Indirect calorimetry-guided nutrition during weaning from prolonged mechanical ventilation: a double-blind randomized controlled trial

To determine whether indirect calorimetry (IC)-guided nutritional prescriptions improve weaning success and time to liberation from prolonged mechanical ventilation (PMV) compared with predictive-equation-guided feeding. In this double-blind randomized controlled trial conducted at Reuth Tel-Aviv Rehabilitation Hospital (Nov 2019-Apr 2023), with 1-year follow-up, adults ventilated ≥ 21 days were randomized to receive IC-guided energy targets or predictive-equation-guided feeding. Primary outcomes were successful weaning (≥ 7 consecutive days of spontaneous breathing) and time to successful weaning. Secondary outcomes included number of weaning cycles and 1-year mortality. Metabolic/nutritional safety parameters were recorded. Analyses followed the intention-to-treat principle, with additional per-protocol analyses. Time-to-event outcomes were evaluated using Kaplan–Meier estimates and Cox proportional hazards models. Among 211 randomized patients (111 IC; 100 control), successful weaning was achieved in 58% of the IC arm and 50% of the control arm (absolute difference 8%; p = 0.33). Median time to successful weaning was 27 vs. 31 days, respectively ( p = 0.58). One-year mortality was 48% in the IC arm and 56% in the control arm (absolute difference of -8%, 95%CI: -21.2%, 5.5%; p = 0.29). In a post hoc analysis of the per-protocol cohort ( n = 198), a smaller difference between measured energy expenditure and delivered energy intake (energy-gap) was independently associated with a higher likelihood of successful weaning (HR = 1.02 per 50-kcal/day reduction in the energy-gap; 95%CI: 1.00, 1.05; p = 0.02). IC-guided feeding resulted in closer alignment between measured energy expenditure and delivered energy intake and reduced the tendency toward overfeeding observed with predictive-equation–based prescriptions. Successful weaning was independently associated with lower one-year mortality (HR = 0.54; 95%CI: 0.36–0.82), adjusting for study arm. The observed rates of successful weaning and one-year survival were numerically higher, and median time to liberation was shorter, with IC-guided nutrition than with predictive-equation-guided feeding, although between-group differences were not statistically significant. Closer alignment between measured energy expenditure and delivered energy intake was independently associated with successful weaning. These findings support further evaluation of energy delivery guided by measured energy expenditure in adequately powered multicenter trials. ClinicalTrials.gov identifier NCT04825717. Registered March 15, 2021.