Study

FEEDS Trial

Our overarching hypothesis is that in most mechanically ventilated patients, preoperative fasting is: (1) unnecessary due to the presence of a secure airway and low incidence of aspiration,4-7 and (2) harmful due to exacerbation of pre-existing nutritional compromise.5,8-10 The proposed pragmatic comparative trial of two prevalent, but conflicting, preoperative practices of fasting for more than 8 hours vs. not fasting in tube-fed Figure 3. Preventable periprocedural starvation in tube-fed patients.Adapted from a figure produced by A. Nagrebetsky (PI) for American Society of Anesthesiologists Committee on Critical Care Medicine. Mass General Brigham Institutional Review Board Intervention/Interaction Detailed Protocol Version 15 2025-12-17 Page 12 of 46 patients with a secure airway will leverage our existing Perioperative Research Network30-32 to address the following aims:  Aim 1: To compare the risk of pulmonary complications and mortality from: (1) perioperative pulmonary aspiration6,33,34 due to not fasting vs. (2) systemic effects of nutritional loss18-24 due to preoperative fasting. We will quantify the risk of pulmonary complications and mortality as the number of postoperative days alive and free from mechanical ventilation (DAFV)35,36 in the target population of critically ill patients with a secure airway who undergo interventional procedures.  Aim 2: To compare length of ICU and hospital stay, discharge to home, need for organ support, infectious complications, safety outcomes, and nutritional outcomes in tube-fed mechanically ventilated patients with a secure airway who are fasted vs. not fasted prior to procedure.  Aim 3: To define the relationship between perioperative fasting duration, calorie/protein delivery, and clinical outcomes in mechanically ventilated patients who receive tube feeding. We anticipate that: (1) not fasting preoperatively will be non-inferior to fasting based on the risk of perioperative pulmonary aspiration measured as days alive and ventilator-free on postoperative day 28; (2) preoperative fasting will result in a substantial loss of calories and protein compared to not fasting; (3) due to nutritional loss, patients in the fasting group may have longer ICU and hospital stay and may have a higher frequency of infectious complications and need for organ support, compared to those in the non-fasting group. Such findings will inform preoperative fasting practice in tube-fed patients with a secure airway. Moreover, our results may improve outcomes in this population through establishing a standard of care that minimizes systematic harm from starvation in the critically ill.

Why this Research Matters

Trial Design: Phase III pragmatic multicenter parallel-group randomized controlled non-inferiority trial with patient-level randomization and assessor blinding. If non-inferiority is demonstrated, we will perform a pre-specified superiority test. The study flow diagram (schema) is provided in Section 6/Figure 5. Treatment Arms: Study participants will be randomized with a 1:1 allocation ratio to one of the following preprocedural interventions: (1) fasting - stopping tube feeding at least 8 hours prior to the scheduled procedure time; (2) not fasting - tube feeding until call for transfer to the procedure area. Primary Outcome: Days alive and free from mechanical ventilation on postoperative day 28. Secondary Outcomes: Our secondary outcomes reflect recovery from critical illness, immediate perioperative safety, and delivery of nutrition (Section 6/Outcomes). Patient Population: Critically ill patients in the ICU who are: mechanically ventilated, receiving tube feeding (enteral nutrition), with a planned surgery or procedure. Up to 1072 subjects will be enrolled. Enrollment Period: Approximately two years. Locations: ICUs at a subset of Perioperative Research Network hospitals.

Who can Participate

Adult

1. Age => 18 2. Current admission to ICU 3. Secure airway with no plans for its removal prior to procedure 4. Current non-trophic (> 10 mL/hr) tube (enteral) feeding with no plans to discontinue prior to procedure for reasons other than preoperative fasting 5. Planned eligible procedure with anesthesia care or nursing sedation 1. Age => 18 2. Current admission to ICU* 3. Secure airway** with no plans for its removal prior to procedure 4. Current non-trophic (> 10 mL/hr) tube (enteral) feeding*** with no plans to discontinue prior to procedure for reasons other than preoperative fasting 5. Planned eligible procedure (Examples are listed in Appendix C) with anesthesia care or nursing sedation. Eligible procedures are defined as non-emergent diagnostic or therapeutic interventions that: Do NOT have a well-established practice of preoperative fasting. (For example, bedside placement of a vascular catheter [arterial, central venous, peripheral venous] by the ICU team is NOT eligible for this trial since it has a widely established practice of no preoperative fasting and is not generally scheduled for a specific time.) Do NOT require fasting for preoperative gastrointestinal tract preparation Do NOT require removal/replacement of the endotracheal or tracheostomy tube Do NOT require prone or Trendelenburg (head-down) positioning. Typically require procedural sedation or anesthesia care. Generally, are scheduled for a specific time (although this time can change, or procedure may be cancelled). Are performed in the operating room, non-operating room procedural areas, or at the patient's bedside. * All ICU types are eligible: surgical, medical, cardiac, neurological, trauma, mixed etc. ** Secure airway is defined as a cuffed endotracheal tube or a cuffed tracheostomy tube. *** Patients with all types of feeding tubes are eligible, regardless of tube insertion site (nasal, oral, surgically implanted) and tube tip location (pre- and post-pyloric) Exclusion Criteria 1. Inability to obtain informed consent 2. Inability to enroll and randomize > 8 hours prior to planned procedure time 3. Inability to deliver trial interventions 4. Expected survival < 48 hours as determined by the enrolling physician-investigator 5. Critically ill burn patient 6. Emergency procedure 7a. Gastrointestinal tract procedure that requires fasting based on surgical indications or airway/lung procedure that requires removal of endotracheal or tracheostomy tube 8. Plan for prone or Trendelenburg (head down) positioning during most of the procedure 9. Major impairment of gastrointestinal motility or major structural disease of the gastrointestinal tract (e.g., severe gastroparesis, bowel obstruction, severe ileus, severely compromised lower esophageal sphincter, active gastrointestinal bleeding) 10. Plan for postoperative extubation in the procedure area 11. Prisoner 12. Pregnant woman, woman of childbearing potential without a documented negative urine or serum pregnancy test during the current hospitalization, or woman who is breast feeding 13. Refusal to enroll patient by treating physician 14. Extracorporeal Membrane Oxygenation (ECMO) at the time of potential enrollment, except patients scheduled for ECMO decannulation as the study procedure and patients expected to be off of ECMO at the time of study procedure. 15. Chronic mechanical ventilation at pre-admission level of care