Effectiveness of Deep Versus Moderate Neuromuscular Blockade
Condition: Neuromuscular Blockade
Study type: Interventional

Summary: 
      The aim of this study is to evaluate the influence of depth of neuromuscular blockade during
      laparoscopic gastrectomy on postoperative pain in surgical patients allocated randomly to
      either deep or moderate neuromuscular blockade group with standard-pressure pneumoperitoneum
      of 13 mmHg.
    

Detailed description: 
      -  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.
    

Intervention name(s): Deep NMB using rocuronium; Moderate NMB using rocuronium
Intervention type(s): Drug; Drug
Intervention description(s): Drug: rocuronium
Bolus dose: 0.7 mg/kg
Continuous infusion : 0.8-1.2 mg/kg/h for maintaining deep NMB (post tetanic count 1-2) during operation.; Drug: rocuronium
Bolus dose: none
Continuous infusion: 0.2-0.6 mg/kg/h for maintaining moderate NMB (train of four 1-2) during operation.
Intervention MeSH terms: Rocuronium
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study is investigator-initiated, randomized, double blinded clinical trial.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment