Electromyographic Activity of the Respiratory Muscles During Neostigmine or Sugammadex Enhanced Recovery After Neuromuscular Blockade
Condition: Respiratory Muscles; Electromyography
Study type: Interventional
Phase: Phase 4

Summary: 
      It was recently shown that neostigmine reversal was associated with increased atelectasis and
      that high-dose neostigmine was associated with longer postoperative length of stay and with
      an increased incidence of pulmonary edema and reintubation. These study results were
      consistent with findings from a previous epidemiological study which revealed an absence of
      beneficial effects of neostigmine on postoperative oxygenation and reintubation. In our
      previous study, the effects of neostigmine / glycopyrrolate and sugammadex on the
      electromyographic activity of the diaphragm showed beneficial effects for sugammadex. This
      could be explained by a possible effect on neuromuscular transmission at the muscle level,
      but can also be explained by a neostigmine-induced decrease in total nerve activity. In a
      study in cats, neostigmine has been shown to reduce efferent phrenic nerve activity. The
      investigators aim to show a difference in phrenic nerve activity between neostigmine and
      sugammadex, administered alone or in combination, in healthy male volunteers.
    

Detailed description: 
      An auxiliary surface EMG will be recorded via ordinary skin electrodes at the diaphragm, and
      intercostal and rectus abdominis muscles. The degree of neuromuscular blockade is
      continuously measured by accelerometry of the adductor pollicis muscle with ulnar nerve
      stimulation (TOF-watch SX®). Anesthesia is induced with propofol and remifentanil. Manually
      assisted ventilation with an air/oxygen mixture of 40% oxygen is started as soon as patients
      are becoming apnoeic. Train-of-four (TOF) monitoring starts after the induction of anesthesia
      (before rocuronium administration) and continues until awakening. The investigators will
      insert a 16 Fr. nasogastric catheter which allows electrical activity of the diaphragm (Edi)
      registration (NAVA, Maquet, Solna, Sweden). After baseline measurements, 0.6 mg/kg rocuronium
      is injected. After tracheal intubation, subjects will be ventilated by a standard ventilation
      mode (tidal volume 7 ml/kg, frequency of 12 breaths per minute, inspired oxygen fraction of
      30%), with end-tidal PCO2 targets of 30-35 mmHg and a PEEP of 5 cmH2O. SpO2 values will be
      maintained at ≥98%. Spontaneous recovery is allowed to progress until the re-appearance of
      the second twitch of the TOF. The volunteers will then receive either sugammadex 2mg/kg or
      neostigmine 50µg/kg + glycopyrrolate 10µg/kg (using the commercially available 5:1
      co-formulation) or neostigmine 50µg/kg followed 3 minutes later by administration of
      sugammadex 2mg/kg. At the onset of spontaneous respiration, an arterial blood gas sample will
      be drawn. NAVA catheter positioning will be confirmed using the 'Edi catheter positioning'
      tool as soon as a signal is received. A second arterial blood gas sample will be drawn at the
      moment of awakening.

      Diaphragm electromyographic activity (Edi, obtained from the NAVA catheter), airway pressure
      and flow are acquired at 100 Hz from the ventilator via an interface connected to a computer
      using commercially available software (Maquet Critical Care, Solna, Sweden). The auxiliary
      surface EMG will be recorded with a dedicated device (Dipha16, InBiolab, Groningen, The
      Netherlands) at the diaphragm, and intercostal and rectus abdominis muscles. All data will be
      stored and later analysed.
    

Intervention name(s): Sugammadex; Neostigmine; Neostigmine-sugammadex
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Administration of sugammadex 2mg/kg for enhanced recovery after neuromuscular blockade with rocuronium; Administration of neostigmine 50µg/kg for enhanced recovery after neuromuscular blockade with rocuronium; Administration of neostigmine 50µg/kg followed 3 minutes later by administration of sugammadex 2mg/kg for enhanced recovery after neuromuscular blockade with rocuronium
Other intervention name(s): Bridion; Robinul-neostigmine
Intervention MeSH terms: Neostigmine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science