Optimal Relaxation Technique for Laparotomies With Rocuronium Infusion Followed by Sugammadex Reversal
Condition: Underdosing of Skeletal Muscle Relaxants for Laparotomy; Reversal of Skeletal Muscle Relaxant
MeSH terms: Muscle Hypotonia
Study type: Interventional
Phase: Phase 4

Summary: 
      Muscle relaxation using rocuronium infusion with sugammadex reversal hypothetically provide
      better quality of muscle relaxation and rapid recovery from anaesthesia compared with
      intermittent bolus of rocuronium muscle relaxant which is reversed with neostigmine.

      50 patients undergoing major laparotomy surgery with predicted surgical time of more than 90
      minutes will be randomised into 2 treatment arms: CI-sugammadex & IB-Neostigmine.

      After a bolus of rocuronium given during induction, patients in CI-Sugammadex arm will be
      started on rocuronium infusion immediately and rate adjusted according to the targeted PTC of
      1-2. Patients randomised to IB-Neostigmine will be given boluses of rocuronium at
      reappearance of TOFC of 2.

      At the end of the surgery, the subject will be reversed with either sugammadex or neostigmine
      at different depth of block, ie PTC 1-2 and TOFC 2 respectively.

      Quality of intraoperative relaxation and effectiveness of reversal of the 2 technique,
      CI-Sugammadex and IB-Neostigmine will be compared with respect to:

        1. Time to full reversal (T4/T1 [TOF] ratios ≥ 0.9) of neuromuscular blockade from:

             -  PTC 1-2 in CI-Sugammadex group

             -  TOFC ≥2 in IB-Neostigmine group

        2. Incidence of residual neuromuscular blockade (T4/T1 ratios < 0.9)

        3. Improved quality of intraoperative neuromuscular relaxation by maintaining profound
           neuromuscular blockade, as reflected by reduced incidence of intraoperative events and
           high VAS grading of relaxation quality by surgeon
    

Detailed description: 
      Epidural will be established before induction of a standard balanced general anesthesia.
      After the epidural, they will be randomized into 2 groups, the CI-Sugammadex group and the
      IB-Neostigmine group.

      Intra operative analgesia will be achieved with epidural boluses. Adjuvant drugs were
      administered as per routine clinical practice and their use compared between the groups.

      For patients randomized to the CI-Sugammadex group, intravenous infusion of 0.3 mg/kg/hr
      (organon product insert) will be administered 30 minutes after the intubation dose or the
      return of PTC, whichever comes first. Then, the infusion rate will be titrated according to
      PTC (target to keep PTC between 1 to 2). Infusion rate will be increased or reduced at a rate
      of 0.1 mg/kg/hr if PTC is > or < than 1-2 and adequate muscle relaxation is maintained
      throughout the surgery. A dose of Sugammadex (4 mg/kg) will be administered at the end of the
      surgery (last stitch).

      For patients allocated to IB-Neostigmine group, a bolus of Rocuronium at a dose of 10mg will
      be administered after reappearance of TOFC > 2 and depth of neuromuscular blockade will be
      maintained at TOFC of 1-2. At the end of surgery, a dose of Neostigmine (50mcg/kg) will be
      given at the reappearance of TOFC of 2.

      Rescue boluses of Rocuronium will be given if clinically indicated regardless of the depth of
      neuromuscular block appear on the TOF-watch.

      The patient will be excluded if his/her epidural fail to function and full dose of opioid is
      needed intra operatively for analgesia. Patients whose surgery ends before return of the
      first PTC 1-2 in CI-Sugammadex group or TOFC 2 in IB-Neostigmine group will also be excluded
      as drop outs

      Central core temperature (measured by nasopharyngeal probe) will be maintained above 35°C
      throughout the surgery. Heart rate, oxygen saturation, blood pressure, end-tidal
      concentration of volatile agent and end-tidal carbon dioxide concentration will be monitored
      throughout the surgery.

      After operation, the patient will be monitored for the peri anesthetic period in post
      anesthetic care unit (PACU) for at least 60min and post-anesthetic monitoring includes
      post-operative visit by a safety assessor and a follow-up surveillance up to 24H after
      surgery.

      Time to full reversal (T4/T1 ratios ≥ 0.9) of neuromuscular blockade and all the secondary
      variables will be documented. In PACU, they will be assessed for clinical signs of adequate
      neuromuscular recovery and T4/T1 ratio (best of 3 readings will be recorded) to detect
      incidence of residual and recurrence of neuromuscular blockade. All patients' oxygen
      saturation, blood pressure, heart rate and respiratory rate will be monitored for 24H after
      the surgery and adequate analgesia provided.

      Surgeons who are blinded to treatment arms will be given a visual analogue scale (VAS) to
      assess the quality of relaxation during the surgery immediately after he or she is ungowned
      at the end of surgery.

      All subjects will be assessed for adverse events and serious adverse events (Itching &
      erythematous reactions at the site of injection and/or generalized histaminoid reactions for
      example bronchospasm & cardiovascular changes).

      Patients, surgeons, post-operative assessors and nurses in the ward are blinded to group
      allocation. The non-blinded attending anesthetist, who is responsible for the individual
      patients' relaxation technique, should have no vested interest in the reversal agent or the
      outcome of the trial, and will not participate in postoperative clinical assessment, data
      entry, or statistical analysis.
    

Intervention name(s): Neostigmine, atropine; Sugammadex
Intervention type(s): Drug; Drug
Intervention description(s): 0.05 mg/KG NEOSTIGMINE AND 0.02 MG/ KG ATROPINE at TOF 2; 4 mg/kg sugammadex will be given stat at the end of surgery at PTC 1-2
Other intervention name(s): Bridion
Intervention MeSH terms: Atropine; Neostigmine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: reversal; muscle relaxant; sugammadex