Aging induces significant changes in the GI and hepatic systems, resulting in decreased motility in the esophagus and intestines, reduced gastric acid secretion, and diminished digestive enzyme production [1]. These changes slow gastric emptying, hinder nutrient absorption, and may lead to complications like anemia and osteoporosis [1,2]. Such issues are exacerbated in ANI, increasing residual gastric volume in patients receiving enteral nutrition (EN) [3]. Additionally, aging affects liver functionality by reducing liver volume and blood flow, which impairs the ability of the liver to process medications and extend the effects of drugs [1,8]. This reduction in hepatic efficiency necessitates careful medication management, especially in the treatment of older adults with ANI, to adjust drug dosages for safety and efficacy in neurocritical care (Table 1) [4,9-11].

Hormonal regulation changes significantly in aging and affects physiological processes. Decreased growth hormone secretion reduces muscle mass, whereas diminished renal function affects the renin-aldosterone system, increasing the risk [1]. The effectiveness of insulin decreases owing to heightened insulin resistance, potentially lowering production and causing prolonged high blood glucose levels, which elevates diabetes risk [1,8]. These hormonal changes complicate hyperglycemia management in acute brain injuries, making glucose stabilization challenging (Table 1) [4,9-11].

As individuals age, there is a discernible increase in chronic health conditions, leading to a heightened risk of “multimorbidity,” where 2 or more chronic diseases are present simultaneously [1]. Key comorbidities prevalent among older adults include but are not limited to hypertension, diabetes mellitus, chronic obstructive pulmonary disease, heart failure, malignancies, and cognitive decline [1]. The convergence of aging and such comorbidities significantly increases the likelihood of frailty, a syndrome characterized by a comprehensive decline in physiological functions that critically diminishes an individual's ability to cope with stressors, thus increasing their susceptibility to adverse health outcomes [2,3]. In the realm of neurocritical care, older patients often present with a spectrum of coexisting conditions, such as diabetes and hypertriglyceridemia, which complicate their management and prognosis.

In older patients, a notable shift in body composition is observed, with a decrease in muscle mass and an increase in fat mass, compared to younger individuals of similar body weight [4]. Sarcopenia prevalence is reported to be 5%-13% in individuals aged 60-70 years and increases to 11%-50% in those aged >80 years [12]. Sarcopenia is characterized by distinct features that deviate significantly from the pattern of healthy muscle aging [13]. The etiology of sarcopenia extends beyond aging and malnutrition, encompassing a reduction in physical activity, endocrine dysfunction, and neurodegenerative diseases, among other factors. In neurocritically ill older patients, the confluence of these factors increases sarcopenia development risk. Sarcopenia progression imposes barriers to recovery from neurological disorders. Alterations in mitochondrial function play a crucial role in sarcopenia, and nutritional interventions may ameliorate both mitochondrial dysfunction and the clinical manifestations of sarcopenia. Older patients, particularly those who are critically ill or have undergone surgery or trauma and present with sarcopenia, have increased mortality rates, a higher incidence of postoperative complications, fewer ventilator-free days, and fewer intensive care unit (ICU)-free days [5,6]. This disparity is partly due to the reduced capacity of older individuals to initiate an anabolic response to protein supplementation, a phenomenon observed in both healthy and critically ill individuals. Consequently, to counteract this “anabolic resistance,” older patients may necessitate a higher protein intake. While older critically ill patients typically exhibit increased ureagenesis with similar protein intakes as younger patients, the difference in serum urea nitrogen levels across age groups does not reach clinical significance for most [7].

Recommended strategies to combat muscle loss, sarcopenia, and ICU-acquired weakness include maintaining euglycemia during hospitalization, minimizing immobilization duration, applying electrical muscle stimulation, and implementing early EN [8]. However, the early catabolic phase characteristic of critical illness cannot be averted by the administration of early parenteral nutrition (PN) alone [8]. Early mobilization of ICU patients has emerged as a pivotal approach to mitigate physical decline post-critical illness, potentially curbing muscle loss and dysfunction [8]. This multifaceted approach highlights the importance of tailored nutritional and rehabilitation strategies to improve outcomes in aging and critically ill populations.

Every patient admitted to the NCCUs for >48 hours should undergo a nutritional risk assessment for malnutrition using a validated screening tool within the first 24 to 48 hours NCCU admission [17-19]. This is based on the understanding that alterations in the gut barrier, including signs of intestinal ischemia, increased permeability, bacterial translocation, and dysbiosis, can occur within the first 24 hours [20].

Although numerous tools have been proposed for screening the nutritional status of critically ill patients, none have been specifically validated for neurological patients [21-24]. Many existing tools involve comprehensive questionnaires not well suited for neurocritically ill older patients, often owing to the complexity of these assessments and the patients' difficulties with communication and cooperation. Therefore this study aimed to introduce some of the screening tools currently in use and discuss their applicability in the NCCU setting, to identify an appropriate tool that can be effectively implemented for this patient population.

Current guidelines recommend early implementation of oral or EN within 48 hours (<70% of estimated needs) rather than delaying EN. Then slowly ramps up to full nutritional requirements within 3 to 7 days (80%-100% estimated needs) of admission to avoid overfeeding (110% estimated needs). The Society of Critical Care Medicine guidelines recommend efforts to provide >80% of the estimated energy and protein needs within 48 to 72 hours to achieve the clinical benefit of EN over the first week of hospitalization [17]. It is critical when early PN is utilized; guidelines recommend a ramped approach to energy/protein delivery with initial doses ≤70% of resting energy expenditure (REE) and protein starting at <0.8 g/kg/d with advancement over the first ICU week [31].

After ANI, increased energy requirements can cause hypermetabolism and hypercatabolism, increasing morbidity and weight loss [15]. There is an ongoing debate about the optimal energy needed to reduce morbidity and mortality in NCCUs [32,33]; however, avoiding overfeeding is generally considered crucial [34]. The 2022 American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines note no significant outcome differences between higher and lower energy intakes, recommending 12 to 25 kcal/kg in the initial 7 to 10 days of ICU admission [34]. Hypocaloric enteral feeding in NCCUs is associated with less GI intolerance and shorter duration of ventilator use and hospital stay [32]. Without indirect calorimetry (IC), energy needs should be estimated at 25-30 kcal/kg body weight after adjusting for weight and clinical changes [15].

EN was associated with fewer infections, higher feasibility, and lower costs than PN [17]. It maintains intestinal function in older ICU patients [43] and is not reliably indicated by the absence of bowel sounds [17]. Total parenteral nutrition (TPN), a treatment for intestinal failure, increases morbidity and mortality rates [44]. The literature supports starting EEN within 24 to 48 hours of admission [18,45,46], even for patients who are paralyzed, have an open abdomen, are on extracorporeal membrane oxygenation, or are in prone positions [9,28,31,46]. Adequately resuscitated patients on low-dose vasopressors should receive trophic EEN soon after admission [9,46]. EN should not be discontinued for diarrhea without further evaluation [17].

If oral intake or EN is contraindicated, PN should be considered between 3 and 7 days post-admission [18,19]. EN should be postponed under several specific conditions, as outlined in the literature [19,43]. (1) Uncontrolled shock and hemodynamic instability (tissue hypoperfusion state): mean arterial pressure <60 mmHg; (2) Uncontrolled life-threatening hypoxemia, hypercapnia, or acidosis; (3) Active upper GI bleeding, whereas EN can be started when the bleeding has stopped, and no signs of rebleeding are observed; (4) Overt bowel ischemia, high-output intestinal fistula, abdominal compartment syndrome; (5) gastric tube volume is above 200 mL/6 h. in neurological patient.

Guidelines differ regarding the use of PN when EN cannot meet nutritional needs. ASPEN asserts that because PN and EN provide similar energy without differential harm, both are viable [17]. ESPEN suggests integrating EN and PN if targets are not met within 3 days [18,19], advocating patient-specific judgment on starting PN within the first week. It is advised to reduce PN as patients meet over 60% of their energy needs from EN [17]. Effective PN management depends on monitoring the patient’s capacity to handle dextrose, intravenous lipid emulsions (ILE), and amino acids [44], ensuring that the PN adapts to individual needs and minimizes risks. This patient-centered approach ensures that PN is tailored to meet the needs and tolerances of each patient, thereby optimizing nutritional support and minimizing potential complications.

No single tool can encompass all the nutritional requirements of a patient. Employing various monitoring techniques, conducting regular assessments, and involving a comprehensive nutritional team are essential for a thorough evaluation of patients’ nutritional needs [8]. Decisions regarding temporary and permanent nutritional support methods should align with the overarching objectives of patient care [8]. The involvement of an Nutritional Support Team facilitates the earlier initiation of EN and ensures appropriate nutritional support. These personalized strategies have the potential to significantly enhance patient outcomes significantly [12]. Furthermore, the implementation of EN protocols tailored to the specifics of an institution is critical for optimizing EN administration [17].

Although a pathogenic microbiome has been identified in critically ill patients, evidence regarding the impact of nutritional administration on the microbiome during critical illness remains scarce. Current research primarily examines the modulation of the microbiome via pre- and probiotics to address GI alterations such as diarrhea. However, variability in fiber composition and bacterial species has led to inconsistent results. Consensus guidelines recommend probiotic soluble fiber for diarrhea treatment, favoring it over mixed-fiber formulas due to its ability to ferment and produce short-chain fatty acids [20,37]. The diversity of probiotic preparations and dosages among existing studies has made it challenging to provide consistent results, underscoring the need for further research in this area.

Vitamins C and E reduce oxidative stress at the cellular level by exerting antioxidant effects. A combination of antioxidant vitamins and trace minerals, considered safe for critically ill patients, is recommended for those needing specialized nutritional therapy [17,19]. However, supplemental enteral glutamine should not be routinely added to EN regimens for critically ill patients [17]. The ESPEN partially revised 2019 guidelines suggest that in critically ill trauma patients, additional EN doses of glutamine (0.2-0.3 g/kg/d) can be given for the first 5 days with EN and extended from 10 to 15 days for complicated wound healing [18,19].

Vitamin E has been linked to improved mortality rates and Glasgow coma scale scores at discharge in patients with TBI [44]. High-dose vitamin C is associated with the stabilization of perilesional edema in TBI. All at-risk patients should have their vitamin D status (25(OH)D) checked [19]. Critically ill patients with low plasma levels (25-hydroxy-vitamin D <12.5 ng/mL, or 50 nmol/L) can receive a high dose of vitamin D3 (500,000 IU) within a week of admission [18]. A combination of vitamin D and progesterone in ischemic stroke shows a trend toward better survival and functional outcomes at 6 months [45,46]. IV magnesium sulfate, along with oral nimodipine for SAH treatment, has proven effective in reducing delayed cerebral ischemia and secondary cerebral infarction with good safety but does not reduce rebleeding or death [9].

The use of arginine-containing immune-modulating formulas or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplements with standard enteral formulas in patients with TBI [17] and offering either fish oil or non-fish oil lipid emulsions early in the ICU for suitable patients are considered practices. ILE enriched with EPA and DHA (0.1-0.2 g/kg/d) can be administered to patients on PN [19]. Nutritional doses of EN rich in omega-3 fatty acids are recommended [19]. Due to the diversity of study participants and small sample sizes, more extensive clinical research is needed before these methods can be widely used [37]. Further research is required on the role of antioxidants and immune-modulating diets in the NCCU before making definitive recommendations.

The assessment of RFS risk should consider various factors, including periods of fasting, weight loss, recent nutrient consumption, degree of fat and muscle depletion, and existing comorbidities (Table 9) [27,47]. RFS is a metabolic complication that may arise within the first 2 weeks of initiating high-calorie nutrition in undernourished patients and is marked by significant metabolic shifts in glucose, potassium, magnesium, and phosphate levels [25,44]. The reintroduction of nutrient-dense foods prompts insulin secretion, leading to the intracellular movement of glucose, potassium, magnesium, phosphate, and water, consequently causing a rapid reduction in serum levels [25,44,45]. Hypophosphatemia is frequently cited as a primary sign of this syndrome [44] and thiamine deficiency is recognized as a potential outcome of RFS [44]. These metabolic alterations can severely affect various body systems, potentially resulting in critical cardiovascular, neurological, and hematological issues, including heart failure, arrhythmias, seizures, and anemia. Early identification of individuals at risk for RFS is essential, enabling preemptive management of electrolyte imbalances, vitamin shortages, and fluid discrepancies before the initiation of nutritional support [19]. Regular monitoring of electrolytes and weekly assessments for those suspected of having RFS are imperative [19].

Several precautionary measures have been suggested to prevent RFS in vulnerable groups, several precautionary measures are suggested [44,46]: (1) Start with 100-150 g dextrose or 5-10 kcal/kg/day and gradually increase to the target caloric intake over 4-7 days. (2) Administer thiamine (100 mg/day), a multivitamin, and trace elements for 5-7 days before starting dextrose-containing IV fluids in at-risk patients. (3) Patients receiving oral/EN include a complete oral/enteral multivitamin daily for 10 days or longer, depending on their clinical status, especially in cases of severe starvation, chronic alcoholism, and/or signs of thiamin deficiency [44]. (4) In the presence of refeeding hypophosphatemia (<0.65 mmol/L or a drop of >0.16 mmol/L), hypokalemia, and hypomagnesemia, nutritional support should be limited for 48 hours, with electrolytes measured 2-3 times daily and supplemented as necessary. Resuming and increasing nutritional support are recommended after correction [18,19,27,44].