REGARD-VAP: Routine Gastric Aspiration in Ventilated Patients (2020)

“Among adult patients receiving mechanical ventilation, a strategy of not monitoring gastric residual volume was not inferior to a strategy of routine monitoring of gastric residual volume with regard to the incidence of ventilator-associated pneumonia.”

  • The REGARD-VAP Investigators

1. Publication Details

  • Trial Title: Routine Gastric Residual Volume Measurement and Aspiration in Critically Ill Adults Receiving Enteral Nutrition: A Multicenter, Randomized, Open-Label, Noninferiority Clinical Trial
  • Citation: Reignier J, Le Gouge A, Lascarrou JB, et al. Routine Gastric Residual Volume Measurement and Aspiration in Critically Ill Adults Receiving Enteral Nutrition: A Multicenter, Randomized, Open-Label, Noninferiority Clinical Trial. JAMA Intern Med. 2021;181(1):59-67. DOI: 10.1001/jamainternmed.2020.5916. Note: The definitive publication for the REGARD-VAP trial was in 2021.
  • Published: January 1, 2021, in JAMA Internal Medicine
  • Author: Jean Reignier, M.D., Ph.D.
  • Funding: French Ministry of Health

2. Keywords

  • Enteral Nutrition, Gastric Residual Volume (GRV), Ventilator-Associated Pneumonia (VAP), Critical Care, Randomized Controlled Trial

3. The Clinical Question

  • In adult ICU patients receiving mechanical ventilation and enteral nutrition (Population), is a strategy of not monitoring gastric residual volume (GRV) (Intervention) non-inferior to a strategy of routine GRV monitoring (Comparison) with regard to the incidence of ventilator-associated pneumonia (VAP) (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Routine monitoring of gastric residual volume (GRV) was a long-standing and widespread nursing practice in the ICU. It was based on the theory that high GRVs indicated poor gastric motility and an increased risk of aspiration and ventilator-associated pneumonia (VAP).
  • Knowledge Gap: The practice of routine GRV monitoring was time-consuming, had poor reproducibility, and frequently led to the unnecessary interruption of enteral nutrition. There was no high-quality evidence from a large randomized trial to determine if this common practice actually prevented VAP or if it was simply a ritual that led to underfeeding.
  • Proposed Hypothesis: The authors hypothesized that a strategy of abandoning routine GRV monitoring would be non-inferior (no worse than) a strategy of routine GRV monitoring for the outcome of VAP incidence.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, open-label, non-inferiority controlled trial (used to test the effectiveness of interventions).
  • Setting: 27 intensive care units (ICUs) in France.
  • Trial Period: Enrollment ran from May 2016 to April 2018.
  • Population:
    • Inclusion Criteria: Adult patients (≥18 years) who were receiving invasive mechanical ventilation and were expected to require it for at least 48 hours, and for whom enteral nutrition was planned.
    • Exclusion Criteria: Included contraindications to enteral feeding and a history of major gastric surgery.
  • Intervention: A “no GRV monitoring” strategy. Gastric residual volumes were not measured. Enteral nutrition was held only for regurgitation or vomiting.
  • Control: A “routine GRV monitoring” strategy. Nurses measured GRV every 6 hours and held enteral nutrition if the volume was greater than 250 mL.
  • Management Common to Both Groups: All patients were managed with a standardized enteral nutrition protocol, and all other aspects of ICU care were at the discretion of the treating clinicians.
  • Power and Sample Size: The authors calculated that a sample size of 448 patients would be required to have 90% power to establish non-inferiority, with a pre-specified non-inferiority margin of 10%. (Power is a study’s ability to find a real difference between treatments if one truly exists; 90% power means the study had a 90% chance of detecting the specified effect, which is considered very high).
  • Outcomes:
    • Primary Outcome: The incidence of ventilator-associated pneumonia (VAP) within the first 90 days.
    • Secondary Outcomes: Included mortality, duration of mechanical ventilation, and the proportion of caloric goals achieved.

6. Key Results

  • Enrollment and Baseline: 449 patients were randomized (227 to the no-monitoring group and 222 to the monitoring group). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: The incidence of VAP was not significantly different between the groups. VAP occurred in 38 of 227 patients (16.7%) in the no-monitoring group and in 35 of 222 patients (15.8%) in the monitoring group. The non-inferiority criterion was met.
  • Secondary Outcomes: There were no significant differences between the groups in 90-day mortality, duration of mechanical ventilation, or length of ICU stay. Patients in the no-monitoring group received a significantly higher proportion of their prescribed caloric target.
  • Adverse Events: The incidence of vomiting was higher in the no-monitoring group, but the overall rate of adverse events was similar.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a non-inferiority statistical model.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of patients who developed VAP between the two groups to test for non-inferiority.
  • Key Statistic(s) Reported: The key statistics were the absolute rates of the primary outcome and the confidence interval for the difference.
  • Interpretation of Key Statistic(s):
    • Non-inferiority: The absolute difference in the VAP rate was 0.9 percentage points, and the upper boundary of the 95% confidence interval was 7.8 percentage points. Because this upper boundary was less than the pre-specified non-inferiority margin of 10%, the trial concluded that the no-monitoring strategy was non-inferior to the monitoring strategy.
  • Clinical Impact Measures: As the trial was a non-inferiority trial, ARR and NNT are not directly applicable. The key clinical impact is the demonstration of safety for a simpler, less-invasive strategy.
  • Subgroup Analyses: No significant differences were found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, controlled design provided high-quality evidence on a common clinical practice. The use of a non-inferiority design was appropriate for the clinical question.
  • Generalizability: The pragmatic design and inclusion of 27 diverse ICUs make the findings highly generalizable to real-world practice.
  • Statistical Power: The study was adequately powered for its primary outcome.
  • Patient-Centered Outcomes: The study focused on the important patient-centered outcome of VAP.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which introduces a risk of performance bias.
  • External Validity (Generalizability): The findings are highly generalizable to the broad population of critically ill patients receiving enteral nutrition.
  • Other: The overall VAP rate was lower than anticipated, which can make it more difficult to show a difference between groups.

10. Conclusion of the Authors

  • The authors concluded that among critically ill adults receiving mechanical ventilation, a strategy of not monitoring gastric residual volume was not inferior to a strategy of routine monitoring with regard to the incidence of ventilator-associated pneumonia.

11. To Summarize

  • Impact on Current Practice: This was a landmark “negative” trial that provided strong evidence to refute a long-standing, ritualistic, and time-consuming nursing practice. It demonstrated that abandoning routine GRV monitoring is safe and may improve nutritional delivery.
  • Specific Recommendations:
    • Patient Selection: For the broad population of adult ICU patients receiving mechanical ventilation and enteral nutrition.
    • Actionable Intervention: Do not routinely measure gastric residual volumes.
  • What This Trial Does NOT Mean: This trial does NOT mean that clinicians should ignore signs of feeding intolerance. It only argues against the routine, scheduled measurement of GRV. Patients with overt signs of intolerance, like vomiting or abdominal distension, still require clinical assessment.
  • Implementation Caveats: The key takeaway is that a simpler, less-invasive approach to managing enteral nutrition is safe and effective. This can free up significant nursing time for other essential tasks.

12. Context and Related Studies

  • Building on Previous Evidence: The REGARD-VAP trial (2021) was designed to provide a definitive answer to a question that was based on dogma and physiological theory but lacked high-quality evidence.
  • Influence on Subsequent Research: The definitive non-inferiority result of this trial, along with the earlier NUTRIREA-2 trial which showed similar findings, has been highly influential in shaping international nutrition and nursing guidelines, which now recommend against the routine measurement of gastric residual volumes.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: This trial definitively answered its primary question with a clear non-inferiority result.
  • Future Directions: The results of this trial have shifted the focus of research towards other methods of assessing feeding intolerance and on strategies to optimize the delivery of enteral nutrition.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was of the highest relevance, testing a ubiquitous, routine clinical practice that was not evidence-based and consumed significant nursing resources.
  • Methods: The large, multicenter, randomized non-inferiority trial design was appropriate and robust. The main methodological weakness is the open-label design, but the primary outcome of VAP was adjudicated by a blinded committee.
  • Results: The study successfully demonstrated non-inferiority for its primary outcome. The finding that the simpler strategy resulted in better delivery of nutrition without an increase in harm is a key secondary finding.
  • Conclusions and Applicability: The authors’ conclusion is strongly supported by the data. The trial is a classic example of a high-quality “negative” (non-inferiority) trial that was profoundly practice-changing by providing strong evidence to de-adopt a long-standing but ultimately unnecessary clinical ritual.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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