In the emergency department (ED), clinicians must rely on a rapid, comprehensive clinical evaluation to suspect and identify organ dysfunction in sepsis patients. Vital signs such as hypotension and tachypnea are often the first indicators that prompt further management, as they suggest cardiovascular or respiratory compromise. Beyond vital signs, a focused physical examination is essential for detecting more specific signs of organ dysfunction. Signs such as altered mental status, poor peripheral perfusion (e.g., skin mottling or delayed capillary refill), myocardial dysfunction on echocardiography, decreased urine output, jaundice, bleeding tendencies, and ileus may raise suspicion for sepsis in patients with suspected infection (Fig. 1) [7,9].

The Sequential Organ Failure Assessment (SOFA) score was initially developed in 1994 by the Working Group of the European Society of Intensive Care Medicine during a consensus conference to objectively quantify the degree of organ dysfunction in intensive care unit (ICU) patients [13]. It assesses dysfunction across six essential organ systems: respiratory (PaO₂ to fraction of inspired oxygen [FiO₂] ratio), coagulation (platelet count), hepatic (bilirubin level), cardiovascular (mean arterial pressure, vasopressor and inotropic use), renal (creatinine and urine output), and central nervous system (Glasgow Coma Scale) function [14,15]. While the SOFA score was not originally designed to predict mortality, numerous studies have shown a significant correlation between higher SOFA scores and worse clinical outcomes [16–19]. Today, the SOFA score is widely used for assessing organ failure, prognostication, scientific research, and defining sepsis in both EDs and ICUs [6,15,17,18,20–26]. It is designed to be simple and easy to use, allowing for frequent reassessment of organ dysfunction over time. Its minimal number of variables makes it straightforward to compute with data that are readily available in most healthcare settings.

While the SOFA score remains an important tool in assessing organ dysfunction, there may be a need for updates to better reflect recent advances and practices in critical care [14,19,27]. For instance, the SOFA score system does not incorporate certain aspects of current critical care practice. The Surviving Sepsis Campaign guidelines now recommend norepinephrine as the first-line vasopressor rather than dopamine, and vasopressin along with other agents have become more commonly used [11]. Additionally, extracorporeal membrane oxygenation (ECMO), cardiac assist devices, high-flow oxygen therapy, and noninvasive positive pressure ventilation are frequently used in managing critically ill patients. These aspects could be incorporated in the future update of the cardiovascular and respiratory SOFA components. Also, it would be helpful to develop strategies that allow for an alternative assessment of organ dysfunction based on clinical assessment or additional information in the ED (e.g., jaundice, oxygen saturation as measured by pulse oximetry [SpO₂], and AVPU [alert, verbal, pain, unresponsive] system) [14,15,19,28]. Global collaborative efforts to collect and analyze large datasets from diverse clinical settings will be the first important step in developing a comprehensive and useful SOFA score update.

Assessment of organ failure in sepsis patients must begin as soon as they arrive in the ED. Early recognition, whether through clinical signs or scoring systems like SOFA, is crucial. Moving forward, the integration of more advanced and adaptable tools that combine clinical evaluation with real-time data analysis may offer even greater accuracy in identifying high-risk patients. Artificial Intelligence (AI) in sepsis care could aid sepsis identification, prediction of progression, phenotyping for personalized treatments, and clinical decision to prioritize interventions for those most likely to benefit [29,30]. In the future, AI could be further developed to create more advanced tools for assessing organ failure, improving the precision and speed of diagnostics and treatment strategies in sepsis.

Furthermore, beyond traditional organ failure assessments, future tools may incorporate cellular, metabolic, and immune markers of dysfunction [7,14,31]. Metabolic failure at the cellular level, such as impaired mitochondrial function, may provide early indicators of organ failure before clinical signs manifest. Currently, there are no widely implemented tools or markers for objective grading in clinical practice, but further research and development are essential, and these innovations could transform sepsis management.