Clinical trial NCT02284412: Functional Respiratory Imaging After Neostigmine or Sugammadex
Official title: Visualization of Regional Lung Ventilation During Neostigmine or Sugammadex Enhanced Recovery From Moderate Residual Neuromuscular Blockade in the Anaesthetized Rat Using Functional Respiratory Imaging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Respiratory-Gated Imaging Techniques
Keywords: Neostigmine
Sugammadex
Lead sponsor: Onze Lieve Vrouw Hospital
Sponsor class: OTHER
Collaborators: name: Universiteit Antwerpen
name: MSD Belgium BVBA
First posted: 2014-11-06
Enrollment: 13
Sex: MALE
Minimum age (years): 3
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* male Sprague-Dawley rats

Exclusion Criteria:

* N/A

Primary outcomes:
measure: Regional lung ventilation assessed by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block.
timeFrame: CT scanning will take between 5 to 8 minutes, followed by post-processing of the images.
Secondary outcomes:
measure: Tidal volume (TV, mL) of breaths recorded by means of micro-CT scanning during spontaneous breathing after recovery from neuromuscular block.
timeFrame: CT scanning will take between 5 to 8 minutes, followed by post-processing of the images.
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: OLV Hospital
Study officials:
affiliation: OLV Hospital, Aalst, Belgium
name: GUY CAMMU, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berg H, Roed J, Viby-Mogensen J, Mortensen CR, Engbaek J, Skovgaard LT, Krintel JJ. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997 Oct;41(9):1095-1103. doi: 10.1111/j.1399-6576.1997.tb04851.x.
citation: Cammu GV, Smet V, De Jongh K, Vandeput D. A prospective, observational study comparing postoperative residual curarisation and early adverse respiratory events in patients reversed with neostigmine or sugammadex or after apparent spontaneous recovery. Anaesth Intensive Care. 2012 Nov;40(6):999-1006. doi: 10.1177/0310057X1204000611.
citation: Grosse-Sundrup M, Henneman JP, Sandberg WS, Bateman BT, Uribe JV, Nguyen NT, Ehrenfeld JM, Martinez EA, Kurth T, Eikermann M. Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study. BMJ. 2012 Oct 15;345:e6329. doi: 10.1136/bmj.e6329.
citation: Schepens T, Cammu G, Saldien V, De Neve N, Jorens PG, Foubert L, Vercauteren M. Electromyographic activity of the diaphragm during neostigmine or sugammadex-enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers. Eur J Anaesthesiol. 2015 Jan;32(1):49-57. doi: 10.1097/EJA.0000000000000140.
citation: De Backer JW, Vos WG, Burnell P, Verhulst SL, Salmon P, De Clerck N, De Backer W. Study of the variability in upper and lower airway morphology in Sprague-Dawley rats using modern micro-CT scan-based segmentation techniques. Anat Rec (Hoboken). 2009 May;292(5):720-7. doi: 10.1002/ar.20877.
citation: Eikermann M, Zaremba S, Malhotra A, Jordan AS, Rosow C, Chamberlin NL. Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing. Br J Anaesth. 2008 Sep;101(3):344-9. doi: 10.1093/bja/aen176. Epub 2008 Jun 16.