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Functional Respiratory Imaging After Neostigmine or Sugammadex (FRINeoS)

O

Onze Lieve Vrouw Hospital

Status and phase

Completed
Phase 4

Conditions

Respiratory-Gated Imaging Techniques

Treatments

Drug: Neostigmine
Drug: Water for injection
Drug: Sugammadex

Study type

Interventional

Funder types

Other
Industry

Identifiers

Details and patient eligibility

About

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.

Full 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.

Enrollment

13 patients

Sex

Male

Ages

3 to 6 months old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • male Sprague-Dawley rats

Exclusion criteria

  • N/A

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

13 participants in 3 patient groups, including a placebo group

neostigmine
Active Comparator group
Description:
Neostigmine will be dosed as 60 μg/kg, and glycopyrrolate 12 μg/kg (commercially available 5:1 co-formulation), as a single iv bolus administered over 10sec, for reversal of rocuronium-induced moderate neuromuscular blockade.
Treatment:
Drug: Neostigmine
Sugammadex
Experimental group
Description:
Sugammadex will be dosed 15 mg/kg, as a single iv bolus administered over 10sec, for reversal of rocuronium-induced moderate neuromuscular blockade.
Treatment:
Drug: Sugammadex
Water for injection
Placebo Comparator group
Description:
Water will be dosed arbitrarily as a 1 mL single iv bolus administered over 10sec.
Treatment:
Drug: Water for injection

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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