| Summary: | Background: Peripheral parenteral nutrition allows repletion of acute nutrient deficiencies and could prevent further nutrition deficits before and after colorectal surgery. A randomized open study was performed to evaluate the effect of perioperative peripheral parenteral nutrition (PPN) support on postoperative morbidity after colorectal cancer surgery within an enhanced recovery program. Methods: Patients were randomized into two groups: peripheral parenteral nutrition (PPN) (with Peri-Olimel N4-E) versus conventional fluid therapy (FT). Ninety-day postoperative complications, laboratory parameters, length of hospital stay, and compliance with the ERAS protocol were assessed. Results: A total of 158 patients were analysed. The overall 90-day complication rate was 38.6% (61 patients), and 24 patients had major complications (Clavien–Dindo III–V) (15.2%). In the multivariate analysis, the intervention (PPN vs. FC) showed a protective effect against postoperative complications (<i>p</i> = 0.0031, OR = 0.2 (CI: 0.08–0.87)). Following ordinal regression, PPN and early oral tolerance showed a protective effect, being less likely to develop complications or to move from minor to major complications. In patients with low compliance to ERAS during the first postoperative day, PPN showed a protective effect, preventing 28% of morbidity. Conclusions: Perioperative peripheral parenteral nutrition (PPN) support with Peri-Olimel N4-E in colorectal cancer surgery associated with early oral intake could reduce postoperative complications.
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