Functional Respiratory Imaging After Neostigmine or Sugammadex
Condition: Respiratory-Gated Imaging Techniques
Study type: Interventional
Phase: Phase 4

Summary: 
      The use of neuromuscular blocking agents (NMBAs) is still associated with postoperative
      pulmonary complications. The investigators rely on acceleromyography (AMG) of a peripheral
      nerve/muscle to assess the patients' breathing capability at the end of surgery. It is
      possible that respiratory complications after surgery (e.g. desaturation and atelectasis) are
      related to the lack of diaphragm activity.

      A previous trial by our study group links the use of sugammadex, a novel selective relaxant
      binding agent (SRBA) for reversal of neuromuscular blockade, to an increase in diaphragm
      electrical activity, compared to reversal with neostigmine. Our hypothesis is that by making
      nicotinergic acetylcholine receptors free from rocuronium in the diaphragmatic neuromuscular
      junctions, instead of increasing the amount of acetylcholine (like neostigmine does),
      sugammadex will result in a better neuromuscular coupling. This may have its subsequent
      effects on the central control of breathing, influencing the balance between intercostal and
      diaphragm activity.

      The investigators now propose a study in rats, where the investigators will use Functional
      Respiratory Imaging (FRI, property of FluidDA n.v., Groeningenlei 132, B-2550 Kontich) to
      assess regional lung ventilation after sugammadex, neostigmine or spontaneous reversal. The
      images obtained through micro-CT scans allow us to accurately reconstruct airway morphology
      in the free-breathing rat. It will provide us with new insights into breathing physiology
      after reversal of neuromuscular blockade.
    

Detailed description: 
      This study is designed to assess the effect of sugammadex, neostigmine/glycopyrrolate and
      spontaneous reversal of a moderate rocuronium-induced neuromuscular blockade on regional lung
      ventilation. This is a randomized, controlled, parallel-group double blind trial in rats. A
      total of 18 adult male Sprague-Dawley rats will be used, 6 in each treatment group. The
      animals will be randomized in one of three groups, in a 1:1:1 ratio. This randomization will
      be performed according to a computer-generated randomization list. The first group will
      receive neostigmine/glycopyrrolate. The second group will receive sugammadex. The third group
      will receive water for injection. Reversal agents will be administered at a train-of-four
      (TOF) of 0.5, as measured with AMG.

      The investigators will assess regional ventilation by means of micro-CT scanning during
      spontaneous breathing after the TOF ratio has reached ≥ 0.9. This way, the investigators can
      accurately reconstruct airway morphology. The different airway sections can then be linked to
      the corresponding lung tissue, and a full anatomical picture is thus rendered. A comparison
      of morphological scans at different breathing levels (e.g. end-inspiratory and
      end-expiratory) will allow us to model breath-by-breath regional airway and alveolar
      recruitment.
    

Intervention name(s): Neostigmine; Sugammadex; Water for injection
Intervention type(s): Drug; Drug; Drug
Intervention description(s): At a train-of-four (TOF) ratio of 0.5: administration of neostigmine 0.06 mg/kg for reversal of neuromuscular blockade.; At a train-of-four (TOF) ratio of 0.5: administration of sugammadex 15 mg/kg for reversal of neuromuscular blockade.; At a train-of-four (TOF) ratio of 0.5: administration of placebo for spontaneous recovery of neuromuscular blockade.
Other intervention name(s): Robinul-Neostigmine; Bridion; Aqua ad iniectabilia
Intervention MeSH terms: Neostigmine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Neostigmine; Sugammadex