Clinical trial NCT03646266: Partial Neuromuscular Blockade for Lung Protective Mechanical Ventilation
Official title: Partial Neuromuscular Blockade to Facilitate Lung and Diaphragm Protective Mechanical Ventilation in Intensive Care Unit Patients: a Randomized Controlled Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Respiratory Insufficiency
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2018-08-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: pilot randomized controlled trial (RCT)
Primary purpose: TREATMENT

Brief summary: Controlled mechanical ventilation may lead to the development of diaphragm muscle atrophy, which is associated with weakness and adverse clinical outcome. Therefore, it seems reasonable to switch to partially supported ventilator modes as soon as possible. However, in patients with high respiratory drive, the application of partially supported modes may result in high lung distending pressures and diaphragm injury.

Recently, the investigators published a study that demonstrated that a low dose of neuromuscular blocking agents (NMBA) facilitates lung-protective ventilation and maintains diaphragm activity in intensive care unit (ICU) patients. That study was conducted in a small (N=10), selected group of patients and partial neuromuscular blockade was applied for only 2 hours (proof-of-concept study). Therefore, further research has to be done before this strategy can be applied in clinical practice.

The primary goal is to investigate the feasibility and safety of prolonged (24 hours) partial neuromuscular blockade in patients with high respiratory drive in partially supported mode. The secondary goals are to evaluate the effect of this strategy diaphragm function, lung injury, hemodynamics and systemic inflammation.


Eligibility criteria: Inclusion Criteria:

* high respiratory drive, defined as tidal volume \> 8ml/kg PBW on inspiratory support of 12 cmH2O.
* sedation level: richmond agitation-sedation scale (RASS) ≤ -3
* ventilated in pressure support mode

Exclusion Criteria:

* recent use of NMBA (\< 2 hrs)
* arterial pH \< 7.25
* hemodynamic instability, i.e. high dose vasopressors (\>0.5 μg/kg/min) or inotropes (dobutamine \>15 μg/kg/min or enoximone \>25 μg/kg/min)
* intracranial pressure \> 20 cmH2O
* past medical history of neuromuscular disorders
* known pregnancy
* known previous anaphylactic reaction to NMBA's.

Primary outcomes:
measure: The percentage of breaths with tidal volume 6ml/kg predicted body weight (PBW)
timeFrame: At five time points of 1hr during the first 24hrs of the study period
measure: Incidence of directly related serious adverse events
timeFrame: During the 48hrs study period
Secondary outcomes:
measure: Number of patients completing the study without meeting the stopping criteria
timeFrame: At four time points during the first 24hrs of the study period
measure: Effect on partial carbon dioxide (pCO2)
timeFrame: During the 48hrs study period
measure: Effect on pH
timeFrame: During the 48hrs study period
measure: Effect on heart rate
timeFrame: During the 48hrs study period
measure: Effect on blood pressure
timeFrame: During the 48hrs study period
measure: Effect on respiratory rate
timeFrame: During the 48hrs study period
measure: Effect on peripheral capillary oxygen saturation (SpO2)
timeFrame: During the 48hrs study period
measure: Effect on partial oxygen pressure (pO2)
timeFrame: During the 48hrs study period
measure: Effect on work of breathing (WOB)
timeFrame: During the first 24hrs of the study period
measure: Effect on pressure time product (PTP)
timeFrame: During the first 24hrs of the study period
measure: Effect on tumor necrosis factor (TNF)-alfa
timeFrame: During the first 24hrs of the study period
measure: Effect on interleukin(IL)-6 and IL-8
timeFrame: During the first 24hrs of the study period
measure: Amount of days on mechanical ventilation
timeFrame: Until 30 days after the end of the study period
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: VUmc
Study officials:
References: