Electromyographic Activity of the Respiratory Muscles During Neostigmine or Sugammadex Enhanced Recovery After Neuromuscular Blockade

NCT02403063 | Completed Phase 4 DMC

• 1 other identifier: TSGC03
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

It was recently shown that neostigmine reversal was associated with increased atelectasis and that high-dose neostigmine was associated with longer postoperative length of stay and with an increased incidence of pulmonary edema and reintubation. These study results were consistent with findings from a previous epidemiological study which revealed an absence of beneficial effects of neostigmine on postoperative oxygenation and reintubation. In our previous study, the effects of neostigmine / glycopyrrolate and sugammadex on the electromyographic activity of the diaphragm showed beneficial effects for sugammadex. This could be explained by a possible effect on neuromuscular transmission at the muscle level, but can also be explained by a neostigmine-induced decrease in total nerve activity. In a study in cats, neostigmine has been shown to reduce efferent phrenic nerve activity. The investigators aim to show a difference in phrenic nerve activity between neostigmine and sugammadex, administered alone or in combination, in healthy male volunteers.

Conditions

Respiratory Muscles; Electromyography

Outcome Measures

Primary Outcomes (1)

• Electromyographic activity of the respiratory muscles during recovery enhanced by sugammadex, neostigmine or neostigmine followed by sugammadex

  EMG activity of the diaphragm (EMGdi), and of the rectus abdominis and of the intercostal muscles during recovery enhanced by sugammadex 2mg/kg or neostigmine 50µg/kg or neostigmine 50µg/kg followed 3 minutes later by administration of sugammadex 2mg/kg

  Participants will be followed from administration of study drug until tracheal extubation, an expected average of 1 hour

Secondary Outcomes (3)

• Tidal volume of breaths recorded by the ventilator

  Participants will be followed from administration of study drug until tracheal extubation, an expected average of 1 hour

• The partial pressure of O2 and of carbon dioxide in arterial blood

  Participants will be followed from administration of study drug until tracheal extubation, an expected average of 1 hour

• The arterial oxygen saturation

  Participants will be followed from induction of anesthesia until two hours after extubation of the trachea, an expected average of 3 hours

Study Arms (3)

sugammadex

ACTIVE COMPARATOR

Selective relaxant binding agent

Drug: Sugammadex

neostigmine

ACTIVE COMPARATOR

Acetylcholinesterase inhibitor

Drug: Neostigmine

neostigmine-sugammadex

EXPERIMENTAL

Acetylcholinesterase inhibitor followed by a selective relaxant binding agent

Drug: Neostigmine-sugammadex

Interventions

Sugammadex DRUG

Administration of sugammadex 2mg/kg for enhanced recovery after neuromuscular blockade with rocuronium

Also known as: Bridion

sugammadex

Neostigmine DRUG

Administration of neostigmine 50µg/kg for enhanced recovery after neuromuscular blockade with rocuronium

Also known as: Robinul-neostigmine

neostigmine

Neostigmine-sugammadex DRUG

Administration of neostigmine 50µg/kg followed 3 minutes later by administration of sugammadex 2mg/kg for enhanced recovery after neuromuscular blockade with rocuronium

neostigmine-sugammadex

Eligibility Criteria

• Age: 18 Years - 39 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Only male, healthy volunteers will be enrolled after an in-depth interview.
• Each participant must have the mental capacity to decide whether he takes part in the trial or not. Each participant must voluntarily give his written informed consent.
• Each participant must be between 18 and 40 years of age.
• Each participant must meet the American Society of Anaesthesiologists class I criteria.

You may not qualify if:

• The participant is known or suspected to have a neuromuscular disorder.
• The participant is known or suspected to have an allergic reaction to sugammadex, rocuronium, anaesthetic medications, or any drugs used during general anaesthesia.
• The participant is known or suspected to have an anatomical malformation impeding a proper intubation.
• The participant is known or suspected to have a history of malignant hyperthermia.
• The participant is known to have a renal insufficiency .
• The participant is known or suspected to have a chronic obstructive pulmonary disease GOLD classification 2 or higher.
• The participant is known to have an infection of the upper or lower airways, as diagnosed by clinical findings.

Sponsors & Collaborators

• Onze Lieve Vrouw Hospital: lead

Study Sites (1)

OLV Hospital

Aalst, 9300, Belgium

Location

Related Publications (7)

• Sasaki N, Meyer MJ, Malviya SA, Stanislaus AB, MacDonald T, Doran ME, Igumenshcheva A, Hoang AH, Eikermann M. Effects of neostigmine reversal of nondepolarizing neuromuscular blocking agents on postoperative respiratory outcomes: a prospective study. Anesthesiology. 2014 Nov;121(5):959-68. doi: 10.1097/ALN.0000000000000440.

  PMID: 25225821 BACKGROUND

• Eikermann M, Fassbender P, Malhotra A, Takahashi M, Kubo S, Jordan AS, Gautam S, White DP, Chamberlin NL. Unwarranted administration of acetylcholinesterase inhibitors can impair genioglossus and diaphragm muscle function. Anesthesiology. 2007 Oct;107(4):621-9. doi: 10.1097/01.anes.0000281928.88997.95.

  PMID: 17893459 BACKGROUND

• Herbstreit F, Zigrahn D, Ochterbeck C, Peters J, Eikermann M. Neostigmine/glycopyrrolate administered after recovery from neuromuscular block increases upper airway collapsibility by decreasing genioglossus muscle activity in response to negative pharyngeal pressure. Anesthesiology. 2010 Dec;113(6):1280-8. doi: 10.1097/ALN.0b013e3181f70f3d.

  PMID: 20980910 BACKGROUND

• Meyer MJ, Bateman BT, Kurth T, Eikermann M. Neostigmine reversal doesn't improve postoperative respiratory safety. BMJ. 2013 Mar 19;346:f1460. doi: 10.1136/bmj.f1460. No abstract available.

  PMID: 23512446 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

• Fleming NW, Henderson TR, Dretchen KL. Mechanisms of respiratory failure produced by neostigmine and diisopropyl fluorophosphate. Eur J Pharmacol. 1991 Mar 19;195(1):85-91. doi: 10.1016/0014-2999(91)90384-3.

  PMID: 2065714 BACKGROUND

• Cammu G, Schepens T, De Neve N, Wildemeersch D, Foubert L, Jorens PG. Diaphragmatic and intercostal electromyographic activity during neostigmine, sugammadex and neostigmine-sugammadex-enhanced recovery after neuromuscular blockade: A randomised controlled volunteer study. Eur J Anaesthesiol. 2017 Jan;34(1):8-15. doi: 10.1097/EJA.0000000000000543.

  PMID: 27902641 DERIVED

MeSH Terms

Interventions

Sugammadex; Neostigmine

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates; Phenylammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds

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: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Anesthesiologist

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: March 31, 2015
• Study Start: September 1, 2015
• Primary Completion: October 1, 2015
• Study Completion: November 1, 2015
• Last Updated: November 20, 2015

Record last verified: 2015-11

Locations

BE (1)