Comparison of Mechanomyographic 100 Versus 200 Hz 5 Second Tetanic Fade Ratios During Neuromuscular Block Recovery
Condition: Neuromuscular Blockade
Study type: Interventional

Summary: 
      Two recent pilot studies suggested the potential interest of 100 and 200 Hz tetanic
      stimulations to detect with mechanomyography (MMG) very low levels of residual neuromuscular
      blockade (NMB). The Tetanic Fade Ratio (TFR, residual force after 5 seconds / maximal force)
      measured quantitatively by MMG during tetanic stimulation at 100 or 200 Hz could provide
      today a more consistent response than the train-of-four (TOF) ratio provided by
      acceleromyography (AMG) to this search for detection of low levels of residual NMB.

      This study was designed to evaluate for the first time in anesthetized patients the evolution
      of NMB spontaneous recovery with 5-second 100 and 200 Hz tetanic stimulations compared to
      TOF, and to test the hypothesis that a 200 Hz TFR would better and longer detect low levels
      of residual paralysis than AMG TOF ratio and 100 Hz TFR.
    

Detailed description: 
      MATERIALS AND METHODS Patient management The monocentric study protocol was approved before
      patients' inclusion by the Institutional Ethical Committee (CHU UCL Namur, Yvoir, Belgium, OM
      050, under unique belgian registration number B0392022000035).

      It was performed in accordance with the ethical standards of the Declaration of Helsinki and
      was included in the Clinical Trials Registry (XXX).

      After obtaining written informed consent from all participants, 20 patients with American
      Society of Anesthesiologists (ASA) grades I to II (aged 18 to 65 years), who were scheduled
      to undergo rhinoplasty or rhinoseptoplasty under general anaesthesia, were included in the
      study. The exclusion criteria were pregnant or breastfeeding women, patients with renal or
      hepatic insufficiency, patients with neurological disorders, and any patient with a suspected
      allergy to the drugs used in the protocol or receiving medications that could interfere with
      neuromuscular transmission. The patient's height, weight, age, and sex were recorded in the
      protocol to define the population investigated.

      The patients were conventionally monitored with a pulse oximeter, a three-lead
      electrocardiogram and a non-invasive blood pressure monitor scheduled in automatic mode at
      5-minute intervals. An intravenous catheter was inserted into their forearm for crystalloid
      infusion (side at random). Neuromuscular transmission monitoring (NMTM) was set up according
      to a specific protocol.

      Total intravenous anaesthesia was induced with continuous infusion of remifentanil 0.25
      µg/kg/min and continuous infusion of propofol 1% to obtain theoretical plasma concentrations
      ranging from 3 to 6 µg/mL (Diprifusor Cardinal Health, Basingstoke, UK). Lidocaine 1 mg/kg
      was also given as an intravenous bolus. After loss of consciousness, manual ventilation was
      provided during NMTM calibration and the initial NMB baseline measurements. Then, rocuronium
      0.45 mg/kg was administered. Non-invasive automatic blood pressure measurement was suspended
      during the neuromuscular onset to avoid dissimilar distribution of the rocuronium in the two
      arms. Tracheal intubation was performed when the TOF count reached zero. Automatic
      non-invasive blood pressure measurement was reactivated. Mechanical ventilation (closed
      circuit, 40% oxygen in air) maintained end-tidal CO2 within the normal range. Anesthesia was
      maintained with the continuous intravenous administration of remifentanil 0.15 µg/kg/min and
      propofol with a target plasma concentration of 2 to 4 µg/mL. Blankets prevented heat loss
      from the body and both arms, and the oropharyngeal temperature was kept stable. Postoperative
      analgesia was provided with paracetamol, tramadol and alizapride at the end of surgery.

      Neuromuscular transmission monitoring

      All recordings were performed during general anesthesia. The skin was cleaned with diethyl
      ether, and two electrodes were placed above the ulnar nerve on each wrist.

      A TOF-Watch SX® (Alvesia Pharma, France) (TWSX) was set on the left hand. The accelerometric
      transducer was taped on the thumb's pulp, and the hand was inserted and held inside an SL TOF
      tube. Another TOF-Watch® (Organon-Technika, Copenhagen, Denmark) designed to deliver
      high-frequency tetanic stimulations (including 100 and 200 Hz) was connected to the
      electrodes on the right arm, which was equipped with an Isometric Thumb Force (ITF®) handgrip
      designed to record the force (N) of isometric thumb adduction during electrical stimulations.
      The Visual-ITF® software recorded all measurements for further off-line analysis. Each
      tetanic signal was described in a 5 sec window starting from the 1 Newton value. If this 1N
      threshold was not reached, the recording was excluded from the analysis.

      Both arms were positioned alongside the body on soft padding to protect nerve structures from
      any extra focal pressure.

      Supra-maximal stimulation and initial calibration were obtained using the TWSX internal
      automatic sequence, and the current intensity displayed was applied on both sides. Then, TOF
      stimulations were applied at 15-second intervals during a short stabilisation period. On the
      TWSX side, four T4/T1 ratios were recorded to determine the initial baseline (mean of four
      values) before NMBA administration. On the ITF side, two consecutive tetanic stimulations
      (100 and 200 Hz at random) were applied for 5 seconds, with a two-minute interval to avoid
      any potentiation. Consecutive TOF stimulations every 15 seconds were applied to monitor the
      NMB, from the onset and, during surgery, until the spontaneous recovery of a normalized TOF
      ratio of 0.9 on the TWSX side and even further. Both tetanic stimulations (same order as
      previously) were applied alternately with 2-minute intervals on several steps of recovery and
      until recovering 90% of the initial TFR with both stimulation patterns.

      Data collection and statistical analysis On the TWSX side, the TOF ratio provided after each
      2Hz TOF stimulation was displayed and recorded. We calculated 90% of the initial baseline
      mean value to determine the normalised TOF ratio 0.9 recovery threshold using the following
      formula: normalised TOF ratio 0.9 = sum of 4 TOF ratio × 9/40, with the result rounded up.

      On the ITF side, a Tetanic Fade Ratio (TFR) was determined to quantify any fade occurring
      during the muscle contraction: referring to the resting level just before the contraction,
      the residual force at the end of 5 seconds of stimulation was divided by the maximal force
      obtained during the contraction to provide a ratio.

      Based on a previous pilot study using the same material and the same stimulating patterns, a
      sample of 20 patients was determined to provide a significant difference between the TFRs
      recorded with 100 and 200 Hz tetanic stimulations at the time of AMG TOF ratio 0.9 recovery.
      We expected to have enough power (0.8 at that stage) to detect a significant difference
      during an additional period of recovery. The alpha error was 0.05.

      Off-line data analysis was based on the archived files. Using R software version 3.3.6 (R
      Project for Statistical Computing, Vienna, Austria), Student's t-tests were performed to
      compare the TFR obtained after 100- or 200-Hz stimulations at initial baseline and at several
      classical levels of spontaneous recovery on the TWSX side:

        -  TOF count 1,

        -  TOF ratio 0.5,

        -  TOF ratio 0.9

        -  Normalized TOF ratio 0.9

        -  TOF ratio 0.95

        -  TOF ratio 1.0 Then, both tetanic stimulations were repeated every 5 minutes until TFR
           reached 0.9 to quantify any further period of analysis of low levels of residual
           blockade.
    

Intervention name(s): Isometric Thumb Force (isometric mechanomyography) compared to TOF-Watch SX (acceleromyography)
Intervention type(s): Device
Intervention description(s): Comparison of mechanomyographic measurements of thumb adduction's force induced by 100 versus 200 Hz 5 seconds tetanic ulnar nerve stimulation during neuromuscular block spontaneous recovery monitored by acceleromyography on the controlateral arm.
Intervention model: Single Group Assignment
Intervention model description: Controlateral and simultaneous comparison of two different neuromuscular transmission monitorings in a cohort of 20 anesthetised patients.
Masking: None (Open Label)
Primary purpose: Diagnostic
Keywords: Residual neuromuscular block; Mechanomyography; Tetanic nerve stimulation