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Trial registered on ANZCTR


Registration number
ACTRN12617000759392
Ethics application status
Approved
Date submitted
22/04/2017
Date registered
23/05/2017
Date last updated
23/05/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Diaphragmatic dysfunction in brain injured patients.
Scientific title
Diaphragmatic dysfunction in brain injured patients: a pilot study.
Secondary ID [1] 291737 0
None
Universal Trial Number (UTN)
None
Trial acronym
None
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Brain injured patients 302934 0
Neurological 303102 0
Respiratory 303103 0
Condition category
Condition code
Anaesthesiology 302411 302411 0 0
Other anaesthesiology
Neurological 302563 302563 0 0
Other neurological disorders
Respiratory 302564 302564 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
For one year, we will study diaphragmatic dysfunction measured by ultrasound (excursion and thikening) in all brain injured patients entering the intensive care unit of the "Maggiore della Carita" hospital in Novara. In all included newly intubated brain injured patients the ultrasonographic measurements of diaphragm will be performed within 24 hours after the start of mechanical ventilation in volume controlled mode, 48 hours after intubation, 7 days after intubation, during the spontaneous breathing trial (SBT) and after extubation/tracheostomy during spontaneus breathing. Briefly, ultrasound evaluation of the diaphragm will be performed with the patients in the supine position. Diaphragmatic movement will be measured with a 3.5 MHz US probe placed over one of the lower intercostals spaces in the right anterior axillary line for the right diaphragm and the left midaxillary line for the left diaphragm using an ultrasound machine. The liver or spleen will be used as a window for each hemidiaphragm. A two- dimensional mode will be used to find the best approach and to select the exploration line of each hemidiaphragm. With the probe fixed on the chest wall during respiration, the ultrasound beam will be directed to the hemidiaphragmatic domes at an angle of not inferior to 70 degree. During inspiration, the normal diaphragm contracts and moves caudally toward the transducer; this is recorded as an upward motion
of the M-mode tracing. The amplitude of excursion is measured on the vertical axis of the tracing from the baseline to the point of maximum height of inspiration on the graph. Four measurements will be recorded and averaged for each side. All measurements will be performed during tidal breathing at 6–12 mL per kg, excluding smaller or deeper breaths. Ultrasonographic diaphragmatic disfunction will be diagnosed if an excursion will be less than 10 mm or negative, the latter indicating paradoxic diaphragmatic movement. Diaphragm thickness (tdi) will be measured using a 7–10 MHz linear ultrasound probe set to B mode. The right hemidiaphragm will be imaged at the zone of apposition of the diaphragm and rib cage in the midaxillary line between the 8th and 10th intercostal spaces. The tdi will be measured at end-expiration and end-inspiration. The per cent change in tdi between end-expiration and end-inspiration will be calculated as (tdi end-inspiration-tdi end-expiration/tdi end-expiration)×100. The per cent change in tdi for each patient represented the mean of four breaths.
Intervention code [1] 297844 0
Not applicable
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 301820 0
We aim to investigate the course of diaphragmatic dysfunction measured by ultrasound in brain injured patients
Timepoint [1] 301820 0
Diaphragmatic dysfunction will be assessed at time zero i.e., within 24 hours after the start of mechanical ventilation in volume controlled mode, 48 hours after intubation, 7 days after the beginning of mechanical ventilation, during the spontaneous breathing trial (SBT) and 48 hours after extubation/tracheostomy during spontaneus breathing.
Secondary outcome [1] 333960 0
We aim to investigate whether diaphragmatic dysfunction measured by ultrasound represents a major determinant of respiratory failure in brain injured patients. Respiratory failure is defined as reintubation at 48 hours after extubation or connection to the ventilator through the tracheotomy 48 hours after the first disconnection.
Timepoint [1] 333960 0
Reintubation at 48 hours after extubation or connection to the ventilator through the tracheotomy 48 hours after the first disconnection.

Eligibility
Key inclusion criteria
Patients with the following inclusion criteria will be considered eligible: 1) age between 18 and 80, 2) mechanical ventilation for less than 24 hours, 3) ICU admission for intraparenchimal hemorrhage, subacnoid hemorrhage, or traumatic brain injury, 4) expected requirement of more than 48 hours of mechanical ventilation.
Minimum age
18 Years
Maximum age
80 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria will be: 1) known diaphragmatic dysfunction, and 2) preexisting decision to limit life support, 3)cervical spine injury, 4) neuromuscular
disease (myasthenia gravis, Guillain-Barre´ syndrome, amyotrophic lateral sclerosis); 5) current thoracostomy, pneumothorax, or pneumomediastinum.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Statistical analyses were performed with STATA. Results will be reported as mean+/-standard deviation (SD) or median (interquartile range (IQR). The relationships between patient characteristics (including the risk factors) and diaphragm thickness changes were assessed using the Mann-Whitney U test and linear regression models. Changes in baseline and nadir diaphragm thickness were analysed using the Wilcoxon signed-rank test. All analysed risk factors for atrophy were entered in a multivariate regression model. The level of statistical significance was set at 0.05.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 8837 0
Italy
State/province [1] 8837 0
Novara

Funding & Sponsors
Funding source category [1] 296233 0
University
Name [1] 296233 0
Universita del Piemonte Orientale Amedeo Avogadro
Address [1] 296233 0
Via Solaroli 17
28100 Novara
Italy
Country [1] 296233 0
Italy
Primary sponsor type
University
Name
Universita del Piemonte Orientale Amedeo Avogadro
Address
Via Solaroli 17
28100 Novara
Italy
Country
Italy
Secondary sponsor category [1] 295150 0
Hospital
Name [1] 295150 0
Ospedale Maggiore della Carita
Address [1] 295150 0
Corso Mazzini 18
28100 Novara
Italy
Country [1] 295150 0
Italy

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297472 0
Comitato etico Interaziendale Novara
Ethics committee address [1] 297472 0
Corso Mazzini 18
28100
Novara
Ethics committee country [1] 297472 0
Italy
Date submitted for ethics approval [1] 297472 0
02/02/2017
Approval date [1] 297472 0
13/03/2017
Ethics approval number [1] 297472 0
Protocollo 217/CE Studio n. CE 36/17

Summary
Brief summary
BACKGROUND:
Extubation failure in brain injured patients is high compared with the expected rates in general ICU patients, and ranges from 15-20%. The rate of reconnection to the ventilator in tracheostomized brain injured patients seems to be even higher. Independent associations between extubation failure and increased mortality have been noted previously, though largely in the medical ICU. Respiratory failure represents the primary reason for reintubation and resumption of mechanical ventilation in both intubated and tracheostomized patients.
AIM:
We aim to investigate the course of diaphragmatic dysfunction measured by ultrasound in brain injured patients and whether diaphragmatic dysfunction represents the major determinant of ventilatory failure.
METHODS:
Patients with the following inclusion criteria will be considered eligible: 1) age between 18 and 80, 2) mechanical ventilation for less than 24 hours, 3) ICU admission for intraparenchimal hemorrhage, subacnoid hemorrhage, or traumatic brain injury, 4) requirement of more than 48 hours of mechanical ventilation. Exclusion criteria will be: 1) known diaphragmatic dysfunction, and 2) preexisting decision to limit life support, 3)cervical spine injury, 4) neuromuscular
disease (myasthenia gravis, Guillain-Barre´ syndrome, amyotrophic lateral sclerosis); 5) current thoracostomy, pneumothorax, or pneumomediastinum.
In all included newly intubated brain injured patients the ultrasonographic measurement of diaphragm will be performed within 24 hours after the start of mechanical ventilation, 48 hours after intubation, 7 days after intubation, during the spontaneous breathing trial (SBT) and after extubation.
MEASUREMENTS: Demographic variables, including the Simplified Acute Physiology Score II (SAPS II) will be recorded. Furthermore will be recorded all the parameters associated with a decrease in diaphragm thickness: age, sex, SAPS II, duration of MV, percentage of time in controlled MV modes, use of corticosteroids during ICU stay, sepsis, continued use of neuromuscular blocking agents and aminoglycosides antibiotic use. All patients will be sedated in accordance with our sedation protocol. During SBT, rapid shallow breathing index, Ultrasound evaluation of the diaphragm thikening and excursion will be performed at ICU entrance, 48 hours after intubation, 7 days after intubation, during the spontaneous breathing trial and 48 hours after extubation.
Before commencing the study, after one month training, both intra- and inter-observer variability of diaphragm ultrasound recordings in both ventilated patients and non-ventilated volunteers on different time points will be performed and the coefficients of reproducibility for intra-observer variability will be calculated.
Trial website
NONE
Trial related presentations / publications
None
Public notes
None

Contacts
Principal investigator
Name 74154 0
Dr Rosanna Vaschetto
Address 74154 0
Ospedale Maggiore della Carita
Anestesia e Rianimazione
Corso Mazzini 18
28100 Novara
Italy
Country 74154 0
Italy
Phone 74154 0
+393213733380
Fax 74154 0
+393213733393
Email 74154 0
rosanna.vaschetto@med.uniupo.it
Contact person for public queries
Name 74155 0
Dr Rosanna Vaschetto
Address 74155 0
Ospedale Maggiore della Carita
Anestesia e Rianimazione
Corso Mazzini 18
28100
Novara
Country 74155 0
Italy
Phone 74155 0
+393213733380
Fax 74155 0
+393213733973
Email 74155 0
rosanna.vaschetto@med.uniupo.it
Contact person for scientific queries
Name 74156 0
Dr Rosanna Vaschetto
Address 74156 0
Ospedale Maggiore della Carita
Anestesia e Rianimazione
Corso Mazzini 18
28100 Novara
Italy
Country 74156 0
Italy
Phone 74156 0
+39321373380
Fax 74156 0
+393213733973
Email 74156 0
rosanna.vaschetto@med.uniupo.it

No data has been provided for results reporting
Summary results
Not applicable