A case of prone position combined with iNO therapy under EIT monitoring in the treatment of refractory hypoxemia after lung transplantation

A case of prone position combined with iNO therapy under EIT monitoring in the treatment of refractory hypoxemia after lung transplantation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A case of prone position combined with iNO therapy under EIT monitoring in the treatment of refractory hypoxemia after lung transplantation Yan Dong, Zhongping Xu, Jing Tian, Dapeng Wang, Jingyu Chen, Hongyang Xu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5277719/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Apr, 2025 Read the published version in BMC Anesthesiology → Version 1 posted 14 You are reading this latest preprint version Abstract We report a case of severe primary graft dysfunction (PGD) and refractory hypoxemia after bilateral lung transplantation in our center. The effect of conventional therapy of the patient was inadequate, and the patient was unable to be weaned off extracorporeal membrane oxygenation (ECMO). Employing electrical impedance tomography (EIT) monitoring technology, we implemented a series of interventions including prone position, inhaled nitric oxide (iNO) therapy, tracheotomy and other treatment methods. After undergoing a rigorous treatment process, the patient was successfully transitioned out of intensive care unit (ICU) on the 24th day after operation. In conclusion, the utilization of EIT for visual respiratory management, in conjunction with a multifaceted therapeutic approach, substantially contributed to the improved prognosis of lung transplant recipients. Lung transplants Electrical impedance tomography (EIT) Prone position ventilation treatment iNO therapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Lung transplantation is the most effective treatment for end-stage pulmonary disease. Primary graft dysfunction (PGD) occurring within 72 hours post-operation is a major factor leading to early mortality in lung transplants recipients. In January 2024, our department successfully treated a patient who experienced PGD after lung transplant. The patient presented with refractory hypoxemia following the transplant surgery, to address this critical condition, we employed electrical impedance tomography (EIT) for monitoring, along with prone positioning and inhaled nitric oxide (iNO) therapy. The subsequent sections provide a detailed account of the case. Case report The 54-year-old female patient was diagnosed with pulmonary interstitial fibrosis at the age of 52, treated with oral pirfenidone and prednisone. Despite ongoing cough and expectoration, there was a slight improvement in chest tightness and asthma as compared to before. However, discontinuing pirfenidone in April 2023 resulted in worsening dyspnea, necessitating continuous home oxygen therapy. Minimal exertion was found to elicit significant asthmatic symptoms, rendering the patient unable to be weaned off oxygen. A lung biopsy revealed usual interstitial pneumonia (UIP). Pre-transplant evaluation indicated a body mass index(BMI) of 25.59 kg/m^2. Pulmonary function tests showed FVC: 1.0L, 35.6%; FEV1: 1.093L, 39. 1%; FEV1/FVC: 92.94%. Diffusing capacity test was inconclusive. The 6-minute walk test distance was 150m, with an oxygen flow rate of 4L/min, a lowest SpO2 at 82%, and a highest heart rate of 110 beats per minute. Physical examination revealed coarse breath sounds and Velcro crackles in both lungs. The patient was listed for lung transplant in late December and underwent bilateral lung transplantation with venovenous extracorporeal membrane oxygenation (V-V ECMO) support on January 26, 2024. The surgery lasted 7.8 hours, with a peak cold ischemia time of 630 minutes. Intraoperative blood loss was 1200 ml, and blood transfusion amounted to 1450 ml. Postoperatively, the patient remained hemodynamically stable but necessitated additional ECMO support in the ICU due to suboptimal oxygenation. Upon ICU admission, the patient was provided with mechanical ventilatory support and V-V ECMO (via internal jugular-femoral vein) cardiopulmonary support. Treatment included anti-infective therapy with imipenem/cilastatin sodium combined with caspofungin, immunosuppression with methylprednisolone and tacrolimus, sedation, analgesia, muscle relaxation, blood transfusion support, expectorant therapy, and acid suppression among other interventions. Despite ventilator and V-V ECMO support, arterial blood gas (ABG) indicated inadequate oxygenation with PaO2: 78.5mmHg, PaCO2: 43.6mmHg and FIO2: 80%. A chest X-ray showed bilateral pulmonary exudative changes (Figure 1). Lung ultrasonography revealed scattered B-lines in the anterior and lateral thoracic walls, and extensive confluent B-lines with a few fragmentary signs in the posterior thoracic wall. EIT examination showed center of ventilation (CoV) of 48%, left lung heterogeneity index (LHI) of 67, and global inhomogeneity index (GI) of 79.6. The treatment strategy was temporarily altered to enhance d iuresis and replenish colloidal osmotic pressure to mitigate pulmonary edema. Within the first 3 days post-operation, the patient's oxygenation remained poor. Intermittent fiberoptic bronchoscopy was performed and revealed moderate congestion and edema in the airways, with a small amount of edema fluid observed bilaterally. Considering that the patient was at the peak of PGD, ECMO support was continued along with enhanced fluid management. On the morning of the 4th day post-operation, we initiated our first attempt to wean the patient off ECMO support. ABG analysis showed: PaO2: 71.7mmHg, PaCO2: 86.2mmHg, FIO2: 90%. Following assessment, it was determined that the withdrawn of ECMO was not feasible. Subsequent bronchoscopy indicated significant airways contamination with moderate yellow mucus, and the patient's oxygenation remained suboptimal. Therefore, a decision was made to initiate prone positioning ventilation treatment. The initial prone position session lasted 22 hours, during which ABG analysis showed improved oxygenation. The EIT results were as follows: CoV: 55%, LHI: 72, GI: 68. Unfortunately, oxygenation deteriorated again following discontinuation of prone positioning (Figure 2). On the 6th day post-operation, given the patient’s strong dependence on ECMO and the prolonged inability to improve oxygenation, inhaled NO therapy (INOwill N200 Nitric Oxide Generator and Delivery System, Novlead Biotechnology, China) was initiated to improve the ventilation-perfusion ratio of the lungs. The NO concentration was set at 20ppm, with a monitored concentration of 17ppm, and an NO2 concentration of 0.2ppm . ABG analysis showed: PaO2 : 88.3mmHg , PaCO2 : 52.2mmHg, FIO2 : 80% . Six hours after initiating NO therapy, the ABG indicated: PaO2 : 119mmHg, PaCO2 : 39.2mmHg , FIO2 : 80% . EIT results were: LHI: 79, GI: 67. Subsequent treatments led to a marked improvement in oxygenation (Figure 3), optimization of ventilation-perfusion ratio, stabilization of circulation, and clearance of the lung fields (Figure 4), demonstrating the effectiveness of the treatment. On the morning of the 10th day post-operation, we were pleasantly surprised to find that the patient's tidal volume had improved to 390 ml. We attempted to wean the patient off the ECMO again and performed a fiberoptic bronchoscopy to assess the airway condition. Ultimately, the ECMO was successfully withdrawn after 3 hours, at which time EIT showed: CoV: 54%, LHI: 80, GI: 63. Unfortunately, upon performing the bronchoscopy, a significant amount of sputum was still observed, accompanied by moderate congestion and edema of the respiratory mucosa, and the mucosa of the right airway appeared grayish-black. Sputum culture indicated pan-resistant Acinetobacter baumannii and Pseudomonas aeruginos . The anti-infective treatment regimen was altered to a combination of eravacycline, ceftazidime-avibactam, and isavuconazole . Given the patient's poor oxygenation and lung compliance, inability to cough up sputum independently, and the inability to be weaned off the ventilator and extubated in the short term, a tracheotomy was planned for the following day. After the tracheotomy, bronchoscopy showed a reduction in the amount of sputum and an improvement in its characteristics. The edema of the airway mucosa had improved compared to before, the infection markers gradually decreased without fluctuations, and the antibiotics were gradually reduced. The level of ventilator support was reduced compared to before. On the 24th day post-operation, the patient was successfully transferred out of the ICU (Figure 5). 52 days after the operation, the patient was successfully weaned off the ventilator and the tracheostomy tube was removed. Discussion PGD is the leading cause of early mortality in lung transplantation recipients [ 1, 2], typically occurring within 24 to 72 hours post-ransplantation. This patient exhibited severe hypoxemia within 72 hours after lung transplantation, with an oxygenation index <200 mm Hg (ABG on the 3th day post-operation showed an oxygenation index of 133mmHg) . Bronchoscopy revealed moderate to severe congestion and edema of the respiratory mucosa, and chest X-ray examination showed diffuse exudative changes in both lung fields, meeting the clinical diagnostic criteria for PGD 3, indicating a poor prognosis [2, 3] . Despite the support of V-V ECMO, the patient experienced persistent hypoxemia. Our department used EIT technology to provide real-ime information on regional pulmonary ventilation and blood perfusion, combined with bedside chest ultrasound to form a visual respiratory management. Based on the imaging results provided by EIT, we adjusted the patient’s treatment strategy to improve lung ventilation or perfusion, aiming for better therapeutic outcomes. Effective gas exchange and improved oxygenation can only be achieved when lung ventilation and perfusion are well-matched. Prone position ventilation refers to the practice of placing the patient in a prone position during mechanical ventilation, which, through the effect of gravity, improves the ventilation-perfusion ratio [4], facilitates the drainage of pulmonary secretions, and enhances oxygenation [5] . From a pathophysiological standpoint, prone position ventilation, effective in treating acute respiratory distress syndrome (ARDS), may also be applicable for improving PGD conditions in lung transplant recipients. In 2017, the American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine strongly recommended that patients with severe ARDS receive prone positioning for more than 12 hours daily [6] . A meta-analysis evaluating the impact of prone positioning on ARDS (8 randomized trials, 2129 patients) [7] showed that patients with moderate to severe ARDS could benefit from daily prone positioning for more than 12 hours in terms of survival. Considering the extensive surgical wounds of the patient and the numerous tubes (ECMO jugular- femoral cannulation, mechanical ventilation orotracheal intubation, chest tubes, etc.), to avoid serious complications such as tube dislodgement the patient's first prone position lasted 22 hours. We simultaneously set the ventilator's tidal volume at 300-400 ml to reduce the risks of atelectasis and hyperinflation, and minimize the physical damage to the alveoli caused by mechanical ventilation [8] . During prone position ventilation treatment, the patient did not experience pressure sores, surgical wound dehiscence with bleeding, tube dislodgement, or other complications. After prone position treatment, the improvement in LHIx was not significant, oxygenation could not be maintained, and the patient still could not successfully pass the ECMO independent test. Concurrently, postoperative sputum culture showed pan-drug resistant Acineto bacter baumannii and Pseudomonas aeruginosa infection, contributing to refractory hypoxemia. NO is a selective pulmonary dilator, which can reduce pulmonary artery pressure and increase pulmonary blood flowand improve ventilator-perfusion mismatch. Previous basic studies have shown that NO can inhibit the proliferation and replication of a variety of bacteria in the lungs, inhibit the production of pulmonary inflammatory chemokines [9], and its effect is similar to the application of local glucocorticoids [ 10]. When prone position therapy for 22 hours was ineffective, we promptly initiated iNO therapy as a remedial measure. After continuous NO inhalation for 6 hours, the oxygenation index of the patients increased significantly. Although the benefit diminished over time with long-term use, iNO still showed a good effect in improving ventilation and blood perfusion. During the treatment period, the patient’s ventilator support gradually decreased, circulation stabilized, and the treatment was effective. Performing a tracheostomy during ECMO carries a significant risk of bleeding. The interaction between the blood of an ECMO patient and the surface of the circuit leads to an imbalance between pro-coagulation and anticoagulation mechanisms [ 11] . Additionally, the patient was concurrently undergoing iNO therapy, which can inhibit platelet aggregation [ 12] , thereby affecting coagulation function and the use of anticoagulants during treatment. The patient's anticoagulation management was already facing significant challenges. Therefore, choosing the right timing for the tracheostomy is crucial. Performing the tracheostomy after weaning off ECMO can significantly reduce the risk of bleeding complications. In this case, the tracheostomy was timely performed after ECMO weaning and discontinuation of iNO, playing a certain role in the patient's recovery. Conclusion The application of EIT for monitoring and evaluating alterations in lung ventilation and perfusion in patients at critical stages following lung transplantation,facilitates visual respiratory management strategies. This approach ,combined with the implementation of diverse therapeutic interventions such as prone positioning and iNO therapy, contributes to the enhancement of prognostic outcomes for lung transplant recipients. Abbreviations PGD Primary graft dysfunction ECMO Extracorporeal membrane oxygenation EIT Electrical impedance tomography iNO Inhaled nitric oxide ICU Intensive care unit UIP Usual interstitial pneumonia BMI Body mass index V-V ECMO Venovenous extracorporeal membrane oxygenation ABG Arterial blood gas CoV Center of ventilation LHI Lung heterogeneity index GI Global inhomogeneity index ARDS Acute respiratory distress syndrome Declarations Acknowledgements Not applicable. Author contributions All authors contributed to this case report. All provided input and critique on the final manuscript. Funding This case report was financially supported by no funding. Data availability No datasets were generated or analysed during the current study. Ethics approval and consent to participate The Institutional Ethics Committees of Wuxi People’s Hospital affiliated to Nanjing Medical University approved this study. Informed consents in written form were obtained from the patients or their next of kin in written. Consent for publication Written informed consent was obtained from the patients for publication of this article. Competing interests The authors declare no competing interests. References Shah RJ, Diamond JM, Cantu E, et al. Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation. Chest. 2013;144(2):616–22. Clausen E, Cantu E. Primary graft dysfunction: what we know. J Thorac Dis. 2021;13(11):6618–27. Cantu E, Diamond JM, Cevasco M, et al. Contemporary trends in PGD incidence, outcomes, and therapies. J Heart Lung Transpl. 2022;41(12):1839–49. Glenny RW, Lamm WJ, Albert RK, et al. Gravity is a minor determinant of pulmonary blood flow distribution. J Appl Physiol (1985). 1991;71(2):620–9. Cardinale M, Boussen S, Cungi PJ, et al. Lung-Dependent Areas Collapse, Monitored by Electrical Impedance Tomography, May Predict the Oxygenation Response to Prone Ventilation in COVID-19 Acute Respiratory Distress Syndrome. Crit Care Med. 2022;50(7):1093–102. Fan E, Del Sorbo L, Goligher EC, An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline, et al. Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2017;195(9):1253–63. Munshi L, Del Sorbo L, Ad hikari NKJ, et al. Prone Position for Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2017;14(Supplement4):S280–8. Beitler JR, Shaefi S, Montesi SB, et al. Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis. Intensive Care Med. 2014;40(3):332–41. Gore A, Gauthier AG, Lin M, et al. The nitric oxide donor, (Z)-1-[N-(2- aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA- NONOate/D-NO), increases survival by attenuating hyperoxia-compromised innate immunity in bacterial clearance in a mouse model of ventilator- associated pneumonia. Biochem Pharmacol. 2020;176:113817. Kirov MY, Evgenov OV, Bjertnaes LJ. Combination of intravenously infused methylene blue and inhaled nitric oxide ameliorates endotoxin- induced lung injury in awake sheep. Crit Care Med. 2003;31(1):179–86. Brodie D, Slutsky AS, Combes A. Extracorporeal Life Support for Adults With Respiratory Failure and Related Indications: A Review. JAMA. 2019;322(6):557–68. Germann P, Braschi A, Della Rocca G, et al. Inhaled nitric oxide therapy in adults: European expert recommendations. Intensive Care Med. 2005;31(8):1029–41. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 23 Apr, 2025 Read the published version in BMC Anesthesiology → Version 1 posted Editorial decision: Revision requested 15 Jan, 2025 Reviews received at journal 14 Jan, 2025 Reviews received at journal 14 Jan, 2025 Reviewers agreed at journal 14 Jan, 2025 Reviewers agreed at journal 14 Jan, 2025 Reviews received at journal 10 Jan, 2025 Reviews received at journal 09 Jan, 2025 Reviewers agreed at journal 09 Jan, 2025 Reviewers agreed at journal 09 Jan, 2025 Reviewers invited by journal 05 Nov, 2024 Editor invited by journal 17 Oct, 2024 Editor assigned by journal 17 Oct, 2024 Submission checks completed at journal 17 Oct, 2024 First submitted to journal 16 Oct, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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University","correspondingAuthor":true,"prefix":"","firstName":"Hongyang","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2024-10-16 17:38:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5277719/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5277719/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-025-03033-x","type":"published","date":"2025-04-23T15:58:08+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":67730761,"identity":"adaa4e18-57e9-48c3-aed9-b7519d794ca3","added_by":"auto","created_at":"2024-10-29 07:09:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":102728,"visible":true,"origin":"","legend":"\u003cp\u003ePostoperative chest imaging\u003c/p\u003e","description":"","filename":"figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-5277719/v1/dde8559d6bb3602a7e35ca35.png"},{"id":67730760,"identity":"506e949e-cf03-4c1e-bc25-9d492df49a52","added_by":"auto","created_at":"2024-10-29 07:09:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":91776,"visible":true,"origin":"","legend":"\u003cp\u003eABG at various time points during and after prone treatment\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-5277719/v1/881ecdd9405f534bbe10c75a.png"},{"id":67730758,"identity":"4c5c18b8-0375-4918-a776-ad16016547bb","added_by":"auto","created_at":"2024-10-29 07:09:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":103634,"visible":true,"origin":"","legend":"\u003cp\u003eABG during inhalation of NO\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-5277719/v1/1f7a38be76e794e8c7374402.png"},{"id":67730759,"identity":"6c0767bc-2974-4641-8512-4d974bd97310","added_by":"auto","created_at":"2024-10-29 07:09:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":107479,"visible":true,"origin":"","legend":"\u003cp\u003eLung field become clear\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-5277719/v1/14439fb648a993c7343d3bf3.png"},{"id":67730765,"identity":"c890bec1-cd0f-43b1-81e7-bb890050ef79","added_by":"auto","created_at":"2024-10-29 07:09:22","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":427477,"visible":true,"origin":"","legend":"\u003cp\u003eEIT images at each points in time. T0: transferred to ICU. T1: prone position for 6hours. T2: NO application for 16hours.T3: transferred out ICU\u003c/p\u003e","description":"","filename":"figure5.png","url":"https://assets-eu.researchsquare.com/files/rs-5277719/v1/64c8b0e38e26acff40c6855c.png"},{"id":81569880,"identity":"eb6c19f8-6814-4ce6-85de-063604ad939d","added_by":"auto","created_at":"2025-04-28 16:12:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1443243,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5277719/v1/3905b373-c3ee-47fd-8f5c-4efa7612eb40.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A case of prone position combined with iNO therapy under EIT monitoring in the treatment of refractory hypoxemia after lung transplantation","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLung transplantation is the most effective treatment for end-stage pulmonary disease. Primary graft dysfunction (PGD) occurring within 72 hours post-operation is a major factor leading to early mortality in lung transplants recipients. In January 2024, our department successfully treated a patient who experienced PGD after lung transplant. The patient presented with refractory hypoxemia following the transplant surgery, to address this critical condition, we employed electrical impedance\u003c/p\u003e \u003cp\u003etomography (EIT) for monitoring, along with prone positioning and inhaled nitric oxide (iNO) therapy. The subsequent sections provide a detailed account of the case.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eThe 54-year-old female patient was diagnosed with pulmonary interstitial fibrosis at the age of 52, treated with oral pirfenidone and prednisone. Despite ongoing cough and expectoration, there was a slight improvement in chest tightness and asthma as compared to before. However, discontinuing pirfenidone in April 2023 resulted in worsening dyspnea, necessitating continuous home oxygen therapy. Minimal exertion was found to elicit significant asthmatic symptoms, rendering the patient unable to be weaned off oxygen. A lung biopsy revealed usual interstitial pneumonia (UIP). Pre-transplant evaluation indicated a body mass index(BMI) of 25.59 kg/m^2. Pulmonary function tests showed FVC: 1.0L, 35.6%; FEV1: 1.093L, 39. 1%; FEV1/FVC: 92.94%. Diffusing capacity test was inconclusive. The 6-minute walk test distance was 150m, with an oxygen flow rate of 4L/min, a lowest SpO2 at 82%, and a highest heart rate of 110 beats per minute. Physical examination revealed coarse breath sounds and Velcro crackles in both lungs. The patient was listed for lung transplant in late December and underwent bilateral lung transplantation with venovenous extracorporeal membrane oxygenation (V-V ECMO) support on January 26, 2024. The surgery lasted 7.8 hours, with a peak cold ischemia time of 630 minutes. Intraoperative blood loss was 1200 ml, and blood transfusion amounted to 1450 ml. Postoperatively, the patient remained hemodynamically stable but necessitated additional ECMO support in the ICU due to suboptimal oxygenation.\u003c/p\u003e\n\u003cp\u003eUpon ICU admission, the patient was provided with mechanical ventilatory support and V-V ECMO (via internal jugular-femoral vein) cardiopulmonary support. Treatment included anti-infective therapy with imipenem/cilastatin sodium combined with caspofungin, immunosuppression with methylprednisolone and tacrolimus, sedation, analgesia, muscle relaxation, blood transfusion support, expectorant therapy, and acid suppression among other interventions. Despite ventilator and V-V ECMO support, arterial blood gas (ABG) indicated inadequate oxygenation with PaO2: 78.5mmHg, PaCO2: 43.6mmHg and FIO2: 80%. A chest X-ray showed bilateral pulmonary exudative changes (Figure 1). Lung ultrasonography revealed scattered B-lines in the anterior and lateral thoracic walls, and extensive confluent B-lines with a few fragmentary signs in the posterior thoracic wall. EIT examination showed center of ventilation (CoV) of 48%, left lung heterogeneity index (LHI) of 67, and global inhomogeneity index (GI) of 79.6. The treatment strategy was temporarily altered to enhance d iuresis and replenish colloidal osmotic pressure to mitigate pulmonary edema.\u003c/p\u003e\n\u003cp\u003eWithin the first 3 days post-operation, the patient\u0026apos;s oxygenation remained poor. Intermittent fiberoptic bronchoscopy was performed and revealed moderate congestion and edema in the airways, with a small amount of edema fluid observed bilaterally. Considering that the patient was at the peak of PGD, ECMO support was continued along with enhanced fluid management.\u003c/p\u003e\n\u003cp\u003eOn the morning of the 4th day post-operation, we initiated our first attempt to wean the patient off ECMO support. ABG analysis showed: PaO2: 71.7mmHg, PaCO2: 86.2mmHg, FIO2: 90%. Following assessment, it was determined that the withdrawn of ECMO was not feasible. Subsequent bronchoscopy indicated significant airways contamination with moderate yellow mucus, and the patient\u0026apos;s oxygenation remained suboptimal. Therefore, a decision was made to initiate prone positioning ventilation treatment. The initial prone position session lasted 22 hours, during which ABG analysis showed improved oxygenation. The EIT results were as follows: CoV: 55%, LHI: 72, GI: 68. Unfortunately, oxygenation deteriorated again following discontinuation of prone positioning (Figure 2).\u003c/p\u003e\n\u003cp\u003eOn the 6th day post-operation, given the patient\u0026rsquo;s strong dependence on ECMO and the prolonged inability to improve oxygenation, inhaled NO therapy (INOwill N200 Nitric Oxide Generator and Delivery System, Novlead Biotechnology, China) was initiated to improve the ventilation-perfusion ratio of the lungs. The NO concentration was set at 20ppm, with a monitored concentration of 17ppm, and an NO2 concentration of 0.2ppm . ABG analysis showed: PaO2 : 88.3mmHg , PaCO2 : 52.2mmHg, FIO2 : 80% . Six hours after initiating NO therapy, the ABG indicated: PaO2 : 119mmHg, PaCO2 : 39.2mmHg , FIO2 : 80% . EIT results were: LHI: 79, GI: 67.\u003c/p\u003e\n\u003cp\u003eSubsequent treatments led to a marked improvement in oxygenation (Figure 3), optimization of ventilation-perfusion ratio, stabilization of circulation, and clearance of the lung fields (Figure 4), demonstrating the effectiveness of the treatment.\u003c/p\u003e\n\u003cp\u003eOn the morning of the 10th day post-operation, we were pleasantly surprised to find that the patient\u0026apos;s tidal volume had improved to 390 ml. We attempted to wean the patient off the ECMO again and performed a fiberoptic bronchoscopy to assess the airway condition. Ultimately, the ECMO was successfully withdrawn after 3 hours, at which time EIT showed: CoV: 54%, LHI: 80, GI: 63. Unfortunately, upon performing the bronchoscopy, a significant amount of sputum was still observed, accompanied by moderate congestion and edema of the respiratory mucosa, and the mucosa of the right airway appeared grayish-black. Sputum culture indicated pan-resistant \u003cem\u003eAcinetobacter baumannii\u0026nbsp;\u003c/em\u003eand \u003cem\u003ePseudomonas\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eaeruginos\u003c/em\u003e\u003cem\u003e\u0026nbsp;.\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e The anti-infective treatment regimen was altered to a combination of eravacycline, ceftazidime-avibactam, and isavuconazole . Given the patient\u0026apos;s poor oxygenation and lung compliance, inability to cough up sputum independently, and the inability to be weaned off the ventilator and extubated in the short term, a tracheotomy was planned for the following day.\u003c/p\u003e\n\u003cp\u003eAfter the tracheotomy, bronchoscopy showed a reduction in the amount of sputum and an improvement in its characteristics. The edema of the airway mucosa had improved compared to before, the infection markers gradually decreased without fluctuations, and the antibiotics were gradually reduced. The level of ventilator support was reduced compared to before. On the 24th day post-operation, the patient was successfully transferred out of the ICU (Figure 5). 52 days after the operation, the patient was successfully weaned off the ventilator and the tracheostomy tube was removed.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePGD is the leading cause of early mortality in lung transplantation recipients [ 1, 2], typically occurring within 24 to 72 hours post-ransplantation. This patient exhibited severe hypoxemia within 72 hours after lung transplantation, with an oxygenation index \u0026lt;200 mm Hg (ABG on the 3th day post-operation showed an oxygenation index of 133mmHg) . Bronchoscopy revealed moderate to severe congestion and edema of the respiratory mucosa, and chest X-ray examination showed diffuse exudative changes in both lung fields, meeting the clinical diagnostic criteria for PGD 3, indicating a poor prognosis [2, 3] .\u003c/p\u003e\n\u003cp\u003eDespite the support of V-V ECMO, the patient experienced persistent hypoxemia. Our department used EIT technology to provide real-ime information on regional pulmonary ventilation and blood perfusion, combined with bedside chest ultrasound to form a visual respiratory management. Based on the imaging results provided by EIT, we adjusted the patient\u0026rsquo;s treatment strategy to improve lung ventilation or perfusion, aiming for better therapeutic outcomes. Effective gas exchange and improved oxygenation can only be achieved when lung ventilation and perfusion are well-matched.\u003c/p\u003e\n\u003cp\u003eProne position ventilation refers to the practice of placing the patient in a prone position during mechanical ventilation, which, through the effect of gravity, improves the ventilation-perfusion ratio [4], facilitates the drainage of pulmonary secretions, and enhances oxygenation [5] . From a pathophysiological standpoint, prone position ventilation, effective in treating acute respiratory distress syndrome (ARDS), may also be applicable for improving PGD conditions in lung transplant recipients. In 2017, the American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine strongly recommended that patients with severe ARDS receive prone positioning for more than 12 hours daily [6] . A meta-analysis evaluating the impact of prone positioning on ARDS (8 randomized trials, 2129 patients) [7] showed that patients with moderate to severe ARDS could benefit from daily prone positioning for more than 12 hours in terms of survival. Considering the extensive surgical wounds of the patient and the numerous tubes (ECMO jugular- femoral cannulation, mechanical ventilation orotracheal intubation, chest tubes, etc.), to avoid serious complications such as tube dislodgement the patient\u0026apos;s first prone position lasted 22 hours. We simultaneously set the ventilator\u0026apos;s tidal volume at 300-400 ml to reduce the risks of atelectasis and hyperinflation, and minimize the physical damage to the alveoli caused by mechanical ventilation [8] . During prone position ventilation treatment, the patient did not experience pressure sores, surgical wound dehiscence with bleeding, tube dislodgement, or other complications.\u003c/p\u003e\n\u003cp\u003eAfter prone position treatment, the improvement in LHIx was not significant, oxygenation could not be maintained, and the patient still could not successfully pass the ECMO independent test. Concurrently, postoperative sputum culture showed pan-drug resistant \u003cem\u003eAcineto\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003ebacter\u003c/em\u003e\u003cem\u003e\u0026nbsp;baumannii\u0026nbsp;\u003c/em\u003eand \u003cem\u003ePseudomonas\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eaeruginosa\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003einfection, contributing to refractory hypoxemia. NO is a selective pulmonary dilator, which can reduce pulmonary artery pressure and increase pulmonary blood flowand improve ventilator-perfusion mismatch. Previous basic studies have shown that NO can inhibit the proliferation and replication of a variety of bacteria in the lungs, inhibit the production of pulmonary inflammatory chemokines [9], and its effect is similar to the application of local glucocorticoids [ 10]. When prone position therapy for 22 hours was ineffective, we promptly initiated iNO therapy as a remedial measure. After continuous NO inhalation for 6 hours, the oxygenation index of the patients increased significantly. Although the benefit diminished over time with long-term use, iNO still showed a good effect in improving ventilation and blood perfusion. During the treatment period, the patient\u0026rsquo;s ventilator support gradually decreased, circulation stabilized, and the treatment was effective.\u003c/p\u003e\n\u003cp\u003ePerforming a tracheostomy during ECMO carries a significant risk of bleeding. The interaction between the blood of an ECMO patient and the surface of the circuit leads to an imbalance between pro-coagulation and anticoagulation mechanisms [ 11] . Additionally, the patient was concurrently undergoing iNO therapy, which can inhibit platelet aggregation [ 12] , thereby affecting coagulation function and the use of anticoagulants during treatment. The patient\u0026apos;s anticoagulation management was already facing significant challenges. Therefore, choosing the right timing for the tracheostomy is crucial. Performing the tracheostomy after weaning off ECMO can significantly reduce the risk of bleeding complications. In this case, the tracheostomy was timely performed after ECMO weaning and discontinuation of iNO, playing a certain role in the patient\u0026apos;s recovery.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe application of EIT for monitoring and evaluating alterations in lung ventilation and perfusion in patients at critical stages following lung transplantation,facilitates visual respiratory management strategies. This approach ,combined with the implementation of diverse therapeutic interventions such as prone positioning and iNO therapy, contributes to the enhancement of prognostic outcomes for lung transplant recipients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePGD Primary graft dysfunction\u003c/p\u003e\n\u003cp\u003eECMO Extracorporeal membrane oxygenation \u003c/p\u003e\n\u003cp\u003eEIT Electrical impedance tomography \u003c/p\u003e\n\u003cp\u003eiNO Inhaled nitric oxide \u003c/p\u003e\n\u003cp\u003eICU Intensive care unit \u003c/p\u003e\n\u003cp\u003eUIP Usual interstitial pneumonia \u003c/p\u003e\n\u003cp\u003eBMI Body mass index\u003c/p\u003e\n\u003cp\u003eV-V ECMO Venovenous extracorporeal membrane oxygenation \u003c/p\u003e\n\u003cp\u003eABG Arterial blood gas \u003c/p\u003e\n\u003cp\u003eCoV Center of ventilation \u003c/p\u003e\n\u003cp\u003eLHI Lung heterogeneity index \u003c/p\u003e\n\u003cp\u003eGI Global inhomogeneity index \u003c/p\u003e\n\u003cp\u003eARDS Acute respiratory distress syndrome \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eAuthor contributions \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to this case report. All provided input and critique on the final manuscript.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report was financially supported by no funding.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo datasets were generated or analysed during the current study.\u003c/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Institutional Ethics Committees of Wuxi People\u0026rsquo;s Hospital affiliated to Nanjing Medical University approved this study. Informed consents in written form were obtained from the patients or their next of kin in written.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patients for publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eShah RJ, Diamond JM, Cantu E, et al. Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation. Chest. 2013;144(2):616\u0026ndash;22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClausen E, Cantu E. Primary graft dysfunction: what we know. J Thorac Dis. 2021;13(11):6618\u0026ndash;27.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCantu E, Diamond JM, Cevasco M, et al. Contemporary trends in PGD incidence, outcomes, and therapies. J Heart Lung Transpl. 2022;41(12):1839\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGlenny RW, Lamm WJ, Albert RK, et al. Gravity is a minor determinant of pulmonary blood flow distribution. J Appl Physiol (1985). 1991;71(2):620\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCardinale M, Boussen S, Cungi PJ, et al. Lung-Dependent Areas Collapse, Monitored by Electrical Impedance Tomography, May Predict the Oxygenation Response to Prone Ventilation in COVID-19 Acute Respiratory Distress Syndrome. Crit Care Med. 2022;50(7):1093\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFan E, Del Sorbo L, Goligher EC, An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline, et al. Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2017;195(9):1253\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMunshi L, Del Sorbo L, Ad hikari NKJ, et al. Prone Position for Acute Respiratory Distress Syndrome. A Systematic Review and Meta-Analysis. Ann Am Thorac Soc. 2017;14(Supplement4):S280\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeitler JR, Shaefi S, Montesi SB, et al. Prone positioning reduces mortality from acute respiratory distress syndrome in the low tidal volume era: a meta-analysis. Intensive Care Med. 2014;40(3):332\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGore A, Gauthier AG, Lin M, et al. The nitric oxide donor, (Z)-1-[N-(2- aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA- NONOate/D-NO), increases survival by attenuating hyperoxia-compromised innate immunity in bacterial clearance in a mouse model of ventilator- associated pneumonia. Biochem Pharmacol. 2020;176:113817.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKirov MY, Evgenov OV, Bjertnaes LJ. Combination of intravenously infused methylene blue and inhaled nitric oxide ameliorates endotoxin- induced lung injury in awake sheep. Crit Care Med. 2003;31(1):179\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrodie D, Slutsky AS, Combes A. Extracorporeal Life Support for Adults With Respiratory Failure and Related Indications: A Review. JAMA. 2019;322(6):557\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGermann P, Braschi A, Della Rocca G, et al. Inhaled nitric oxide therapy in adults: European expert recommendations. Intensive Care Med. 2005;31(8):1029\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Lung transplants, Electrical impedance tomography (EIT), Prone position ventilation treatment, iNO therapy","lastPublishedDoi":"10.21203/rs.3.rs-5277719/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5277719/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWe report a case of severe primary graft dysfunction (PGD) and refractory hypoxemia after bilateral lung transplantation in our center. The effect of conventional therapy of the patient was inadequate, and the patient was unable to be weaned off extracorporeal membrane oxygenation (ECMO). Employing electrical impedance tomography (EIT) monitoring technology, we implemented a series of interventions including\u003c/p\u003e \u003cp\u003eprone position, inhaled nitric oxide (iNO) therapy, tracheotomy and other treatment methods. After undergoing a rigorous treatment process, the patient was successfully transitioned out of intensive care unit (ICU) on the 24th day after operation. In conclusion, the utilization of EIT for visual respiratory management, in conjunction with a multifaceted therapeutic approach, substantially contributed to the improved prognosis of lung transplant recipients.\u003c/p\u003e","manuscriptTitle":"A case of prone position combined with iNO therapy under EIT monitoring in the treatment of refractory hypoxemia after lung transplantation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-29 07:09:12","doi":"10.21203/rs.3.rs-5277719/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-01-15T06:46:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-14T15:49:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-14T11:32:13+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"280509273434246702607382130530014112924","date":"2025-01-14T11:18:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"631748448147029458743324016699727387","date":"2025-01-14T05:28:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-11T01:01:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-01-09T19:40:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"139288077888168641091562014418548579879","date":"2025-01-09T17:43:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"121468710927027834881323570593524281529","date":"2025-01-09T17:25:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-11-06T03:53:07+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-10-17T10:21:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-17T05:02:53+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-10-17T05:01:05+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2024-10-16T17:22:38+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e636124d-981e-45ec-b12b-86a81836c7a3","owner":[],"postedDate":"October 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-04-28T16:06:50+00:00","versionOfRecord":{"articleIdentity":"rs-5277719","link":"https://doi.org/10.1186/s12871-025-03033-x","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2025-04-23 15:58:08","publishedOnDateReadable":"April 23rd, 2025"},"versionCreatedAt":"2024-10-29 07:09:12","video":"","vorDoi":"10.1186/s12871-025-03033-x","vorDoiUrl":"https://doi.org/10.1186/s12871-025-03033-x","workflowStages":[]},"version":"v1","identity":"rs-5277719","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5277719","identity":"rs-5277719","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}