APLICS: Anesthetics to Prevent Lung Injury in Cardiac Surgery

• Sponsor: Beth Israel Deaconess Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02918877
• Collaborator: (none)
• Enrollment: 51
• Location: 1
• Arms: 2
• Actual Duration (Months): 43.8
• Patients Per Site Per Month: 1.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Lung Injury; Ischemia-Reperfusion Lung Injury; Postoperative Pulmonary Complications	Drug: Sevoflurane; Drug: Propofol	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Anesthetics to Prevent Lung Injury in Cardiac Surgery
• Actual Study Start Date: Jun 9, 2017
• Actual Primary Completion Date: Dec 24, 2018
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Inhaled Anesthesia Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass.	Drug: Sevoflurane; Volatile Anesthetic
Active Comparator: 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.	Drug: Propofol; Intravenous Anesthetic; Other Names: Diprivan

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. 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

3. 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

4. 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

5. 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

6. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Beth Israel Deaconess Medical Center

Investigators

• Principal Investigator: Brian O'Gara, MD, Beth Israel Deaconess Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 27, 2018

More Information

Publications

None provided.

• Responsible Party: Brian O'Gara, MD, Beth Israel Deaconess Medical Center
• ClinicalTrials.gov Identifier: NCT02918877
• Other Study ID Numbers: 2016P000306
• First Posted: Sep 29, 2016
• Last Update Posted: May 5, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Brian O'Gara, MD, Beth Israel Deaconess Medical Center: Volatile Anesthetics; Intravenous Anesthetics; Inflammatory Lung Injury; Postoperative Pulmonary Complications; Cardiac Surgery; Cardiopulmonary Bypass
• Additional relevant MeSH terms: Lung Injury; Ischemia; Wounds and Injuries; Propofol; Sevoflurane

Study Results

Participant Flow

Recruitment Details	51 Enrolled
Pre-assignment Detail	49 Randomized Withdrew consent (1) Surgery cancelled (1)

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic	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
Period Title: Overall Study
STARTED	24	25
COMPLETED	18	22
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia	Total
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic	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	Total of all reporting groups
Overall Participants	18	22	40
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.3 (10.1)	64.6 (10.9)	62.9 (10.5)
Sex: Female, Male (Count of Participants)
Female	2 11.1%	5 22.7%	7 17.5%
Male	16 88.9%	17 77.3%	33 82.5%
Race/Ethnicity, Customized (Count of Participants)
White	16 88.9%	15 68.2%	31 77.5%
Black/African American	0 0%	1 4.5%	1 2.5%
Hispanic or Latino	2 11.1%	3 13.6%	5 12.5%
Unknown	0 0%	3 13.6%	3 7.5%
Weight (Pounds) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Pounds]	207.82 (39.60)	194.10 (42.54)	200.96 (41.07)
Height (Inches) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Inches]	69.11 (3.65)	68.41 (3.49)	68.76 (3.57)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.20 (4.34)	29.61 (5.02)	30.41 (4.68)
Comorbidities (Count of Participants)
Hypertension	15 83.3%	18 81.8%	33 82.5%
Hyperlipidemia	15 83.3%	14 63.6%	29 72.5%
Congestive Heart Failure	3 16.7%	1 4.5%	4 10%
Arrhythmia	1 5.6%	3 13.6%	4 10%
Obesity	6 33.3%	3 13.6%	9 22.5%
Chronic Obstructive Pulmonary Disease/Asthma	2 11.1%	2 9.1%	4 10%
Diabetes without Complications	1 5.6%	4 18.2%	5 12.5%
Diabetes with End Organ Damage	3 16.7%	5 22.7%	8 20%
Moderate or Severe Renal Disease	3 16.7%	0 0%	3 7.5%
Solid (Non-Metastatic) Tumor	3 16.7%	2 9.1%	5 12.5%
ASA Score (American Society of Anesthesiologists) (scores on a scale.) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale.]	3.67 (0.48)	3.82 (0.39)	3.75 (0.44)
ARISCAT Score (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	50.28 (10.20)	47.86 (8.15)	49.07 (9.18)

Outcome Measures

1. Primary Outcome

Title	Bronchoalveolar Lavage (BAL) Concentration of TNF Alpha (pg/mL)
Description	Inflammatory mediator found in BAL fluid during lung inflammation
Time Frame	Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic	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
Measure Participants	18	22
Pre-Bypass	0.53	0.53
Post-Bypass	22.06	102.04
Difference	17.24	101.51

2. Secondary Outcome

Title	Number of Patients With Postoperative Pulmonary Complications
Description	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic	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
Measure Participants	18	22
Prolonged intubation (greater than 48hrs)	0 0%	3 13.6%
Failed extubation (re-intubated within 24hrs)	0 0%	1 4.5%
Reintubation (greater than 24hrs after extubation)	0 0%	2 9.1%
Pulmonary edema	4 22.2%	8 36.4%
Pleural effusion	17 94.4%	21 95.5%
Atelectasis	16 88.9%	19 86.4%
Infiltrate/consolidation	6 33.3%	6 27.3%
Pneumothorax	1 5.6%	5 22.7%
ARDS	0 0%	0 0%
Pneumonia	0 0%	1 4.5%
Brochospasm	1 5.6%	1 4.5%
Exacerbation of chronic lung disease	0 0%	0 0%
Hypoxia (PaO2/FiO2 < 300)	16 88.9%	15 68.2%
Respiratory acidosis (PaCO2 > 45)	12 66.7%	15 68.2%
Any postoperative pulmonary complication	18 100%	22 100%

3. Secondary Outcome

Title	BAL Concentration of IL1b (pg/mL)
Description	Inflammatory mediator found in BAL fluid during lung inflammation
Time Frame	Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic	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
Measure Participants	18	22
Pre-Bypass	0.42	0.87
Post-Bypass	8.56	14.37
Difference	8.30	11.00

4. Secondary Outcome

Title	BAL Concentration of IL6 (pg/mL)
Description	Inflammatory mediator found in BAL fluid during lung inflammation
Time Frame	Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic	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
Measure Participants	18	22
Pre-Bypass	30.70	31.35
Post-Bypass	275.19	297.35
Difference	220.68	259.32

5. Secondary Outcome

Title	BAL Concentration of IL8 (pg/mL)
Description	Inflammatory mediator found in BAL fluid during lung inflammation
Time Frame	Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic	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
Measure Participants	18	22
Pre-Bypass	2008.50	6528.50
Post-Bypass	8019.50	27789.50
Difference	4701.00	16230.00

6. Secondary Outcome

Title	BAL Concentration of MCP1 (pg/mL)
Description	Inflammatory mediator found in BAL fluid during lung inflammation
Time Frame	Change from baseline and 2-4 hours after exposure to cardiopulmonary bypass

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic	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
Measure Participants	18	22
Pre-Bypass	509.50	977.50
Post-Bypass	496.00	883.50
Difference	148.00	479.50

7. Secondary Outcome

Title	BAL Concentration of sRAGE (pg/mL)
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Inhaled Anesthesia	Intravenous Anesthesia
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic	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
Measure Participants	18	22
Pre-Bypass	156.50	164
Post-Bypass	597.00	465.00
Difference	402.50	224.50

Adverse Events

Time Frame	During hospital length of stay ~7 days
Adverse Event Reporting Description	During this study, the research team did not record every adverse event. As shown in the table below (as well as the Outcome Measure 2 data), only study related events were recorded.
Arm/Group Title	Inhaled Anesthesia		Intravenous Anesthesia
Arm/Group Description	Patients in the inhaled anesthesia arm will be given sevoflurane anesthesia maintenance for the duration of the procedure including cardiopulmonary bypass. Sevoflurane: Volatile Anesthetic		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
All Cause Mortality
	Inhaled Anesthesia		Intravenous Anesthesia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		1/22 (4.5%)
Serious Adverse Events
	Inhaled Anesthesia		Intravenous Anesthesia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Inhaled Anesthesia		Intravenous Anesthesia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/18 (100%)		22/22 (100%)
Respiratory, thoracic and mediastinal disorders
Prolonged intubation (greater than 48hrs)	0/18 (0%)	0	3/22 (13.6%)	3
Failed extubation (re-intubated within 24hrs)	0/18 (0%)	0	1/22 (4.5%)	1
Reintubation (greater than 24hrs after extubation)	0/18 (0%)	0	2/22 (9.1%)	2
Pulmonary edema	4/18 (22.2%)	4	8/22 (36.4%)	8
Pleural effusion	17/18 (94.4%)	17	21/22 (95.5%)	21
Atelectasis	16/18 (88.9%)	16	19/22 (86.4%)	19
Infiltrate/consolidation	6/18 (33.3%)	6	6/22 (27.3%)	6
Pneumothorax	1/18 (5.6%)	1	5/22 (22.7%)	5
Pneumonia	0/18 (0%)	0	1/22 (4.5%)	1
Brochospasm	1/18 (5.6%)	1	1/22 (4.5%)	1
Hypoxia (PaO2/FiO2 < 300)	16/18 (88.9%)	16	15/22 (68.2%)	15
Respiratory acidosis (PaCO2 > 45)	12/18 (66.7%)	12	15/22 (68.2%)	15

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.