Written by Carmen Wolfe
Spoon Feed
In this phase 2b randomized clinical trial of scheduled intravenous acetaminophen for critically ill sepsis patients, authors confirmed the safety of this strategy, but found no improvement in days alive and free of organ support.
Acetaminophen for all?
In addition to its analgesic and antipyretic properties, acetaminophen also blocks hemoglobin-induced oxidation of lipids and other substrates, which might be beneficial in sepsis, given that circulating cell-free hemoglobin levels are associated with organ dysfunction and death. After observational studies and phase 2a trial shows promising results, authors designed this phase 2b multi-center, randomized, double-blind trial to evaluate the safety and efficacy of intravenous acetaminophen (1 gram administered every 6 hours for 5 days) in critically-ill sepsis patients.
A large list of exclusion criteria limited the pool of 4,557 sepsis patients screened, and only 447 were ultimately randomized to acetaminophen or placebo. In this patient population (free from previous liver disease, elevated LFTs, home oxygen use, alcohol use disorder, transplant, etc), acetaminophen was safe, with no difference detected in liver enzymes. The primary endpoint of days alive and free of organ support (ventilation, vasopressors, dialysis) was not statistically different between the groups. Even with a negative primary outcome, this study still generates hypotheses about future patient populations who might benefit. Evaluation of secondary outcomes revealed that SOFA scores and development of ARDS were improved in the intervention group.
How will this change my practice?
I won’t be reaching for scheduled acetaminophen in sepsis quite yet, but will look forward to future trials to better define which subset of patients might benefit from this safe intervention.
Source
Acetaminophen for Prevention and Treatment of Organ Dysfunction in Critically Ill Patients With Sepsis: The ASTER Randomized Clinical Trial. JAMA. 2024;332(5):390-400. PMID: 38762798.
