Andriulli et al: Early Enteral Nutrition in Acute Pancreatitis (2008)

“In patients with acute pancreatitis, early nasoenteric feeding was not superior to a strategy of on-demand oral refeeding, as shown by the similar rates of complications and mortality.”

  • Andriulli A, et al.

1. Publication Details

  • Trial Title: Early versus On-Demand Nasoenteric Tube Feeding in Acute Pancreatitis
  • Citation: Andriulli A, Annese V, Caruso N, et al. Early versus on-demand nasoenteric tube feeding in acute pancreatitis. Dig Liver Dis. 2008;40(10):818-824. DOI: 10.1016/j.dld.2008.01.012
  • Published: October 2008, in Digestive and Liver Disease
  • Author: A. Andriulli
  • Funding: Italian Ministry of Health

2. Keywords

  • Acute Pancreatitis, Enteral Nutrition, Nasoenteric Feeding, Critical Care, Randomized Controlled Trial

3. The Clinical Question

  • In adult patients with a first episode of acute pancreatitis (Population), does early and routine nasoenteric tube feeding (Intervention) compared to an on-demand oral refeeding strategy (Comparison) reduce the overall rate of complications (Outcome)?

4. Background and Rationale

  • Existing Knowledge: The traditional management of acute pancreatitis involved keeping the pancreas “at rest” by withholding all oral or enteral intake (NPO). However, emerging evidence suggested that this could lead to gut atrophy and bacterial translocation, potentially worsening outcomes. Early enteral nutrition was hypothesized to maintain gut integrity and modulate the inflammatory response.
  • Knowledge Gap: While early enteral nutrition seemed promising, it was unclear if it was truly superior to a more conservative strategy of simply waiting for the patient’s clinical improvement and hunger to return before reintroducing an oral diet.
  • Proposed Hypothesis: The authors hypothesized that early nasoenteric tube feeding would be superior to on-demand oral refeeding in reducing the rate of complications in patients with acute pancreatitis.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 10 hospitals in Italy.
  • Trial Period: Enrollment period not explicitly stated in the publication.
  • Population:
    • Inclusion Criteria: Adult patients (18-80 years) with a first episode of acute pancreatitis, diagnosed based on clinical and biochemical criteria.
    • Exclusion Criteria: Included chronic pancreatitis, post-ERCP pancreatitis, pregnancy, and contraindications to nasoenteric tube placement.
  • Intervention: Patients in the “early feeding” group had a nasoenteric feeding tube placed within 24 hours of admission and received continuous enteral nutrition.
  • Control: Patients in the “on-demand” group were kept NPO and received only intravenous fluids. Oral feeding was initiated only when abdominal pain had resolved and the patient felt hungry.
  • Management Common to Both Groups: All patients received standard medical care, including intravenous fluid hydration and analgesia.
  • Power and Sample Size: The authors calculated that a sample of 142 patients would be required to have 80% power to detect a 20% absolute risk reduction in the complication rate. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: A composite of any pancreatitis-related complication (e.g., pancreatic necrosis, pseudocyst, abscess) or death.
    • Secondary Outcomes: Included length of hospital stay and individual complication rates.

6. Key Results

  • Enrollment and Baseline: 145 patients were randomized (72 to early feeding and 73 to on-demand refeeding). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in the primary composite outcome. Complications or death occurred in 18 of 72 patients (25.0%) in the early-feeding group and in 17 of 73 patients (23.3%) in the on-demand group (p=0.81).
  • Secondary Outcomes: There were no significant differences in the length of hospital stay or in the rates of any individual complications between the two groups.
  • Adverse Events: The study reported on pancreatitis-related complications as part of the primary outcome. There were no significant differences in these events between the groups.

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 chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of patients who experienced a complication or death between the two groups.
  • Key Statistic(s) Reported: The key statistics were the absolute incidence rates and the associated P-value.
  • Interpretation of Key Statistic(s):
    • P-value: The p-value of 0.81 is much higher than the 0.05 threshold, indicating that the small difference in the primary outcome between the groups was not statistically significant and was very likely due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the trial was neutral (showed no difference), ARR and NNT are not applicable.
  • Subgroup Analyses: No significant subgroup analyses were reported.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, controlled design provides a high level of evidence.
  • Generalizability: The inclusion of patients from 10 different hospitals increases the applicability of the findings.
  • Statistical Power: The study was adequately powered for its primary outcome.
  • Patient-Centered Outcomes: The primary outcome was a composite of clinically important complications and death.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label (unblinded), which introduces a risk of performance bias, as clinicians’ knowledge of the group assignment could have influenced their decisions about co-interventions.
  • External Validity (Generalizability): The study population consisted of patients with predominantly mild to moderate pancreatitis. The findings may not be generalizable to patients with severe, necrotizing pancreatitis who are managed in an ICU.
  • Other: The “on-demand” strategy is subjective and depends on patient reporting and clinician interpretation, which can be variable.

10. Conclusion of the Authors

  • In patients with acute pancreatitis, a strategy of early nasoenteric feeding was not superior to a more conservative strategy of on-demand oral refeeding in preventing complications or death.

11. To Summarize

  • Impact on Current Practice: This trial challenged the growing trend of routine early enteral feeding for all patients with acute pancreatitis, suggesting that a more conservative, patient-guided approach is a safe and reasonable alternative, particularly in non-severe cases.
  • Specific Recommendations:
    • Patient Selection: For adult patients with a first episode of mild to moderate acute pancreatitis.
    • Actionable Intervention: It is reasonable to adopt a strategy of keeping the patient NPO with IV fluids and reintroducing an oral diet when they are clinically improving and hungry, rather than routinely placing a feeding tube for early nutrition.
  • What This Trial Does NOT Mean: This trial does NOT mean that early enteral nutrition is not beneficial for all patients. Its findings are specific to a population with less severe pancreatitis and should not be extrapolated to critically ill patients with severe, necrotizing pancreatitis in the ICU, where early enteral nutrition is still recommended to prevent gut-related complications.
  • Implementation Caveats: The “on-demand” strategy requires regular clinical reassessment of the patient’s symptoms and readiness to eat.

12. Context and Related Studies

  • Building on Previous Evidence: The Andriulli et al. trial (2008) provided important nuance to the “early enteral nutrition” debate, which had been largely driven by studies in more severely ill patient populations.
  • Influence on Subsequent Research: The findings of this trial have been influential in shaping guidelines that now recommend a stratified approach to nutritional support in acute pancreatitis, with early enteral feeding reserved for those with predicted or confirmed severe disease.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The optimal timing and route of nutrition in patients with severe, necrotizing pancreatitis remains an area of active research.
  • Future Directions: Future research is focused on identifying which specific patients with pancreatitis benefit most from early enteral nutrition and on the role of different nutritional formulations.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a common and important clinical decision in the management of acute pancreatitis.
  • Methods: The multicenter RCT design was appropriate. The main methodological weakness is the open-label design, which introduces a risk of performance bias. The patient population was well-defined but represents a less severe cohort than many other nutrition trials in critical care.
  • Results: The study reported a clear neutral finding for its primary outcome, with no significant difference in complications or mortality between the two strategies.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The trial’s findings are most applicable to the management of non-critically ill patients with mild to moderate pancreatitis on a general hospital ward.

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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