Reversal of Skeletal Muscle Relaxant Clinical Trial
Official title:
Phase 4 Study of Optimal Relaxation With Rocuronium Infusion Followed by Rapid Reliable Reversal With Sugammadex: A Comparison With Conventional Practice
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
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.
;
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment