Partial Neuromuscular Blockade for Lung Protective Mechanical Ventilation

Respiratory Insufficiency Clinical Trial

Official title:

Partial Neuromuscular Blockade to Facilitate Lung and Diaphragm Protective Mechanical Ventilation in Intensive Care Unit Patients: a Randomized Controlled Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03646266
• Other study ID #: NL65192.029.18
• Status: Recruiting
• Phase: Phase 4
• Start date: August 15, 2018
• Est. completion date: December 31, 2020

Study information

• Verified date: May 2020
• Source: VU University Medical Center
• Contact: Diana Jansen, Drs.
• Phone: +31(0)613225643
• Email: diana.jansen[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pulmonary Valve Insufficiency
• Respiratory Insufficiency

Intervention

Drug:
• Rocuronium Bromide
Titration with rocuronium bromide until tidal volume 6ml/kg PBW

Locations

Country	Name	City	State
Netherlands	VUmc	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The percentage of breaths with tidal volume 6ml/kg predicted body weight (PBW)	During the study period we measure at five time points of 1 hour (T0, T1, T5, T12, T24) all breaths and determine the percentage of breaths with a tidal volume of 6ml/kg PBW.	At five time points of 1hr during the first 24hrs of the study period
Primary	Incidence of directly related serious adverse events	A serious adverse event is any untoward medical occurence or effect that: results in death; is life threatening; requires prolongation of existing inpatients' hospitalization; results in persistent or significatn disability or incapacity; is a new event of the trial medication to affect the safety of the subjects, such as adverse events which are not already were described	During the 48hrs study period
Secondary	Number of patients completing the study without meeting the stopping criteria	After each time point (T0, T1, T5 and T12) we screen if the patient meets one of the stopping criteria, defined as: potential of hydrogen (pH) < 7.20; heart rate > 100 beats per minute or an increase of > 20% from baseline for more than 20 minutes; increase in mean arterial blood pressure of > 20% for more than 20 minutes	At four time points during the first 24hrs of the study period
Secondary	Effect on partial carbon dioxide (pCO2)	At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on pCO2 (in kPa), in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups	During the 48hrs study period
Secondary	Effect on pH	At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on pH, in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the 48hrs study period
Secondary	Effect on heart rate	During the study period we will collect at six time points (T0, T1, T5, T12, T24 and T48) the heart rate (in beats per minute), in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the 48hrs study period
Secondary	Effect on blood pressure	During the study period we will collect at six time points (T0, T1, T5, T12, T24 and T48) the blood pressure (millimetre(s) of mercury (mmHg)), in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the 48hrs study period
Secondary	Effect on respiratory rate	During the study period we will collect at six time points (T0, T1, T5, T12, T24 and T48) the respiratory rate (in breaths per minute) in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the 48hrs study period
Secondary	Effect on peripheral capillary oxygen saturation (SpO2)	During the study period we will collect at six time points (T0, T1, T5, T12, T24 and T48) the SpO2 (%) in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the 48hrs study period
Secondary	Effect on partial oxygen pressure (pO2)	At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on pO2 (in kPa), in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the 48hrs study period
Secondary	Effect on work of breathing (WOB)	During the study period we will collect at five time points (T0, T1, T5, T12 and T24) the WOB (in Joule) in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the first 24hrs of the study period
Secondary	Effect on pressure time product (PTP)	During the study period we will collect at five time points (T0, T1, T5, T12 and T24) the PTP (in cmH2O per second) in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the first 24hrs of the study period
Secondary	Effect on tumor necrosis factor (TNF)-alfa	At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on TNF-alfa concentration (in pg/ml), in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the first 24hrs of the study period
Secondary	Effect on interleukin(IL)-6 and IL-8	At three time points (T0, T24, T48) during the study period we will collect a blood sample from the arterial catheter, to measure the effect of prolonged NMB administration on IL-6 and IL-8 concentration (in pg/ml), in order to: determine if there were differences between the start and end of the study period; investigate if there were differences between both study groups.	During the first 24hrs of the study period
Secondary	Amount of days on mechanical ventilation	After 30 days we will investigate if there were differences between both groups in the duration of mechanical ventilation.	Until 30 days after the end of the study period