You just assumed care of a 35-year-old man with severe septic shock and acute respiratory distress syndrome (ARDS) resulting from necrotizing pancreatitis and aspiration pneumonia. He has a combined metabolic and respiratory acidosis secondary to his underlying pancreatitis and permissive hypercapnia from the appropriate ventilatory strategy necessary for treatment of ARDS. His arterial pH remains <7.15 and mean arterial pressure (MAP) is 50 mm Hg despite being on a sodium bicarbonate (NaHCO₃) drip and multiple vasoactive agents. His serum sodium is 165 mEq/L and his serum creatinine is 1.0 mg/L. Your critical care attending physician suggests stopping the bicarbonate infusion and switching to tris-hydroxymethyl aminomethane (THAM) instead.

Acidemia, in critically ill patients, can have devastating consequences if it is not corrected in a timely fashion. These major adverse consequences often include impairment of cardiac contractility, cardiac arrhythmias, elevated pulmonary artery pressures, decreased responsiveness to catecholamines, hyperventilation, insulin resistance, hyperkalemia, increased metabolic demands, and changes in mental status. The role of buffers in treating severe acidosis (i.e., arterial pH < 7.20) remains controversial. Sodium bicarbonate is the most commonly used buffer used to treat severe acidosis in North America, but the use of sodium bicarbonate is not without consequences. Its use can be associated with hypernatremia, hyperosmolality, volume overload, and exacerbation of acidosis through an increase in CO₂ production.

THAM is a biologically inert weak base that has a greater buffering capacity than sodium bicarbonate (pK_a 7.8 vs. pK_a 6.8, respectively). THAM is effective in buffering severe metabolic acidosis, permissive hypercapnia associated with Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS), and mixed acidoses. THAM can buffer both metabolic acids (THAM + H⁺ = THAM+) and respiratory acids (THAM + H₂CO₃ = THAM⁺ + HCO^–₃). Unlike sodium bicarbonate, THAM does not generate CO₂ but uses CO₂ to generate bicarbonate and also buffers other sources of protons in body fluids, such as lactic acid.