Patients with trauma are at risk of malnutrition [4], which becomes more frequent after treatment [17]. In particular, patients with traumatic brain injury (TBI) often show impaired consciousness, and exhibits a Glasgow coma scale (GCS) score ≤8, indicating the need for endotracheal intubation to protect the airway [7]. These patients usually require prolonged mechanical ventilation and intensive care unit (ICU) stay, increasing the risk of aspiration and ventilator-associated pneumonia [6,13]. Therefore, clinicians hesitate to provide sufficient oral or tube feeding to these patients, albeit having hyperglycemia and protein wasting from hypermetabolism and increased catabolism [11,20]. Consequently, the risk of malnutrition is even higher in patients with TBI.

Several critical care guidelines have been published, including those on nutrition in the ICU. van Zanten et al. [23] recommended providing 70-100% of required calories and 1.3-1.5 g/kg/day of protein to ICU patients on the fourth day of hospital admission. The American Society of Parenteral and Enteral Nutrition recommends 12-25 kcal/kg with 1.2-2.0 g/kg protein daily [1]. They recommended that either parenteral nutrition (PN) or enteral nutrition (EN) is reasonable, as they have no significant differences in the clinical outcomes. However, these guidelines do not specifically consider patients with trauma. Conversely, another nutritional guideline for the ICU by the European Society of Parenteral and Enteral Nutrition suggested early initiation of EN instead of PN [21]. This has been demonstrated in several studies. Kompan et al. [10] compared early EN with PN and reported better prognosis in the early EN group. However, their study included patients with various trauma types. Fan et al. [2] analyzed only patients with severe TBI, reporting low morbidity and mortality rates in the early EN than in the PN group. However, the amounts of calories and protein supplied were lacking.

Although patients with TBI are at risk of malnutrition, guidelines or analyses of nutrition designed especially for this population remain insufficient. In particular, evidence of early nutritional support in the ICU, where severely ill patients are admitted, is lacking. We hypothesized that early sufficient nutrition is associated with better clinical outcomes and aimed to analyze the effect of nutrition supply in patients with TBI.

This retrospective cohort study was planned based on the mortality rates of patients with TBI. The study was approved by Uijeongbu St. Mary’s Hospital Institutional Review Board (UC24RISI0055), and the requirement for informed consent was waived because of the retrospective nature of the study. All methods were performed in accordance with the relevant guidelines and regulations.

Between January 2022 and December 2023, patients with TBI admitted to the ICU of a regional trauma center in Korea were selected. Regional trauma centers in Korea have similar roles in level 1 trauma centers in the USA and provide definitive treatments to patients with major trauma [12]. Patients diagnosed with TBI were included in this study. Patients aged <18 years, those with missing data, and those who were discharged from the ICU within 7 days of admission were excluded. In addition, patients using steroids, anticancer drugs, immunosuppressants, and renal replacement therapy were excluded to reduce potential bias. These conditions could influence the basic metabolism of the patients and were regarded as potential confounding factors.

Basic data, including sex, age, ICU length of stay, hospital stay, Abbreviated injury score, Injury severity score (ISS), operation, mortality during initial hospitalization, initial GCS score, height and body weight, and body mass index (BMI) of patients with TBI, were collected. BMI was calculated from the measured height and weight. Hemoglobin, white blood cell count, segmented neutrophils, lymphocyte percentage, neutrophil-lymphocyte ratio, C-reactive protein (CRP), albumin, and CRP/albumin ratio were checked during the initial laboratory examination.

The calories and protein supplied were the main variables of interest. They were measured by adding up the amount of calories and protein provided through PN, EN, and oral feeding on the fourth day of ICU stay. Target caloric need was calculated by multiplying ideal body weight by 25, and target protein need was decided as 1.2 g/kg/day. The ratio of supplied calories and protein to the total requirement was calculated.

The patients were classified into survival and mortality groups, and their characteristics were analyzed. Patients in the survival group survived until discharge, and patients in the mortality group died during hospitalization. An independent t-test was used for quantitative analysis, and the chi-square test was used for qualitative analysis. Subgroup analyses were performed according to the severity of TBI. Patients with initial GCS scores ranging from 3 to 8 were regarded as having severe TBI, and those with scores >8 were classified as having non-severe TBI. Finally, a logistic regression analysis was performed to verify the risk factors for mortality. Variables with a p-value <0.05 within univariate analyses were included in the final multivariate analysis. All statistical analyses were performed using IBM SPSS Statistics for Windows version 25.0 (IBM Corp., Armonk, NY, USA).

Over a 2-year study period, 864 patients with TBI were admitted to the trauma ICU, of whom 637 patients were excluded. Among the excluded patients, 587 patients, including 93 who died, were discharged from the ICU within 7 days of admission. Missing data were mainly identified based on the exact amount of oral intake (Fig. 1).

In total, 227 patients were included in the statistical analysis, of whom 172 (75.8%) were male and 34 (15%) died. The mean age and ISS of the patients were 62.9 years and 26.3 points, respectively.

The characteristics of the survival and mortality groups were compared. The survival group had a younger age, a higher initial GCS score, and more calorie supply on the fourth day of ICU stay (Table 1) than the mortality group. However, these parameters did not show statistical significance in the logistic regression analysis used to identify risk factors.

Subgroup analyses was performed to patients with severe and non-severe TBI. No significant differences were observed among patients with severe TBI. Thirteen cases of mortality were recorded, and the causes of death include multiorgan failure/sepsis (n=9, 69.2%) and respiratory failure (n=2, 15.4%). The survival group of patients with non-severe TBI had a younger age, more calorie supply, a higher percentage of total calories, and more protein supply on the fourth day of ICU stay, compared with the mortality group. Higher initial hemoglobin and albumin levels were also observed (Table 2).

Finally, risk factors for mortality were assessed using logistic regression analysis in patients with non-severe TBI. Calorie supply on the fourth day of ICU stay and initial hemoglobin level showed statistical significance (Table 3). Protein supply and other nutrition-related variables were not significant risk factors of mortality.

In the present study, we aimed to identify the effects of early sufficient nutrition in patients with TBI admitted to the ICU. Our findings demonstrated that increased calorie supply on the fourth day of ICU stay is associated with better survival in patients with TBI, showing the effect of early sufficient nutrition in patients with critical illness.

Many studies have emphasized the benefits of early nutrition in critically ill patients. Jeong et al. [8] compared high and low calorie and protein supply in patients with sepsis and reported improved outcomes in high calorie and protein supply groups. Lv et al. [16] reported that hypocaloric nutrition during 3-7 days of critical illness was associated with mortality in ICU patients. They reported that calorie supply <70% of estimated requirement was associated 28-day mortality. Similarly, high calorie supply resulted in survival gain in the present study. We primarily analyzed patients with TBI admitted to the ICU. They commonly have nutritional problems due to poor mental health status and related endotracheal intubation. However, analyses regarding nutrition support in these patients are lacking. The findings of the present study may have important clinical implication, supporting the survival benefits of early and sufficient nutrition in patients with TBI admitted to the ICU.

Many studies excluded patients with ICU stay less than 7 days [8,14,16], including those who were discharged within 7 days. The investigators planned to include patients requiring nutritional therapy and excluded those who died early. Gunst et al. [5] reported the characteristics of trauma-related deaths. Patients with non-survivable or severe injury died several minutes to hours after injury, and TBI was the most common cause of death in the study. Providing nutritional support to improve mortality rates in severely injured patients proves difficult. In this study, caloric and protein supply were not associated with mortality in patients with severe TBI. In addition, one more late mortality peak occurred after 1 week, with common causes of late death include multi-organ failure and sepsis, which were similarly reported in patients with non-severe TBI (69.2%). These conditions, coupled with inadequate nutritional support, potentially contributed to the longer ICU stay in the mortality group. Proper nutrition support has been proven to have better outcomes in previous studies, and its effect was observed in patients with non-severe TBI in the present study.

The amounts of calories and protein supplied were less than those recommended in the guidelines. van Zanten et al. [23] suggested a gradual increase in nutrient supply to 70-100% of the target amount on the fourth day of critical illness. However, only approximately 50% of target calories and protein were achieved in the present study. Although the delivered nutrition was less than that recommended in the guidelines, supplying more calories to patients with TBI in the early stages of ICU admission possibly improved their survival.

Protein is a critical component for trauma patients, as it helps reduce muscle loss and promotes wound healing by serving as a primary building blocks for tissue growth, cell renewal, and repair [3,22,24]. In particular, patients under neurocritical care require higher protein intake than general recommendations [9]. In this study, the survival group received more protein compared to the mortality group (37.5 vs. 22.1 g); however, protein supply was not statistically significant in the final logistic regression analysis. Further analysis with large sample size may potentially generate different result.

This study has several limitations. This study was conducted in a retrospective cohort setting. Therefore, the reason for undernutrition was not evaluated because of the lack of exact medical records. Oh et al. [18] reported that approximately 70-80% of recommended calories and protein were actually delivered to patients in the trauma and surgical ICU. Common reasons for this mismatch were accordance and examination, procedures that required fasting. Another study reported that the common causes of EN interruption were radiological examination, tube malfunction, and surgical procedures [19]. In the present study, we focused on assessing the actual calories and protein supplied, as in similar studies. The admitted patients were mostly those with major trauma (mean ISS, 26.3) with multiple injuries that required many examinations and operations. Furthermore, the superiority of EN over PN, which is an important issue in critical care nutrition, was not assessed. However, in several studies, the amount of nutrient was calculated by combining EN and PN [25,26]. Moreover, factors such as underlying medical conditions and treatment refusal, which could confound the results, were not included in the analysis. Future well-designed randomized controlled studies analyzing various components of patients with TBI may provide further insights and improve clinical management.

Additionally, the survival group of patients with non-severe TBI had high initial hemoglobin and albumin levels. Hemoglobin levels decrease after trauma-induced hemorrhage. Hemoglobin and albumin levels reflect the general nutritional status of patients. Luo et al. [15] reported that albumin was superior to hemoglobin in predicting mortality in pediatric patients with moderate-to-severe TBI. Both hemoglobin and albumin levels were associated with patient mortality; however, albumin level had a greater area under the curve than hemoglobin level in the receiver operating characteristic analysis for mortality. In contrast, only hemoglobin level was a risk factor for mortality in the logistic regression analysis in the present study. Other nutritional markers, including neutrophil-to-lymphocyte ratio, CRP, albumin, and CRP/albumin ratio did not show statistical significance. Further analysis of the nutritional status of patients with TBI will help understand the pathophysiology of this condition.

Early sufficient nutrition is associated with survival gains in patients with TBI admitted to the ICU. Additional protein was delivered to the survival group; however, this was not proven to be a risk factor for mortality. Further studies on nutritional support in patients with TBI are warranted to increase our understanding of the pathophysiology of TBI and improve its prognosis.