Early supplemental enteral nutrition was associated with a lower overall postoperative complication burden compared with oral nutrition alone among patients at nutritional risk undergoing pancreatoduodenectomy, according to a randomized clinical trial published in JAMA Surgery.
In the NUTRIWHI randomized clinical trial, researchers enrolled patients with a nutritional risk screening score of 3 or higher at three tertiary centers in Switzerland and France. Of 142 randomized patients, 118 who underwent pancreatoduodenectomy were included in the modified intention-to-treat analysis.
Patients assigned to the intervention received early enteral nutrition through a nasojejunal tube placed intraoperatively under direct vision — meaning the decision to use enteral feeding must be made before or during surgery, not reactively — in addition to standard oral intake. The control group received oral nutrition alone. Parenteral nutrition was initiated in both groups if caloric intake remained below 50% of requirements by postoperative day 3.
Primary outcome: lower complication burden, not fewer patients with complications
At 90 days, the mean Comprehensive Complication Index score — a continuous measure capturing cumulative complication burden on a scale of 0 to 100 — was significantly lower in the enteral nutrition group than in the oral nutrition group (25.5 vs 35.8; P=.02).
However, overall morbidity rates were similar between groups (76% vs 86%) and did not reach statistical significance. Major complications occurred in 27% vs 44%, respectively, also not statistically significant (P=.06).
This divergence reflects the nature of the index: patients in both groups experienced complications at similar rates, but those receiving enteral nutrition had fewer and/or less severe complications per patient.
Secondary outcomes: signal driven by infections and pulmonary events
The reduction in complication burden was driven primarily by fewer infectious and pulmonary complications — both statistically significant differences. Infectious complications occurred in 20% of patients receiving enteral nutrition compared with 37% receiving oral nutrition alone (P=.04), and pulmonary complications occurred in 5% vs 19% (P=.02).
Rates of delayed gastric emptying, pancreatic fistula, postoperative hemorrhage, and surgical site infection were similar between groups. Length of stay and 90-day readmission rates also did not differ.
Nutritional support context: EN supplemented, rather than replaced, PN
Approximately half of patients in both groups required supplemental parenteral nutrition during recovery, indicating that enteral feeding functioned as an adjunct rather than a replacement for intravenous nutritional support.
Feasibility and implementation considerations
Enteral feeding was feasible but associated with notable practical challenges. Nasojejunal tubes were unintentionally removed in 24% of patients and required replacement. Three patients assigned to enteral nutrition did not receive it due to technical issues. Ten patients were discharged with ongoing tube feeding.
Subgroup findings are hypothesis-generating
Post hoc subgroup analyses suggested greater benefit among patients older than 65 years, those undergoing preoperative biliary drainage, and those with higher nutritional risk scores. These analyses were underpowered and subject to multiple testing; the apparent benefit in patients with diabetes was not statistically significant after Bonferroni adjustment.
Interpretation limited by center dominance and postoperative physiology
Although conducted at three centers, approximately 80% of patients were enrolled at a single site, effectively making the trial heavily center-dependent and limiting generalizability.
In an invited commentary, Yuqi Zhang, MD, Krista Haines, DO, and Suresh Agarwal, MD, of Duke University noted that delayed gastric emptying occurred in nearly half of patients, often requiring nasogastric decompression. In this setting, patients in the oral nutrition group unable to take meaningful oral intake were effectively compared against postpyloric tube feeding — diverging from the trial's original intent and potentially amplifying the apparent benefit of enteral nutrition. The nonblinded design may have further contributed to observed differences.
"The addition of [early enteral nutrition] to oral intake was safe, with no increase in major complications, and generally well tolerated, providing a dependable method for supplemental nutrition in high-risk patients," Zhang, Haines, and Agarwal wrote.
Bottom line for clinicians
Among patients at nutritional risk undergoing pancreatoduodenectomy, early supplemental enteral nutrition — delivered via intraoperatively placed nasojejunal tube — was associated with a lower overall burden of complications, largely driven by fewer infectious and pulmonary events. It did not significantly reduce the proportion of patients experiencing complications, requires a pre- or intraoperative commitment, and carries meaningful implementation considerations including tube dislodgement and the likelihood of concurrent parenteral nutrition needs.
Disclosures
Study author Gaëtan-Romain Joliat, MD, PhD, reported grant support from the Livio-Glauser Foundation and the Valery Foundation, which funded the study. No other study authors reported disclosures. Commentary author Krista Haines, DO, reported research and education support from Baxter and Fresenius. Suresh Agarwal, MD, reported grant support from the National Institutes of Health and Department of Defense. No other commentary disclosures were reported.
Source: JAMA Surgery