Trial Outcomes & Findings for Aerosolized Endotracheal Lidocaine to Avoid Intracranial Pressure Spikes in Patients With Severe Traumatic Brain Injury (NCT NCT05058677)
NCT ID: NCT05058677
Last Updated: 2026-08-07
Results Overview
A Codman Intraparenchymal Catheter will measure the ICP. The ICP will be transduced and measured numerically and continuously in real time on the patient's bedside monitor. ICP Values were recorded at baseline and at 2, 5, and 15 minutes after administration of aerosolized lidocaine, instilled saline solution, or instilled lidocaine solution. Change from baseline is calculated at post intervention time point.
COMPLETED
PHASE4
10 participants
Baseline and 2, 5, and 15 minutes post-intervention
2026-08-07
Participant Flow
Participant milestones
| Measure |
Aerosolized Lidocaine Then Instilled Lidocaine Solution Then Instilled Saline Solution
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Aerosolized Lidocaine Then Instilled Saline Solution Then Instilled Lidocaine Solution
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Lidocaine Solution Then Aerosolized Lidocaine Then Instilled Saline Solution
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Lidocaine Solution Then Instilled Saline Solution Then Aerosolized Lidocaine
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Saline Solution Then Aerosolized Lidocaine Then Instilled Lidocaine Solution
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Saline Solution Then Instilled Lidocaine Solution Then Aerosolized Lidocaine
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
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|---|---|---|---|---|---|---|
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Overall Study
STARTED
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0
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0
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0
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0
|
0
|
10
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
10
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Aerosolized Lidocaine Then Instilled Lidocaine Solution Then Instilled Saline Solution
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Aerosolized Lidocaine Then Instilled Saline Solution Then Instilled Lidocaine Solution
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Lidocaine Solution Then Aerosolized Lidocaine Then Instilled Saline Solution
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Lidocaine Solution Then Instilled Saline Solution Then Aerosolized Lidocaine
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Saline Solution Then Aerosolized Lidocaine Then Instilled Lidocaine Solution
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Saline Solution Then Instilled Lidocaine Solution Then Aerosolized Lidocaine
n=10 Participants
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe.
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The instilled solution will be given with a standard 3-5 ml syringe.
After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Customized
< 1 year
|
—
|
—
|
—
|
—
|
—
|
1 Participants
n=10 Participants
|
1 Participants
n=10 Participants
|
|
Age, Customized
≥ 1 year to < 5 years
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=10 Participants
|
0 Participants
n=10 Participants
|
|
Age, Customized
≥5 years to < 10 years
|
—
|
—
|
—
|
—
|
—
|
1 Participants
n=10 Participants
|
1 Participants
n=10 Participants
|
|
Age, Customized
≥10 years to < 18 years
|
—
|
—
|
—
|
—
|
—
|
8 Participants
n=10 Participants
|
8 Participants
n=10 Participants
|
|
Sex: Female, Male
Female
|
—
|
—
|
—
|
—
|
—
|
5 Participants
n=10 Participants
|
5 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
—
|
—
|
—
|
—
|
—
|
5 Participants
n=10 Participants
|
5 Participants
n=10 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
—
|
—
|
—
|
—
|
—
|
10 participants
n=10 Participants
|
10 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Baseline and 2, 5, and 15 minutes post-interventionA Codman Intraparenchymal Catheter will measure the ICP. The ICP will be transduced and measured numerically and continuously in real time on the patient's bedside monitor. ICP Values were recorded at baseline and at 2, 5, and 15 minutes after administration of aerosolized lidocaine, instilled saline solution, or instilled lidocaine solution. Change from baseline is calculated at post intervention time point.
Outcome measures
| Measure |
Aerosolized Lidocaine
n=10 Participants
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Saline Solution
n=10 Participants
Treatment will be performed before the endotracheal suctioning
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe. After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Lidocaine Solution
n=10 Participants
Treatment will be performed before the endotracheal suctioning
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The instilled solution will be given with a standard 3-5 ml syringe. After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
|---|---|---|---|
|
Change From Baseline Intracranial Pressure (ICP) at 2, 5 and 15 Minutes.
2 minutes
|
1.1 mmHg
Standard Deviation 2.8
|
1.6 mmHg
Standard Deviation 2.6
|
1.9 mmHg
Standard Deviation 2.9
|
|
Change From Baseline Intracranial Pressure (ICP) at 2, 5 and 15 Minutes.
5 minutes
|
0.1 mmHg
Standard Deviation 1.8
|
1.4 mmHg
Standard Deviation 1.8
|
1.2 mmHg
Standard Deviation 2.6
|
|
Change From Baseline Intracranial Pressure (ICP) at 2, 5 and 15 Minutes.
15 minutes
|
-0.5 mmHg
Standard Deviation 2.8
|
1.5 mmHg
Standard Deviation 1.6
|
1.7 mmHg
Standard Deviation 4.1
|
SECONDARY outcome
Timeframe: from baseline to up to 15 minutes after ETSThis will be measured by increasing oxygenation index or worsening compliance, measured by any increase in the peak pressure for volume ventilated patients.
Outcome measures
| Measure |
Aerosolized Lidocaine
n=10 Participants
Treatment will be performed before the endotracheal suctioning
aerosolized 2% lidocaine (20mg/ml): The aerosolized solution to be used is 2% lidocaine (20 mg/ml) at a dose of 1.5 mg/kg with a maximum volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution.The aerosolized solution will be administered with an Aerogen ultrasonic nebulizer, which is standard of care for administering aerosolized solutions in our pediatric intensive care unit (PICU).After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Saline Solution
n=10 Participants
Treatment will be performed before the endotracheal suctioning
instilled 0.9% sodium chloride (NS): The instilled solution will be given with a standard 3-5 ml syringe. After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
Instilled Lidocaine Solution
n=10 Participants
Treatment will be performed before the endotracheal suctioning
instilled 2% lidocaine solution: The instilled 2 % lidocaine solution used will be 1.5 mg/kg, with a max volume of 3 ml or adjusted to a volume of 3 ml with addition of NS solution. The instilled solution will be given with a standard 3-5 ml syringe. After each treatment a 3-minute interval will be allowed prior to ETS and there will be a 4-6 hour wash out period between each treatment.
Endotracheal Suctioning (ETS): ETS will be performed in a single pass using a closed-system suctioning. Suction will be applied only on withdrawal of the catheter and fraction of inspired oxygen (FIO2) will remain at 100% for 60 seconds following suctioning and then returned to the preprocedural level (baseline).
|
|---|---|---|---|
|
Number of Patients With Worsening Respiratory Dynamics
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Aerosolized Lidocaine
Instilled Saline Solution
Instilled Lidocaine Solution
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Thao L Nguyen, DO, FAAP
The University of Texas Health Science Center at Houston
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place