The early feeders among the more severely ill patients experienced significantly more frequent feeding complications than late feeders, but their caloric and protein intake did not differ from the other groups. This was due to their major feeding complications being diarrhea and/or GI bleeding and not gastric retention or vomiting, which would significantly affect nutritional intake. Severely ill patients commonly develop GI problems such as mucosal damage, motility disturbances, and hypoalbuminemia-related mucosal edema due to severe physiological stress [22, 23]. Therefore, we inferred that the higher incidence of diarrhea might have been due to early aggressive feeding placing stress on damaged mucosa and/or a higher usage of antibiotics in these patients. However, diarrhea among the more severely ill early feeders was not severe and it subsided after adjusting the feeding rate and/or administration of anti-diarrhea medicines. Additionally, the higher incidence of GI bleeding among these patients is related to stress ulcers and not active bleeding. GI bleeding subsided after controlling shock or use of medications such as proton pump inhibitors or histamine type 2 receptor antagonists. Consequently, as we were able to control diarrhea and GI bleeding, neither significantly affected nutritional intake. These results, however, are inconsistent with previous reports of early feeding improving GI function [4, 6]. Critically ill patients suffer from a combination of physiological disturbances likely to influence GI function [22, 24]. Our results show an association between illness severity and enteral feeding commencement. In more severely ill patients, feeding within 24 to 48 h of ICU admission may be too early as it can cause further stress to the GI tract, and result in diarrhea and stress-induced ulcers.
We also observed that the higher the APACHE II score, the longer the ICU stay for early feeders after adjusting for confounding factors. These results are consistent with Ibrahim et al., who observed greater incidence of diarrhea and longer ICU stays among early feeders . We hypothesize that the greater incidence of feeding complications is a confounding factor increasing the length of ICU stay in the early feeding group among more severely ill patients .
Our observations indicate that mortality is unaffected by enteral feeding commencement time. The meta-analysis study conducted by Marik and Zaloga also found no relationship between early enteral nutrition and decreased mortality . Expectably, our study demonstrates that illness severity governs the mortality rate and neither late enteral feeding nor early enteral feeding reduces the mortality rate.
Clinically, serum albumin level most likely acts as a prognostic rather than nutritional indicator . Previous studies have indicated that inflammatory mediators and cytokines released during injury are major contributors in lowering serum albumin and prealbumin levels [28, 29]. Serum prealbumin is more sensitive to changes in protein-energy status than serum albumin is, and its concentration reflects recent dietary intake rather than an overall nutritional status . In critical illness, hypoalbuminemia and hypoprealbuminemia are very common and inversely related to C-reactive protein . Therefore, increases in these two serum protein levels (in response to enteral feeding on days 4 and 7) only in the case of more severely ill early feeders might relate to early feeding inducing the release of trophic endogenous agents and the inhibitory effects of inflammatory mediators and cytokines released during severe illness [26, 31].
Negative NB indicates inadequate protein intake or excessive catabolism. We observed no differences in protein intake between both feeding groups but significantly higher 24-h UUN losses in more severely ill early feeders. This implies that levels of stress are higher among these patients. Briassoulis et al. demonstrated that severity of illness independently contributes to negative NB status during acute stress phases . As disease becomes more severe, more stress hormones are secreted, leading to greater GI disturbances and nitrogen loss . Therefore, the lower 24-h UUN loss and better NB in the more severely ill of late feeding group is more likely due to improved metabolic stress.
This study has important strengths. Firstly, it is observational and feeding commencement was decided solely by the ICU team in accordance with actual treatment protocol. This connotes the de facto aspects of intensive care. Second, our 21-d study period is longer than those of previous studies. There were also limitations in our study. First, the study population was within a single medical ICU, meaning generalizations must be treated cautiously. Second, the sample size of the early feeding group limits the study’s power to analyze the measured outcomes. However, the results of multiple linear regression and logistic regression analyses strongly support our findings eliminating the issue of power insufficiency. Further, larger randomized sample-sizes, controlled trials with mixed ICU patients, data analyzed on tertiles, quartiles or quintiles of APACHE II scores and enteral feeding commencement time are required to fully investigate the optimal timing of initial enteral feeding in managing patients with varied illness severity.