Tris-Hydroxymethyl Aminomethane in Critically Ill Adults: A Systematic Review

Tris-hydroxymethyl aminomethane (THAM) is an amino alcohol used clinically to buffer acid loads and raise pH in acidotic conditions. Unlike sodium bicarbonate, which increases plasma sodium levels with use and produces carbon dioxide (CO₂) as part of the buffering process, THAM does neither. Although not widely used in modern critical care and unavailable for clinical use in 2016, THAM has been available in the United States since 2020. Clinical experience and existing literature suggest that THAM may have clinical utility in acid-base management in conditions such as liver transplantation where rising sodium levels during perioperative care may be dangerous, and in managing acid-base derangements during care of patients with acute respiratory distress syndrome (ARDS). To clarify the evidence base supporting the clinical use of THAM, we conducted a systematic review to assess the efficacy and safety of THAM as a buffering agent in critically ill adults using Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science Core Collection. Randomized-, crossover-, retrospective cohort-, parallel-designed clinical trials, case series, and case reports of adult patients who received THAM in the operative or critical care setting were included. Conference abstracts of qualifying study designs were also included. Two independent reviewers extracted the data regarding the study details, demographics, treatment, and outcomes data. A third reviewer adjudicated discrepancies. A total of 21 studies including 3 randomized controlled trials, 5 observational studies, 4 case series, and 9 case reports met inclusion criteria. Eight studies (38%) were abstracts published in conference proceedings. In total, 417 critically ill patients received THAM to treat acidosis in critically ill surgical and nonsurgical patients, during liver transplantation, and in ARDS. In general, THAM corrected acidosis with an efficacy equivalent to sodium bicarbonate and did so with less hypercarbia and hypernatremia. Adverse effects of THAM included hyperkalemia, hypoglycemia, ventilator depression, and tissue damage with extravasation. We conclude that THAM may have potential advantages in some critical care settings, but that clinical evidence is limited, and high-quality evaluations are necessary.