A Double-blind, Randomized, Parallel Design to Compare the Effectiveness of Deep Versus Moderate Neuromuscular Blockade With Standard-pressure Pneumoperitoneum During Laparoscopic Gastrectomy on Postoperative Pain in Surgical Patients

• All patients were fasted from midnight without premedication
• Once in the operating room, the patients were monitored using electrocardiography, pulse oximetry, end-tidal carbon dioxide partial pressure, non-invasive blood pressure, and bispectral index (Aspect 2000; Aspect Medical Systems, Inc., Newton, MA, USA) measurements.
• Neuromuscular transmission was monitored using the M-NMT® module at the adductor pollicis muscle (Carescape® B850, GE Healthcare, Milwaukee, WI, USA).
• Throughout the surgery, these data were continuously downloaded to personal computers by using RS232C cables.
• Following pre-oxygenation with 100% O2, anesthesia was induced with propofol and remifentanil, which were administered using a target effect-site concentration-controlled infusion pump (Perfusor® Space, B. Braun Melsungen, Germany) by using the models suggested by Schnider et al. and Minto et al (Minto et al., 1997; Schnider et al., 1998).
• Tracheal intubation was facilitated with rocuronium 0.6 mg/kg.
• After tracheal intubation, the lungs of the patients were then ventilated with oxygen in air (1:1) and the ventilation rate was adjusted to maintain the end-tidal carbon dioxide partial pressure between 35 and 45 mmHg.
• For deep NMB group, an intravenous bolus of rocuronium (0.7 mg/kg) was given 2 minutes after intubation, followed by a continuous infusion of rocuronium of 0.8-1.2 mg/kg/h for maintaining deep NMB (post tetanic count 1-2) during operation. PTC was measured every 5 minutes. In the case of deviations from the target PTC, the pump speed could be increased or decreased or a bolus dose (10 mg) could be given.
• For moderate NMB group, no further loading dose of rocuronium was given. An intravenous infusion with rocuronium (0.2-0.6 mg/kg/h) was started at a TOF count of 1 for maintaining moderate NMB (train of four 1-2) during operation. TOF was measured every 5 minutes. In the case of deviations from the target TOF, the pump speed could be increased or decreased or a bolus dose (10 mg) could be given.
• The target effect-site concentrations of propofol were adjusted within a range of 2.5-3 μg/ml to maintain the bispectral index values at less than 60 during the induction and maintenance of anesthesia.
• The target effect-site concentrations of remifentanil were titrated to prevent signs of inadequate anesthesia and to maintain stable hemodynamics (SBP > 80 mmHg and HR > 45 beats/min).

• Signs of inadequate anesthesia: systemic arterial blood pressure increased to greater than 15 mm Hg higher than the patient's normal value; heart rate exceeding 90 beats/min in the absence of hypovolemia; somatic responses, such as body movements (minimal muscle paralysis allowed physical movement), swallowing, coughing, grimacing, or opening of the eyes; and autonomic signs of inadequate anesthesia (Ausems, Vuyk, Hug, & Stanski, 1988)

• If necessary, ephedrine or atropine is administered to maintain systolic blood pressure above 80 mmHg and heart rate above 45 beats/min during anesthesia.
• An abdominal pressure of 13 mmHg was maintained during the laparoscopic surgery.
• When the surgeon asks for muscle relaxation due to the inability to obtain a visible laparoscopic field, additional bolus dose of rocuronium (10 mg) should be given.
• All patients were administered a bolus dose of oxycodone of 0.05 mg/kg at the end of pneumoperitoneum.
• IV PCA with oxycodone is started after the administration of loading dose. A semi-electronic pump (Automed 3200; Ace Medical, Seoul, South Korea) is used for PCA with demand bolus of 1 ml, background infusion of 1 ml/h and lock-out time of 15 min. The concentration of oxycodone in IV PCA bag is 1 mg/ml, and the volume of oxycodone-normal saline mixture delivered to patients for approximately 4 days is 200 ml.
• Rocuronium infusions are discontinued after deflation of CO2.
• After the end of surgery, a single intravenous bolus dose of sugammadex 2 or 4 mg/kg was administered for reversal of moderate and deep NMB, respectively.
• After the end of surgery, patients were taken to the PACU, and assessed for pain every 10 min using a VAS (0=no pain; 10=the most severe pain).
• Researchers who evaluate postoperative pain will be blinded to the patient's allocation
• Pain was measured at rest and when the wound areas were compressed with a force of 20 N (i.e., 2 kg of pressure imposed by three fingers on a 10 cm2 area). The wound compression was performed by a blinded researcher who was trained with an algometer (Commander Algometer, J Tech Medical Industries, Midvale, UT, USA) to apply this force consistently.
• The patient was administered intravenous oxycodone 2 mg (body weight <80 kg) or 3 mg (>80 kg) every 10 min until the VAS assessments showed that the pain intensity had decreased to <3 at rest and <5 on wound compression. At this point, MEAD of oxycodone was determined.
• VAS for wound and shoulder pain were also assessed at 6 and 24 h after the end of surgery.
• Postoperative nausea and vomiting were evaluated using the Rhodes index of nausea vomiting retching (RINVR) at 6 and 24 h after the end of surgery (Lee et al., 2016).
• After the end of surgery, the surgeon scored the surgical working conditions according to a five-point ordinal scale ranging from 1 (extremely poor conditions) to 5 (optimal conditions) (Martini et al., 2014).
• If the surgeon requests blind cessation for patient safety reasons, blindness is lifted.