After obtaining Ethics approval (Ethical Committee N° 2017-141) from the Ethical Committee of West China Hospital, Chengdu, China (Chairperson Prof MZ. Liang) on 16 June 2017, we conducted this prospective cohort study in West China hospital according to the principles expressed in the Declaration of Helsinki from July 2017 to April 2018. The study was retrospectively registered at July 2017, after enrollment of the first participant. Type 2 diabetic and non-diabetic patients admitted to the surgical department were screened and recruited to participate in the study. Inclusion criteria were as follows: type 2 diabetic (two fasting plasma glucose concentration≥7mmol/L or casual plasma glucose concentration≥11.1mmol/L with classic symptoms of hyperglycemia)  or non-diabetic patient; age≥18 yr; ASA physical status I-III; body mass index (BMI) <35 Kg/m2; elective surgery; be able to understand the rationale of the study and provide informed consent. Exclusion criteria were as follows: pregnancy; a history of upper gastrointestinal disease or previous surgery on the esophagus, stomach or upper abdomen; documented abnormalities of the upper gastrointestinal tract such as gastric tumors; recent upper gastrointestinal bleeding (within the preceding 1 month); taking medicines that may delay gastric emptying (e.g., anticholinergic agents, opioid); hypothyroidism. Written informed consent was obtained from all included subjects.
Eligible type 2 diabetic and non-diabetic subjects were recruited in a 1:1 ratio. Subjects in both groups were fasted overnight (at least 10h) from the last meal. After enrollment, patients will be randomized to ingesting either clear fluid or light meal (a standardized portion of noodles or toast, and clear fluid). Randomization was performed using computer-generated random numbers and group assignments were delivered in sealed, opaque envelopes. An attending anesthesiologist, who had an experience with at least 100 gastric ultrasound examinations previously, performed all ultrasound examinations in the study. The anesthesiologist was blinded to group allocation or the history of the participants. Ultrasound examinations were carried out 2h after ingesting clear fluid or 6h after a light meal, according to preoperative fasting guidelines by ASA released in early 2017.
2.1 Ultrasound examination
Ultrasound examinations were conducted with a low-frequency (2-5MHz) curvilinear array probe from a Philips (CX50) (Bothell, WA, USA). As previously described, a sagittal cross-section of the antrum in a plane including the left lobe of the liver anteriorly, and the pancreas and aorta posteriorly was acquired. All quantitative and qualitative examinations were performed in the semi-recumbent and then the right lateral decubitus (RLD) positions. A three-point grading scale described by Perlas was used for the qualitative assessment: Grade 0, no gastric content was detected in antrum in either semi-recumbent or RLD position (Figure 1a); Grade1, the gastric content was detected in the RLD only; Grade2, the content was detected in both semi-recumbent and RLD positions (Figure 1b – Figure 1c). For the quantitative assessment, the antral cross-sectional area (CSA) was calculated as follows: measuring the anterior-posterior (D1) and cranio-caudal diameters (D2) of the antrum at antral resting, from serosa to serosa, using the formula: Antral cross-sectional area= D1×D2× π/4.
Ultrasound examinations were conducted with a low-frequency curvilinear array probe from a Philips (CX50) (Figure 1), showing an empty gastric antrum (a), liquid (b) and semi-solid(c) food in the gastric antrum. A sagittal cross-section of the antrum in a plane, including the left lobe of the liver anteriorly, the pancreas and aorta posteriorly was acquired. A, antrum; L, liver; P, pancreas; SA, splenic artery; SV, splenic vein; Ao, aorta; SMV, superior mesenteric vein.
The stomach was considered as empty in either Perlas Grade 0 regardless of the CSA, or Grade 1 with CSA <340 mm2. Intermediate stomach contents were defined as Grade 1 with CSA>340mm2. A full stomach that increases risk of pulmonary aspiration of gastric contents in the event of general anesthesia was defined as Grade 2 regardless of CSA[2, 17].
For patients with full or intermediate stomach, consecutive ultrasound scan was performed every 10 min until empty stomach were detected. The antral cross-sectional area (CSA) was measured and recorded at each examination.
Patient characteristic data were recorded for analysis, including age, sex, Body Mass Index (BMI), ASA physical status classification, and scores of Self-Rating Anxiety Scale (SAS), fasting duration (defined as the time between the fluid or light meal ingestion and ultrasound examination), comorbidities, and surgery scheme. Other relevant data, including the postprandial plasma glucose concentration, hemoglobin A1c level and the diabetes complications, e.g., peripheral neuropathy defined as scores of Michigan Neuropathy Screening Instrument >2, cardiovascular autonomic neuropathy defined using the American Diabetes Association criteria and the Toronto Consensus Panel on Diabetic Neuropathy, diabetic nephropathy, and diabetes mellitus-related eye disease (including diabetic retinopathy, macular edema, rubeosis iridis, vitreous hemorrhage and diabetic related-visual injury), were recorded for analysis, as well.
The primary outcome was the prevalence of full stomach in diabetic elective surgical patients. The secondary outcome was the gastric emptying time of clear liquids and light meal in diabetic patients. Using logistic regression analyses we examined the risk factors associated with full stomach.
2.2 Sample size and statistical analysis
Based on the original data from our preliminary study and other study, the estimated occurrence of full stomach was 40% in diabetic patients, and 6.2% in elective surgical patients. Thus, twenty-four patients per group would be expected to detect a significant difference with a type 1 error<0.05 and a power of 80%. Taking into account a drop-out rate of about 10%, we originally plan to enroll 54 patients (27 in each group) to compare the incidence of full stomach. In order to investigate the risk factors for full stomach, we enlarged sample size to 108 patients for multivariate logistic regression analysis in our study (54 patients in each group). Statistical analysis was performed with SPSS 21.0(IBM Corp; Armonk, New York, USA).
After a Shapiro-Wilk test for normality of data distribution, continuous data (i.e., age, BMI, plasma glucose concentration, and hemoglobin A1c level) were expressed as the mean±SD for normally distributed data, or median [interquartile range] for non-normally distributed data. The normally distributed continuous data were analyzed by student’s test and the non-normally distributed data were analyzed by Wilcoxon Rank Sum Test. Chi-square test or Fisher exact test were performed to compare incidence data (i.e., the percentage of co-morbidities, Perlas grade and the incidence of full stomach). Two-tailed tests will be used in all statistical analysis, and P value of less than 0.05 will be considered to be of statistical significance.
Univariate logistic regression analysis was used to identify variables associated with a full stomach, described as odds ratios (OR) with 95% confidence interval (CI). All variables that differed between groups (P<0.05) together with the related-factors reported in previous studies were entered into a multivariate logistical regression analysis to investigate the risk factors for delayed gastric emptying in diabetic patients.