Alveolar pentraxin 3 as an early marker of microbiologically confirmed pneumonia: a threshold-finding prospective observational study

Introduction: Timely diagnosis of pneumonia in intubated critically ill patients is rather challenging. Pentraxin 3 (PTX3) is an acute-phase mediator produced by various cell types in the lungs. Animal studies have shown that, during pneumonia, PTX3 participates in fine-tuning of inflammation (for example, microbial clearance and recruitment of neutrophils). We previously described an association between alveolar PTX3 and lung infection in a small group of intubated patients. The aim of the present study was to determine a threshold level of alveolar PTX3 with elevated sensitivity and specificity for microbiologically confirmed pneumonia. Methods: We recruited 82 intubated patients from two intensive care units (San Gerardo Hospital, Monza, Italy, and Massachusetts General Hospital, Boston, MA, USA) undergoing bronchoalveolar lavage (BAL) as per clinical decision. We collected BAL fluid and plasma samples, together with relevant clinical and microbiological data. We assayed PTX3 and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in BAL fluid and PTX3, sTREM-1, C-reactive protein (CRP) and procalcitonin (PCT) in plasma. Two blinded independent physicians reviewed patient data to confirm pneumonia. We determined the PTX3 threshold in BAL fluid for pneumonia and compared it to other biomarkers. Results: Microbiologically confirmed pneumonia of bacterial (n =12), viral (n =4) or fungal (n =8) etiology was diagnosed in 24 patients (29%). PTX3 levels in BAL fluid predicted pneumonia with an area under the receiving operator curve of 0.815 (95% CI =0.710 to 0.921, P <0.0001), whereas none of the other biomarkers were effective. In particular, PTX3 levels ≥1 ng/ml in BAL fluid predicted pneumonia in univariate analysis (β =2.784, SE =0.792, P <0.001) with elevated sensitivity (92%), specificity (60%) and negative predictive value (95%). Net reclassification index PTX3 values ≥1 ng/ml in BAL fluid for pneumonia indicated gain in sensitivity and/or specificity vs. all other mediators. These results did not change when we limited our analyses only to confirmed cases of bacterial pneumonia. Moreover, when we considered only the 70 patients who fulfilled the clinical criteria for the diagnosis of pneumonia at BAL fluid sampling, the diagnostic accuracy of PTX levels was confirmed in univariate and ROC curve analysis. Conclusions: In this hypothesis-generating convenience sample, a PTX3 level ≥1 ng/ml in BAL fluid was discriminative of microbiologically confirmed pneumonia in mechanically ventilated patients. Electronic supplementary material The online version of this article (doi:10.1186/s13054-014-0562-5) contains supplementary material, which is available to authorized users

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

Bronchopleural fistulae and pulmonary ossification in posttraumatic acute respiratory distress syndrome: Successful treatment with extracorporeal support

We report a case of severe posttraumatic acute respiratory distress syndrome (ARDS) complicated by bronchopleural fistulae (BPF). The stiff ARDS lung and huge air leaks from BPF resulted in the failure of different protective mechanical ventilation strategies to provide viable gas exchange. Lung rest, achieved by extracorporeal carbon dioxide removal (ECCO2R), allowed weaning from mechanical ventilation, closure of BPF, and resumption of spontaneous breathing. Copyright \uc2\ua9 American Society of Artificial Internal Organs

Use of extracorporeal respiratory support during pregnancy: A case report and literature review

We describe the case of a 25 year-old woman at 27 weeks of gestation who was admitted to our intensive care unit (ICU) for acute respiratory distress syndrome (ARDS) caused by pandemic 2009 H1N1 influenza A. She presented with septic shock and refractory hypoxemia unresponsive to rescue therapies such as recruitment maneuvers, prone positioning, and nitric oxide inhalation. Extracorporeal membrane oxygenation (ECMO) for respiratory support was instituted, and the patient's clinical conditions progressively improved: she was extubated after 16 days and discharged from the ICU 3 days later. No fetal complications were observed. At 38 weeks of gestation she gave birth to a healthy baby. Copyright \uc2\ua9 2012 by the American Society for Artificial Internal

Pentraxin 3 in acute respiratory distress syndrome: An early marker of severity

OBJECTIVE: Pentraxin 3 is a fluid phase receptor involved in innate immunity. It belongs to the Pentraxins family, as C-reactive protein does. Pentraxin 3 is produced by a variety of tissue cells, whereas only the liver produces C-reactive protein. Pentraxin 3 plays a unique role in the regulation of inflammation. Acute lung injury and acute respiratory distress syndrome are characterized by an important inflammatory reaction. We investigated the role of pentraxin 3 as a marker of severity and outcome predictor of acute lung injury and acute respiratory distress syndrome. DESIGN: We measured circulating pentraxin 3 and C-reactive protein levels within 24 hrs from intubation (day 1), after 24 hrs from the first sample, then every 3 days for the first month and then once a week, until discharge from the intensive care unit. Pentraxin 3 was also measured in bronchoalveolar lavages, performed when clinically indicated. SETTING: One university medical center general intensive care unit. PATIENTS: The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pentraxin 3 plasma levels were high with a peak on the first day (median 71.05 ng/mL, interquartile range 52.37-117.38 ng/mL, normal values &lt;2 ng/mL), declining thereafter. C-reactive protein peaked later and remained at relatively high values. Out of several day 1 parameters, pentraxin 3 was the only significant difference between survivors and nonsurvivors. Pentraxin 3 levels were positively correlated with lung injury score values (p &lt; 0.001) and number of organ failures (p &lt; 0.001). Pentraxin 3 was present in bronchoalveolar lavages fluids (5.03 ng/mL, interquartile range 1.52-8.48 ng/mL) and bronchoalveolar lavages positive to bacterial culture were associated with significantly higher pentraxin 3 values (p &lt; 0.05). CONCLUSIONS: The results presented here show that pentraxin 3 is elevated in acute lung injury and acute respiratory distress syndrome and that its levels correlate with parameters of lung injury and systemic involvement. The clinical and pathophysiological significance of pentraxin 3 in acute lung injury and acute respiratory distress syndrome deserves further scrutiny. \uc2\ua9 2008 by the Society of Critical Care Medicine and Lippincott Williams &amp; Wilkins

Extracorporeal membrane oxygenation for interhospital transfer of severe acute respiratory distress syndrome patients: A 5-year experience

Purpose: Transfer of severely hypoxic patients is a high-risk procedure. Extracorporeal Membrane Oxygenation (ECMO) allows safe transport of these patients to tertiary care institutions. Our ECMO transportation program was instituted in 2004; here we report results after 5 years of activity. Methods: This is a clinical observational study. Criteria for ECMO center activation were: potentially reversibile respiratory failure, PaO2&lt;50 mmHg with FiO2&gt;0.6 for &gt;12 hours, PEEP &gt;5 cmH20, Lung Injury Score (LIS) \ue2\u89\ua53 or respiratory acidosis with pH&lt;7.2, no intracranial bleeding, and no absolute contraindication to anticoagulation. If eligible, a skilled crew applied ECMO at the referral hospital. Transportation was performed with a specially equipped ambulance. Results: Sixteen patients were possible candidates for ECMO transfer. Two patients were excluded while 14 (mean\uc2\ub1SD, age 35.4\uc2\ub118.6, SOFA 8.4\uc2\ub13.7, Oxygenation Index 43.7\uc2\ub113.4) were transported to our institution (distance covered 102\uc2\ub1114 km, global duration of transport 589\uc2\ub1186 minutes). Two patients improved after iNO-trial and were transferred and subsequently managed without ECMO. The remaining 12 patients were transferred on veno-venous ECMO with extracorporeal blood flow 2.7\uc2\ub11 L\uc2\ub7min-1, gas flow 3.8\uc2\ub11.8 L\uc2\ub7min-1, and FiO21. Data were recorded 30 minutes before and 60 minutes after initiation of ECMO. ECMO improved PCO2(75\uc2\ub123 vs. 53\uc2\ub19 mmHg, p&lt;0.01) thus improving pH (7.28\uc2\ub10.13 vs. 7.39\uc2\ub10.05, p&lt;0.01) and allowing a reduction in respiratory rate (35\uc2\ub114 vs. 10\uc2\ub14 breaths/min, p&lt;0.01), minute ventilation (10.1\uc2\ub13.8 vs. 3.7\uc2\ub11.7 L\uc2\ub7min-1, p&lt;0.01), and mean airway pressure (26\uc2\ub16.5 vs. 22\uc2\ub15 cmH2O, p&lt;0.01). No major clinical or technical complications were observed. Conclusions: ECMO effectively enabled high-risk ground transfer of severely hypoxic patients. \uc2\ua9 2011 Wichtig Editore

ECMO for intractable status asthmaticus following atracurium

Intraoperative allergic reactions are rare but serious events associated with increased morbidity and mortality. We report the salvage of intraoperative anaphylaxis leading to extreme hypercapnic respiratory failure by veno-venous extracorporeal membrane oxygenation (ECMO). A 38-year-old woman undergoing thyroidectomy developed intractable bronchospasm after administration of atracurium, leading to extreme hypercapnic respiratory failure (PaCO2\uc2\ua0>\uc2\ua0250\uc2\ua0mmHg, pH 6.773). After the failure of conventional medical therapy and ventilatory optimization, the patient was connected to a veno-venous ECMO circuit. PaCO2of 45.6\uc2\ua0mmHg and pH of 7.25 were achieved in 1\uc2\ua0h, by slowly increasing sweep gas flows up to 3.5 L/min and using continuous end-tidal CO2monitoring to gauge the procedure. After extubation and disconnection from ECMO, the patient was discharged on the 6th day without sequelae. Rapid reversal of extreme hypercapnic acidosis by ECMO was feasible, without any neurologic sequelae. Veno-venous ECMO support may be a valuable option for the salvage of intraoperative anaphylaxis

Elevated plasma and alveolar levels of soluble receptor for advanced glycation endproducts are associated with severity of lung dysfunction in ARDS patients

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are severe forms of bilateral lung inflammation with poor clinical outcomes. However, the pathophysiology of ALI/ARDS remains largely obscure. Soluble receptor for advanced glycation endproducts (sRAGE) plays a key regulatory role during the acute phase of inflammation, and baseline plasma levels of sRAGE were recently found to be associated with severity of ALI/ARDS. We analyzed, in ALI/ARDS patients, plasma and alveolar levels of sRAGE over time and the association with severity of lung injury. We enrolled 21 ALI/ARDS patients admitted to our intensive care unit (ICU) and assayed plasma sRAGE on the first 2 days after diagnosis, every three days for the first month and then once a week, until ICU discharge or death. We also measured sRAGE levels in bronchoalveolar lavage fluids, obtained when clinically indicated. At each sampling time, we recorded physiological and clinical data of the patients. Plasma sRAGE levels peaked at day 1 and decreased over time. When all samples were considered, plasma and alveolar sRAGE levels were significantly higher in patients with worse oxygenation and higher need for ventilatory support (i.e., patients with more severe lung dysfunction). Moreover, the presence of lung infection yielded higher alveolar sRAGE levels. In conclusion, we show that the plasma and alveolar levels of sRAGE in ALI/ARDS patients are correlated to lung injury severity and to lung infection. Our findings may, in time, lead to the development of more effective therapies against ALI/ARDS. \uc2\ua9 2010 Tohoku University Medical Press

A mathematical model of oxygenation during venovenous extracorporeal membrane oxygenation support

Purpose To develop a mathematical model of oxygenation during venovenous extracorporeal membrane oxygenation (vv-ECMO). Material and methods Total oxygen consumption, cardiac output, blood flow, recirculation, intrapulmonary shunt, hemoglobin, natural lung, and membrane lung oxygen fractions were chosen as inputs. Content, partial pressure, and hemoglobin saturation of oxygen in arterial, venous, pulmonary, and extracorporeal blood were outputs. To assess accuracy and predictive power of the model, we retrospectively analyzed data of 25 vv-ECMO patients. We compiled 2 software (with numerical, 2D and 3D graphical outputs) to study the impact of each variable on oxygenation. Results The model showed high accuracy and predictive power. Raising blood flow and oxygen fraction to the membrane lung or reducing total oxygen consumption improves arterial and venous oxygenation, especially in severe cases; raising oxygen fraction to the natural lung improves oxygenation only in milder cases; raising hemoglobin always improves oxygenation, especially in the venous district; recirculation fraction severely impairs oxygenation. In severely ill patients, increasing cardiac output worsens arterial oxygenation but enhances venous oxygenation. Oxygen saturation of ECMO inlet is critical to evaluate the appropriateness of oxygen delivery. Conclusions The model with the software can be a useful teaching tool and a valuable decision-making aid for the management of hypoxic patients supported by vv-ECMO