Postoperative vasoplegia in lung transplantation: incidence and relation to outcome in a single-centre retrospective study.

BACKGROUND: The incidence and clinical importance of vasoplegia after lung transplantation remains poorly studied. We describe the incidence of vasoplegia and its association with complications after lung transplantation. METHODS: Perioperative data of 279 lung transplant recipients operated on from 2015 to 2020 in a UK hospital were analysed retrospectively. RESULTS: Vasoplegia occurred in 41.6% of patients after lung transplantation (mild, 31.0%; moderate, 55.2%; severe, 13.8%). Compared with non-vasoplegic patients, vasoplegic patients had a higher incidence of any acute kidney injury, defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria (78.5% vs 65%, P=0.015), renal replacement therapy (47.4% vs 24.5%, P<0.001), and delayed chest closure (18.4% vs 9.2%, P=0.025); were ventilated longer (70 [32-368] vs 34 [19-105] h, P<0.001); and stayed longer in the ICU (12.9 [5-30] vs 6.8 [3-20] days, P<0.001). Mortality at 30 days and 1 yr was higher in patients with vasoplegia (11.2% vs 5.5% and 20.7% vs 11.7%, P=0.039, respectively). Severe vasoplegia represented a predictor of longer-term mortality (hazard ratio=1.65, P=0.008). Underlying infectious disease, increased BMI, higher preoperative pulmonary artery systolic pressure and bilirubin levels, lower glomerular filtration rate, and increased fresh frozen plasma transfusion were predictors of vasoplegia severity. Neutrophilia, leucocytosis, and increased C-reactive protein were associated with vasoplegia, but release of the neutrophil activation markers myeloperoxidase and heparin-binding protein was similar between groups. CONCLUSIONS: Influenced by preoperative status as well as procedural factors and inflammatory response, vasoplegia is a common and critical condition after lung transplantation with worse short-term outcomes and long-term survival.

Thoracic surgery in patients on veno-venous extracorporeal membrane oxygenation for COVID-19 associated acute respiratory distress syndrome.

OBJECTIVES: The COVID-19 pandemic has generated a new type of acute respiratory distress syndrome (ARDS) arising as a complication of COVID-19 pneumonia. Extreme cases require the support of extracorporeal membrane oxygenation (ECMO). Here we present the outcomes of patients that underwent surgical tracheostomy or thoracic surgery at a single tertiary centre whilst on ECMO support for COVID-19 related ARDS. METHODS: 18 patients requiring thoracic input whilst on ECMO support during the first wave of COVID-19 (March-June 2020) were included. Thoracic surgery was required both for performing surgical tracheostomies in the operating theatre and for treating emergencies arising under the ECMO treatment such as bleeding complications. RESULTS: Thirteen patients underwent a surgical tracheostomy, whilst five patients had an invasive thoracic procedure. Anticoagulation was withheld for at least 12 h in the perioperative setting regardless of the indication. One patient was re-operated for haemothorax immediately after the end of the primary operation. 94.5% of the patients were successfully decannulated from ECMO support. Overall 30-day mortality in the cohort was 5.5% (1/18). CONCLUSIONS: Thoracic surgeons can play a valuable role in supporting an ECMO unit during the COVID pandemic, by treating ECMO related complications and by safely performing surgical tracheostomies. Withholding anticoagulation in the perioperative window was not associated with increased thromboembolic events and is desirable when interventions or surgery is indicated in this patient cohort to avoid excessive bleeding.

Pulmonary Angiopathy in Severe COVID-19: Physiologic, Imaging, and Hematologic Observations.

Rationale: Clinical and epidemiologic data in coronavirus disease (COVID-19) have accrued rapidly since the outbreak, but few address the underlying pathophysiology.Objectives: To ascertain the physiologic, hematologic, and imaging basis of lung injury in severe COVID-19 pneumonia.Methods: Clinical, physiologic, and laboratory data were collated. Radiologic (computed tomography (CT) pulmonary angiography [n = 39] and dual-energy CT [DECT, n = 20]) studies were evaluated: observers quantified CT patterns (including the extent of abnormal lung and the presence and extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography.Measurements and Results: In 39 consecutive patients (male:female, 32:7; mean age, 53 ± 10 yr [range, 29-79 yr]; Black and minority ethnic, n = 25 [64%]), there was a significant vascular perfusion abnormality and increased physiologic dead space (dynamic compliance, 33.7 ± 14.7 ml/cm H2O; Murray lung injury score, 3.14 ± 0.53; mean ventilatory ratios, 2.6 ± 0.8) with evidence of hypercoagulability and fibrinolytic "shutdown". The mean CT extent (±SD) of normally aerated lung, ground-glass opacification, and dense parenchymal opacification were 23.5 ± 16.7%, 36.3 ± 24.7%, and 42.7 ± 27.1%, respectively. Dilated peripheral vessels were present in 21/33 (63.6%) patients with at least two assessable lobes (including 10/21 [47.6%] with no evidence of acute pulmonary emboli). Perfusion defects on DECT (assessable in 18/20 [90%]) were present in all patients (wedge-shaped, n = 3; mottled, n = 9; mixed pattern, n = 6).Conclusions: Physiologic, hematologic, and imaging data show not only the presence of a hypercoagulable phenotype in severe COVID-19 pneumonia but also markedly impaired pulmonary perfusion likely caused by pulmonary angiopathy and thrombosis.

Intravascular donor monocytes play a central role in lung transplant ischaemia-reperfusion injury.

RATIONALE: Primary graft dysfunction in lung transplant recipients derives from the initial, largely leukocyte-dependent, ischaemia-reperfusion injury. Intravascular lung-marginated monocytes have been shown to play key roles in experimental acute lung injury, but their contribution to lung ischaemia-reperfusion injury post transplantation is unknown. OBJECTIVE: To define the role of donor intravascular monocytes in lung transplant-related acute lung injury and primary graft dysfunction. METHODS: Isolated perfused C57BL/6 murine lungs were subjected to warm ischaemia (2 hours) and reperfusion (2 hours) under normoxic conditions. Monocyte retention, activation phenotype and the effects of their depletion by intravenous clodronate-liposome treatment on lung inflammation and injury were determined. In human donor lung transplant samples, the presence and activation phenotype of monocytic cells (low side scatter, 27E10+, CD14+, HLA-DR+, CCR2+) were evaluated by flow cytometry and compared with post-implantation lung function. RESULTS: In mouse lungs following ischaemia-reperfusion, substantial numbers of lung-marginated monocytes remained within the pulmonary microvasculature, with reduced L-selectin and increased CD86 expression indicating their activation. Monocyte depletion resulted in reductions in lung wet:dry ratios, bronchoalveolar lavage fluid protein, and perfusate levels of RAGE, MIP-2 and KC, while monocyte repletion resulted in a partial restoration of the injury. In human lungs, correlations were observed between pre-implantation donor monocyte numbers/their CD86 and TREM-1 expression and post-implantation lung dysfunction at 48 and 72 hours. CONCLUSIONS: These results indicate that lung-marginated intravascular monocytes are retained as a 'passenger' leukocyte population during lung transplantation, and play a key role in the development of transplant-associated ischaemia-reperfusion injury.

Volatile organic compound profiling to explore primary graft dysfunction after lung transplantation.

Primary graft dysfunction (PGD) is a major determinant of morbidity and mortality following lung transplantation. Delineating basic mechanisms and molecular signatures of PGD remain a fundamental challenge. This pilot study examines if the pulmonary volatile organic compound (VOC) spectrum relate to PGD and postoperative outcomes. The VOC profiles of 58 bronchoalveolar lavage fluid (BALF) and blind bronchial aspirate samples from 35 transplant patients were extracted using solid-phase-microextraction and analyzed with comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry. The support vector machine algorithm was used to identify VOCs that could differentiate patients with severe from lower grade PGD. Using 20 statistically significant VOCs from the sample headspace collected immediately after transplantation (< 6 h), severe PGD was differentiable from low PGD with an AUROC of 0.90 and an accuracy of 0.83 on test set samples. The model was somewhat effective for later time points with an AUROC of 0.80. Three major chemical classes in the model were dominated by alkylated hydrocarbons, linear hydrocarbons, and aldehydes in severe PGD samples. These VOCs may have important clinical and mechanistic implications, therefore large-scale study and potential translation to breath analysis is recommended.

Follow the Lead: The Challenges of Cardiogenic Shock in Device-Related Infective Endocarditis.

We present the challenging case of a young man with congenital heart disease who survived severe device-related infective endocarditis and new pulmonary hypertension. He required prolonged mechanical circulatory support and had multiple significant complications. His case posed a management dilemma that was successfully resolved by effective multidisciplinary, tertiary center care. (Level of Difficulty: Beginner.).

Rapid deployment of virtual ICU support during the COVID-19 pandemic.

The COVID-19 pandemic brought many serious challenges to the clinical workplace, and was a catalyst to novel approaches to the way in which we practice medicine. These challenges include extreme numbers of critically ill patients overwhelming many intensive care units, how to maintain the flow of communication between clinicians, patients and their families, and how to prevent the spread of infection working on quarantined units in personal protective equipment. The Royal Brompton and Harefield Hospitals deployed a series of digital solutions to try to address some of those challenges and a series of case studies describes their clinical application in three clinical domains: communicating with families, clinical communication between clinicians and the delivery of clinical education.

Mechanical ventilation after lung transplantation.

INTRODUCTION: To explore the hypothesis that early ventilation strategies influence clinical outcomes in lung transplantation, we have examined our routine ventilation practices in terms of tidal volumes (Vt) and inflation pressures. METHODS: A total of 124 bilateral lung transplants between 2010 and 2013 were retrospectively assigned to low (<6 mL/kg), medium (6-8 mL/kg), and high (>8 mL/kg) Vt groups based on ventilation characteristics during the first 6 hours after surgery. Those same 124 patients were also stratified to low-pressure (<25 cm H2O) and high-pressure (≥25 cm H2O) groups. RESULTS: Eighty percent of patients were ventilated using pressure control mode. Low, medium, and high Vt were applied to 10%, 43%, and 47% of patients, respectively. After correcting for patients requiring extracorporeal support, there was no difference in short-term to midterm outcomes among the different Vt groups. Low inflation pressures were applied to 61% of patients, who had a shorter length of intensive care unit stay (5 vs 12 days; P = .012), higher forced expiratory volume in 1 second at 3 months (77.8% vs 60.3%; P < .001), and increased 6-month survival rate (95% vs 77%; P = .008). CONCLUSION: Low Vt ventilation has not been fully adopted in our practice. Ventilation with higher inflation pressures, but not Vt, was significantly associated with poorer outcomes after lung transplantation.