fREMS for Mortality Prediction in TBI

Development and Validation of a Novel FOUR-Rapid Emergency Medicine Score (fREMS) for Mortality Prediction in Traumatic Brain Injury Patients

This prospective observational study aims to develop and internally validate a new clinical score, the FOUR-Rapid Emergency Medicine Score (fREMS), for predicting in-hospital mortality in patients with traumatic brain injury (TBI). The study will assess whether combining the Full Outline of UnResponsiveness (FOUR) score with physiological and clinical parameters from the Rapid Emergency Medicine Score (REMS) can improve early mortality prediction. The main question it aims to answer is:

Can the fREMS score accurately predict the risk of in-hospital mortality in patients with traumatic brain injury?

Data on demographic characteristics, vital signs, neurological assessment, and other relevant clinical variables will be collected from eligible patients with TBI and used to develop and validate the fREMS score.

Background Trauma is the leading cause of death worldwide, particularly in those younger than 35 years of age. Injuries and violence represent a major global public health issue. According to the World Health Organization (WHO), injuries and violence cause approximately 4.4 million deaths worldwide each year, accounting for nearly 8% of all deaths. Of these, about 3.16 million deaths are attributable to unintentional injuries and 1.25 million to violence-related injuries. Injuries and violence also contribute substantially to disability, with an estimated 10% of all years lived with disability attributed to these conditions.

Trauma severity scoring systems are important adjuncts to trauma care and are used to characterize the nature and extent of injury. They can support triage and assist in assessing and predicting patient outcomes, thereby helping to organize and improve trauma care systems. Trauma scoring systems can be divided into anatomical, physiological, and combined scores, each with advantages and disadvantages. The combination of the anatomic scoring system and the physiological scoring system is better than a single scoring system for death prediction in patients with severe trauma in the ICU, and it may be considered to be a new method for early identification of death risk in patients with severe trauma.

The Rapid Emergency Medicine Score (REMS) is a physiological scoring system developed from the Acute Physiology and Chronic Health Evaluation II (APACHE II), which is considered a more rapid and less invasive version and is used for rapid risk stratification and prediction of mortality. It includes several parameters: age, mean arterial pressure, respiratory rate, pulse rate, peripheral oxygen saturation, and Glasgow Coma Scale (GCS). The modified REMS (mREMS) was subsequently developed specifically for trauma by substituting systolic blood pressure for mean arterial pressure, reducing the weighting of age, and increasing the weighting of GCS; in a large validation cohort, mREMS showed an AUROC of 0.967 for predicting in-hospital mortality.

The Glasgow Coma Scale (GCS) provides an objective method for assessing the level of impaired consciousness in patients with acute medical conditions or trauma and is one of the most widely used neurological assessment scales. It evaluates three components of responsiveness: eye-opening, verbal, and motor responses, with each component reported separately to provide a detailed description of neurological status. The individual scores can also be combined into a total GCS score, providing a concise indication of overall severity. The GCS is widely used in trauma, emergency, and critical care settings and supports clinical assessment, triage, monitoring, and communication among healthcare professionals.

The Glasgow Coma Scale (GCS) has several limitations that can affect its reliability and clinical interpretation. The verbal component cannot be assessed reliably in patients who are intubated, pharmacologically sedated, or unable to speak, resulting in missing GCS values and limiting the use of the total score for prognostic models. The Glasgow Coma Scale (GCS) is limited in its ability to evaluate patients with concomitant head and spinal cord injury. Also, a comatose patient receives a GCS score of 3, which coincidentally matches the Glasgow Coma Scale (GCS) assigned to a deceased individual. Drug and alcohol intoxication can interfere with GCS assessment in trauma patients. DiGiorgio et al. found that intoxicated patients had greater changes in Glasgow Coma Scale (GCS) assigned scores than patients without detected substances, suggesting that intoxication may contribute to an initially depressed or variable Glasgow Coma Scale (GCS) assigned. The authors therefore recommended considering and addressing intoxicants when interpreting GCS scores to improve the accuracy of assessment and benchmarking. Painful stimuli used in the Best Eye and Best Motor Response assessments can complicate scoring, especially in polytrauma patients with spinal cord injuries.

The Full Outline of UnResponsiveness (FOUR) score is a coma scale consisting of four components: eye response, motor response, brainstem reflexes, and respiration, with each component assigned a maximum score of 4.

A study prospectively evaluated the Full Outline of UnResponsiveness (FOUR) score in 120 intensive care unit patients and compared it with the GCS among neuroscience nurses, neurology residents, and neurointensivists. The Full Outline of Unresponsiveness (FOUR) score further distinguished patients with the lowest Glasgow Coma Scale (GCS) scores and provided greater neurological detail by assessing brainstem reflexes, breathing patterns, different stages of herniation, and recognizing locked-in syndrome. The probability of in-hospital mortality was higher among patients with the lowest total FOUR score compared with those with the lowest total Glasgow Coma Scale (GCS) score.

In patients with traumatic brain injury, the Full Outline of Unresponsiveness (FOUR) score has been used as a predictor of outcome, and all components of the Full Outline of UnResponsiveness (FOUR) score can be assessed in intubated patients, because it does not include a verbal component. In a study of 51 Traumatic brain injury (TBI) patients, the area under the ROC curve for predicting in-hospital mortality was 0.93 for the Full Outline of UnResponsiveness (FOUR) score and 0.89 for the Glasgow Coma Scale (GCS).

Despite the established prognostic value of REMS and the FOUR score in critically ill and trauma patients, their combined use for mortality prediction in patients with traumatic brain injury (TBI) remains insufficiently explored. The incorporation of GCS within REMS may limit its applicability in severe TBI, particularly when the verbal component cannot be reliably assessed in intubated or sedated patients. The FOUR score may overcome this limitation by providing a more comprehensive neurological assessment without requiring a verbal response. Therefore, integrating the FOUR score with the physiological parameters of REMS may provide a simple and clinically applicable tool for early mortality risk stratification in TBI. Accordingly, this study aimed to develop and internally validate the FOUR-Rapid Emergency Medicine Score (fREMS) for predicting in-hospital mortality among patients with TBI.

Inclusion Criteria:

• Patients with sufficient clinical data to calculate the fREMS score, including the FOUR Score and other required physiological variables.
• Patients with a documented mortality outcome .

Exclusion Criteria:

• Patients transferred from another hospital after initial resuscitation.
• Patients who died before the required initial clinical assessment