The study was conducted at six institutions: Tokai University Hospital, Saitama Medical University Saitama Medical Center, Jichi Medical University Saitama Medical Center, Nippon Medical School Hospital, Kyorin University Hospital, and Kawasaki Medical School Hospital. The study was approved by the Institutional Ethics Committee of each institution and was conducted in accordance with Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects and with the Ethical Guidelines for Clinical Research issued by Ministry of Health, Labour, and Welfare.
Patients were eligible for the study if they were between 20 and 80 years old; scheduled to have elective, morning surgery requiring general anesthesia between January 2010 and March 2011; and were ASA physical status I or II. Exclusion criteria were dysphagia, esophagostenosis, the inability to take food orally as a result of neurological and other disorders; gastrointestinal obstruction; renal dysfunction (a creatinine clearance of 20 ml min−1 or lower or dialysis); electrolyte abnormalities; body mass index (BMI) of 35 kg m−2 or larger; and pregnancy. Also excluded were patients receiving intravenous fluid for any reasons preoperatively; a premedication; an H2 receptor blocker or a proton pump inhibitor; a diuretic; or steroids. Patients otherwise deemed unsuitable for the study were also excluded.
Before the study, written informed consents were obtained after the patients were extensively informed about the study procedure. The enrolled patients were assigned at random to either an ORS group or to a fasting group at each institution. Randomization was performed according to a computer-generated schedule with a permuted-block design.
Primary endpoints were gastric volume and its pH immediately after anesthesia induction. Secondary endpoints included the incidence of vomiting and aspiration associated with anesthesia induction, the relationships of gastric fluid volume and with age and with BMI in the ORS group, the effect of rehydration, vital signs, and the patient’s comfort.
Patients in both groups were allowed to have food or drink until 2100 on the night before surgery (Fig. 1). Patients in the ORS group consumed up to 1,000 ml of ORS (OS-1; Otsuka Pharmaceutical Factory, Tokushima, Japan; Table 1): 500 ml between 2100 the night before surgery and the time they woke up the next morning and 500 ml in the morning of surgery up until 2 h before surgery. Patients in the fasting group started fasting at 2100 the night before surgery. Patients in either group who needed to take medications orally before surgery were allowed to do so with 20–50 ml water until 2 h before surgery. Types of surgery, anesthesia methods, and intraoperative fluid management were at the discretion of each institution.
Gastric fluid volume and gastric fluid pH of the patients were measured in supine position immediately after anesthesia induction. Any incidences of vomiting or aspiration were recorded. Patients were intubated by mouth or nose with a nasogastric tube (the tube was inserted until 60 cm of the tube was placed inside the body). Correct placement of the tube in the stomach was confirmed by hearing the air with a stethoscope, and gastric contents were suctioned at 60, 55, and 50 cm from the top of the catheter with a catheter syringe . This procedure was repeated three times. Gastric fluid was sampled by the same person at each institution, whenever possible. Gastric fluid pH was measured by SRL (SRL, Inc., Clinical Laboratory Testing Company, Tokyo, Japan). We evaluated the efficacy of the ORS to provide hydration and electrolytes by measuring the fractional excretion of sodium (FENa), the fractional excretion of urea nitrogen (FEUN), ratio of serum urea nitrogen to serum creatinine, hematocrit, serum total protein, serum albumin, serum electrolytes (sodium, potassium, and chlorine), urine output (between 2100 the night before surgery and start of surgery and during surgery), and the amount of vasoconstrictors or intravenous solutions used during surgery. Blood was taken immediately after anesthesia induction, and the first urine sample was taken after a urinary catheter was placed. Patients were asked whether they were thirsty, hungry, or anxious before they entered the operating room. They were also asked twice whether they were nauseous or had vomited, on the night after surgery and at noon the next day. Patients completed the questionnaire form. Vital signs (blood pressure, pulse rate, and body temperature) were measured after dinner the night before surgery; before entering the operating room; at 5, 10, 15, 30, and 60 min after anesthetic induction; and every 1 h afterwards. Blood and urine samples were tested by SRL.
In this noninferiority study, gastric volumes were compared between the ORS group and the fasting group. Sample size calculation was based on a Cochrane review of studies on preoperative fasting and assumed that between-group difference in the residual gastric volume was 0 ml, noninferiority margin was +8 ml, standard deviation of residual gastric volume was 25 ml, two-tailed significance level was 0.05, and power was 0.80 . The needed sample size was 122 per group, which was increased to 150 per group to allow for withdrawals.
For the primary endpoint, mean, standard deviation, maximum, median, minimum, third quartile, and first quartile of the gastric fluid volume and gastric fluid pH were calculated for each group. For the secondary endpoints, mean standard deviation, maximum, median, minimum, third quartile, and first quartile of FENa and FEUN were calculated. For other results, mean and standard deviation were calculated for each group. The SAS statistical software package, version 9.1.3 (SAS Institute Japan, Tokyo, Japan), was used for statistical analyses. Differences were considered statistically significant at the 0.05 level for both unpaired t tests and Chi-square test. Differences in patient demographic characteristics were considered significant at the 0.15 level. Pearson product-moment correlation coefficient was used for correlation analyses. Analysis of variance was performed on gastric fluid volume and gastric fluid pH with institutions and groups used as factors to check for confounding.