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

Electromyography Clinical Trial

— REDNESII  

Official title:

Electromyographic Activity of the Diaphragm and of the Rectus Abdominis and Intercostal Muscles During Neostigmine, Sugammadex, or Neostigmine-sugammadex Enhanced Recovery After Neuromuscular Blockade With Rocuronium. A Randomised Controlled Study in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02403063
• Other study ID #: TSGC03
• Status: Completed
• Phase: Phase 4
• First received: March 17, 2015
• Last updated: November 19, 2015
• Start date: September 2015
• Est. completion date: November 2015

Study information

• Verified date: November 2015
• Source: Onze Lieve Vrouw Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

Description:

An auxiliary surface EMG will be recorded via ordinary skin electrodes at the diaphragm, and intercostal and rectus abdominis muscles. The degree of neuromuscular blockade is continuously measured by accelerometry of the adductor pollicis muscle with ulnar nerve stimulation (TOF-watch SX®). Anesthesia is induced with propofol and remifentanil. Manually assisted ventilation with an air/oxygen mixture of 40% oxygen is started as soon as patients are becoming apnoeic. Train-of-four (TOF) monitoring starts after the induction of anesthesia (before rocuronium administration) and continues until awakening. The investigators will insert a 16 Fr. nasogastric catheter which allows electrical activity of the diaphragm (Edi) registration (NAVA, Maquet, Solna, Sweden). After baseline measurements, 0.6 mg/kg rocuronium is injected. After tracheal intubation, subjects will be ventilated by a standard ventilation mode (tidal volume 7 ml/kg, frequency of 12 breaths per minute, inspired oxygen fraction of 30%), with end-tidal PCO2 targets of 30-35 mmHg and a PEEP of 5 cmH2O. SpO2 values will be maintained at ≥98%. Spontaneous recovery is allowed to progress until the re-appearance of the second twitch of the TOF. The volunteers will then receive either sugammadex 2mg/kg or neostigmine 50µg/kg + glycopyrrolate 10µg/kg (using the commercially available 5:1 co-formulation) or neostigmine 50µg/kg followed 3 minutes later by administration of sugammadex 2mg/kg. At the onset of spontaneous respiration, an arterial blood gas sample will be drawn. NAVA catheter positioning will be confirmed using the 'Edi catheter positioning' tool as soon as a signal is received. A second arterial blood gas sample will be drawn at the moment of awakening.

Diaphragm electromyographic activity (Edi, obtained from the NAVA catheter), airway pressure and flow are acquired at 100 Hz from the ventilator via an interface connected to a computer using commercially available software (Maquet Critical Care, Solna, Sweden). The auxiliary surface EMG will be recorded with a dedicated device (Dipha16, InBiolab, Groningen, The Netherlands) at the diaphragm, and intercostal and rectus abdominis muscles. All data will be stored and later analysed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2015
• Est. primary completion date: October 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 39 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Electromyography
• Respiratory Muscles

Intervention

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

Locations

Country	Name	City	State
Belgium	OLV Hospital	Aalst

Sponsors (1)

Lead Sponsor	Collaborator
Onze Lieve Vrouw Hospital

Country where clinical trial is conducted

Belgium, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	The arterial oxygen saturation	Saturation of hemoglobin with oxygen as measured by Pulse Oximetry	Participants will be followed from induction of anesthesia until two hours after extubation of the trachea, an expected average of 3 hours	Yes