Serotonin as a means of preventing gastrointestinal failure in the early postoperative period: a randomized clinical study

BACKGROUND: In patients with gastrointestinal cancers, preoperative malnutrition is associated with decreased plasma serotonin levels and an increased risk of gastrointestinal failure in the postoperative period.

AIM: The work aimed to evaluate the safety and clinical efficacy of serotonin compared with standard prokinetic therapy for the correction of gastrointestinal failure in patients with malnutrition.

METHODS: It was a randomized pilot clinical study including 42 patients aged ≥ 65 years after elective gastrointestinal surgery for cancer. All participants had malnutrition (NRS 2002 ≥ 2) and gastrointestinal failure (LIFE ≥ 2). Patients were randomized as follows: the main group (n = 24) received serotonin at a dose of 20 mg/day intravenously until gastrointestinal failure is resolved; the control group (n = 18) received standard therapy (metoclopramide, 10 mg, and neostigmine methyl sulfate, 0.1 mg, three times daily). Both groups received standardized enteral nutritional support with a semi-elemental formula. Changes in LIFE scores, plasma serotonin and albumin levels, inflammatory markers, hemostasis parameters (piezoelectric thromboelastography), and the incidence of thrombotic complications were assessed. Thromboprophylaxis was performed with enoxaparin sodium, 40 mg/day, administered subcutaneously.

RESULTS: Baseline characteristics of the groups did not differ significantly. Serotonin levels were decreased in both groups (50.37 ng/mL in the control group; 51.6 ng/mL in the main group; p = 0.782). During serotonin administration, its concentration was maintained within the reference range, whereas in the control group it continued to decrease by day 2. By day 5, the severity of gastrointestinal failure according to the LIFE scale was significantly lower in the main group (0.3 vs 2.6 points; p = 0.045), which was accompanied by earlier recovery of peristalsis and bowel movements. A strong negative correlation was found between serotonin levels and the severity of gastrointestinal failure (r_s = −0.69; p = 0.012). In patients receiving serotonin, hypoalbuminemia was corrected more rapidly (p = 0.0057); albumin levels also negatively correlated with the severity of gastrointestinal failure (r_s = −0.71; p = 0.010). Inflammatory markers and hemostasis parameters did not differ between the groups. Thrombotic events were not observed in either group.

CONCLUSION: In patients with gastrointestinal cancers and preoperative malnutrition, serotonin as part of complex therapy for gastrointestinal failure was associated with faster resolution and correction of hypoalbuminemia without signs of increased inflammatory response or an increased risk of thrombotic events.