Comparison of sedation between the endoscopy room and operation room during endoscopic submucosal dissection for neoplasms in the upper gastrointestinal tract

From January 2011 to December 2016, 297 consecutive patients with early upper gastrointestinal tumors who underwent ESD procedures at the National Hospital Organization Ureshino Medical Center were included in the present retrospective chart review. Patients aged >20 years who fulfilled the following criteria were candidates for the study: i) clinical indications for ESD of early esophageal cancer diagnosed as intramucosal squamous cell carcinoma and ii) diagnosis of early gastric cancer according to the absolute indications and expanded indications in the Gastric Cancer Treatment Guidelines [15]. The exclusion criteria were circumferential lesions of early esophageal cancer and suspected early gastric cancer falling outside of the indications for ESD.

Informed consent for the procedures was obtained from all patients. This retrospective study was conducted according to the Ethical Guidelines for Medical and Health Research Involving Human Subjects. The present study was approved by the Ethics Review Committee of National Hospital Organization Ureshino Medical Center (approval number 16–25).

During the observation period, seven endoscopists performed the ESD procedures in either the endoscopy room or operation room based on their judgment. The distribution of the endoscopists was not different between the endoscopy room and the operation room. In the endoscopy room, sedation for the ESD procedures was introduced by the combination of benzodiazepines and opioids. Specifically, diazepam or midazolam was used as a sedative agent, and buprenorphine, pentazocine, or pethidine hydrochloride was used as an analgesic agent. The sedative and analgesic drugs were selected by the individual endoscopist in charge of the patient’s condition.

A dose of 5 to 10 mg of diazepam was infused intravenously [5]. An initial bolus of 3 mg of midazolam for patients with a body weight of <50 kg and 4 mg for patients weighing >50 kg was administered through an intravenous catheter as the main sedative drug, followed by incremental doses (2 mg) when the patient showed signs of discomfort, restlessness, agitation, and/or a response to verbal commands [5]. A midazolam reversal agent was administered after the ESD procedure as necessary. For analgesia, a dose of 0.2 mg of buprenorphine, 15 mg of pentazocine, or 35 mg of pethidine hydrochloride was intravenously injected at the start of ESD. All medications were administered by the physician in the endoscopy division, who did not participate in the actual endoscopic procedure. At least one physician with advanced training in basic and cardiac life support supported the ESD procedure. The anesthesiologist was on standby in case of an emergency but did not support the ESD procedure. Resuscitation devices were equipped in the endoscopy room.

In the operation room, the medical agents for sedation during the ESD procedure (propofol for sedation and fentanyl for analgesia) were administered under the anesthesiologist’s supervision. The patient received an initial intravenous bolus of 0.8 mg/kg of 1% propofol emulsion (10 mg/ml). Additional intravenous boluses of 0.5 mg/kg of 1% propofol emulsion were administered until the patient was fully sedated. An automatic infusion pump was applied to maintain a continuous infusion of 3 mg/kg/h and thus maintain the patient’s sedation. The objective was to maintain a sedation level between moderate (proper response to verbal commands either alone or accompanied by light tactile stimulation) and deep (proper response only to repeated or painful stimulation) [6]. As an adjuvant to the sedation, fentanyl was given intravenously at a dose of 1 to 3 μg/kg.

In the endoscopy room and operation room, the patient received supplemental oxygen (2 L/min) by a nasal cannula while his or her vital signs and oxygen saturation were continuously monitored and recorded every 5 min using standard three-lead electrocardiography, pulse oximetry, and automatic blood pressure equipment. Chest excursions and the respiratory rate were monitored visually, and the consciousness level was assessed initially after induction of sedation and throughout the ESD procedure. With respect to adverse events, desaturation was defined as a decrease in the oxygen saturation to <90%, hypotension was defined as a decrease in the systolic blood pressure to <80 mmHg, and bradycardia was defined as a decrease in the heart rate to <60 bpm. When oxygen desaturation occurred for >10 s, the supplemental oxygen flow was immediately increased to the >95% saturation level. When the supplemental oxygen did not improve the patient’s oxygenation condition within 3 min, the ESD procedure was interrupted to secure the airway with administration of the reversal agent as necessary. If hypotension developed, the intravenous drip rate was increased by bolus intravenous injection of 8 mg of ephedrine. For treatment of bradycardia, 0.5 mg of atropine sulfate was injected intravenously. In the operation room, these adverse events were managed by the anesthesiologist.

Patients were discharged from the endoscopy room or operation room after the ESD procedure when they showed stable vital signs (blood pressure, oxygen saturation, and heart rate). Vital signs were recorded at the beginning of the ESD procedure until the patient showed sufficient alertness and activity.

The patients were divided into two groups: those who underwent ESD in the endoscopy room (Group E) and those who underwent ESD in the operation room (Group O). The χ² test was used to compare the two groups’ clinical characteristics, including sex, current drinking and smoking habits, American Society of Anesthesiologists classification, and comorbidities (e.g., cardiovascular diseases, cerebrovascular diseases, chronic liver damage, chronic kidney diseases, diabetes mellitus, and hypertension). Continuous variables were summarized as the mean ± standard deviation for a normal distribution, or median [IQR] for a skewed distribution. The patients’ mean age and body mass index were evaluated by Student’s t-test. The tumor characteristics, including the location, number, historical classification, macroscopic classification, and depth of invasion, were compared between the two groups by the χ² test. In patients with multiple tumors, the largest tumor was evaluated based on the underlying assumption of statistically independent observations. Anesthetic outcomes (intubation, desaturation, hypotension, bradycardia, and aspiration pneumonia) and treatment outcomes (en bloc resection, delayed hemorrhage, perforation, and mortality) were evaluated by the χ² test. The mean ESD procedure time and anesthesia time were analyzed using Student’s t-test. The recovery time was analyzed using the Mann–Whitney U test. The economic outcome including the hospitalization period and cost of hospitalization was analyzed using Student’s t-test. Differences were considered statistically significant at P < 0.05. Statistical analyses were performed with the statistical analysis software EZR version 1.26 [16].