Neostigmine Reversal And Neuromuscular Recovery
Condition: Residual Neuromuscular Block
MeSH terms: Delayed Emergence from Anesthesia
Study type: Interventional
Phase: Phase 4

Summary: 
      Patients undergoing surgery often receive paralytic agents (or neuromuscular blocking agents
      (NMBAs)) to facilitate the procedure. At the end of surgery, the effects NMBAs are reversed
      with a drug called neostigmine. The use of neostigmine significantly reduces the risk that a
      patient will be left with muscle weakness in the recovery room. Many anesthesiologists
      routinely use neostigmine because postoperative muscle weakness may lead to adverse events
      after surgery. Other anesthesiologists do not routinely administer neostigmine in the
      operating room because of concerns about potential side effects. Surprisingly, some
      investigators have reported that neostigmine-induced muscle weakness may occur if the drug is
      given when the effects of the NMBAs have completely worn off. In contrast, other
      investigators have not observed this side effect when neostigmine was given at the end of
      surgery. The aim of this study is to determine whether neostigmine use is associated with
      muscle weakness when it is given at the time of nearly complete recovery from NMBAs. Muscle
      strength will be measured using a sensitive monitor (TOF-Watch-SX) and through an examination
      of the patient for evidence of muscle weakness. Patients will also be evaluated how they
      recover from anesthesia and surgery.
    

Detailed description: 
      120 patients will be enrolled in this randomized clinical trial. Patients will be assigned,
      via a computer-generated randomized table, to either a neostigmine group or a no neostigmine
      group. Patients in the neostigmine group will receive neostigmine 40 µg/kg at the end of the
      surgical procedure when TOF ratios have recovered to 0.9 or greater. Patients in the no
      neostigmine group will be administered saline (control) at the time of neuromuscular
      recovery. Patients with TOF ratios < 0.9 will be excluded from either study cohort. These
      subjects will be administered neostigmine 50 µg/kg at the conclusion of surgery. The same
      postoperative data (see below) will be recorded in this group as will be collected in the two
      study cohorts in order to determine the characteristics of patients not achieving spontaneous
      recovery.

      Anesthetic care will be standardized in both study groups. Patients will be induced with
      propofol 1-2 mg/kg, fentanyl 100 µg/kg, and rocuronium as the NMBA (1 X ed 95 dose). No
      further rocuronium will be administered unless requested by the surgeon. Clinicians will be
      instructed to manage neuromuscular blockade so that full recovery of muscle strength is
      present at the end of the surgical procedure.

      Neuromuscular blockade in the operating room will be quantified with the TOF-Watch-SX, an
      FDA-approved quantitative monitoring device. After induction of anesthesia, baseline data
      will be collected. A 5-second 50 Hz tetanic stimulation will be applied to reduce the time
      required to achieve baseline signal stabilization. After signal stability is achieved, the
      TOF-Watch will be calibrated and then a baseline TOF value recorded. Rocuronium will then be
      administered and the oral endotracheal tube placed 2-4 minutes later. Neuromuscular blockade
      will be managed to allow spontaneous recovery of neuromuscular function to occur, with the
      goal of reaching a TOF ratio of ≥ 0.9 at the end of the surgical procedure. At the time when
      neostigmine is typically administered, one of two syringes will be attached to the
      intravenous line, and the clear solution (neostigmine or saline) given. These syringes will
      be prepared prior to the end of surgery. For patients in the in the neostigmine group, 40
      µg/kg of neostigmine (with an appropriate dose of glycopyrrolate) will be drawn up into the
      syringe and labeled accordingly. For patients in the no neostigmine group, an equal volume of
      saline will be drawn into a syringe, and a neostigmine label applied to the syringe. Both the
      neostigmine and saline solutions are clear and indistinguishable (to be prepared by
      pharmacy). Thereafter, all data collection will be obtained by research assistants blinded to
      group assignment.

      Immediately prior to neostigmine or saline administration, TOF ratios will be recorded, and
      then the syringe attached to the intravenous line and the solution injected. Train-of-four
      ratios will then be recorded every 12 seconds until the time of tracheal extubation.

      During transport from the operating room to the PACU, a research assistant will observe
      oxygen saturation levels, and the lowest value recorded. Oxygenation by pulse oximeter will
      also be monitored and recorded for the first 30 minutes of the PACU admission (every 1 minute
      via the PACU monitoring system). The need for addition oxygen therapy at any time following
      extubation will be noted. During this same time period (from extubation until 30 minutes
      after the PACU arrival) patients will be carefully observed for any evidence of airway
      obstruction or need for maneuvers to maintain a patent airway. This data will be recorded by
      the research assistant and the PACU nursing staff. In addition, 15 minutes after the PACU
      admission, subjects will be examined for 11 signs and 16 symptoms of muscle weakness. This
      examination will be performed by the blinded research assistant. The times required to
      achieve discharge criteria and actual PACU discharge will be recorded.
    

Intervention name(s): Neostigmine Group; No Neostigmine group
Intervention type(s): Drug; Other
Intervention description(s): Neostigmine will be used to reverse neuromuscular block at the conclusion of the surgical procedure. The effect on muscle strength will be determined using the TOF-Watch-SX and clinical examination; Saline will be administered to patients at the end of the surgical procedure when neuromuscular function has recovered
Other intervention name(s): Placebo Comparator
Intervention MeSH terms: Neostigmine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Diagnostic