Comparison of Sequential Feeding and Continuous Feeding on the Blood Glucose of Critically Ill Patients: A Non-Inferiority Randomized Controlled Trial
Introduction
Glucose control is a critical aspect of managing critically ill patients, as both hyperglycemia and hypoglycemia are associated with adverse outcomes, including increased mortality. Enteral nutrition is widely recommended for intensive care unit (ICU) patients, provided their gastrointestinal function allows it. However, the optimal feeding method—continuous feeding (CF) or sequential feeding (SF)—remains a subject of debate. CF, which involves delivering enteral nutrition at a constant rate over 24 hours, has been traditionally favored for its perceived benefits in reducing feeding complications and stabilizing blood glucose levels. However, CF may disrupt the body’s natural circadian rhythms, potentially leading to metabolic dysregulation. In contrast, SF aligns feeding schedules with the body’s circadian rhythms, as outlined in traditional Chinese medicine theory, and may offer a more physiologically appropriate approach. This study aimed to compare the effects of SF and CF on blood glucose levels and feeding intolerance in critically ill patients.
Methods
This study was a prospective, single-blinded, non-inferiority randomized controlled trial conducted in the ICU of the Affiliated Hospital of Qingdao University. Ethical approval was obtained, and written informed consent was provided by all participants or their legal representatives. Patients admitted to the ICU between May and December 2018 who required enteral nutrition via gastric tubes were eligible for inclusion. Exclusion criteria included the ability to eat orally, diabetes, gastrointestinal diseases, or recent gastrointestinal surgery.
Initially, all patients received CF until they achieved at least 80% of their target caloric intake (25–30 kcal/kg/day). Patients were then randomly assigned to either the SF or CF group. In the SF group, the total daily enteral nutrition was divided into three equal portions, delivered at 7:00–9:00, 11:00–13:00, and 17:00–19:00, with each portion administered over two hours using an enteral feeding pump. In the CF group, patients received enteral nutrition at a constant rate throughout the study period.
Blood glucose levels were monitored at five time points (6:00, 11:00, 15:00, 21:00, and 1:00) for seven consecutive days. Feeding intolerance, including diarrhea, abdominal distension, constipation, and gastric residual volume (GRV), was also recorded. Statistical analyses included non-inferiority testing, chi-square or Fisher tests for qualitative data, and Mann-Whitney U tests for quantitative data. Repeated-measures ANOVA was used to assess changes in glucose levels over time.
Results
A total of 62 patients were enrolled, with 32 assigned to the SF group and 30 to the CF group. Baseline characteristics, including age, gender, weight, body mass index, and APACHE II scores, were comparable between the two groups.
The primary outcome, average blood glucose levels over seven days, was significantly lower in the SF group (8.8 mmol/L) compared to the CF group (10.7 mmol/L), meeting the non-inferiority criterion. Hyperglycemia incidence was also lower in the SF group (11.8%) than in the CF group (38.4%). Hypoglycemia was not observed in either group.
Glycemic variability, assessed using standard deviation (GluSD), coefficient of variation (GluCV), and the difference between maximum and minimum glucose levels (Glucosemax-Glucosemin), showed no significant differences in GluSD or Glucosemax-Glucosemin between the groups. However, GluCV was higher in the SF group (24.5%) compared to the CF group (18.9%).
Repeated-measures ANOVA revealed significant time-dependent changes in glucose levels, with lower values in the SF group at 6:00 and 1:00 compared to the CF group. There were no significant differences in feeding intolerance, ICU length of stay, or mortality between the groups. However, the SF group had fewer mechanical ventilation days than the CF group (10 vs. 17 days).
Discussion
This study demonstrated that SF is non-inferior to CF in terms of average blood glucose levels and may offer additional benefits, such as reduced hyperglycemia incidence and shorter mechanical ventilation durations. The findings suggest that SF, which aligns feeding schedules with the body’s circadian rhythms, is a safe and effective alternative to CF for critically ill patients.
CF has traditionally been favored for its perceived benefits in reducing feeding complications and stabilizing blood glucose levels. However, CF may disrupt circadian rhythms, leading to metabolic dysregulation. In contrast, SF, which incorporates intermittent feeding based on traditional Chinese medicine theory, may better align with the body’s natural rhythms and optimize metabolic outcomes.
The lower average glucose levels and reduced hyperglycemia incidence in the SF group may be attributed to the alignment of feeding schedules with circadian rhythms, which enhances glucose metabolism. The higher GluCV in the SF group, while statistically significant, may reflect a more physiologically appropriate fluctuation in glucose levels, potentially benefiting protein synthesis and overall metabolic health.
Feeding intolerance, a common issue in ICU patients, was similar between the SF and CF groups, indicating that SF does not increase the risk of gastrointestinal complications. The shorter mechanical ventilation duration in the SF group may be related to improved metabolic and physiological outcomes associated with circadian-aligned feeding.
Limitations of this study include the exclusion of patients with diabetes or gastrointestinal diseases, which limits the generalizability of the findings. Additionally, the seven-day observation period may not capture longer-term outcomes. Further research is needed to explore the effects of SF in broader patient populations and over extended periods.
Conclusion
In this non-inferiority randomized controlled trial, sequential feeding (SF) was found to be as safe and effective as continuous feeding (CF) for critically ill patients. SF resulted in lower average blood glucose levels and reduced hyperglycemia incidence without increasing the risk of feeding intolerance. These findings suggest that SF, which aligns feeding schedules with the body’s circadian rhythms, is a viable alternative to CF for managing enteral nutrition in critically ill patients. Further studies are needed to validate these results and explore the broader implications of circadian-aligned feeding in ICU settings.
doi.org/10.1097/CM9.0000000000001684
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