Platelet aggregates in lung capillaries in severely decompensated pulmonary hypertension.

The mechanism of thrombocytopenia during acute pulmonary hypertension (PH) decompensation may be partly due to platelet aggregation in the lung. Platelet aggregates in explanted lung from 16 lung transplant patients during acute PH decompensation with and without thrombocytopenia were identified by immunohistochemistry. Scanning electron microscopy (SEM) was performed. 7 explant lung controls without PH and thrombocytopenia were also examined. Compared with controls, the median number of platelet aggregates was higher in patients with acute PH decompensation with thrombocytopenia (19.4 [IQR 3.4-38.3] vs 147.5 [IQR 26.5-203.2]). SEM showed capillaries filled with platelet aggregates. Our study suggests that platelets may aggregate in the lungs during acute PH decompensation.

Probabilistic Prediction of Gastrointestinal Ischemia after Cardiothoracic Surgery.

BACKGROUND: Gastrointestinal ischemia (GIisch) is challenging to diagnose in patients after cardiothoracic surgery. Computed tomography angiography (CTA) carries substantial false-negative and false-positive rates. The aim of the study was to evaluate if a combination of readily available variables improves the diagnosis of GIisch after cardiothoracic surgery. METHODS: This retrospective study included patients receiving intensive care after cardiothoracic surgery. GIisch was confirmed by surgical and/or endoscopic findings. A GIisch prediction score was developed using the Spiegelhalter-Knill-Jones system in a training cohort then tested in a validation cohort (patients without obvious signs of GIisch on CTA). RESULTS: The training cohort comprised 125 consecutive patients with suspected GIisch in 2008 to 2019, including 85 with confirmed GIisch. CTA, performed in 92 patients, had a high false-negative rate of 17/60 (28%) and a lower false-positive rate of 7/32 (22%). The score included cardiopulmonary bypass, negatively associated with GIisch, and six variables positively associated with GIisch: intraoperative mean arterial pressure < 50 mm Hg, aspartate aminotransferase > 15 N, lactate increase in 24 hour > 20%, and 3 CTA findings, namely, bowel dilation, bowel wall thickening, and mesenteric vasoconstriction. The area under the receiver operating characteristic was 0.82 (95% confidence interval [CI], 0.51-0.93) in the training cohort and 0.82 (95% CI, 0.68-0.96) in the validation cohort (n = 34 patients). Reliability of the predicted probabilities was greatest for probabilities ≤ 30% or ≥ 70%. CONCLUSION: In patients receiving intensive care after cardiothoracic surgery, GIisch cannot be ruled out based solely on CTA findings. A scoring system combining CTA findings with other variables may improve the diagnosis of GIisch in this population.

Impact of Prone Position in COVID-19 Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19-related ARDS. DESIGN: Retrospective analysis of a multicenter cohort. PATIENTS: Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47-61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29-0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients. CONCLUSIONS: Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19-related ARDS but more data are needed to draw definitive conclusions.

Circuit change during extracorporeal membrane oxygenation: single-center retrospective study of 48 changes.

BACKGROUND: Bleeding and thrombosis induce major morbidity and mortality in patients under extracorporeal membrane oxygenator (ECMO). Circuit changes can be performed for oxygenation membrane thrombosis but are not recommended for bleeding under ECMO. The objective of this study was to evaluate the course of clinical, laboratory, and transfusion parameters before and after ECMO circuit changes warranted by bleeding or thrombosis. METHODS: In this single-center, retrospective, cohort study, clinical parameters (bleeding syndrome, hemostatic procedures, oxygenation parameters, transfusion) and laboratory parameters (platelet count, hemoglobin, fibrinogen, PaO2) were collected over the seven days surrounding the circuit change. RESULTS: In the 274 patients on ECMO from January 2017 to August 2020, 48 circuit changes were performed in 44 patients, including 32 for bleeding and 16 for thrombosis. Mortality was similar in the patients with vs. without changes (21/44, 48% vs. 100/230, 43%) and in those with bleeding vs. thrombosis (12/28, 43% vs. 9/16, 56%, P = 0.39). In patients with bleeding, numbers of bleeding events, hemostatic procedures, and red blood cell transfusions were significantly higher before vs. after the change (P < 0.001); the platelet counts and fibrinogen levels decreased progressively before and increased significantly after the change. In patients with thrombosis, numbers of bleeding events and red blood cell transfusions did not change after membrane change. No significant differences were demonstrated between oxygenation parameters (ventilator FiO2, ECMO FiO2, and PaO2) and ECMO flow before vs. after the change. CONCLUSIONS: In patients with severe and persistent bleeding, changing the ECMO circuit decreased clinical bleeding and red blood cell transfusion needs and increased platelets and fibrinogen levels. Oxygenation parameters did not change significantly in the group with thrombosis.

Oxygenation versus driving pressure for determining the best positive end-expiratory pressure in acute respiratory distress syndrome.

OBJECTIVE: The aim of this prospective longitudinal study was to compare driving pressure and absolute PaO2/FiO2 ratio in determining the best positive end-expiratory pressure (PEEP) level. PATIENTS AND METHODS: In 122 patients with acute respiratory distress syndrome, PEEP was increased until plateau pressure reached 30 cmH2O at constant tidal volume, then decreased at 15-min intervals, to 15, 10, and 5 cmH2O. The best PEEP by PaO2/FiO2 ratio (PEEPO2) was defined as the highest PaO2/FiO2 ratio obtained, and the best PEEP by driving pressure (PEEPDP) as the lowest driving pressure. The difference between the best PEEP levels was compared to a non-inferiority margin of 1.5 cmH2O. MAIN RESULTS: The best mean PEEPO2 value was 11.9 ± 4.7 cmH2O compared to 10.6 ± 4.1 cmH2O for the best PEEPDP: mean difference = 1.3 cmH2O (95% confidence interval [95% CI], 0.4-2.3; one-tailed P value, 0.36). Only 46 PEEP levels were the same with the two methods (37.7%; 95% CI 29.6-46.5). PEEP level was ≥ 15 cmH2O in 61 (50%) patients with PEEPO2 and 39 (32%) patients with PEEPDP (P = 0.001). CONCLUSION: Depending on the method chosen, the best PEEP level varies. The best PEEPDP level is lower than the best PEEPO2 level. Computing driving pressure is simple, faster and less invasive than measuring PaO2. However, our results do not demonstrate that one method deserves preference over the other in terms of patient outcome. CLINICAL TRIAL NUMBER: #ACTRN12618000554268 . Registered 13 April 2018.

Transplantation for pulmonary arterial hypertension with congenital heart disease: Impact on outcomes of the current therapeutic approach including a high-priority allocation program.

Patients with end-stage pulmonary arterial hypertension due to congenital heart disease have limited access to heart-lung transplantation or double-lung transplantation. We aimed to assess the effects of a high-priority allocation program established in France in 2007. We conducted a retrospective study to compare waitlist and posttransplantation outcomes before versus after implementation of the high-priority allocation program. We included 67 consecutive patients (mean age at listing, 33.2 ± 10.5 years) with pulmonary arterial hypertension due to congenital heart disease listed for heart-lung transplantation or double-lung transplantation from 1997 to 2016. At one month, the incidences of transplantation and death before transplantation were 3.5% and 24.6% in 1997-2006, 4.8% and 4.9% for patients on the regular list in 2007-2016, and 41.2% and 7.4% for patients listed under the high-priority allocation program (p < .001 and p = .0001, respectively). Overall survival was higher in patients listed in 2007-2016 (84.2% and 61.2% at 1 and 10 years vs. 36.8% and 22.1%, p = .0001). Increased incidence of transplantation, decreased waiting list mortality, and improved early and long-term outcomes were observed in patients with pulmonary arterial hypertension due to congenital heart disease listed for transplantation in the recent era, characterized by implementation of a high-priority allocation program.

Urgent desensitization in patients bridged to heart transplantation under extracorporeal membrane oxygenation support: A preliminary experience.

Antihuman leukocyte antigen (HLA) antibodies restrict the access to cardiac allografts. Desensitization therapy is a major challenge in patients with cardiogenic shock waiting for urgent heart transplantation (HT). We retrospectively reviewed six patients (mean age of 37.5 years [16-70]) who underwent plasmapheresis (PP) under extracorporeal membrane oxygenation (ECMO) before transplant between January 2017 and September 2018. The average duration of follow-up was 25 months [20-32]. Mean fluorescence intensity (MFI) of HLA-specific antibodies was reported as follows: score 4 for MFI < 1000, score 6 for 1000 < MFI < 3000 and score 8 for MFI > 3000. The mean duration of ECMO support was 29 days [1-74] and 6.8 [1-29] PP sessions were performed per patient before transplant. The mean number of HLA-specific antibodies before HT was 9.6 for score 6 [4-13] and 5.8 for score 8 [1-12]. Four patients had major complications after transplantation (2 hemorrhagic shocks, 5 infectious events). Mean MFI reduction rate was 94% [79-100] for Class I and 44.2% for Class II [0-83]. Hospital survival was 100%, and early antibody-mediated rejection was diagnosed in one patient at 7 days after HT. Plasmapheresis under ECMO support was associated with favorable early outcomes in highly sensitized candidates for urgent heart transplantation.

Neuromuscular Blockade Monitoring in Acute Respiratory Distress Syndrome: Randomized Controlled Trial of Clinical Assessment Alone or With Peripheral Nerve Stimulation.

BACKGROUND: Whether train-of-four (TOF) monitoring is more effective than clinical monitoring to guide neuromuscular blockade (NMB) in patients with acute respiratory distress syndrome (ARDS) is unclear. We compared clinical monitoring alone or with TOF monitoring to guide atracurium dosage adjustment with respect to drug dose and respiratory parameters. METHODS: From 2015 to 2016, we conducted a randomized controlled trial comparing clinical assessments every 2 hours with or without corrugator supercilii TOF monitoring every 4 hours in patients who developed ARDS (Pao2/Fio2 <150 mm Hg) in a cardiothoracic intensive care unit. The primary outcome was the cumulative atracurium dose (mg/kg/h). Secondary outcomes included respiratory parameters during the neuromuscular blockade. RESULTS: A total of 38 patients in the clinical + TOF (C + TOF) group and 39 patients in the clinical (C) group were included in an intention-to-treat (ITT) analysis. The cumulative atracurium dose was higher in the C + TOF group (1.06 [0.75-1.30] vs 0.65 [0.60-0.89] mg/kg/h in the C group; P < .001) compared to C group, as well as the atracurium daily dose (C + TOF - C group mean difference = 0.256 mg/kg/h [95% confidence interval {CI}, 0.099-0.416], P = .026). Driving pressures during neuromuscular blocking agent (NMBA) administration did not differ between groups (P = .653). Intensive care unit (ICU) mortality was 22% in the C group and 27% in the C + TOF group (P = .786). Days on ventilation were 17 (8-26) in the C group and 16 (10-35) in the C + TOF group. CONCLUSIONS: In patients with ARDS, adding TOF to clinical monitoring of neuromuscular blockade did not change ICU mortality or days on mechanical ventilation (MV) but did increase atracurium consumption when compared to clinical assessment alone. TOF monitoring may not be needed in all patients who receive neuromuscular blockade for ARDS.

Ultrasound Assessment of Respiratory Workload With High-Flow Nasal Oxygen Versus Other Noninvasive Methods After Chest Surgery.

OBJECTIVE: To compare the respiratory workload using the diaphragm thickening fraction (DTf) determined by sonography during high-flow nasal oxygen (HFNO), standard oxygen therapy (SOT), and noninvasive bilevel positive airway pressure support (BIPAP) in patients with acute respiratory failure (ARF) after cardiothoracic surgery. DESIGN: Prospective controlled clinical trial. SETTING: A French 23-bed cardiothoracic surgical intensive care unit. PARTICIPANTS: Nonintubated patients with ARF after cardiothoracic surgery or while awaiting lung transplantation. INTERVENTIONS: HFNO (50 L/min), SOT via a standard facemask, and BIPAP (pressure support, 4 cmH2O; positive end-expiratory pressure [PEEP], 4 cmH2O), with FIO2 kept constant were successively applied and compared. With BIPAP, pressure support or PEEP increments up to 8 cmH2O were compared with baseline settings. Each measurement was made after stable breathing for 5 minutes. MEASUREMENTS AND MAIN RESULTS: Fifty patients aged 60.0 ± 12.2 years were enrolled, including 14 (28%) with obesity. Mean PaO2/FIO2 was 153 ± 55 mmHg. DTf was lower with HFNO and BIPAP than with SOT (respectively 21.2% ± 15.1% v 30.9% ± 21.1% and 17.8% ± 19.1% v 30.9% ± 21.1%, p < 0.001) and was not different with HFNO versus BIPAP (p = 0.22). With BIPAP, increasing pressure support to 8 cmH2O decreased DTf (21.0% ± 14.3% v 28.8% ± 19.8%, p = 0.009), whereas increasing PEEP to 8 cmH2O did not (25.2% ± 17.2% v 28.8% ± 19.8%, p = 0.79). Tidal volume increased to 10.6 ± 3.4 mL/kg with 8 cmH2O pressure support v 8.8 ± 2.7 mL/kg with 4 cmH2O pressure support (p < 0.001). CONCLUSION: HFNO provides a comparable respiratory workload decrease compared with BIPAP at lower levels of pressure support and PEEP compared with SOT. Increasing BIPAP pressure support may provide higher levels of assistance but carries a risk of overdistension.

Tracheal replacement.

Tracheal reconstruction is one of the greatest challenges in thoracic surgery when direct end-to-end anastomosis is impossible or after this procedure has failed. The main indications for tracheal reconstruction include malignant tumours (squamous cell carcinoma, adenoid cystic carcinoma), tracheoesophageal fistula, trauma, unsuccessful surgical results for benign diseases and congenital stenosis. Tracheal substitutes can be classified into five types: 1) synthetic prosthesis; 2) allografts; 3) tracheal transplantation; 4) tissue engineering; and 5) autologous tissue composite. The ideal tracheal substitute is still unclear, but some techniques have shown promising clinical results. This article reviews the advantages and limitations of each technique used over the past few decades in clinical practice. The main limitation seems to be the capacity for tracheal tissue regeneration. The physiopathology behind this has yet to be fully understood. Research on stem cells sparked much interest and was thought to be a revolutionary technique; however, the poor long-term results of this approach highlight that there is a long way to go in this research field. Currently, an autologous tissue composite, with or without a tracheal allograft, is the only long-term working solution for every aetiology, despite its technical complexity and setbacks.

Evaluation of Reperfusion Pulmonary Edema by Extravascular Lung Water Measurements After Pulmonary Endarterectomy.

OBJECTIVES: Reperfusion pulmonary edema is a specific complication of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Extravascular lung water measurement may be valuable for diagnosing reperfusion pulmonary edema. The primary objective of this study was to describe and assess the clinical significance of extravascular lung water variations after pulmonary endarterectomy. DESIGN: Prospective observational study. SETTING: Nineteen-bed cardiothoracic ICU. PATIENTS: Consecutive patients who were hemodynamically stable after pulmonary endarterectomy were divided into two groups based on whether their preoperative pulmonary vascular resistance indicated severe or nonsevere chronic thromboembolic pulmonary hypertension (> 900 or ≤ 900 dynes·s/cm, respectively). INTERVENTIONS: Hemodynamic variables obtained by right heart catheterization and transpulmonary thermodilution measurements were recorded 1 hour, 1 day, and 2 days after pulmonary endarterectomy. Extravascular lung water was indexed to predicted body weight (EVLWPBW). MEASUREMENTS AND MAIN RESULTS: We studied 31 patients. Overall, 26 patients (84%) experienced reperfusion pulmonary edema during the first 72 hours after pulmonary endarterectomy. EVLWPBW significantly increased between the first hour after pulmonary endarterectomy and day 2 (10.2 ± 2.6 vs 11.4 ± 3.6; p = 0.03). EVLWPBW measured at the first hour after pulmonary endarterectomy is closely associated with reperfusion pulmonary edema occurrence in the next 48 hours (area under the receiver-operating characteristics curve = 0.88 ± 0.07). EVLWPBW correlated with duration of mechanical ventilation (ρ = 0.59; p < 0.0001) and ICU stay (ρ = 0.52; p < 0.0001). Patients with severe chronic thromboembolic pulmonary hypertension (n = 15) had higher EVLWPBW values at day 2 compared with those without (n = 16) (13.2 ± 3.6 vs 9.7 ± 2.7 mL/kg; p = 0.004). Cardiac output was measured simultaneously by pulmonary artery catheter and aortic transpulmonary thermodilution on 92 occasions; agreement was good, with a bias of 0.50 ± 0.95 L/min (95% CI, -1.36-2.36). CONCLUSIONS: Accurate extravascular lung water measurements were obtained after pulmonary endarterectomy. Extravascular lung water may prove valuable for diagnosing reperfusion pulmonary edema after pulmonary endarterectomy and had prognostic value. Extravascular lung water values were significantly higher in patients with severe compared with nonsevere chronic thromboembolic pulmonary hypertension.

Extracorporeal life support in lung and heart-lung transplantation for pulmonary hypertension in adults.

After bilateral lung and heart-lung transplantation in adults with pulmonary hypertension, hemodynamic and oxygenation deficiencies are life-threatening complications that are increasingly managed with extracorporeal life support (ECLS). The primary aim of this retrospective study was to assess 30-day and 1-year survival rates in patients managed with vs without post-operative venoarterial ECLS in 2008-2013. The secondary endpoints were the occurrence rates of nosocomial infection, bleeding, and acute renal failure. Of the 93 patients with pulmonary hypertension who received heart-lung (n=29) or bilateral lung (n=64) transplants, 28 (30%) required ECLS a median of 0 [0-6] hours after surgery completion and for a median of 3.0 [2.0-8.5] days. Compared to ECLS patients, controls had higher survival at 30 days (95.0% vs 78.5%; P=.02) and 1 year (83% vs 64%; P=.005), fewer nosocomial infections (48% vs 79%; P=.0006), and fewer bleeding events (17% vs 43%; P=.008). The need for renal replacement therapy was not different between groups (11% vs 17%; P=.54). Venoarterial ECLS is effective in treating pulmonary graft dysfunction with hemodynamic failure after heart-lung or bilateral lung. However, ECLS use was associated with higher rates of infection and bleeding.

High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial.

IMPORTANCE: Noninvasive ventilation delivered as bilevel positive airway pressure (BiPAP) is often used to avoid reintubation and improve outcomes of patients with hypoxemia after cardiothoracic surgery. High-flow nasal oxygen therapy is increasingly used to improve oxygenation because of its ease of implementation, tolerance, and clinical effectiveness. OBJECTIVE: To determine whether high-flow nasal oxygen therapy was not inferior to BiPAP for preventing or resolving acute respiratory failure after cardiothoracic surgery. DESIGN AND SETTING: Multicenter, randomized, noninferiority trial (BiPOP Study) conducted between June 15, 2011, and January 15, 2014, at 6 French intensive care units. PARTICIPANTS: A total of 830 patients who had undergone cardiothoracic surgery, of which coronary artery bypass, valvular repair, and pulmonary thromboendarterectomy were the most common, were included when they developed acute respiratory failure (failure of a spontaneous breathing trial or successful breathing trial but failed extubation) or were deemed at risk for respiratory failure after extubation due to preexisting risk factors. INTERVENTIONS: Patients were randomly assigned to receive high-flow nasal oxygen therapy delivered continuously through a nasal cannula (flow, 50 L/min; fraction of inspired oxygen [FiO2], 50%) (n = 414) or BiPAP delivered with a full-face mask for at least 4 hours per day (pressure support level, 8 cm H2O; positive end-expiratory pressure, 4 cm H2O; FiO2, 50%) (n = 416). MAIN OUTCOMES AND MEASURES: The primary outcome was treatment failure, defined as reintubation, switch to the other study treatment, or premature treatment discontinuation (patient request or adverse effects, including gastric distention). Noninferiority of high-flow nasal oxygen therapy would be demonstrated if the lower boundary of the 95% CI were less than 9%. Secondary outcomes included mortality during intensive care unit stay, changes in respiratory variables, and respiratory complications. RESULTS: High-flow nasal oxygen therapy was not inferior to BiPAP: the treatment failed in 87 of 414 patients with high-flow nasal oxygen therapy (21.0%) and 91 of 416 patients with BiPAP (21.9%) (absolute difference, 0.9%; 95% CI, -4.9% to 6.6%; P = .003). No significant differences were found for intensive care unit mortality (23 patients with BiPAP [5.5%] and 28 with high-flow nasal oxygen therapy [6.8%]; P = .66) (absolute difference, 1.2% [95% CI, -2.3% to 4.8%]. Skin breakdown was significantly more common with BiPAP after 24 hours (10% vs 3%; 95% CI, 7.3%-13.4% vs 1.8%-5.6%; P < .001). CONCLUSIONS AND RELEVANCE: Among cardiothoracic surgery patients with or at risk for respiratory failure, the use of high-flow nasal oxygen therapy compared with intermittent BiPAP did not result in a worse rate of treatment failure. The findings support the use of high-flow nasal oxygen therapy in similar patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01458444.

Incidence of nosocomial pneumonia and risk of recurrence after antimicrobial therapy in critically ill lung and heart-lung transplant patients.

Little is known about the resolution of symptoms of nosocomial pneumonia (NosoP) after lung and heart-lung transplantation. The aim of this study was to describe the clinical response to antimicrobial therapy in (ICU) patients with NosoP after lung or heart-lung transplantation. Between January 2008 and August 2010, 79 lung or heart-lung transplantations patients were prospectively studied. NosoPwas confirmed by quantitative cultures of bronchoalveolar lavage or endotracheal aspirates. Clinical variables, sequential organ failure assessment (SOFA) score, and radiologic score were recorded from start of therapy until day 9. Thirty-five patients (44%) experienced 64 episodes of NosoP in ICU. Fourteen patients (40%) had NosoP recurrence. Most frequently isolated organisms were Enterobacteriaceae (30%), Pseudomonas aeruginosa (25%), and Staphylococcus aureus (20%). Sequential organ failure assessment (SOFA) score improved significantly at day 6 and C-reactive protein level at day 9. SOFA and radiologic scores differed significantly between patients with and without NosoP recurrence at day 3 and 9. The ICU mortality rate did not differ between patients with and without NosoP recurrence, and free of NosoP (14.3%, 9.5%, 11.4%, respectively) (p = 0.91). Severities of illness and lung injury were the two major risk factors for NosoP recurrence. Occurrence of NosoP has no impact on ICU mortality.