OBJECTIVE: Previous randomized controlled trials (RCTs) comparing intermittent feeding versus continuous feeding used different methods, employed shorter fasting intervals, ignored patients\' posture in bed during feeds, and showed mixed results. Prolonged fasting intervals are hypothesized to have several benefits. Additionally, there is evidence for more efficient gastric emptying in the right lateral position. In this multicenter RCT, we aimed to compare the effects of three-times-a-day gastric feeding while in the right lateral tilt position (intermittent postural feeding) versus standard continuous gastric feeding (standard feeding) on gastrointestinal intolerance and mortality among mechanically ventilated patients in ICU.
METHODS: Adult ICU patients with gastric feeding tube in-situ and requiring invasive mechanical ventilation were randomized to either intermittent postural feeding group or to the standard feeding group. The feeding formula, target daily feed volume and posture turns were determined as per standard practice for all patients. Primary outcome was an incidence rate per 100 patient-days of gastrointestinal intolerance, a composite outcome of vomiting, diarrhea or constipation. Secondary outcomes were all-cause hospital mortality, gastrointestinal intolerance-free days, ventilator-free days, episodes of vomiting or diarrhea per patient, and mean diet volume ratio (diet received/diet prescribed).
RESULTS: At five multidisciplinary ICUs, 120 mechanically ventilated, adult ICU patients (median age 65 years, 60% males) were randomly allocated to intermittent postural feeding (n = 61) and standard feeding (n = 59). The primary outcome did not differ between intermittent feeding arm versus standard arm (8.5, 95% confidence interval (CI): 5.9-11.8, versus 6.2, 95% CI: 4.1-9.1 per 100 patient-days; p = 0.23). Gastrointestinal intolerance-free days until day 14 were similar (6 [2-8] versus 5 [2-10]; p = 0.68) in both groups. Number of episodes per patient of vomiting, diarrhea, or constipation also did not differ in between groups. All-cause hospital mortality between intermittent feeding arm versus standard arm was 20% versus 31% (p = 0.17). There were no significant between-group differences in any of the other secondary outcomes.
CONCLUSIONS: Intermittent gastric feeds delivered three-times-a-day while in the right lateral tilt position among mechanically ventilated patients was as well tolerated as the continuous enteral feeding. A definitive RCT to assess other clinically important outcomes is justified.
BACKGROUND: ACTRN12616000212459 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365526&isReview=true.

Critically ill children are fed day and night, assuming this improves enteral tolerance and the probability of achieving nutritional goals. It was previously shown that a fasting response, reflected by increased ketosis, at least partly explained the beneficial outcome of delayed initiation of supplemental parenteral nutrition. This study aims to investigate whether an overnight fast increases ketosis and is feasible and safe in critically ill children.
The Continuousversus Intermittent Nutrition in Paediatric Intensive Care (ContInNuPIC) study is a randomised controlled trial in a tertiary referral Paediatric Intensive Care Unit (PICU) in the Netherlands. Critically ill children (term newborn-18 years) with an expected PICU stay ≥48 h, dependent on artificial nutrition, were eligible. Participants were randomly assigned (1:1, stratified for age group) to intermittent feeding, with interruption of feedings during an age-dependent overnight period of eight to 12 h, or to continuous feeding, with the administration of feedings day and night. In both groups, similar daily caloric targets were pursued. For children younger than one year, mandatory minor glucose infusions were provided during fasting. The primary outcome was the feasibility, defined as two conditions (1): a significant difference in the patients\' highest daily ketone (3-β-hydroxybutyrate, BHB) levels during each overnight period, and (2): non-inferiority regarding daily caloric intake, examined using a two-part mixed-effects model with a predefined non-inferiority margin of 33%, in an intention-to-treat analysis. The study is registered in the Netherlands Trial Register (NL7877).
Between May 19, 2020, and July 13, 2022, 140 critically ill children, median (first quartile; third quartile) age 0.3 (0.1; 2.7) years, were randomised to intermittent (n = 67) or continuous feeding (n = 73). In the intermittent feeding group, BHB levels were significantly higher (median 0.4 (0.2; 1.0) vs. 0.3 (0.1; 0.7) mmol/L, p < 0.001). The ratio of total caloric intake in the intermittent feeding group to the intake in the continuous feeding group was not consistently significantly more than 0.67, thus not proving non-inferiority. No severe, resistant hypoglycaemic events, nor severe gastrointestinal complications related to the intervention occurred, and feeding intolerance did not occur more often in the intermittent than in the continuous feeding group.
Compared with day and night feeding, intermittent feeding with an overnight fast and mandatory glucose infusion for children younger than one year marginally increased ketosis and did not lead to more hypoglycaemic incidents in critically ill children. Because non-inferiority regarding daily caloric intake was not proven, the feasibility of an overnight fast could not be shown in the current study. However, as feeding intolerance did not increase during the condensed feeding periods, the nutritional intake was probably limited by the prescription of nutrition and interruptions. More research is needed to determine the optimal level and duration of clinically relevant ketosis and the best method to achieve this.

The main purpose of this study was to evaluate the impact of drip versus intermittent feeding on splanchnic oxygenation in preterm infants with intrauterine growth restriction. The second objective was to assess the relationship between fetal splanchnic circulation parameters and splanchnic oxygenation during the first week of life. A single-center, prospective, randomized study with 51 fetuses/infants was conducted. Fetal Doppler measurements including umbilical artery, middle cerebral artery, and superior mesenteric artery (SMA) were recorded in IUGR fetuses. After preterm delivery, the infants were randomly assigned to one of two feeding modalities: drip (3-h continuous) or intermittent (bolus in 10 min). Continuous regional splanchnic saturation (rSO2S) monitoring was carried out during the first week of life, simultaneously with continuous oxygen arterial saturation (SaO2) monitoring, and the infants\' fractional oxygen extractions (FOE) were calculated. These parameters were evaluated as means on a daily basis for the first week of life, as well as pre-prandial and post-prandial measurements on the seventh day. Fetal Doppler flow velocimetry disturbances were present in 72.5% of the study cohort. The drip (26 infants) and intermittent (25 infants) groups were similar in demographic and clinical characteristics, as well as the prevalence of feeding intolerance and necrotizing enterocolitis. During the first week of life, there was no difference in daily mean rSO2S and FOE values between the drip and intermittent groups, whereas unfed infants had mostly lower rSO2S values. Pre-prandial and post-prandial rSO2S values remained stable in both groups. Also, no association was detected between fetal splanchnic circulation parameters and neonatal splanchnic oxygenation. RSO2S values were strongly correlated to gestational age and birth weight. During the whole week, except for the first 2 days, infants with umbilical catheters had significantly lower rSO2S values than infants without.  Conclusion: Our data suggest that the key factor in splanchnic oxygenation is feeding, not the feeding modality. In addition, the umbilical vein catheter had a negative impact on splanchnic oxygenation.  Clinical Trial Registration: The Effect of Neonatal Feeding Modalities on Splanchnic Oxygenation, NCT05513495,  https://clinicaltrials.gov/ct2/results cond=&term=NCT05513495&cntry=TR&state=&city=&dist= . Retrospectively registered, date of registration: August 2022. What is Known: • It is known that preterm infants with IUGR are at increased risk of hypoxic-ischemic intestinal damage and impaired splanchnic oxygenation. What is New: • The key factor in splanchnic oxygenation of preterm infants with IUGR is feeding, not the feeding modality (drip or intermittent). • In addition, the umbilical vein catheter had a negative impact on splanchnic oxygenation.