Correlation analysis of norepinephrine dose on enteral nutrition tolerance and prognosis in patients with septic shock
Authors: Qi Fan , Huang Guangqing , Li Hunian , Zhao Xu , Liu Jie 
Published: June 2023

Abstract
Background
To explore correlation between the dose of norepinephrine and the timing of starting enteral nutrition in septic shock (SS) patients.

Methods
Totally 150 SS patients treated with enteral nutrition (EN) in Shiyan People’s Hospital from Dece20 to July 2022 were included in this retrospective analysis. Patients were divided into tolerance group (n = 97) and intolerance group (n = 53) according to whether EN was tolerated or not. The study indexes include baseline characteristics [gender, age, weight, body mass index (BMI), scores of acute physiology and chronic health evaluation II system (APACHE II), comorbidity, time in-hospital, prognosis], clinical indexes [mean arterial pressure (MAP), time of mechanical ventilation (MV), norepinephrine dose at the time of starting EN, using of sedative drug, gastrointestinal motility drugs and cardiotonic drugs], EN indexes (timing of starting EN, speed of EN infusion, calorie of EN per day, EN target percent), and gastrointestinal intolerance index [residual gastric volume > 250 ml, vomiting, aspiration, gastrointestinal bleeding, blood lactic acid (BLA)]. Student-t test and Mann-Whitney test were used for test of measurement data. Chi-square test and fisher exact test were used for comparison of categorical data.

Results
There were 51 (52.58%) male and 46 (47.42%) female patients with a median age of 66.4 ± 12.8 years old in tolerance group. There were 29 (54.72%) male and 24 (45.28%) female patients with a median age 67.3 ± 12.5 years old in intolerance group. The weight and BMI were significantly higher in intolerance group than those of tolerance group (both P < 0.001). There was no significant difference of comorbidity rate between two groups (all P > 0.05). Before the overlapping time of EN and norepinephrine, there were significantly more patients receiving gastrointestinal motility drugs in intolerance group compared with tolerance group (58.49% vs. 20.62%, P < 0.001). Patients in tolerance group had significantly less residual volume in gastric than that of intolerance group (188.00 ± 52.32 vs. 247.83 ± 34.95, P < 0.001). The rate of residual volume in gastric > 250ml (9.28% vs. 37.74%, P < 0.001), vomiting (15.46% vs. 35.85%, P = 0.004) and aspiration(16.49% vs. 33.96%, P = 0.018) were significantly lower in tolerance group than those of intolerance group. The BLA in tolerance group was significantly lower than that of intolerance group (1.84 ± 0.63 vs. 2.90 ± 1.5 3mmol/L,P < 0.001). There were significantly more patients with increased BLA (75.47% vs. 30.93%, P < 0.001) and > 2mmol BLA rising (43.40% vs. 8.25%, P < 0.001) in intolerance group than those of tolerance group. Patients in tolerance group had significantly lower time of starting EN (40.97 ± 9.53 vs. 49.85 ± 11.61 h, P < 0.001), dose of NE(0.23 ± 0.07 vs. 0.28 ± 0.10 ug/kg/min, P = 0.049), mortality in hospital (18.56% vs. 49.06%, P < 0.001) and mortality in ICU (16.49% vs. 37.74%, P < 0.001) compared with intolerance group. The EN target percent (92.78% vs. 56.60%, P < 0.001) and calorie of EN during overlapping period (20.22 ± 5.99 vs. 16.21 ± 2.52 kcal/kg/day, P < 0.001) in tolerance group were significantly higher than those of intolerance group.

Conclusions
SS patients should be comprehensively evaluated according to their condition. Obese patients are more prone to EN intolerance, and those who can tolerate EN should be implemented as soon as possible. The use dose of NE is significantly related to EN tolerance. When the use dose is low, EN tolerance is greater.