromethamine (THAM) is an intravenous medication that corrects metabolic acidosis by acting as a proton acceptor, binding hydrogen ions to restore blood pH. Unlike sodium bicarbonate, it does so without generating carbon dioxide. While its availability has changed in the U.S., it was used for severe acidosis associated with cardiac bypass and cardiac arrest and had distinct side effects and monitoring requirements.

Key Points

Proton Acceptor: THAM works by directly accepting hydrogen ions ($H^+$) in the blood, increasing blood pH and correcting acidosis.
CO2-Sparing Buffer: Unlike sodium bicarbonate, THAM does not generate carbon dioxide ($CO_2$) during buffering, making it advantageous for patients with impaired respiratory function.
Key Indications: Historically used to correct metabolic acidosis during cardiac bypass surgery and cardiac arrest.
Common Side Effects: Watch for potential side effects including hypoglycemia (low blood sugar), respiratory depression, and tissue damage from extravasation.
Renal Considerations: Use with extreme caution in patients with renal impairment due to the risk of hyperkalemia.
Limited Availability: The only US manufacturer discontinued THAM in 2016, making its availability potentially limited.
Alternative to Bicarbonate: THAM was sometimes preferred over sodium bicarbonate in patients with hypernatremia or mixed acidosis where avoiding extra sodium or $CO_2$ load was beneficial.

The Mechanism Behind THAM's Buffering Power

THAM, or tromethamine, is a proton acceptor designed to correct systemic acidosis in medical emergencies. Its unique mechanism of action differentiates it from other buffers, most notably sodium bicarbonate. When administered intravenously, tromethamine directly binds to hydrogen ions ($H^+$) in the blood. This direct buffering effect helps to increase the overall pH of the blood, restoring it to a more normal range.

One of its key advantages is that it achieves this without contributing to the body's carbon dioxide ($CO_2$) load. The buffering reaction of THAM actually consumes hydrogen ions and, by extension, hydrogen ions from carbonic acid ($H_2CO_3$), which helps to increase bicarbonate anions ($HCO_3^-$). This differs from sodium bicarbonate, which produces $CO_2$ as a byproduct, a problematic effect for patients with respiratory issues. Furthermore, a significant portion of tromethamine can penetrate cells, allowing it to neutralize intracellular acidic ions as well, providing a broader buffering effect.

Clinical Applications in Acute Acidosis

THAM's specific properties made it a valuable tool in several critical care scenarios where other buffering agents were suboptimal. Its primary approved uses were centered around situations where rapid and effective correction of metabolic acidosis was necessary.

Cardiac Bypass Surgery: During cardiopulmonary bypass, acidosis is a common complication. THAM was used to correct this metabolic acidosis and to neutralize the acidity of the stored ACD (acid citrate dextrose) blood used to prime the pump-oxygenator. By doing so, it helped reduce the acid load on the patient during surgery.
Cardiac Arrest: In cases of cardiac arrest, severe acidosis often occurs. Administered during resuscitation efforts, THAM helped to correct this acidosis, sometimes allowing the heart to respond to resuscitative measures when standard methods had failed.
Respiratory Acidosis: For patients with both metabolic and respiratory acidosis, especially infants with respiratory failure, THAM was used because it can help lower blood $CO_2$ levels. This contrasted with sodium bicarbonate, which would increase $CO_2$.

Adverse Effects and Precautions

Despite its benefits, THAM therapy was not without risks and required careful monitoring. Side effects, while infrequent, could be serious.

Hypoglycemia: Rapid administration or large doses could cause a transient but prolonged drop in blood glucose levels, requiring frequent blood glucose monitoring during and after therapy.
Respiratory Depression: Large doses or a rapid infusion could depress ventilation due to the effects of increased blood pH and reduced $CO_2$. This was especially concerning in patients with existing respiratory issues and often required mechanical ventilation.
Extravasation: THAM is a vesicant, meaning it can cause tissue damage if it leaks out of the vein during intravenous administration. Extravasation could lead to inflammation, necrosis, and tissue sloughing, so careful placement and monitoring of the IV site were critical.
Hyperkalemia: Extreme caution was needed in patients with renal disease or reduced urinary output, as they were at risk of elevated serum potassium levels and decreased excretion of the drug. Frequent serum potassium and ECG monitoring were necessary.
Fluid Overload: The intravenous administration could cause fluid and solute overload, potentially leading to pulmonary edema in susceptible patients.

THAM vs. Sodium Bicarbonate: A Comparative Table

While THAM and sodium bicarbonate are both systemic alkalizers, their mechanisms and side effect profiles differ significantly, which influenced their clinical use.


Feature	THAM (Tromethamine)	Sodium Bicarbonate ($NaHCO_3$)
Mechanism	Directly binds $H^+$ ions, consuming $CO_2$.	Adds $HCO_3^-$ ions, which buffer $H^+$ and generate $CO_2$.
$CO_2$ Effect	Does not generate $CO_2$; can help reduce it.	Increases $CO_2$ load, which can worsen respiratory acidosis.
Sodium Content	Sodium-free, avoids hypernatremia.	Increases serum sodium levels.
Intracellular Buffering	Penetrates cells for intra- and extracellular buffering.	Primarily buffers extracellular fluid.
Potassium Effect	Minimal effect on serum potassium; may cause hyperkalemia with renal impairment.	May decrease serum potassium levels.
Hypoglycemia	Risk of hypoglycemia, especially with rapid or high doses.	Not a primary risk.
Extravasation	Vesicant; risk of tissue damage.	Less severe tissue damage risk.
Current Status	Discontinued by sole US manufacturer (2016); availability may be limited.	Widely available as the standard alkali therapy.

The Fate of THAM and the Ongoing Role of Bicarbonate

In 2016, the only U.S. manufacturer of THAM, Pfizer/Hospira, discontinued the medication, and no direct therapeutic equivalent exists. This shifted standard practice back towards sodium bicarbonate as the primary treatment for severe acidosis. However, clinical evidence suggests that THAM may offer advantages in specific, complex situations, such as metabolic acidosis combined with respiratory failure or hypernatremia, where avoiding an additional $CO_2$ or sodium load is critical. The discontinuation of THAM highlights a potential gap in therapeutic options for these challenging cases. Despite this, clinicians trained in managing critical acid-base disorders may still consider its unique characteristics and advantages in specific patient populations, relying on alternative sourcing or compounded preparations where feasible.

Conclusion

In summary, THAM (tromethamine) is an intravenous buffer that historically played a niche but important role in critical care by correcting severe metabolic acidosis, especially during cardiac bypass surgery and cardiac arrest. Its primary distinction from sodium bicarbonate is its ability to buffer acids without generating $CO_2$, making it particularly useful for patients with impaired respiration. While it offers unique benefits in certain acid-base disturbances and had specific advantages over bicarbonate in select patients, it is also associated with distinct side effects and risks, including hypoglycemia and respiratory depression. Given its discontinuation by a major manufacturer, sodium bicarbonate remains the standard of care for severe acidosis, but the legacy of THAM's unique pharmacological profile continues to inform the treatment of complex acid-base disorders.

Frequently Asked Questions

THAM works by directly binding hydrogen ions ($H^+$) to increase blood pH, and importantly, it does so without producing carbon dioxide ($CO_2$). Sodium bicarbonate, on the other hand, buffers $H^+$ and creates $CO_2$ as a byproduct, which can be problematic for patients with respiratory issues.

THAM was primarily used for the prevention and correction of severe metabolic acidosis in critical care settings, particularly during cardiac bypass surgery and cardiac arrest.

Significant side effects of THAM include hypoglycemia (low blood sugar), respiratory depression, hyperkalemia (in patients with kidney issues), and the risk of severe tissue damage if the drug leaks from the vein (extravasation).

No, THAM was discontinued by its sole manufacturer in the U.S. in 2016, and there is no direct therapeutic equivalent. It may still be available via other means or in other countries, but sodium bicarbonate is the standard replacement.

While THAM was primarily for metabolic acidosis, it can also buffer respiratory acids. Its ability to lower $CO_2$ made it useful in specific cases of respiratory acidosis, especially in neonates.

Rapid or excessive administration of THAM can lead to a prolonged drop in blood glucose (hypoglycemia), so frequent monitoring is essential to prevent this complication.

THAM is contraindicated in patients with uremia and anuria (no urine production). In neonates, it is also contraindicated in cases of chronic respiratory acidosis and salicylate intoxication.

THAM was considered advantageous in cases where an increased sodium load (from sodium bicarbonate) or a rise in $CO_2$ (due to buffering) would be detrimental. This included patients with hypernatremia, severe respiratory failure, or increased intracranial pressure.