Ignite Creation Date:
2024-07-17 @ 11:39 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06502002
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2023-08-31
Brief Title:
Dexmedetomidine Infusion and Postoperative Lung Aeration After Thoracic Surgery
Sponsor:
Brigham and Womens Hospital
Organization:
Brigham and Womens Hospital
Study Overview
Official Title:
Dexmedetomidine Infusion and Postoperative Lung Aeration After Thoracic Surgery A Randomized Placebo-Controlled Pilot Trial
Status:
RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This will be a randomized placebo-controlled double-blinded pilot trial with two parallel groups 11 ratio receiving either dexmedetomidine initial bolus of 1 mcgkg over 30 min after induction followed by an infusion rate of 03 mcgkghr that will be stopped 30-45 minutes before the end of the surgery or upon reaching maximum dose of 2mcgkg whichever comes first or placebo normal saline as a bolus followed by maintenance infusion at the same rate of the intervention group
Dexmedetomidine is frequently administered in thoracic surgery Using local data from the Brigham and Womens Hospital dexmedetomidine was used in a third of the thoracic procedures performed over the past three years However there is no consensus as to the optimal protocol of administration therefore clinical practice is highly heterogeneous bolus versus continuous infusion and mostly depends on the preferences of anesthesia providers In our institution the dose of dexmedetomidine is typically 05 mcgkg but varies based on attending preferences and experience Given the heterogenous practices in dexmedetomidine administration one of the objectives is to assess the feasibility of adhering to a dexmedetomidine protocol using an initial loading dose of 1 mcgkg over 30 minutes after induction followed by a continuous infusion of 03 mcgkghr The infusion will stop 30-45 minutes prior to the end of surgery or once a maximum dose of 2mcgkg has been achieved whichever comes first The control group will receive normal saline similar bolus followed by maintenance infusion at the same rate of the intervention group
Dexmedetomidine is frequently administered in thoracic surgery Using local data from the Brigham and Womens Hospital dexmedetomidine was used in a third of the thoracic procedures performed over the past three years However there is no consensus as to the optimal protocol of administration therefore clinical practice is highly heterogeneous bolus versus continuous infusion and mostly depends on the preferences of anesthesia providers In our institution the dose of dexmedetomidine is typically 05 mcgkg but varies based on attending preferences and experience Given the heterogenous practices in dexmedetomidine administration one of the objectives is to assess the feasibility of adhering to a dexmedetomidine protocol using an initial loading dose of 1 mcgkg over 30 minutes after induction followed by a continuous infusion of 03 mcgkghr The infusion will stop 30-45 minutes prior to the end of surgery or once a maximum dose of 2mcgkg has been achieved whichever comes first The control group will receive normal saline similar bolus followed by maintenance infusion at the same rate of the intervention group
Detailed Description:
Dexmedetomidine is an opioid-sparing anesthetic with minimal effect on adaptive physiologic processes such as respiratory drive and hypoxic pulmonary vasoconstriction HPV Recent translational research has demonstrated that dexmedetomidine is associated with less alveolar inflammation and better respiratory mechanics in thoracic surgery under one-lung ventilation OLV However it is unclear whether such results translate into better postoperative lung aeration and superior pulmonary outcomes Several biological mechanisms have been postulated to explain the lung protective effects of dexmedetomidine Based on experimental models under OLV dexmedetomidine has been shown to minimize mechanical ventilation-induced lung injury through the inhibition of inflammatory pathways thus enhancing pulmonary function recovery improving respiratory mechanics and potentially preventing postoperative pulmonary complications PPCs There is also clinical evidence to suggest dexmedetomidine may improve respiratory mechanics as well as prevents non-cardiopulmonary complications such as acute kidney injury AKI in adult cardiac surgical patients as well as delirium in both cardiac and non-cardiac patients
The research group from the BWH anesthesia department recently conducted a meta-analysis about the current evidence on dexmedetomidine in thoracic surgery demonstrating beneficial effects in atelectasis and hypoxemia with low to moderate certainty Unfortunately current trials on this topic have limited sample size and do not provide accurate and standardized outcome measurements Dexmedetomidine has been shown to have organ protection properties but there is no conclusive evidence to support its use for pulmonary protection in thoracic surgery This trial would be the first to demonstrate an effect of dexmedetomidine on the trajectory of postoperative lung aeration and diaphragmatic excursion measured by ultrasound Furthermore the feasibility of a large randomized controlled trial on dexmedetomidine for the prevention of pulmonary complications in thoracic surgery will be assessed It is important to note that all the trials conducted on this topic have been conducted in Asia limiting its generalizability are relatively small sample size of 30-50 patients and have studied mainly respiratory mechanics
Postoperative pulmonary complications are relatively common among patients undergoing thoracic surgery The development of PPCs raises hospital costs 5000-10000 USD prolong length of hospital stay 2-3 days and affects quality of recovery Similarly lung aeration loss is considered a subclinical characteristic of lung injury induced by OLV which can persist for several days after thoracic surgery Several protective ventilatory strategies have been proposed to prevent PPCs such as low tidal volume TV ie TV 6mLkg and alveolar recruitment yet the literature shows conflicting results and the incidence of pulmonary complications continues to occur Therefore it is imperative to study and implement novel pharmacologic lung protective interventions in thoracic surgery for the prevention of lung aeration loss and subsequent pulmonary complications
In this study protocol dexmedetomidine is postulated as an adjunct with possible pulmonary clinical benefits Previous evidence suggests a possible effect on atelectasis hypoxemia and pneumonia but the certainty of the evidence is low to moderate Undertaking a pilot trial on dexmedetomidine and lung aeration in thoracic surgery would be useful to assess the feasibility for a large randomized trial
2 Specific Aims and Objectives
Objective 1 To determine the feasibility of a trial assessing the effect of dexmedetomidine administration on postoperative lung aeration after thoracic surgery
Objective 2 To compare the effect of dexmedetomidine administration protocol versus placebo on postoperative lung aeration and diaphragmatic excursion measured by lung ultrasound
Objective 3 To evaluate the adherence to a protocol of dexmedetomidine administration during thoracic surgery under one-lung ventilation
3 General Description of Study Design
This will be a randomized placebo-controlled double-blinded pilot trial with two parallel groups 11 ratio receiving either dexmedetomidine initial bolus of 1 mcgkg over 30 min after induction followed by an infusion rate of 03 mcgkghr that will be stopped 30-45 minutes before the end of the surgery or once a maximum dose of 2mcgkg has been achieved whichever comes first or placebo normal saline as a bolus followed by maintenance infusion at the same rate of the intervention group
Dexmedetomidine is frequently administered in thoracic surgery Using local data from the Brigham and Womens Hospital dexmedetomidine was used in a third of the thoracic procedures performed over the past three years However there is no consensus as to the optimal protocol of administration therefore clinical practice is highly heterogeneous bolus versus continuous infusion and mostly depends on the preferences of anesthesia providers At the Brigham and Womens Hospital the dose of dexmedetomidine is typically 05 mcgkg but varies based on attending preferences and experience Given the heterogenous practices in dexmedetomidine administration one of the objectives is to assess the feasibility of adhering to a dexmedetomidine protocol using an initial loading dose of 1 mcgkg over 30 minutes after induction followed by a continuous infusion of 03 mcgkghr The infusion will be stopped 30-45 minutes prior to the end of surgery or once a maximum dose of 2mcgkg has been achieved whichever comes first The control group will receive normal saline similar bolus followed by maintenance infusion at the same rate of the intervention group
4 Subject Selection
Inclusion criteria
Adult patients Age 18 years until 80 years undergoing lobectomy andor segmentectomy
Exclusion Criteria
Urgent or emergency thoracic surgery
Other concomitant non-pulmonary procedures pleurectomy diaphragmatic procedures pericardiocentesis esophageal procedures thymectomy
Prior lung resection surgery
Epidural block for intraoperative or postoperative analgesia
Preoperative arrhythmia first or second degree AV block without pacemaker or significant bradycardia heart rate 50
Preoperative hypotension mean arterial blood pressure 65 mmHg
Severe functional liver or kidney disease
Non-English speakers
Consent withdrawal
Identification of individuals will be completed every day through Epic The list of thoracic surgeries will be reviewed each day by one of the co-investigators Individuals will be contacted via phone 24-48 hours prior to the surgery for pre-screening questions and to determine their interest in participating in the study Individuals will be consented on the day of surgery at the preoperative area by one of the co-investigators
Women and minorities will be represented in this study and will reflect the thoracic surgery population at Brigham and Womens Hospital BWH undergoing the eligible procedures Based on prior studies conducted on this patient population we estimate that the sample population will be 57 women approximately 6 African American 5 Asian and 11 Latino Patients over 65 years old comprise 52 and low-income population is 4 The investigators will make every effort to ensure proportional representation by sexgender race and ethnicity subjects are a sample of thoracic surgical patients so the investigators do not expect significant deviations from these estimates
5 Subject Enrollment
Allocation of individuals to the groups will be performed using a predetermined randomized sequence which will be generated using the asymptotic maximal procedure httpsctrandomizationcancergovabout Eligible patients will be contacted via phone call within 24-48 hours prior to surgery for pre-screening questions and assess possible participation in the study On the day of surgery the participant will be approached by one of the investigators who will explain further details of the trial and provide an electronic informed consent e-Consent on a tablet
6 STUDY PROCEDURES
Pharmacy will be contacted the day before to start processing the study drug based on the randomization list A research collaborator will collect intraoperative information prospectively including time to start study drug time of lung isolation time of two lung ventilation respiratory mechanics and compliance with administration protocol In the postoperative period patients will be followed up for 2 days In the PACU an investigator will scan anterior lateral and posterior quadrants of both lungs estimate the lung ultrasound score see Appendix and save the images A second independent investigator will estimate the scores independently Serial assessments will be performed preoperatively in the preoperative area immediately after surgery in the recovery area and at postoperative days 1 and 2 The assessment of complications will end at post-operative day 30 Safety outcomes and pulmonary complications will be collected by another blinded investigator
Primary outcome
Lung aeration score measured by ultrasound at the post-anesthesia care unit PACU as described by Monastesse et al Serial assessments will be performed at postoperative days 1 and 2 POD1 and POD2 time frame of measurements 2 days
Secondary outcomes
Diaphragmatic dysfunction defined as a diaphragmatic excursion 1cm
Intraoperative hypoxemia SpO2 90
Postoperative atelectasis radiographic evidence of lung collapse descriptive parameter
Pneumonia
- radiologic evidence of consolidation descriptive parameter
- fever temperature T385C
white cell count WBC 10GL
Acute respiratory distress syndrome ARDS - PaO2FiO2 200
- acute onset
bilateral lung infiltrates on chest radiograph
absence of heart failure
Pulmonary edema clinical description from chest radiograph
Reintubation - Timeframe for assessment of complications 30 days
7 Risks and Discomforts
Protection Of Human Subjects
- Human Subject Involvement and Characteristics There is a risk of breach of confidentiality with individually identifiable health information The database will have de-identified data using an assigned ID on all study related documents Once the patient consents to the protocol he or she will be assigned a unique patient identifier number As a result the study database will hold strictly de-identified data using an arbitrary participant ID paper forms will be stored in a secure location and referenced only for scheduling contacts and a bridging table associating the two entities will be stored in yet another secure location
Upon initiating the study all data will be collected and processed using rigorous quality-control methods As the data forms are completed they will be entered by the research staff into the secure access de-identified database All paper forms will be stored in a locked cabinet in a locked room in a secure building Neither the name of the patient nor any other personally identifying information will be used in any reports or publications that result from this study
Potential Risks
The study will not alter the surgeons or patients plan for surgery A participant may be at risk if they have an adverse reaction to the medication dexmedetomidine Dexmedetomidine has been reported to have the following clinical side effects
Bradycardia
Hypotension
Somnolence
8 Benefits Increasing understanding of the possible lung protective mechanisms of dexmedetomidine
Patients in the dexmedetomidine group may also benefit from better pain control given the long-acting analgesic effects of dexmedetomidine
9 Statistical Analysis
An exploratory analysis of baseline demographic and clinical characteristics will be performed Compliance with the protocol of dexmedetomidine andor placebo will be calculated as a percentage of complete adherence to the administration of either solution as stated above Feasibility will be defined as a compliance greater than 80 Both groups will be compared in terms of lung ultrasound score in each side operative vs non-operative of the thorax at PACU and postoperative days 1 and 2 Similarly secondary outcomes diaphragmatic dysfunction pulmonary complications will be compared between both groups Our analysis will be adjusted for multiple testing hypothesis The estimated sample size is 100 patients 50 patients in each group assuming a mean LUS of 14 vs 11 between the control and intervention groups respectively with a standard deviation of 5 a missing follow-up of 10 an alpha error of 005 and 80 power All statistical analyses will be performed in Stata v140 College Station TX USA
Analysis
Continuous variables will be reported as means standard deviation SD or median with their corresponding interquartile ranges based on the distribution of the data which will be determine using Kolmogorov test Dichotomous variables will be reported as numbers percentages Between-group comparisons of continuous variables will be performed using the independent Student t test P values 005 will be considered statistically significant Descriptive statistics will be used to report patient demographics and baseline characteristics
Proportion of participants with postoperative pulmonary complications during admission will be reported units percentage This will be extracted from the patients electronic medical health records by a co-investigator
The research group from the BWH anesthesia department recently conducted a meta-analysis about the current evidence on dexmedetomidine in thoracic surgery demonstrating beneficial effects in atelectasis and hypoxemia with low to moderate certainty Unfortunately current trials on this topic have limited sample size and do not provide accurate and standardized outcome measurements Dexmedetomidine has been shown to have organ protection properties but there is no conclusive evidence to support its use for pulmonary protection in thoracic surgery This trial would be the first to demonstrate an effect of dexmedetomidine on the trajectory of postoperative lung aeration and diaphragmatic excursion measured by ultrasound Furthermore the feasibility of a large randomized controlled trial on dexmedetomidine for the prevention of pulmonary complications in thoracic surgery will be assessed It is important to note that all the trials conducted on this topic have been conducted in Asia limiting its generalizability are relatively small sample size of 30-50 patients and have studied mainly respiratory mechanics
Postoperative pulmonary complications are relatively common among patients undergoing thoracic surgery The development of PPCs raises hospital costs 5000-10000 USD prolong length of hospital stay 2-3 days and affects quality of recovery Similarly lung aeration loss is considered a subclinical characteristic of lung injury induced by OLV which can persist for several days after thoracic surgery Several protective ventilatory strategies have been proposed to prevent PPCs such as low tidal volume TV ie TV 6mLkg and alveolar recruitment yet the literature shows conflicting results and the incidence of pulmonary complications continues to occur Therefore it is imperative to study and implement novel pharmacologic lung protective interventions in thoracic surgery for the prevention of lung aeration loss and subsequent pulmonary complications
In this study protocol dexmedetomidine is postulated as an adjunct with possible pulmonary clinical benefits Previous evidence suggests a possible effect on atelectasis hypoxemia and pneumonia but the certainty of the evidence is low to moderate Undertaking a pilot trial on dexmedetomidine and lung aeration in thoracic surgery would be useful to assess the feasibility for a large randomized trial
2 Specific Aims and Objectives
Objective 1 To determine the feasibility of a trial assessing the effect of dexmedetomidine administration on postoperative lung aeration after thoracic surgery
Objective 2 To compare the effect of dexmedetomidine administration protocol versus placebo on postoperative lung aeration and diaphragmatic excursion measured by lung ultrasound
Objective 3 To evaluate the adherence to a protocol of dexmedetomidine administration during thoracic surgery under one-lung ventilation
3 General Description of Study Design
This will be a randomized placebo-controlled double-blinded pilot trial with two parallel groups 11 ratio receiving either dexmedetomidine initial bolus of 1 mcgkg over 30 min after induction followed by an infusion rate of 03 mcgkghr that will be stopped 30-45 minutes before the end of the surgery or once a maximum dose of 2mcgkg has been achieved whichever comes first or placebo normal saline as a bolus followed by maintenance infusion at the same rate of the intervention group
Dexmedetomidine is frequently administered in thoracic surgery Using local data from the Brigham and Womens Hospital dexmedetomidine was used in a third of the thoracic procedures performed over the past three years However there is no consensus as to the optimal protocol of administration therefore clinical practice is highly heterogeneous bolus versus continuous infusion and mostly depends on the preferences of anesthesia providers At the Brigham and Womens Hospital the dose of dexmedetomidine is typically 05 mcgkg but varies based on attending preferences and experience Given the heterogenous practices in dexmedetomidine administration one of the objectives is to assess the feasibility of adhering to a dexmedetomidine protocol using an initial loading dose of 1 mcgkg over 30 minutes after induction followed by a continuous infusion of 03 mcgkghr The infusion will be stopped 30-45 minutes prior to the end of surgery or once a maximum dose of 2mcgkg has been achieved whichever comes first The control group will receive normal saline similar bolus followed by maintenance infusion at the same rate of the intervention group
4 Subject Selection
Inclusion criteria
Adult patients Age 18 years until 80 years undergoing lobectomy andor segmentectomy
Exclusion Criteria
Urgent or emergency thoracic surgery
Other concomitant non-pulmonary procedures pleurectomy diaphragmatic procedures pericardiocentesis esophageal procedures thymectomy
Prior lung resection surgery
Epidural block for intraoperative or postoperative analgesia
Preoperative arrhythmia first or second degree AV block without pacemaker or significant bradycardia heart rate 50
Preoperative hypotension mean arterial blood pressure 65 mmHg
Severe functional liver or kidney disease
Non-English speakers
Consent withdrawal
Identification of individuals will be completed every day through Epic The list of thoracic surgeries will be reviewed each day by one of the co-investigators Individuals will be contacted via phone 24-48 hours prior to the surgery for pre-screening questions and to determine their interest in participating in the study Individuals will be consented on the day of surgery at the preoperative area by one of the co-investigators
Women and minorities will be represented in this study and will reflect the thoracic surgery population at Brigham and Womens Hospital BWH undergoing the eligible procedures Based on prior studies conducted on this patient population we estimate that the sample population will be 57 women approximately 6 African American 5 Asian and 11 Latino Patients over 65 years old comprise 52 and low-income population is 4 The investigators will make every effort to ensure proportional representation by sexgender race and ethnicity subjects are a sample of thoracic surgical patients so the investigators do not expect significant deviations from these estimates
5 Subject Enrollment
Allocation of individuals to the groups will be performed using a predetermined randomized sequence which will be generated using the asymptotic maximal procedure httpsctrandomizationcancergovabout Eligible patients will be contacted via phone call within 24-48 hours prior to surgery for pre-screening questions and assess possible participation in the study On the day of surgery the participant will be approached by one of the investigators who will explain further details of the trial and provide an electronic informed consent e-Consent on a tablet
6 STUDY PROCEDURES
Pharmacy will be contacted the day before to start processing the study drug based on the randomization list A research collaborator will collect intraoperative information prospectively including time to start study drug time of lung isolation time of two lung ventilation respiratory mechanics and compliance with administration protocol In the postoperative period patients will be followed up for 2 days In the PACU an investigator will scan anterior lateral and posterior quadrants of both lungs estimate the lung ultrasound score see Appendix and save the images A second independent investigator will estimate the scores independently Serial assessments will be performed preoperatively in the preoperative area immediately after surgery in the recovery area and at postoperative days 1 and 2 The assessment of complications will end at post-operative day 30 Safety outcomes and pulmonary complications will be collected by another blinded investigator
Primary outcome
Lung aeration score measured by ultrasound at the post-anesthesia care unit PACU as described by Monastesse et al Serial assessments will be performed at postoperative days 1 and 2 POD1 and POD2 time frame of measurements 2 days
Secondary outcomes
Diaphragmatic dysfunction defined as a diaphragmatic excursion 1cm
Intraoperative hypoxemia SpO2 90
Postoperative atelectasis radiographic evidence of lung collapse descriptive parameter
Pneumonia
- radiologic evidence of consolidation descriptive parameter
- fever temperature T385C
white cell count WBC 10GL
Acute respiratory distress syndrome ARDS - PaO2FiO2 200
- acute onset
bilateral lung infiltrates on chest radiograph
absence of heart failure
Pulmonary edema clinical description from chest radiograph
Reintubation - Timeframe for assessment of complications 30 days
7 Risks and Discomforts
Protection Of Human Subjects
- Human Subject Involvement and Characteristics There is a risk of breach of confidentiality with individually identifiable health information The database will have de-identified data using an assigned ID on all study related documents Once the patient consents to the protocol he or she will be assigned a unique patient identifier number As a result the study database will hold strictly de-identified data using an arbitrary participant ID paper forms will be stored in a secure location and referenced only for scheduling contacts and a bridging table associating the two entities will be stored in yet another secure location
Upon initiating the study all data will be collected and processed using rigorous quality-control methods As the data forms are completed they will be entered by the research staff into the secure access de-identified database All paper forms will be stored in a locked cabinet in a locked room in a secure building Neither the name of the patient nor any other personally identifying information will be used in any reports or publications that result from this study
Potential Risks
The study will not alter the surgeons or patients plan for surgery A participant may be at risk if they have an adverse reaction to the medication dexmedetomidine Dexmedetomidine has been reported to have the following clinical side effects
Bradycardia
Hypotension
Somnolence
8 Benefits Increasing understanding of the possible lung protective mechanisms of dexmedetomidine
Patients in the dexmedetomidine group may also benefit from better pain control given the long-acting analgesic effects of dexmedetomidine
9 Statistical Analysis
An exploratory analysis of baseline demographic and clinical characteristics will be performed Compliance with the protocol of dexmedetomidine andor placebo will be calculated as a percentage of complete adherence to the administration of either solution as stated above Feasibility will be defined as a compliance greater than 80 Both groups will be compared in terms of lung ultrasound score in each side operative vs non-operative of the thorax at PACU and postoperative days 1 and 2 Similarly secondary outcomes diaphragmatic dysfunction pulmonary complications will be compared between both groups Our analysis will be adjusted for multiple testing hypothesis The estimated sample size is 100 patients 50 patients in each group assuming a mean LUS of 14 vs 11 between the control and intervention groups respectively with a standard deviation of 5 a missing follow-up of 10 an alpha error of 005 and 80 power All statistical analyses will be performed in Stata v140 College Station TX USA
Analysis
Continuous variables will be reported as means standard deviation SD or median with their corresponding interquartile ranges based on the distribution of the data which will be determine using Kolmogorov test Dichotomous variables will be reported as numbers percentages Between-group comparisons of continuous variables will be performed using the independent Student t test P values 005 will be considered statistically significant Descriptive statistics will be used to report patient demographics and baseline characteristics
Proportion of participants with postoperative pulmonary complications during admission will be reported units percentage This will be extracted from the patients electronic medical health records by a co-investigator
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None