Functional Respiratory Imaging After Neostigmine or Sugammadex

NCT02284412 | Completed Phase 4 DMC

• 1 other identifier: TSGC02
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Respiratory-Gated Imaging Techniques

Keywords

Neostigmine; Sugammadex

Outcome Measures

Primary Outcomes (1)

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

  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.

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

Secondary Outcomes (1)

• 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 Arms (3)

neostigmine

ACTIVE COMPARATOR

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.

Drug: Neostigmine

Sugammadex

EXPERIMENTAL

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

Drug: Sugammadex

Water for injection

PLACEBO COMPARATOR

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

Drug: Water for injection

Interventions

Neostigmine DRUG

At a train-of-four (TOF) ratio of 0.5: administration of neostigmine 0.06 mg/kg for reversal of neuromuscular blockade.

Also known as: Robinul-Neostigmine

neostigmine

Sugammadex DRUG

At a train-of-four (TOF) ratio of 0.5: administration of sugammadex 15 mg/kg for reversal of neuromuscular blockade.

Also known as: Bridion

Sugammadex

Water for injection DRUG

At a train-of-four (TOF) ratio of 0.5: administration of placebo for spontaneous recovery of neuromuscular blockade.

Also known as: Aqua ad iniectabilia

Water for injection

Eligibility Criteria

• Age: 3 Months - 6 Months
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• male Sprague-Dawley rats

You may not qualify if:

• N/A

Sponsors & Collaborators

• Onze Lieve Vrouw Hospital: lead
• Universiteit Antwerpen: collaborator
• MSD Belgium BVBA: collaborator

Study Sites (1)

OLV Hospital

Aalst, 9300, Belgium

Location

Related Publications (6)

• 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.

  PMID: 9366929 BACKGROUND

• 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.

  PMID: 23194209 BACKGROUND

• 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.

  PMID: 23077290 BACKGROUND

• 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.

  PMID: 25111539 BACKGROUND

• 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.

  PMID: 19322825 BACKGROUND

• 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.

  PMID: 18559352 BACKGROUND

MeSH Terms

Interventions

Neostigmine; Sugammadex; Water; Injections

Intervention Hierarchy (Ancestors)

Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• GUY CAMMU, MD, PhD

  OLV Hospital, Aalst, Belgium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: October 28, 2014
• First Posted: November 6, 2014
• Study Start: December 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: April 1, 2015
• Last Updated: April 21, 2015

Record last verified: 2015-04

Locations

BE (1)