Role of enteral nutrition in nonthyroidal illness syndrome: a retrospective observational study

This retrospective, observational cohort study was conducted in accordance with the principles of good clinical practice and the Declaration of Helsinki. The study protocol was reviewed and approved by the Institutional Review Board at Jingling Hospital. Informed consent was not obtained as patient records and information were anonymized and de-identified prior to the study.

Based on a detailed medical chart review, we primarily enrolled consecutive patients with enterocutaneous fistula admitted between January 2013 and April 2014. The standard values of the variables assessed at our hospital are as follows: free triiodothyronine (FT3), 3.8–6.5 pmol/L; total triiodothyronine (TT3), 1.23–3.07 nmol/L; free thyroxin (FT4), 7.9–17.2 pmol/L; total thyroxin (TT4), 71–161 nmol/L; and thyroid stimulating hormone (TSH), 0.3–4.5 mU/L.

The criteria for NTIS applied in our study were as follows: (1) FT3 level less than 3.8 pmol/L and (2) TSH upper normal limit of 4.5 mU/L [2, 10]. In our department, all patients underwent thyroid homeostasis measurements upon admission for NTIS scanning, and a thyroid test every week to evaluate the thyroid function. Records of patients with NTIS at admission were primarily collected. The exclusion criteria were as follows (1) current use of EN, thyroid hormone and antithyroid drugs at admission; (2) history of coronary artery disease, myocardial infarction or cerebral infarction in the past month upon admission; (3) pregnancy or lactation; (4) a previous history of thyroidal, hypophyseal or hypothalamic disease; (5) age less than 18; (6) craniocerebral injury; (7) end-stage advanced malignant tumor; (8) medication history of thyroid hormone or antithyroid drugs; (9) and intracranial infection or hemorrhage in the past month. After excluding patients, clinical data of the remaining patients were collected to constitute our cohort. The observational period was limited to 4 weeks. The time point at admission was defined as week 0.

The primary outcome of our study was defined as the resolution of NTIS at week 4 after admission. We defined in this study that patients whose FT3 level is above 3.8 pmol/L at week 4 are those who recovered from NTIS. At the end of the study, patients who experienced resolution of NTIS in this cohort were assigned to Group A while others were assigned to Group B.

In our department, the EN used for patients with enterocutaneous fistula was Peptisorb Liquid (Enteral Nutrition Suspension; Nutricia Company, Amsterdam, Holland). Once the output of intestinal fluid was limited (<200 ml/L) and patients were satisfactorily maintained on enteral feeding, EN was gradually introduced to reach full feeding. The EN therapy in our study was conducted as described in our previous study [11]. Briefly, EN was prescribed through a nasogastric or nasointestinal tube. The formula contained 1 cal/mL and had 500 kcal/bottle. The energy requirements were calculated using Long’s modified equation according to the usual body weight. No oral foods or fluids (except for water and weak tea) were allowed. The nutrition regimen during the study period remained almost unchanged.

For each enrolled patient, the following data were collected from the medical record: primary diseases, fistula location, underlying disease, Acute Physiology and Chronic Health Evaluation Score (APACHE II), time for initiation of enteral nutrition upon admission, white blood cell count (WBC), C-reactive protein (CRP), red blood cell count (RBC), platelet count (PCs), glutamic-pyruvic transaminase (GPT) and blood urine creatinine (Cr), FT3, TT3, FT4, TT4 and TSH. Baseline characteristics, including age and sex, were also collected.

In our department, venous blood for all laboratory tests was drawn between 5 am and 6 am. Serum indexes, including WBC, CRP, RBC, PCs, Cr, GPT FT3, TT3, FT4, TT4 and TSH were measured at least once a week to monitor the patients’ status. Laboratory values were calculated within 2 h after blood collection.

In total, 140 consecutive patients with enterocutaneous fistula were admitted to our department from January 2013 and April 2014. We retrospectively enrolled 90 consecutive patients with enterocutaneous fistula who met the NTIS criteria as primary inclusion. Ten patients met the exclusion criteria and were excluded from the study. Therefore, the final study cohort consisted of 80 patients (Fig. 1).

The general clinical characteristics of the study group at admission are presented in Table 1. Among the 80 cases, there were 58 males and 22 females (male-to-female ratio, 2.64:1). Patient had a mean (±SD) age of 48.05 ± 13.43 years. The most common causes for enterocutaneous fistula development in our study were trauma and surgical complications. The most common location of enterocutaneous fistula was the small bowel. A total of 24 patients had a positive history of diabetes mellitus, and 12 had chronic obstructive pulmonary diseases. The time from admission to start of EN therapy varied during our observational period. During the EN treatment, 8 patients (9.76 %) had diarrhea caused by the EN infusion, and symptoms were managed as stated in the medical records. None of the patients discontinued EN because of poor tolerance to EN therapy during the study period. No mortality occurred among the cohorts.

Figure 2 and Additional file 1: Tables S1 shows the changes of thyroid function in this cohort during the observational period. During our observational period, serum FT3 concentrations were significantly increased, from 3.02 ± 0.138 at the baseline to 4.13 ± 0.052 in the last week (p <0.001), while serum level of FT4, TT4 and TSH kept stable during our observation.

According to our definition, 66 patients experienced resolution of NTIS (Group A) while 14 patients did not (Group B). The overall treatment success rate for both groups was 82.50 % (66/80). Table 2 presents the general clinical condition of both groups. The time from admission to start for EN therapy was significantly different between Groups A and B. Thyroidal function changes between those two groups in our study were displayed in Fig. 2 and Additional file 2: Table S2. Serum FT3 and TT3 level increased significantly faster in group A compared with those in group B. At the end of the second week after admission, serum FT3 and TT3 in group A were significantly higher than those in group B.

The logistic regression were performed with variables that associated with treatment success, respectively, in our study, including age, gender, primary diagnosis, fistula location, underlying disease, APACHEIIscore and time for initiation of enteral nutrition, to demonstrate their association with treatment success. Table 3 revealed that initial time of EN was a significant independent indicator with treatment success in our cohort.

Table 4 shows the changes of other serum indices measured in our study. For all patient populations, all the laboratory tests presented no significant differences over time, except for some isolated indices. CRP kept decreasing over time in our study and reached a significantly low level at the end of our observational period. The same trend was observed for GPT. PCs in all populations kept increasing to a relatively normal level. In subgroup analysis, changes of serum indices measured in our study shared a similar trend between groups, without any significant differences between Groups A and B.