Metabolic control & glycemic stability
IEN VS. CEN
IEN: Mimics physiological feeding patterns, enhancing nutrient absorption and metabolic regulation. Patients achieve more stable blood glucose levels and better insulin sensitivity [14, 20], reducing hyperglycemia-related complications [21].
CEN: Provides stable support for high metabolic demands [22, 23] but increases postoperative hyperglycemia and insulin resistance risk [24].
IPN VS. CPN
IPN: Aligns with physiological rhythms but requires vigilant glucose monitoring due to rapid infusion causing blood glucose spikes [25]. Reduces overfeeding and insulin resistance risks [26].
CPN: Maintains metabolic stability [27] but causes persistent hyperglycemia and insulin resistance due to continuous glucose infusion [28].
Gastrointestinal function & tolerance
IEN VS. CEN
IEN: IEN can stimulate intestinal motility and reduce mucosal atrophy, promoting better nutrient absorption [29, 30]. Additionally, the intermittent nature of feeding reduces gastrointestinal pressure during non-feeding periods, which gives the digestive system time to rest and recover, potentially lowering the incidence of gastrointestinal intolerance, such as bloating or diarrhea [31]. However, the rapid administration of large volumes of nutrients, characteristic of IEN, may still result in discomfort, including symptoms like bloating and diarrhea, particularly in patients with compromised digestive capacity [32].
CEN: CEN has been associated with a potential decline in gastrointestinal function, particularly when used over extended periods. Research indicates that CEN may contribute to mucosal atrophy, as the constant nutrient supply limits the natural stimulation of the gut, which can weaken the intestinal mucosa [33]. Additionally, CEN has been linked to dysbiosis, or an imbalance in gut microbiota, which could increase the risk of gastrointestinal complications such as infections or intolerance [34]. These findings underscore the importance of carefully managing enteral feeding, particularly in critically ill patients, to prevent adverse outcomes.
Infection risk & immune response
IEN VS. CEN
IEN: IEN is associated with lower rates of postoperative infections, particularly in reducing the incidence of pneumonia and intra-abdominal infections. These outcomes may be due to the positive effects of IEN on reducing gastrointestinal pressure, which allows for improved digestion and metabolic regulation, ultimately leading to enhanced immune response [35, 36]. Moreover, the controlled feeding cycles of IEN give the gastrointestinal system time to rest, which may further support immune function and reduce infection risks [37].
CEN: It has been associated with a higher risk of postoperative infections compared to IEN. Studies have shown that patients on long-term CEN may experience higher infection rates, particularly due to the continuous use of enteral feeding tubes, which can increase the risk of pneumonia and other infections [14]. This may be due to factors such as reduced gut motility and immune response in patients receiving CEN.
IPN VS. CPN
IPN: IPN has been demonstrated to better support postoperative immune function. Studies suggest that patients receiving IPN experience lower infection rates, especially in those with compromised immune systems, when compared to those receiving continuous parenteral nutrition (CPN). This effect may be attributed to the intermittent nature of IPN, which allows for better glycemic control, a crucial factor in reducing postoperative infections [19, 38]. By maintaining more stable blood glucose levels, IPN reduces inflammatory responses, further decreasing the risk of infections [39].
CPN: While CPN provides necessary and continuous nutritional support, it has been linked to an increased risk of postoperative infections, particularly in critically ill patients. Studies have shown that infection rates are higher in patients receiving CPN, likely due to the development of persistent hyperglycemia, which is a known complication of CPN [19, 28]. Hyperglycemia contributes to immunosuppressive effects, such as impaired phagocyte function, which in turn raises the susceptibility to infections, including surgical site infections [40, 41].
Liver function & hepatotoxicity
IPN VS. CPN
IPN: Studies have shown that patients on IPN experience a lower incidence of liver dysfunction, particularly in cases requiring long-term parenteral nutrition [42]. The intermittent nature of IPN allows the liver to periodically rest, reducing metabolic stress and promoting self-regulation, which is beneficial for maintaining hepatic function [27]. This is especially important as CPN has been associated with conditions like fatty liver and cholestasis when used over extended periods.
CPN: CPN has been closely associated with liver dysfunction, with a higher risk of complications such as fatty liver and cholestasis. These liver issues are more pronounced during long-term use of CPN due to the sustained metabolic demands placed on the liver, along with the continuous infusion of nutrients, particularly lipids and carbohydrates [43]. The metabolic overload, particularly from excess lipid infusions and phytosterols, contributes to fat accumulation in the liver (steatosis), which can progress to more severe conditions like fibrosis and cirrhosis if not managed properly [44, 45].
Quality of life & mobility
IEN VS. CEN
IEN: Due to the intermittent nature of IEN, non-critically ill patients indeed enjoy greater mobility during non-feeding periods, which may contribute to a higher quality of life and improved postoperative recovery. Studies have highlighted that patients receiving IEN report improved well-being and shorter hospital stays compared to those on CEN [34, 43].
CEN: The continuous infusion required for CEN has been linked to a negative impact on patient quality of life, especially for those relying on long-term enteral feeding. One study noted that CEN patients often experience lower postoperative quality of life scores due to factors such as prolonged feeding times and restricted mobility associated with continuous feeding. Additionally, continuous feeding may lead to feelings of dependency and discomfort caused by the constant use of feeding equipment, further reducing patient autonomy and overall well-being [46].
IPN VS. CPN
IPN: The flexibility of IPN allows non-critically ill patients greater freedom of movement during non-infusion periods, which can significantly enhance their postoperative quality of life. Studies suggest that patients receiving IPN report higher quality-of-life scores during recovery, likely due to fewer restrictions on mobility compared to those on CPN [47]. Moreover, patients on IPN also experience shorter hospital stays, as the intermittent nature of the feeding supports faster recovery and better overall outcomes [48].
CPN: The continuous infusion required by CPN limits patient mobility due to the need for prolonged connection to intravenous equipment, which can significantly impact the quality of life, particularly for those on long-term parenteral nutrition. Patients receiving CPN often experience restrictions in daily activities, which contributes to a reduced quality of life [45, 49]. Furthermore, studies have shown that patients on CPN report lower quality of life scores, especially during the postoperative recovery phase, as the continuous infusion limits their physical mobility and autonomy [50]. This suggests a need for alternative strategies, such as cyclic parenteral nutrition (Cylic PN), which allows for greater mobility and improved patient outcomes.
Gut microbiota & circadian rhythm
IEN VS. CEN
IEN: The flora of the human gut has its own biological rhythms and maintains a dynamic balance of microorganisms throughout the intestinal tract. Different patterns of feeding and nutrient infusion can significantly affect the gut flora; regular feeding cycles and circadian rhythms help to maintain this dynamic balance, while conversely irregular feeding or prolonged and continuous nutrient supply may disrupt this balance, leading to metabolic syndrome or inflammatory diseases or even tumorigenesis [51].
Therefore, from the perspective of biological rhythms, intermittent nutrition is more in line with the body’s natural eating rhythm, can maintain the dynamic balance of intestinal flora in perioperative patients, and can fully stimulate the intestinal tract, promote intestinal peristalsis and secretion of digestive juices, improve nutrient absorption, effectively prevent bacterial translocation, and better maintain the diversity of the composition of the intestinal flora and reduce intestinal permeability [52]. The circadian rhythm of intestinal flora can be restored to some extent under conditions of nutrient intake restriction (e.g., fasting and intermittent feeding), suggesting that we need to pay more attention to the rhythmicity of the timing of feeding when developing clinical nutrition programs [53].
CEN: Continuous enteral nutrition infusion can provide patients with stable nutritional intake. Still, it is also its continuous infusion pattern that conflicts with the body’s biological rhythms (especially those of circadian and feeding rhythms), which may lead to a decrease in the diversity of the intestinal flora, disrupt endogenous rhythm regulation, increase the risk of pathogenic infections, increase the metabolic burden and induce inflammatory responses, thus posing a danger to the patient’s postoperative recovery [54].
Metabolites of intestinal flora affect human circadian rhythms via the gut-brain axis, and this disruptive effect is especially pronounced in the presence of poor synchronization between feeding rhythms and endogenous biological clocks. Metabolites of intestinal flora, such as short-chain fatty acids (SCFAs), can modulate the expression of appetitive and circadian genes in the hypothalamus, which can affect whole-body metabolism and behavior [55].
A comparative summary of these outcomes is presented in Table 1.
