Inflammatory Lung Injury, Ischemia-Reperfusion Lung Injury, Postoperative Pulmonary Complications
Conditions
Keywords
Volatile Anesthetics, Intravenous Anesthetics, Inflammatory Lung Injury, Postoperative Pulmonary Complications, Cardiac Surgery, Cardiopulmonary Bypass
Brief summary
The purpose of this study is to investigate whether the use of inhaled anesthetics, compared to intravenous anesthetics, can affect the amount of lung inflammation and postoperative respiratory complications seen after cardiac surgery.
Detailed description
Randomized, controlled trial involving 45 adult patients undergoing cardiac surgery with cardiopulmonary bypass. Patients will be randomized to receive either inhaled anesthesia with sevoflurane or total intravenous anesthesia (TIVA) with propofol for the maintenance phase of their cardiac anesthetic. Assessment of lung inflammation will take place using fiberoptic bronchoscopic sampling of lung fluid as well as serum collection before and after exposure to cardiopulmonary bypass, and the incidence of compositive postoperative pulmonary complications will take place in the postoperative period.
Interventions
DRUGSevoflurane
Volatile Anesthetic
DRUGPropofol
Intravenous Anesthetic
Sponsors
Beth Israel Deaconess Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (age 18+) * Undergoing cardiac surgery with cardiopulmonary bypass
Exclusion criteria
* Emergency surgery * History of severe COPD, emphysema, or ILD * Recent (\<2wk) or current use of systemic glucocorticoids * Prior history of pneumothorax * Allergy/contraindication to intravenous anesthetics * Personal or family history of malignant hyperthermia or high risk for malignant hyperthermia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL) | Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass | Inflammatory mediator found in BAL fluid during lung inflammation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BAL Concentration of IL1b (pg/mL) | Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass | Inflammatory mediator found in BAL fluid during lung inflammation |
| BAL Concentration of IL6 (pg/mL) | Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass | Inflammatory mediator found in BAL fluid during lung inflammation |
| Number of Patients With Postoperative Pulmonary Complications | Assessed daily, beginning on the first day after surgery, until hospital discharge or death. On average at our institution, most patients are discharged within 7 days so this is the expected time frame for follow up. | Composite endpoint of clinically relevant pulmonary complications |
| BAL Concentration of MCP1 (pg/mL) | Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass | Inflammatory mediator found in BAL fluid during lung inflammation |
| BAL Concentration of sRAGE (pg/mL) | Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass | Biomarker of lung injury (RAGE - receptor for advance glycosylation end products) |
| BAL Concentration of IL8 (pg/mL) | Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass | Inflammatory mediator found in BAL fluid during lung inflammation |
Countries
United States
Participant flow
Recruitment details
51 Enrolled
Pre-assignment details
49 Randomized * Withdrew consent (1) * Surgery cancelled (1)
Participants by arm
| Arm | Count |
|---|---|
| Inhaled Anesthesia Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass.
Sevoflurane: Volatile Anesthetic | 18 |
| Intravenous Anesthesia Patients in the intravenous anesthesia arm will be given total intravenous anesthesia with propofol for the duration of the procedure including cardiopulmonary bypass.
Propofol: Intravenous Anesthetic | 22 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Received intraoperative steroids | 1 | 0 |
| Overall Study | Surgery cancelled | 1 | 0 |
| Overall Study | Unable to obtain lab samples | 1 | 0 |
| Overall Study | Unsafe to perform BAL | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Inhaled Anesthesia | Intravenous Anesthesia | Total |
|---|---|---|---|
| Age, Continuous | 61.3 Years STANDARD_DEVIATION 10.1 | 64.6 Years STANDARD_DEVIATION 10.9 | 62.9 Years STANDARD_DEVIATION 10.5 |
| ARISCAT Score | 50.28 scores on a scale STANDARD_DEVIATION 10.2 | 47.86 scores on a scale STANDARD_DEVIATION 8.15 | 49.07 scores on a scale STANDARD_DEVIATION 9.18 |
| ASA Score (American Society of Anesthesiologists) | 3.67 scores on a scale. STANDARD_DEVIATION 0.48 | 3.82 scores on a scale. STANDARD_DEVIATION 0.39 | 3.75 scores on a scale. STANDARD_DEVIATION 0.44 |
| Body Mass Index | 31.20 kg/m^2 STANDARD_DEVIATION 4.34 | 29.61 kg/m^2 STANDARD_DEVIATION 5.02 | 30.41 kg/m^2 STANDARD_DEVIATION 4.68 |
| Comorbidities Arrhythmia | 1 Participants | 3 Participants | 4 Participants |
| Comorbidities Chronic Obstructive Pulmonary Disease/Asthma | 2 Participants | 2 Participants | 4 Participants |
| Comorbidities Congestive Heart Failure | 3 Participants | 1 Participants | 4 Participants |
| Comorbidities Diabetes with End Organ Damage | 3 Participants | 5 Participants | 8 Participants |
| Comorbidities Diabetes without Complications | 1 Participants | 4 Participants | 5 Participants |
| Comorbidities Hyperlipidemia | 15 Participants | 14 Participants | 29 Participants |
| Comorbidities Hypertension | 15 Participants | 18 Participants | 33 Participants |
| Comorbidities Moderate or Severe Renal Disease | 3 Participants | 0 Participants | 3 Participants |
| Comorbidities Obesity | 6 Participants | 3 Participants | 9 Participants |
| Comorbidities Solid (Non-Metastatic) Tumor | 3 Participants | 2 Participants | 5 Participants |
| Height | 69.11 Inches STANDARD_DEVIATION 3.65 | 68.41 Inches STANDARD_DEVIATION 3.49 | 68.76 Inches STANDARD_DEVIATION 3.57 |
| Race/Ethnicity, Customized Race Black/African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Race/Ethnicity, Customized Race Unknown | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Race White | 16 Participants | 15 Participants | 31 Participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 16 Participants | 17 Participants | 33 Participants |
| Weight | 207.82 Pounds STANDARD_DEVIATION 39.6 | 194.10 Pounds STANDARD_DEVIATION 42.54 | 200.96 Pounds STANDARD_DEVIATION 41.07 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 1 / 22 |
| other Total, other adverse events | 18 / 18 | 22 / 22 |
| serious Total, serious adverse events | 0 / 18 | 0 / 22 |
Outcome results
Primary
Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL)
Inflammatory mediator found in BAL fluid during lung inflammation
Time frame: Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Inhaled Anesthesia | Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL) | Pre-Bypass | 0.53 pg/mL |
| Inhaled Anesthesia | Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL) | Post-Bypass | 22.06 pg/mL |
| Inhaled Anesthesia | Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL) | Difference | 17.24 pg/mL |
| Intravenous Anesthesia | Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL) | Pre-Bypass | 0.53 pg/mL |
| Intravenous Anesthesia | Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL) | Post-Bypass | 102.04 pg/mL |
| Intravenous Anesthesia | Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL) | Difference | 101.51 pg/mL |
Secondary
BAL Concentration of IL1b (pg/mL)
Inflammatory mediator found in BAL fluid during lung inflammation
Time frame: Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Inhaled Anesthesia | BAL Concentration of IL1b (pg/mL) | Pre-Bypass | 0.42 pg/mL |
| Inhaled Anesthesia | BAL Concentration of IL1b (pg/mL) | Post-Bypass | 8.56 pg/mL |
| Inhaled Anesthesia | BAL Concentration of IL1b (pg/mL) | Difference | 8.30 pg/mL |
| Intravenous Anesthesia | BAL Concentration of IL1b (pg/mL) | Pre-Bypass | 0.87 pg/mL |
| Intravenous Anesthesia | BAL Concentration of IL1b (pg/mL) | Post-Bypass | 14.37 pg/mL |
| Intravenous Anesthesia | BAL Concentration of IL1b (pg/mL) | Difference | 11.00 pg/mL |
Secondary
BAL Concentration of IL6 (pg/mL)
Inflammatory mediator found in BAL fluid during lung inflammation
Time frame: Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Inhaled Anesthesia | BAL Concentration of IL6 (pg/mL) | Pre-Bypass | 30.70 pg/mL |
| Inhaled Anesthesia | BAL Concentration of IL6 (pg/mL) | Post-Bypass | 275.19 pg/mL |
| Inhaled Anesthesia | BAL Concentration of IL6 (pg/mL) | Difference | 220.68 pg/mL |
| Intravenous Anesthesia | BAL Concentration of IL6 (pg/mL) | Pre-Bypass | 31.35 pg/mL |
| Intravenous Anesthesia | BAL Concentration of IL6 (pg/mL) | Post-Bypass | 297.35 pg/mL |
| Intravenous Anesthesia | BAL Concentration of IL6 (pg/mL) | Difference | 259.32 pg/mL |
Secondary
BAL Concentration of IL8 (pg/mL)
Inflammatory mediator found in BAL fluid during lung inflammation
Time frame: Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Inhaled Anesthesia | BAL Concentration of IL8 (pg/mL) | Pre-Bypass | 2008.50 pg/mL |
| Inhaled Anesthesia | BAL Concentration of IL8 (pg/mL) | Post-Bypass | 8019.50 pg/mL |
| Inhaled Anesthesia | BAL Concentration of IL8 (pg/mL) | Difference | 4701.00 pg/mL |
| Intravenous Anesthesia | BAL Concentration of IL8 (pg/mL) | Pre-Bypass | 6528.50 pg/mL |
| Intravenous Anesthesia | BAL Concentration of IL8 (pg/mL) | Post-Bypass | 27789.50 pg/mL |
| Intravenous Anesthesia | BAL Concentration of IL8 (pg/mL) | Difference | 16230.00 pg/mL |
Secondary
BAL Concentration of MCP1 (pg/mL)
Inflammatory mediator found in BAL fluid during lung inflammation
Time frame: Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Inhaled Anesthesia | BAL Concentration of MCP1 (pg/mL) | Pre-Bypass | 509.50 pg/mL |
| Inhaled Anesthesia | BAL Concentration of MCP1 (pg/mL) | Post-Bypass | 496.00 pg/mL |
| Inhaled Anesthesia | BAL Concentration of MCP1 (pg/mL) | Difference | 148.00 pg/mL |
| Intravenous Anesthesia | BAL Concentration of MCP1 (pg/mL) | Pre-Bypass | 977.50 pg/mL |
| Intravenous Anesthesia | BAL Concentration of MCP1 (pg/mL) | Post-Bypass | 883.50 pg/mL |
| Intravenous Anesthesia | BAL Concentration of MCP1 (pg/mL) | Difference | 479.50 pg/mL |
Secondary
BAL Concentration of sRAGE (pg/mL)
Biomarker of lung injury (RAGE - receptor for advance glycosylation end products)
Time frame: Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Inhaled Anesthesia | BAL Concentration of sRAGE (pg/mL) | Pre-Bypass | 156.50 pg/mL |
| Inhaled Anesthesia | BAL Concentration of sRAGE (pg/mL) | Post-Bypass | 597.00 pg/mL |
| Inhaled Anesthesia | BAL Concentration of sRAGE (pg/mL) | Difference | 402.50 pg/mL |
| Intravenous Anesthesia | BAL Concentration of sRAGE (pg/mL) | Pre-Bypass | 164 pg/mL |
| Intravenous Anesthesia | BAL Concentration of sRAGE (pg/mL) | Post-Bypass | 465.00 pg/mL |
| Intravenous Anesthesia | BAL Concentration of sRAGE (pg/mL) | Difference | 224.50 pg/mL |
Secondary
Number of Patients With Postoperative Pulmonary Complications
Composite endpoint of clinically relevant pulmonary complications
Time frame: Assessed daily, beginning on the first day after surgery, until hospital discharge or death. On average at our institution, most patients are discharged within 7 days so this is the expected time frame for follow up.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Pleural effusion | 17 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | ARDS | 0 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Failed extubation (re-intubated within 24hrs) | 0 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Pneumonia | 0 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Atelectasis | 16 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Brochospasm | 1 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Pulmonary edema | 4 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Exacerbation of chronic lung disease | 0 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Infiltrate/consolidation | 6 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Hypoxia (PaO2/FiO2 < 300) | 16 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Reintubation (greater than 24hrs after extubation) | 0 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Respiratory acidosis (PaCO2 > 45) | 12 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Pneumothorax | 1 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Any postoperative pulmonary complication | 18 Participants |
| Inhaled Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Prolonged intubation (greater than 48hrs) | 0 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Any postoperative pulmonary complication | 22 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Prolonged intubation (greater than 48hrs) | 3 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Failed extubation (re-intubated within 24hrs) | 1 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Reintubation (greater than 24hrs after extubation) | 2 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Pulmonary edema | 8 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Pleural effusion | 21 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Atelectasis | 19 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Infiltrate/consolidation | 6 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Pneumothorax | 5 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | ARDS | 0 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Pneumonia | 1 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Brochospasm | 1 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Exacerbation of chronic lung disease | 0 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Hypoxia (PaO2/FiO2 < 300) | 15 Participants |
| Intravenous Anesthesia | Number of Patients With Postoperative Pulmonary Complications | Respiratory acidosis (PaCO2 > 45) | 15 Participants |