Mask Ventilation Before and After Neuromuscular Blockade
Condition: Anesthesia
Study type: Interventional
Phase: Phase 4

Summary: 
      Anesthesia providers are taught to "test" that they can properly ventilate a patient's lungs
      before administering a neuromuscular blocking drug (NMBD), rendering the patient apneic. This
      is a traditional teaching, not based on empirical evidence. The investigators primary
      hypothesis is that ventilation after the administration of NMBDs is non-inferior with that
      before their administration with respect to the composite safety endpoint of inadequate (MVi)
      and dead-space only (Vds) ventilation.
    

Detailed description: 
      The following will be carried out per routine standard of care:

      The patient will be met in the pre-operative area by the attending anesthesiologist who
      interviews and examines the patient. A full explanation of the general anesthetic including
      risks and benefit will be given. Patients will be premedicated with 1-2 mg of midazolam at
      the discretion of the attending anesthesiologist. Once in the OR, standard American Society
      of Anesthesiology (ASA) monitors are established. At a minimum, this includes non-invasive
      monitoring of blood pressure by automated cuff, oxygen saturation via pulse oximetry, heart
      rate and rhythm by 3-lead continuous electrocardiographic tracing, core body temperature,
      expired carbon dioxide concentration, and depth of neuromuscular blockade when paralytic
      medications are used. Additional monitoring may be applied as deemed appropriate by the
      attending anesthesiologist on a case-by-case basis. At this time, the patient is given
      fentanyl 1-2 mcg/kg. After a period of breathing 100% oxygen by facemask (typically for 3
      minutes or until the anesthesia monitor shows the exhaled concentration of oxygen to be >80%)
      and when the primary anesthesia team judges denitrogenation to be sufficient, anesthesia will
      be induced intravenously with propofol 2-3 mg/kg. Once the patient is unresponsive to a jaw
      thrust, the patient is ventilated via a facemask. If the anesthesia provider feels that
      ability to move air in and out of the patients lungs is difficult, the may reposition the
      mask on the patient's face, reposition the head, neck, or shoulders of the patient, or place
      a plastic oropharyngeal airway to maintain the mouth in an open position and to help keep the
      base of the tongue from obstructing the upper airway. A drug that causes muscle paralysis is
      given, which takes 1-5 minutes to work depending on the drug administered; during this period
      the patient continues to be ventilated by facemask. However, there is not standard for the
      timing of administration of the paralytic drugs as some anesthesia providers administer them
      near simultaneous to the administration of the other drugs used to induce anesthesia. Often,
      during this time, an inhaled anesthetic agent is started to avoid any gaps in the effect of
      the intravenous medications. Once the muscle relaxant works, a breathing tube is placed in
      the patient's windpipe, and ventilation occurs via the tube connected to a breathing machine.

      The study deviates from the standard anesthesia care described above in the following ways:

      Before the patient arrives in the operating room, a small plastic device called a
      pneumotachograph will be placed in-line between the facemask and the breathing circuit of the
      anesthesia machine. This allows measurements of airway pressure and volumes to be recorded in
      an accurate manner and later sent electronically to a computer for analysis. The in-line
      portion of the device is no larger than a typical circuit connector already used and does not
      hinder the performance of the anesthesia provider in any way. After routine intravenous
      induction, once the patient is unresponsive to a jaw thrust patients will be ventilated by
      facemask for 60 seconds. Breaths will be delivered using the breathing bag of the anesthesia
      circuit as would otherwise be performed. The airway managers will be asked to follow a
      treatment algorithm to resolve any difficulty encountered in providing mask ventilation. This
      algorithm represents common practice. After the initial 60 seconds, the medication to induce
      muscle paralysis will be given. A nerve stimulator placed on the patients wrist will then be
      turned on and will indicate when the medication has taken full effect and the patient is
      paralyzed. During this period of time, approximately 60-90 seconds, with the patients
      unconscious and apneic, their breathing will be supported as would otherwise be done.
      Post-paralysis, data collection will again begin and the anesthesia provider will start again
      breathing for the patient via a facemask as described in figure 2 for another 60 seconds. The
      operator will be blinded to the display on the ventilator machine, which provides information
      about the amount of air going in and out of the patients lungs, but will be able to monitor
      the patient's pertinent vital signs on the anesthesia machine. At all times, one member of
      the primary anesthesia team will have full access to all monitoring as would normally take
      place. After this time, the tracheal tube will be placed for the surgery.

      Appropriate sizing of the adult facemask and oropharyngeal airway will be determined by the
      primary anesthesia team. All breaths will be delivered by hand ventilation using the
      breathing bag of the anesthesia machine. The returned tidal volume will be recorded for each
      minute of the study period from the pneumotachograph placed inline with the anesthesia
      circuit at the level of the mask/elbow connector interface as described above. The total time
      from induction to placement of a breathing tube will be 4-5 minutes and represents an
      additional minute of "study" time to the standard care. This timing was chosen as the
      investigators feel that it will provide sufficient information about ventilation volumes
      without unduly prolonging the anesthetic.

      The study coordinator will remain in the room for the actual intubation to record its ease or
      difficulty per the report of the primary anesthesia provider. The act of placing the
      breathing tube is not part of the study protocol, however.

      Data points to be collected:

      Data regarding tidal volume, minute ventilation, airway pressures, and end-tidal carbon
      dioxide will be recorded directly by the in-line pneumotachograph and then loaded into an
      excel spreadsheet. No manual data collection will be necessary.

      Data and Safety Monitoring Plan

      The study may be terminated by the primary anesthesia team if the one or more of the
      following criteria are met:

        1. Inadequate ventilation by clinical criteria (inadequate chest rise, no fogging in the
           mask, no positive tracing of end-tidal carbon dioxide and/or lack of measurable returned
           tidal volumes on).

        2. Low oxygen saturation (< 90%).

        3. If for any reason, the primary anesthesia team feel that in their clinical judgment,
           immediate tracheal intubation is warranted.

      All unanticipated problems and adverse event will be recorded in the study sheet by a study
      coordinator. At the earliest time, each unanticipated problem and adverse event will be
      examined by at least 2 study investigators. In the event of an unanticipated problem of
      adverse effect (eg inadequate mask ventilation), back-up will be provided by the primary
      anesthesia team caring for the patient and may include placing a laryngeal mask airway or a
      surgical airway. These are the same provisions that would be made for any non-study case as
      mask ventilation by using one or two hands represents standard practice.

      Statistical Considerations:

      The investigators are aiming to show that administration of a neuromuscular blocking agent is
      "safe" with respect to mask ventilation. In other words, that the average exhaled tidal
      volume per breath over one minute after the administration of a NMBD will be non-inferior to
      that measured before their administration. At the time of the planning of this study, no
      studies had reported a mean±SD for tidal volumes before and after NMBDs. However, based upon
      a prior comparative trial of two different mask-hold techniques, the standard deviation (SD)
      of the average exhaled tidal volume after induction of anesthesia, using the anesthesia
      ventilator and a two-hand jaw-thrust mask hold technique was 130 mL. With the equivalence
      limit, d, set as 50 mL per breath, with a significance level (α) of 2.5% and a power (1-β) of
      95%, a total sample size of 208 patients per group (before and after NMBD for a total sample
      of 416 study periods) were required. In other words, if there is truly no difference between
      the mask ventilation before and after NMBD, then 208 patients, each as their own control, are
      required to be 95% sure that the limits of a 2-sided 95% confidence interval will exclude a
      difference in means of >50 mL.
    

Intervention name(s): Rocuronium; Vecuronium Bromide; Succinylcholine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Administration of a NMBD; Administration of a NMBD; Administration of a NMBD
Other intervention name(s): Vecuronium; Sux
Intervention MeSH terms: Bromides; Rocuronium; Vecuronium Bromide; Succinylcholine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Patient Safety