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Clinical Trials/NCT02284412
NCT02284412
Completed
Phase 4

Visualization of Regional Lung Ventilation During Neostigmine or Sugammadex Enhanced Recovery From Moderate Residual Neuromuscular Blockade in the Anaesthetized Rat Using Functional Respiratory Imaging

Onze Lieve Vrouw Hospital1 site in 1 country13 target enrollmentDecember 2014

Overview

Phase
Phase 4
Intervention
Neostigmine
Conditions
Respiratory-Gated Imaging Techniques
Sponsor
Onze Lieve Vrouw Hospital
Enrollment
13
Locations
1
Primary Endpoint
Regional lung ventilation assessed by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block.
Status
Completed
Last Updated
11 years ago

Overview

Brief 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.

Registry
clinicaltrials.gov
Start Date
December 2014
End Date
April 2015
Last Updated
11 years ago
Study Type
Interventional
Study Design
Parallel
Sex
Male

Investigators

Sponsor
Onze Lieve Vrouw Hospital
Responsible Party
Principal Investigator
Principal Investigator

Guy CAMMU

MD, PhD

Onze Lieve Vrouw Hospital

Eligibility Criteria

Inclusion Criteria

  • male Sprague-Dawley rats

Exclusion Criteria

  • Not provided

Arms & Interventions

neostigmine

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.

Intervention: Neostigmine

Sugammadex

Sugammadex will be dosed 15 mg/kg, as a single iv bolus administered over 10sec, for reversal of rocuronium-induced moderate neuromuscular blockade.

Intervention: Sugammadex

Water for injection

Water will be dosed arbitrarily as a 1 mL single iv bolus administered over 10sec.

Intervention: Water for injection

Outcomes

Primary Outcomes

Regional lung ventilation assessed by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block.

Time Frame: CT scanning will take between 5 to 8 minutes, followed by post-processing of the images.

Comparison of the effect of sugammadex, neostigmine/glycopyrrolate and spontaneous recovery on regional lung ventilation in the spontaneously breathing rat, assessed by micro-CT scanning after recovery from neuromuscular block.

Secondary Outcomes

  • Tidal volume (TV, mL) of breaths recorded by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block.(CT scanning will take between 5 to 8 minutes, followed by post-processing of the images.)

Study Sites (1)

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