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

Information source: Onze Lieve Vrouw Hospital
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Respiratory Muscles; Electromyography

Intervention: Sugammadex (Drug); Neostigmine (Drug); Neostigmine-sugammadex (Drug)

Phase: Phase 4

Status: Not yet recruiting

Sponsored by: Onze Lieve Vrouw Hospital

Official(s) and/or principal investigator(s):
GUY CAMMU, MD, PhD, Principal Investigator, Affiliation: OLV Hospital, Aalst, Belgium

Overall contact:
GUY CAMMU, MD, PhD, Phone: +32 (0)53 72 41 11, Email: guy.cammu@olvz-aalst.be

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.

Clinical Details

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

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

Primary outcome: Electromyographic activity of the respiratory muscles during recovery enhanced by sugammadex, neostigmine or neostigmine followed by sugammadex

Secondary outcome:

Tidal volume of breaths recorded by the ventilator

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

The arterial oxygen saturation

Detailed 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.

Eligibility

Minimum age: 18 Years. Maximum age: 39 Years. Gender(s): Male.

Criteria:

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.

Locations and Contacts

GUY CAMMU, MD, PhD, Phone: +32 (0)53 72 41 11, Email: guy.cammu@olvz-aalst.be

OLV Hospital, Aalst 9300, Belgium; Not yet recruiting
Guy Cammu, MD, PhD, Phone: +32 (0)53 724111, Email: guy.cammu@olvz-aalst.be
Benny Desmedt, RN, Phone: +32 (0)475 200 299, Email: bdesmedt@yucom.be
Guy Cammu, MD, PhD, Principal Investigator
Additional Information

Related publications:

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.

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.

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.

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.

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.

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.

Starting date: September 2015
Last updated: April 14, 2015

Page last updated: August 23, 2015

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