ClinicalTrials.gov
ClinicalTrials.gov Menu

Effect of Neuromuscular Blockade and Reversal on Breathing (BREATH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02845375
Recruitment Status : Not yet recruiting
First Posted : July 27, 2016
Last Update Posted : July 27, 2016
Sponsor:
Information provided by (Responsible Party):
Albert Dahan, Leiden University Medical Center

Brief Summary:

In this study the investigators will assess (i) the effect of partial neuromuscular blockade (NMB; TOF ratio 0.8 and 0.6) induced by low-dose rocuronium on the ventilatory response to isocapnic hypoxia and (ii) the effect over time (from TOF 0.6 to TOF 1.0) of the reversal by sugammadex, neostigmine or placebo in healthy volunteers.

Additionally the investigators will assess the effect of partial NMB (TOF ratio 0.6) induced by low-dose rocuronium on the ventilatory response to hypercapnia and effect over time (from TOF 0.6 to TOF 1.0) of the reversal by sugammadex, neostigmine or placebo in healthy volunteers.


Condition or disease Intervention/treatment Phase
Respiratory Insufficiency Drug: Sugammadex Drug: Neostigmine Drug: Placebo Phase 4

Detailed Description:

The carotid bodies, located at the bifurcation of the common carotid artery, play a crucial and life-saving role in the control of breathing in humans. The carotid bodies contain type 1 cells that are primarily sensitive to low oxygen concentrations in arterial blood. In response to low oxygen the carotid bodies send information to the brainstem respiratory centers and a brisk hyperventilatory response will be initiated ensuring an increase in uptake of oxygen via the lungs. Following surgery, a rapid return of the carotid body function is vital and persistent loss of carotid body function may result in respiratory complications that occur independent of the effects of anesthetics (incl. muscle relaxants) on respiratory muscles. Respiratory complications that are related to the loss of carotid body function include the inability to respond properly to hypoxia as well the inability to overcome upper airway obstruction. The latter is especially important in patients with sleep disordered-breathing and obese patients. These patients rely on the optimal function of their carotid bodies in response to hypoxia or upper airway closure.

Important neurotransmitters involved in the carotid body response to hypoxia include acetylcholine, which acts through local nicotinergic acetylcholine receptors. Apart from the observation that muscle relaxants (which are blockers of the acetylcholine receptors) affect the proper functioning of the carotid bodies, the investigators have no knowledge on the dynamic effects of muscle relaxants on carotid body function over time or on the relationship between carotid body function and Train-of-Four (TOF) ratio over time. Additionally, there is no data on the link between the use of NMB antagonists and return of carotid body function. Linking TOF ratio to carotid body function is of clinical importance as a possible relationship will allow clinicians to predict carotid body function from the TOF ratio. The latter is highly relevant as the investigators show in a previous trial that a large proportion of patients is extubated at TOF ratio's < 0.7.

Apart from the carotid bodies, chemoreceptors in the brainstem exist that are sensitive to hypercapnia. This response system is not under control of cholinergic neurotransmission. Since the investigators may assume that the hypercapnic ventilatory response is not influenced by muscle relaxants the investigators can use this response to calibrate the hypoxic ventilatory response as both responses are equally affected by the effect of muscle relaxants on muscle function.

As stated there is data on the effect of muscle relaxants on carotid body function at one fixed TOF ratio (TOF ratio fixed at 0.7). No data are available on:

  1. Dynamic effect of carotid body function as measured by the hypoxic ventilatory response at TOF ratio's slowly changing from 0.6 to 1.0;
  2. Dynamic effect of reversal of NMB by sugammadex versus neostigmine. Sugammadex and neostigmine are both reversal agents of neuromuscular blockade. At their institution the investigators use both agents in clinical practice but remain without knowledge on their effects on carotid body function. The current proposal is designed to study items 1 and 2 in healthy awake volunteers.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Neuromuscular Blockade and Reversal by Sugammadex Versus Neostigmine on Breathing When Hypoxic or Hypercapnic in Volunteers
Study Start Date : September 2016
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Placebo Comparator: PLACEBO
Placebo (normal saline) will be administered following a period of muscle relaxation after which respiratory measurements will be obtained.
Drug: Placebo
Placebo will be administered following a period of muscle relaxation after wich respiratory measurements will be obtained.
Other Name: Normal saline
NEOSTIGMINE
intravenous neostigmine will be administered following a period of muscle relaxation after which respiratory measurements will be obtained.
Drug: Neostigmine
Neostigmine will be administered following a period of muscle relaxation after wich respiratory measurements will be obtained.
Other Name: NEO
Experimental: SUGAMMADEX
intravenous sugammade will be administered following a period of muscle relaxation after which respiratory measurements will be obtained.
Drug: Sugammadex
Sugammadex will be administered following a period of muscle relaxation after wich respiratory measurements will be obtained.



Primary Outcome Measures :
  1. ventilatory responses [ Time Frame: during the 1-2 hours following reversal ]
    The investigators will apply hypoxic and hypercapnic challenges and measure ventilation on a breath-to-breath basis using the Dynamic End-tidal Forcing (DEF) technique. This technique allows the manipulation of inspired gas concentrations to steer the end-tidal concentrations of oxygen and carbon dioxide (CO2) independent of the ventilatory response or the concentrations of O2 and CO2 in mixed venous blood. The technique allows a reliable assessment of carotid body function (in this case hypoxia) without the confounding effects of variations in end-tidal CO2. Additionally the investigators will obtained the ventilatory response to hypercapnia at hyperoxic conditions. This allows assessment of the response activity of the central chemoreceptors in the brainstem.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • male gender
  • age 18 years and older
  • body mass index < 30 kg/m2.

Exclusion Criteria:

  • Known or suspected neuromuscular disorders impairing neuromuscular function;
  • allergies to muscle relaxants, anesthetics or narcotics;
  • a (family) history of malignant hyperthermia or any other muscle disease;
  • any medical, neurological or psychiatric illness (including a history of anxiety).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02845375


Locations
Netherlands
Leiden University Medical Center
Leiden, ZH, Netherlands, 2333 ZA
Sponsors and Collaborators
Leiden University Medical Center

Publications of Results:
Responsible Party: Albert Dahan, Professor, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT02845375     History of Changes
Other Study ID Numbers: P16.025
First Posted: July 27, 2016    Key Record Dates
Last Update Posted: July 27, 2016
Last Verified: July 2016

Additional relevant MeSH terms:
Respiratory Insufficiency
Pulmonary Valve Insufficiency
Respiration Disorders
Respiratory Tract Diseases
Heart Valve Diseases
Heart Diseases
Cardiovascular Diseases
Neostigmine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents