Preoperative preparations and anesthesia protocol
The patients were computer-randomized into three groups, SK0.25 group (0.25 mg.kg−1 esketamine), SK0.5 group (0.5 mg.kg−1 esketamine) and saline control group (equivalent volume of normal saline). The patients, anesthesiologist, gastroenterologists and nurses in the recovery room were blinded to the grouping.
After an overnight fasting, the non-premedicated patients were brought to the endoscopy room, where a 20-gauge intravenous cannula was established in the peripheral vein for Ringer Lactate solution infusion and drugs. Heart rate (HR), noninvasive blood pressure (BP), electrocardiogram (ECG) and peripheral oxygen saturation (SpO2) were monitored continuously during endoscopic procedures (Philips HP Viridia 24/26 M1205A). Oxygen was administered at a rate of 3 L/min by nasal catheter during the study.
After preoxygenation, propofol (AstraZeneca Company, Italy) was administered by a computer-controlled infusion TCI (Graseby™ 3500 TCI Syringe Pump, SIMS Graseby Ltd., Herts, England) using the Marsh pharmacokinetic parameters at an initial plasma target concentration of 2.5 μg/mL in three groups. We started the first dose of propofol at 2.5 μg/mL based on our pre-test. Once the target concentration of propofol achieved, esketamine was injected immediately. All esketamine solutions were diluted into 10 ml and prepared by an anesthesiologist nurse who was no longer involved in the follow-up. Patients were administered with different doses of esketamine: 0.25 mg/kg esketamine (SK0.25 group), 0.5 mg/kg esketamine (SK0.5 group) and blank saline solution (Control group). In our endoscopy center, as a rule, the patients underwent gastroscopy first followed by colonoscopy. Qualified and experienced gastroenterologists started gastroscopy 3 min after esketamine injection and propofol TCI pump was stopped just before the end of the colonoscopy. Coughing, retch, and purposeful movement of the head or limbs during endoscopy are defined as “responsive”. If the patient presented “responsive”, propofol 2-3 mL was given as a rescue medication immediately, and the target plasma concentration of propofol for the subsequent patient would be increased by 0.5 μg/mL. If coughing, or retch, or purposeful movements did not occur, which defined as “non-responsive”, the subsequent target plasma concentration of propofol was decreased by 0.5 μg/mL. This method was called up-and-down method of Dixon, described as early in 1965 [14].
Emergency equipment was available throughout the procedure. A bolus of 6-10 mg ephedrine was given once mean arterial pressure (MBP) decrease by 30 % over the baseline value, and 0.25mg atropine was injected once heart rate (HR) fell below 50 bpm. Appropriate nitroglycerin was injected once MBP rose above 120 mmHg. If spontaneous ventilation was insufficient (SpO2 < 90%), the anesthesiologist performed an unarmed airway opening and an artificial ventilation support as necessary.