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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Titration with rocuronium bromide until tidal volume 6ml/kg PBW
VUmc
Amsterdam, Netherlands
RECRUITINGThe 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.
Time frame: At five time points of 1hr during the first 24hrs of the study period
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
Time frame: During the 48hrs study period
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
Time frame: At four time points during the first 24hrs of the study period
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
Time frame: During the 48hrs study period
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.
Time frame: During the 48hrs study period
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.
Time frame: During the 48hrs study period
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.
Time frame: During the 48hrs study period
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.
Time frame: During the 48hrs study period
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.
Time frame: During the 48hrs study period
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.
Time frame: During the 48hrs study period
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.
Time frame: During the first 24hrs of the study period
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.
Time frame: During the first 24hrs of the study period
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.
Time frame: During the first 24hrs of the study period
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.
Time frame: During the first 24hrs of the study period
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.
Time frame: Until 30 days after the end of the study period
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