Recovery of Diaphragmatic Function After Neuromuscular Blockade and Sugammadex (SUDIA)

Sugammadex and the Diaphragm: Recovery of Diaphragmatic Function and Neuromuscular Blockade. A Double-blind Randomized Controlled Trial

The effect of neuromuscular blocking agents (NMBA, e.g. rocuronium) on respiratory muscle activity is well known. However, since the availability of sugammadex, to our knowledge, no study has been conducted to evaluate the effect of this novel product on these muscles.

Our hypothesis is that by applying a different strategy in the use of neuromuscular blocking agents and their reversal agents we might see a different activity of the respiratory muscles.

Study Overview

• Status: Completed
• Conditions: Muscle Weakness; Muscle Fatigue; Diaphragmatic Dysfunction
• Intervention / Treatment: Drug: placebo; Drug: neostigmine; Drug: Single rocuronium dose; Drug: sugammadex 2mg/kg; Drug: Repeated rocuronium dose; Drug: sugammadex 4mg/kg; Drug: Continuous rocuronium infusion

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Antwerp University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Each participant must have the mental capacity to decide whether he/she takes part in the trial or not. Each participant must voluntarily give his/her written informed consent. In case a participant is physically unable to give a written informed consent, a legal representative is to perform this.
• Each participant must be at least eighteen years of age. Participants can be of either sex and of any ethnical background.
• Each participant must meet the American Society of Anesthesiologists class II, II or III criteria.
• Each participant must be scheduled for intracranial surgery. During general anesthesia rocuronium must be used as a neuromuscular blocking agent.
• Each participant must be a suitable candidate for the rapid reversal of the neuromuscular blockade.
• Each female participant of sexually active age and of childbearing potential must agree to the use of a medically accepted method of contraception through seven days after the day of surgery. Postmenopausal (defined as at least twelve consecutive months without spontaneous menstrual period) women are not obliged to use contraceptives.

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, anesthetic or narcotic medications, or any drugs used during general anesthesia.
• 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 pregnant (or intends to become pregnant within the presurgical period) or lactating.
• The participant is known to have a renal insufficiency (defined as a serum creatinine concentration of two times the upper limit, or a glomerular filtration rate of less than 60 ml/min).
• The participant is known or suspected to have a chronic obstructive pulmonary disease GOLD classification 2 or higher or has any respiratory disease that impairs his respiratory function to a NYHA III level or worse.
• The participant is known to have an infection of the upper or lower airways, as diagnosed by clinical or laboratory findings.
• The participant is known or suspected to have congestive heart failure.
• The participant is obese, as defined by a body mass index of 30 kg/m2 or more.
• The participant is known or suspected to have a major hepatic dysfunction.
• The participant has received or is scheduled to receive toremifene and/or an intravenous administration of fusidic acid within a time span of twenty-four hours before and twenty-four hours after the surgery.
• The participant is known or suspected to have any condition contraindicating the administration of sugammadex, neostigmine, glycopyrrolate or placebo.
• The participant is known or suspected to be directly involved in this study and/or is employed by or is a family member of any person employed by the investigator, at the investigational site, or by the sponsor.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Single rocuronium dose - placebo; The patients will receive a single rocuronium dose, and no reversal agent.	Drug: placebo; Drug: Single rocuronium dose
ACTIVE_COMPARATOR: Single rocuronium dose - sugammadex; The patients will receive a single rocuronium dose and sugammadex 2mg/kg as a reversal agent	Drug: Single rocuronium dose; Drug: sugammadex 2mg/kg
ACTIVE_COMPARATOR: Repeated rocuronium dose - neostigmine; The patients will receive multiple rocuronium doses and neostigmine 70 mcg/kg as a reversal agent	Drug: neostigmine; Drug: Repeated rocuronium dose
ACTIVE_COMPARATOR: Repeated rocuronium dose - sugammadex; The patients will receive multiple rocuronium doses and neostigmine 2mg/kg as a reversal agent	Drug: sugammadex 2mg/kg; Drug: Repeated rocuronium dose
ACTIVE_COMPARATOR: Continuous rocuronium dose; The participants will receive a continuous rocuronium infusion and sugammadex 4 mg/kg as a reversal agent	Drug: sugammadex 4mg/kg; Drug: Continuous rocuronium infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Electric Activity of the Diaphragm (Microvolts)	From the start of spontaneous breathing till extubation, limited to maximum ten minutes after the onset of spontaneous breathing

Secondary Outcome Measures

Outcome Measure	Time Frame
Electric Activity of the Intercostal Muscles	From the start of spontaneous breathing till extubation, limited to maximum ten minutes after the onset of spontaneous breathing

Other Outcome Measures

Outcome Measure	Time Frame
Centroid Frequency of the EMG, as Trend Variability (Change in %) From First to Last Recording	From the start of spontaneous breathing till extubation, limited to maximum one hour after the onset of spontaneous breathing

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp

Publications and helpful links

General Publications

• Dres M, Schmidt M, Ferre A, Mayaux J, Similowski T, Demoule A. Diaphragm electromyographic activity as a predictor of weaning failure. Intensive Care Med. 2012 Dec;38(12):2017-25. doi: 10.1007/s00134-012-2700-3. Epub 2012 Sep 26.
• Schepens T, Janssens K, Maes S, Wildemeersch D, Vellinga J, Jorens PG, Saldien V. Respiratory muscle activity after spontaneous, neostigmine- or sugammadex-enhanced recovery of neuromuscular blockade: a double blind prospective randomized controlled trial. BMC Anesthesiol. 2019 Oct 19;19(1):187. doi: 10.1186/s12871-019-0863-y.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): December 1, 2014

Study Registration Dates

• First Submitted: October 9, 2013
• First Submitted That Met QC Criteria: October 11, 2013
• First Posted (ESTIMATE): October 14, 2013

Study Record Updates

• Last Update Posted (ACTUAL): October 24, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Weakness; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Neuromuscular Agents; Cholinesterase Inhibitors; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Parasympathomimetics; Rocuronium; Neostigmine
• Other Study ID Numbers: EC 13/5/60; 2013-001926-25 (EUDRACT_NUMBER); B300201316844 (REGISTRY: Belgisch Registratienummer)