Changes of plasma acetylcholine and inflammatory markers in critically ill patients during early enteral nutrition: A prospective observational study

Abstract

Background: Acetylcholine (Ach) is the key anti-inflammatory transmitter in the cholinergic anti-inflammatory pathway. In this study, critically ill patients treated with early enteral nutrition (EEN) were observed to explore whether EEN affected Ach levels and inflammation.

Methods: One hundred thirteen patients were included in this prospective observational study. All patients were provided the early enteral nutrition protocol 24-48 h after admission to the intensive care unit (ICU). Blood samples were collected, and the plasma levels of Ach, cholecystokinin (CCK), and inflammatory markers (tumour necrosis factor alpha (TNF-α), interleukin 1beta (IL1-β), and IL6) were measured on Days 0, 1, 3, 5, and 7. Nutritional intervention data were recorded within one week, including the number of patients receiving nutrition, the number of days nutrition was provided, the caloric intake and protein intake, feeding intolerance and prokinetic drug administration. Other collected data included the sequential organ failure assessment score (SOFA score), the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the use of mechanical ventilation (the number of patients and the duration), use of vasoactive drugs and the number of renal replacement treatments (RRT) received by each patient during their ICU stay. The primary outcome was 28-day mortality. Additionally, we analysed the correlation between plasma Ach levels and inflammation, as well as the correlation between plasma Ach and CCK levels. Moreover, a multivariate regression analysis was performed to examine the independent effects of different variables on 28-day mortality and Ach levels.

Results: The overall 28-day mortality was 28.3% (32/113). Eighty-two patients tolerated enteral nutrition. Compared with Day 0 15.6 (2.8) nmol/l, the plasma Ach level was significantly increased on Day 3 18.6 (6.7) nmol/l, Day 5 19.3 (6.2) nmol/l and Day 7 19.7 (4.3) nmol/l (p < .001). Compared with Day 0176.2 (50.4) pg/ml, the plasma TNF-α level was significantly decreased on Day 3144.0 (77.4) pg/ml, Day 5127.3 (51.8) pg/ml and Day 7111.4 (42.5) pg/ml (p < .05). Compared with Day 0, the plasma IL1-β level was significantly decreased on Day 7 (p < .05). The plasma IL6 level was significantly decreased on Day 5 and Day 7 (p < .05) compared with Day 0. Compared with Day 0, the plasma CCK level was significantly increased on Day 3, 5 and 7 (p < .001). The correlation analysis revealed negative correlations between Ach levels and inflammation (p < .001), and a positive correlation between CCK and Ach levels (r = 0.775, p < .001). A comparison of patients who did or did not tolerate EEN revealed significant differences in the plasma levels of Ach, TNF-α, IL6 and CCK (p < .05). Significant differences in plasma levels of Ach, TNF-α, IL1-β, IL6 and CCK were observed between 28-day survivors and non-survivors (p < .05). The multivariate logistic regression analysis identified vasopressor support, RRT, the administration of EEN, SOFA score, APACHE II score at ICU admission and plasma Ach levels as independent determinants of 28-day mortality. Additionally, the multivariate linear regression analysis identified EEN, plasma lactate, mechanical ventilation, the SOFA score and plasma CCK levels as independent determinants of plasma Ach levels.

Conclusions: The administration of EEN to critically ill patients contributed to the increased plasma Ach levels and decreased inflammatory markers. The effect of EEN on Ach levels is partially attributed to the increase in CCK levels. Elevated plasma Ach levels indicate a better prognosis. Clinical trials identifier: NCT03612206.

Keywords: Acetylcholine; Critically ill patients; Early enteral nutrition; Inflammation.