Study design. This study is a single-center prospective randomized controlled study. The study was conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonisation of Good Clinical Practice guidelines. The study protocol was approved by the institutional review board of Samsung Medical Center (IRB number: SMC 2019-05-168-001) and registered at CRIS (https://cris.nih.go.kr; registration number KCT0004422; 05/11/2019). We enrolled female patients scheduled for elective gynecologic laparoscopic surgery between August 2019 and June 2020. Patients were included if they were 19–70 years of age with American Society of Anesthesiologists physical status Ⅰ - II. Patients at increased risk for pulmonary aspiration were excluded. Exclusion criteria were as follows: emergency conditions, body mass ind//ex (BMI) > 30, previous esophageal or gastric surgery, gastroesophageal reflux, gastrointestinal disorders (including gastritis, hiatal hernia, diabetic gastroparesis), ileus and current medication affect gastrointestinal motility40–42. Eligible patients were randomly assigned to either conventional fasting group (control group) or chewing gum with fasting group (gum group) at a ratio of 1:1, according to a randomization list generated by random permuted block design with a block size of two.
Intervention and anesthesia. The internal policy of gynecologic department of our hospital had stipulated the guidelines about preoperative fasting and bowel preparation as follows: All patients scheduled for gynecologic surgery were instructed to ban solid food from 3 p.m. the day before surgery and clear liquids from midnight before surgery according to protocol of the department of gynecology. In addition, 170 mL of Picosolution® (Pharmbio Korea Inc: Seoul, South Korea) was administered orally for bowel preparation at 5 pm on the day before surgery. Our patients were hospitalized around 5 p.m. the day before surgery and invited to participate in this study. After obtaining informed consent, patients were requested to rate their preoperative anxiety as a baseline examination, on a NRS (numeric rating scale) of 0 to 10 by a blinded investigator.
Patients in the control group were requested to follow the fasting guidelines without further treatment. Patients in the gum group were allowed to chew gums during the fasting period, following the fasting protocols described above. We distributed 12 pieces of sugarless xylitol gum (Xylichew: Hayden, Idaho, USA). We asked participants to chew gum during preoperative fasting period and to stop chewing gum from departure time for the operating room on the day of surgery. Participants were basically instructed to chew gum freely. It was recommended to chew gum at least one piece of gum more than 10 miniutes per hour, except for sleep time. All participants in chewing gum group were asked to log their chewing time. On the day of surgery, all patients were instructed to remove any gum from their mouths immediately prior to departure for the operating room, and complete questionnaire about the degree of discomfort associated with fasting and anxiety in the preoperative holding area with the help of attending residents or nurses in anesthesia team who were not aware of group allocation. In the operating theater, just before general anesthesia was induced, US assessment of gastric fluid volume was performed in both groups. All ultrasound (US) exams for estimating gastric volume were performed by independent blinded investigator (YJ, Bang), who was instructed and trained by an experienced radiologist.
Then, a standardized anesthesia protocol was used for all patients. The standard ASA monitoring including noninvasive blood pressure, EKG, pulse oximetry, and bispectral index (BIS) monitoring was applied. After denitrogenation with 80 % oxygen, general anesthesia was induced with propofol and remifentanil using target-controlled infusion (Orchestra® Base Primea; Fresenius Kabi, Brezins, France), and intravenous rocuronium 0.8 mgkg-1. Another investigator who was not aware of group allocation performed intubations and evaluated the degree of oral secretion during intubation. After tracheal intubation via video stylet, the ventilator was set with a tidal volume of 8 mLkg-1of ideal body weight and FiO2 40 %. The respiratory rate and I:E ratio were adjusted to maintain inspiratory peak pressure less than 30 cmH2O and normocapnia. During the whole surgery, propofol and remifentanil effect site concentrations were adjusted to achieve BIS values of 40 to 50 and to maintain mean blood pressure and heart rate within 20 % of pre-induction values. At the end of surgery, the neuromuscular block was reversed with pyridostigmine (250 mcgkg-1) and glycopyrrolate (10 mcgkg-1). After confirming that spontaneous breathing was sufficient and consciousness had returned, tracheal extubation was performed.
Postoperative recovery and bowel complication during the in-hospital period were evaluated and documented by independent gynecologists.
Postoperative management. The postoperative analgesia was standardized for all patients. If patients presented with breakthrough pain (NRS ≥ 4/10), IV ibuprofen 400 mg was administered. If this proved ineffective after 30 minutes IV pethidine 50 mg was administered. Postoperative nausea and vomiting were treated with intravenous metoclopramide 10 mg and ramosetron 0.3 mg. All patients resumed diet and ambulation as soon as possible after full recovery from anesthesia unless gastrointestinal symptoms were noted. Hospital discharge was determined by the surgery team.
Data collection and outcomes. Primary outcomes were preoperative anxiety and severity of symptoms related to preoperative fasting. The parameters used to assess discomfort were as follows: hunger, thirst, dry mouth, fatigue, headache, nausea using a single point NRS; 0 = no suffer to 10 = worst suffer imaginable43. We investigated preoperative anxiety using the Korean version of Amsterdam Preoperative Anxiety and Information Scale (APAIS)44,45. APAIS is a useful tool to evaluate preoperative stress and anxiety, which consists of an anxiety scale and a need for information scale. The scores on the anxiety of APAIS range from 4 (not anxious) to 20 (extremely anxious). For gum group only, the satisfaction with chewing gum during the preoperative fasting period was investigated.
Secondary outcomes included the amount of oral secretion at the timing of tracheal intubation, estimated gastric volume just prior to induction of anesthesia, gastric fluid acidity, recovery of bowel function, composite of postoperative bowel complication, QoR-15 score (Quality of Recovery − 15), and the length of hospital stay (LOS). The amount of oral secretion was graded depending on the degree of interference with intubation as follows; none (no saliva, thick tongue or mucosa causing the endotracheal tube stuck), mild (some saliva with good visual field), moderate (much saliva with limited field), severe (much saliva with blocked field, need for suction). For evaluation of recovery of bowel function, we collected data about time to flatus, time to sips of water, and time to first meal. We collected the data about postoperative bowel complication such as nausea, vomiting, abdominal pain, and abdominal distension. The severity of postoperative bowel complication was classified according to Clavien Dindo classification46. On the day after surgery, patients completed Korean version of QoR-15 questionnaire, which provides an extensive effective evaluation of quality of recovery after surgery and anesthesia47.
Acidity of gastric fluid analysis. ST probe 12Fr G type (SST12; S&S med Inc; Anyang, South Korea) was inserted trans-orally to monitor the core body temperature. ST probe is a multi-orificed silicone tube with suction hole for gastric decompression. After induction of anesthesia, we measured the length from the mouth to the mandible angle, then from the mandible angle to the midpoint between xiphoid and the umbilicus. Then ST probe was advanced through oropharyngeal airway to the previously identified length and the end tip of the ST probe was placed in the stomach. Patients were placed in extreme head down position by surgeon’s request so that gastric fluid could be drained via suction hole, naturally. If gastric fluid does not flow out by the end of surgery, the patient is tilted to the left to promote gastric fluid drainage. The acidity of the gastric fluid was analyzed with pH meter (PH60F Flat PH tester; Apera, Columbus, Ohio, USA) by blinded investigator.
Gastric ultrasonography. The aforementioned-investigator (YJ, Bang) performed US assessment using a portable US unit (Sonosite M- TURBO, Fujifilm Sonosite, Bothell, WA, USA) with a 2-5Hz convex probe. All patients underwent US exams of the epigastrium in the right lateral position. The gastric antrum was identified between the left lobe of the liver and the pancreas, at the level of the aorta, or the inferior vena cava. The cross-sectional area (CSA) was measured from serosa to serosa using the free tracing tool of the ultrasound machine. If the antrum had a perfect elliptical shape, CSA was calculated using the following formula: CSA (cm2) = (anteroposterior diameter [cm] × craniocaudal diameter [cm] × π)/4. Estimated gastric fluid volume (EGFV) was calculated using the following formula: EGFV (mL) = 27.0 + 14.6 × Right lateral CSA – 1.28 × age42.
Sample size calculation and statistical analysis. The standard deviation of the APAIS score derived from the existing literature is 3.244. Assuming that the APAIS value of the gum group compared to the control group must decrease by 2 points to detect clinically meaningful differences, the necessary sample size was 42 participants for each group with a power of 0.8 and an α value of 0.05. We decided that 47 patients in each group were to be enrolled to account for an expected 10% attrition rate, with a total of 94.
All data were tested for normality by the Shapiro–Wilk test and were presented as means (standard deviations [SD]) or as medians (interquartile ranges [IQR]). Differences between groups were analyzed using the chi-square test or Fisher's exact test for categorical variables, and Student’s t test or Wilcoxon’s rank sum test for continuous variables as appropriate. Post hoc analyses were also performed. Statistical significance was defined by p values < 0.05. All analyses were performed using SAS version 9.4 (SAS Institute Inc, Cary, NC, USA).