Early acetaminophen use reduces mortality risk in patients with sepsis-associated encephalopathy

1. Administration of acetaminophen within 48h of intensive care unit admission was associated with reduced short- and long-term mortality in patients with sepsis-associated encephalopathy.

Evidence Rating Level: 2 (Good)

Sepsis-associated encephalopathy (SAE) is a common complication of sepsis that involves neuroinflammation and blood–brain barrier disruption and is associated with morbidity and mortality. Acetaminophen, a drug commonly used to reduce fever in sepsis, has been shown to have additional beneficial effects, including reducing inflammation, improving vascular function, and reducing the risk of sepsis-related multiple organ dysfunction syndrome. Although acetaminophen has been investigated in the context of sepsis, its effect on SAE prognosis remains unknown. This study thus examined the association between early acetaminophen use and survival rates in critically ill SAE patients. This was a retrospective study that used data from the MIMIC-IV database and included adults (>18 years) with SAE admitted to the intensive care unit (ICU) at the Beth Israel Deaconess Medical Center in Boston, Massachusetts, between 2008 and 2022. Patients were divided into the acetaminophen and nonacetaminophen groups. The acetaminophen group received acetaminophen (oral, nasal, or rectal) within the first 48 h of ICU admission. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Out of the 4111 patients included in the study, 1689 were acetaminophen recipients (median [IQR] age, 70.9 [59.9, 81.1]; female, 698 [41.33%]) and 2422 were not (median [IQR] age, 71.3 [60.0, 81.0]; female, 1031 [42.57%]). After PSM, there were 3124 matched patients, with 1562 in each group. After PSM, the receipt of acetaminophen was associated with reduced 30-day, (HR = 0.78, 95%CI [0.65–0.94]), 60-day (HR = 0.71, 95%CI [0.60–0.83]), 90-day (HR = 0.70, 95%CI [0.60–0.81]), 180-day (HR = 0.70, 95%CI [0.60–0.80]) and 365-day (HR = 0.69, 95%CI [0.61–0.79]) mortality rate. Survival rates were higher in the acetaminophen group compared to the non-acetaminophen group, with a consistent trend at 30, 90, 180, and 365 days (log-rank p < 0.05). The protective effect was consistent across subgroups except for patients who received an acetaminophen dosage > 650 mg. Overall, this study found that early acetaminophen use was associated with reduced short- and long-term mortality in SAE patients. These findings suggest that acetaminophen may have a therapeutic role in SAE. Future studies are needed to confirm these findings and investigate underlying mechanisms. 

Click to read the study in EURJ

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