Effect of Tetanus on Neuromuscular Junction Monitor Performance in Pediatric Patients
Condition: Muscle Relaxation
MeSH terms: Tetanus
Study type: Interventional

Summary: 
      The objective of this study is to assess the performance of acceleromyography as a method of
      evaluation of muscle relaxation after application of tetanus stimulation to obtain stability
      of responses before administration of neuromuscular blocking agents.
    

Detailed description: 
      Effect of tetanus on neuromuscular junction monitor performance in pediatric patients
      undergoing abdominal and / or perineal surgical procedures with the use of rocuronium.

      Routine monitoring of neuromuscular function during anesthesia offers some advantages. It
      helps promote proper relaxation according to each patient's individual sensitivity and
      reduces the possibility of postoperative residual block with its serious consequences,
      namely: reducing pulmonary forced vital capacity, decreased ability to increase ventilation
      during periods of hypoxia, increased risk of pulmonary aspiration due to lower strength of
      pharyngeal muscles. It can also reduce the waste of time caused by excessive paralysis.
      Furthermore, the interpretation of data from the monitor may indicate that pharmacological
      reversal of neuromuscular blockade is not required, with potential benefits over costs, as
      well as lower incidence of postoperative nausea and vomiting.

      Acceleromyography was introduced for use in daily clinical practice in 1988 as a simple,
      reliable and easy to apply in the anesthetized patient monitor to assess muscle relaxation.
      The purpose of this neuromuscular junction (NMJ) monitor was replace mechanomyography, this
      modality that has greater complexity of assembling and using. The mechanomyography was
      considered long, the ideal objective neuromuscular monitoring. This measures the strength of
      isometric contraction of a muscle or digit (e.g. thumb) in response to nerve stimulation.
      Moreover, it requires an assembly that demands time and with strict rules for the positioning
      and application of non elastic preload on the thumb. This makes the method impractical for
      everyday use. Furthermore, monitors based on the method of mechanomyography are no longer
      commercially available. Acceleromyography gradually replaced mechanomyography as a method to
      monitor muscle relaxation in clinical practice and research.

      Acceleromyography measures the acceleration (isotonic contraction) of a muscle or finger. The
      method is based on Newton's second law, which states that force is equal to the product of
      mass and acceleration. If the mass (e.g. thumb) is constant, the acceleration is directly
      proportional to the force. This means, in principle, it measures the unrestricted movement of
      the muscle in question.

      Monitoring must present a stable response (baseline) for a period of 2 to 5 minutes before
      administration of neuromuscular blocker. The time required to reach this stable response
      depends on the duration of electrical stimulation and frequency in which electrical
      stimulation are applied. When using single mode stimulus at a frequency of 0.1 Hertz (Hz) or
      train-of-four (TOF) every 12 to 15 seconds, it may take 5 to 20 minutes to obtain a stable
      response. However, the stabilization period may be shortened by applying a short, high
      frequency stimulation (tetanic stimulation). Tetanic stimulation for 5 seconds can decrease
      the stabilization period of 2 to 5 minutes.

      There is no description in the literature on the performance of tetanus stimulation in
      obtaining a stable response of the monitor neuromuscular junction in pediatric patients.

      The objective of this study is to assess the performance of acceleromyography as a method of
      evaluation of muscle relaxation after application of tetanus stimulation to obtain stability
      of responses before administration of neuromuscular blocking agents. This performance will be
      compared by time of onset and recovery, recorded by the monitor during effect of
      neuromuscular blocking agent rocuronium; namely:

        -  Onset of action (height reduction of 95% in T1);

        -  Time to reappearance of T1, T2, T3 and T4;

        -  Time to TOF reaching 0.20; 0.30; 0.40; 0.50; 0.60; 0.70; 0.80; 0.90;

        -  Recovery interval 25-75 (elapsed time between T1 25% and T1 75%)

        -  Final T1 height

      Materials and Methods Patient After obtaining approval by the Ethics Committee and informed
      consent by completing legal guardian, 50 patients (American Society of Anesthesiologists
      [ASA] - Physical Status 1-2, aged 2 to 11 years, regardless of genders) who will undergo
      abdominal and / or perineal surgery, with planned surgical time greater than 60 minutes will
      be included in the study. Patients with diseases or medications that are known to interfere
      with neuromuscular transmission, hepatic or renal dysfunction or allergy to medications used
      in the study will be excluded.

      Anesthesia Patients will be monitored with electrocardiography, noninvasive blood pressure,
      pulse oximetry, capnography, gas analyzer and bispectral index. The anesthesia is induced
      with inhaled (sevoflurane) or intravenous (propofol and opioids) anesthetics according to the
      patient's ability to cooperate in obtaining venous access. The maintenance will be done with
      intravenous anesthesia (propofol and opioid). Peripheral temperature will be measured at the
      thenar eminence of the upper limb where the monitor will be installed and maintained above 32
      degrees Celsius. The core temperature will be monitored in the esophagus and maintained above
      35 degrees Celsius. All patients will be placed under a upper body forced air warming
      blanket. The trachea will be intubated without the use of muscle relaxant. Ventilation will
      be adjusted to maintain normocapnia (end tidal carbon dioxide 32 - 40 mmHg). Before the study
      began, if inhaled agents have been used for induction of anesthesia, the absence will be
      established by the gas analysis monitor.

      Neuromuscular monitoring

      Neuromuscular monitoring will follow the recommendations of good practice in research for
      pharmacodynamic studies of neuromuscular blocking agents. After careful cleaning of the skin,
      two pediatric surface electrodes will be placed in one of the upper limbs on the ulnar nerve
      near the wrist with a distance of 3 to 6 centimeters (cm). Upper limb and fingers will be
      fixed to appropriate support. The acceleromyography monitor (TOF-Watch®, Organon) will be
      installed on this member. Using a system of random numbers generated by computer and stored
      in sealed, opaque envelopes, patients will be placed in one of the following groups:

      Tetanus group (n = 25) After verifying the absence of sevoflurane through the gas analyzer, a
      50-Hz tetanic stimulation will be applied for 5 s and followed after 1 min by TOF stimulation
      every 15 s. When the response to TOF is stable, calibration and supramaximal stimulation will
      be ensured by the built-in calibration function (CAL 2) of the TOF-Watch®.

      Control group (n = 25) After verifying the absence of sevoflurane through the gas analyzer,
      TOF monitor mode starts with stimuli every 12 to 15 seconds. After 1 minute (min) stimulation
      in the form, calibration and supramaximal stimulation will be ensured by the built-in
      calibration function (CAL 2) of the TOF-Watch®. If greater than 5% variation in the height of
      the first response (T1) of the TOF monitor will be recalibrated.

      In both groups, the stability of the response will be documented by at least 2 to 5 min [<5%
      variation in the first response (T1) in the TOF] before administration of rocuronium.

      The IV line will be inserted in the contralateral arm. The choice between the dominant and
      non-dominant arm will be made randomly. The dose of 0,6 milligram / kilogram of rocuronium
      will be administered in fast-running saline infusion within 5 seconds. The data of the
      TOF-Watch® monitor will be collected on a laptop using the neuromuscular junction program
      monitor. If needed, neuromuscular blockade will be reversed with neostigmine and atropine.

      Sample Size Based on the previous study, the mean blocking time to reach TOF 0.9 is averaging
      42.8 minutes, the variability from one patient to another was 9 minutes (SD = 9 minutes). (9)
      It is expected that, using tetanus, the average blocking time will not be less than 35
      minutes on average. With 80% power and 95% confidence the sample required for conducting the
      study is 21 patients in each group.

      Statistical Analysis Recovery times from neuromuscular blockade will be assessed between
      groups up to the value of TOF = 0.90. For quantitative evaluation of these parameters will be
      employed Student's t test or the Mann-Whitney test.

      The sensitivity, parameter set automatically by the monitor, will be compared between groups.
      As it is also a quantitative parameter, the Student's t test or the Mann-Whitney test will be
      used.
    

Intervention name(s): Tetanus
Intervention type(s): Procedure
Intervention description(s): tetanic electric stimulation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Supportive Care