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The purpose of this single-center, prospective study is to evaluate the physiologic effect of changes in PEEP on biventricular mechanics and RV-pulmonary arterial (RV-PA) coupling in adult patients undergoing cardiac surgery.
Positive end-expiratory pressure (PEEP) is a critical modality of mechanical ventilation but has important and often underappreciated effects on biventricular mechanics. PEEP is frequently selected based primarily on respiratory mechanics and oxygenation targets; however, increasing intrathoracic pressure may reduce RV preload by elevating right atrial pressure, while increasing transpulmonary pressure may increase RV afterload by compressing intra-alveolar pulmonary vessels and redistributing pulmonary blood flow. This is important specifically in the context of cardiac surgery where right ventricular (RV) function plays a critical role in determining postoperative morbidity and mortality. Perioperative RV dysfunction has been consistently associated with adverse outcomes, including prolonged vasopressor and inotrope requirements, difficulty weaning from cardiopulmonary bypass, longer intensive care unit stays, and increased mortality.
Right ventricular-pulmonary arterial (RV-PA) coupling provides a physiologically integrated assessment of RV performance by quantifying the relationship between RV contractility and afterload. Animal studies have shown that incremental PEEP increases can impair biventricular mechanics and precipitate RV-PA uncoupling. However, these physiologic effects have not been systematically characterized in the perioperative setting in the cardiac surgery population. This protocol seeks to address this knowledge gap by systematically evaluating biventricular mechanics and RV-PA coupling across varying PEEP levels in a controlled setting, using tools already employed in routine cardiac surgical care (pulmonary artery catheter and intraoperative TEE).
The overarching goal of this proposal is to define how perioperative positive end-expiratory pressure alters biventricular mechanics and right ventricular-pulmonary arterial coupling, to inform physiologically guided, RV-protective ventilatory strategies during cardiac surgery.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Optimized PEEP Group | Experimental | These are patients undergoing cardiac surgery who will undergo an incremental/decremental PEEP trial using Electrical Impedance Tomography (EIT). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EIT Guided PEEP Trial | Procedure | Electrical impedance tomography (EIT) will be used to guide identification of "optimal PEEP" based on lung mechanics. After induction of anesthesia and initiation of controlled mechanical ventilation, EIT data will be collected during a brief standardized PEEP titration maneuver to assess lung recruitment and overdistension. |
| Measure | Description | Time Frame |
|---|---|---|
| Right ventricle-pulmonary artery coupling (Ees/Ea) | Right ventricle-pulmonary artery (RV-PA) coupling ratio (Ees/Ea) assessed using simultaneous transesophageal echocardiography and hemodynamic monitoring at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]) during a standardized stepwise PEEP titration sequence. | During the standardized PEEP titration sequence after induction of anesthesia and before surgical intervention (approximately 20-25 minutes) |
| Measure | Description | Time Frame |
|---|---|---|
| Right ventricular end-diastolic volume at predefined PEEP levels | Three-dimensional right ventricular end-diastolic volume (RVEDV) measured by transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During PEEP titration sequence (approximately 20-25 minutes after induction of anesthesia and prior to surgical incision) |
| Measure | Description | Time Frame |
|---|---|---|
| Oxygen saturation at predefined PEEP levels | Peak airway pressure recorded from the ventilator at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
Inclusion Criteria:
1. Age ≥ 18 years
2. Scheduled to undergo cardiac surgery requiring general anesthesia
3. Planned use of intraoperative transesophageal echocardiography (TEE) as part of routine clinical care
4. Planned placement of a pulmonary artery catheter as part of clinical care (Pulmonary artery catheter placement will be performed solely based on clinical judgment by the treating anesthesia and surgical teams. At our institution, pulmonary artery catheters are routinely placed in cardiac surgery patients with clinical indications including:
5. Able and willing to provide written informed consent prior to surgery
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beth Israel Deaconess Medical Center | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29025899 | Background | Bellofiore A, Vanderpool R, Brewis MJ, Peacock AJ, Chesler NC. A novel single-beat approach to assess right ventricular systolic function. J Appl Physiol (1985). 2018 Feb 1;124(2):283-290. doi: 10.1152/japplphysiol.00258.2017. Epub 2017 Oct 12. | |
| 39946198 | Background | Araos J, Glocker F, Owyang CG, Teran F, Kim J, Nieman G, Heerdt PM. Biventricular Response to Positive End-expiratory Pressure in Swine: Assessment Based on Beat-to-beat Pressure Waveform Analysis. Anesthesiology. 2025 Apr 1;142(4):767-769. doi: 10.1097/ALN.0000000000005363. Epub 2025 Feb 13. No abstract available. |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| Right ventricular end-systolic volume at predefined PEEP levels | Three-dimensional right ventricular end-systolic volume (RVESV) assessed by three-dimensional transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Right ventricular stroke volume at predefined PEEP levels | Right ventricular stroke volume derived from three-dimensional transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Right ventricular end-diastolic pressure at predefined PEEP levels | Right ventricular end-diastolic pressure measured via pulmonary artery catheter at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Right ventricular end-systolic pressure at predefined PEEP levels | Right ventricular end-systolic pressure estimated using waveform-based calculation methods from pulmonary artery catheter data at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Pulmonary artery systolic pressure at predefined PEEP levels | Pulmonary artery systolic pressure measured via pulmonary artery catheter at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Mean pulmonary artery pressure at predefined PEEP levels | Mean pulmonary artery pressure measured via pulmonary artery catheter at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Right ventricular end-systolic elastance at predefined PEEP levels | Right ventricular end-systolic elastance (Ees) derived using single-beat pressure-volume analysis at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Effective arterial elastance at predefined PEEP levels | Effective arterial elastance (Ea) derived from pressure-volume analysis at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Three-dimensional right ventricular ejection fraction | Three-dimensional right ventricular ejection fraction (3D RVEF) assessed by transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]) during a standardized stepwise PEEP titration sequence. | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Left ventricular ejection fraction at predefined PEEP levels | Three-dimensional left ventricular ejection fraction (LVEF) assessed by transesophageal echocardiography at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Left ventricular stroke volume at predefined PEEP levels | Left ventricular stroke volume derived from echocardiographic measurements at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| Plateau pressure at predefined PEEP levels | Plateau airway pressure measured during inspiratory hold maneuvers at four predefined PEEP levels (optimal PEEP + 5 cmH₂O, optimal PEEP, optimal PEEP - 5 cmH₂O, and PEEP 0 cmH₂O [baseline]). | During standardized PEEP titration sequence after induction of anesthesia and prior to surgical incision (approximately 20-25 minutes) |
| 37905995 | Background | Wood G, Madsen TL, Kim WY, Lyhne MD. Increasing Levels of Positive End-expiratory Pressure Cause Stepwise Biventricular Stroke Work Reduction in a Porcine Model. Anesthesiology. 2024 Feb 1;140(2):240-250. doi: 10.1097/ALN.0000000000004821. |
| 17368169 | Background | Acosta P, Santisbon E, Varon J. "The use of positive end-expiratory pressure in mechanical ventilation". Crit Care Clin. 2007 Apr;23(2):251-61, x. doi: 10.1016/j.ccc.2006.12.012. |
| 40483247 | Background | Ahmed U, Mahmood F, Nicoara A, Kiarad V. Right Ventricular Function and Echocardiographic Pressure-Volume Loops: Overview and Perioperative Clinical Implications. J Cardiothorac Vasc Anesth. 2025 Oct;39(10):2857-2865. doi: 10.1053/j.jvca.2025.05.019. Epub 2025 May 17. |
| 39780800 | Background | Kiarad V, Mahmood F, Hedayat M, Yunus R, Nicoara A, Liu D, Chu L, Senthilnathan V, Kai M, Khabbaz K. Intraoperative right ventricular end-systolic pressure-volume loop analysis in patients undergoing cardiac surgery: A proof-of-concept methodology. JTCVS Open. 2024 Sep 26;22:225-234. doi: 10.1016/j.xjon.2024.09.020. eCollection 2024 Dec. |
| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |