[Show abstract][Hide abstract] ABSTRACT: IntroductionTimely 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 showed that, during pneumonia, PTX3 participates in fine-tuning of inflammation (for example, microbes¿ clearance and recruitment of neutrophils). We previously described an association between alveolar PTX3 and lung infection in a small group of intubated patients. The present study aimed 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) undergoing broncho-alveolar lavage (BAL) as per clinical decision. We collected BAL and plasma samples, together with relevant clinical and microbiological data. We assayed: in BAL, PTX3 and soluble triggering receptor expressed on myeloid cells (sTREM-1); in plasma, PTX3, sTREM-1, C-reactive protein (CRP) and Procalcitonin (PCT). Two blinded independent physicians reviewed patients¿ data to confirm pneumonia. Finally, we determined BAL PTX3 threshold for pneumonia and we compared it to other biomarkers.ResultsMicrobiologically confirmed pneumonia of bacterial (n¿=¿12), viral (n¿=¿4) or fungal (n¿=¿8) etiology was diagnosed in 24 patients (29%). BAL PTX3 predicted pneumonia with AUCROC¿=¿0.815 (95% CI¿=¿0.710 to 0.921, P <0.0001), while all other biomarkers were not effective. In particular, BAL PTX3¿¿¿1 ng/mL predicted pneumonia at univariate analysis (ß¿=¿2.784 with SE¿=¿0.792, P <0.001) with elevated sensitivity (92%), specificity (60%) and negative predictive value (95%). Net reclassification index values of BAL PTX3¿¿¿1 ng/mL 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 cases that fulfilled clinical criteria for the diagnosis of pneumonia at BAL sampling, PTX3 diagnostic accuracy was confirmed at univariate and ROC curve analysis.Conclusions
In this hypothesis generating convenience sample, BAL PTX3¿¿¿1 ng/mL was discriminative of microbiologically confirmed pneumonia in mechanically ventilated patients.
Critical care (London, England) 10/2014; 18(5):562. · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The decision to start venovenous extracorporeal membrane oxygenation (VV ECMO) is commonly based on the severity of respiratory failure, with little consideration of the extrapulmonary organ function. The aim of the study was to identify predictors of mortality and to develop a score allowing a better stratification of patients at the time of VV ECMO initiation.
This was a prospective multicenter cohort study on 60 patients with influenza A (H1N1)-associated respiratory distress syndrome participating in the Italian ECMOnet data set in the 2009 pandemic. Criteria for ECMO institution were standardized according to national guidelines.
The survival rate in patients treated with ECMO was 68 %. Significant predictors of death before ECMO institution by multivariate analysis were hospital length of stay before ECMO institution (OR = 1.52, 95 % CI 1.12-2.07, p = 0.008); bilirubin (OR = 2.32, 95 % CI 1.52-3.52, p < 0.001), creatinine (OR = 7.38, 95 % CI 1.43-38.11, p = 0.02) and hematocrit values (OR = 0.82, 95 % CI 0.72-0.94, p = 0.006); and mean arterial pressure (OR = 0.92, 95 % CI 0.88-0.97, p < 0.001). The ECMOnet score was developed based on these variables, with a score of 4.5 being the most appropriate cutoff for mortality risk prediction. The high accuracy of the ECMOnet score was further confirmed by ROC analysis (c = 0.857, 95 % CI 0.754-0.959, p < 0.001) and by an independent external validation analysis (c = 0.694, 95 % CI 0.562-0.826, p = 0.004).
Mortality risk for patients receiving VV ECMO is correlated to the extrapulmonary organ function at the time of ECMO initiation. The ECMOnet score is a tool for the evaluation of the appropriateness and timing of VV ECMO in acute lung failure.
Intensive Care Medicine 02/2013; 39(2):275-281. · 5.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
ASAIO journal (American Society for Artificial Internal Organs: 1992) 03/2012; 58(3):281-4. · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
This is a clinical observational study. Criteria for ECMO center activation were: potentially reversibile respiratory failure, PaO₂ <50 mmHg with FiO₂ >0.6 for >12 hours, PEEP >5 cmH₂0, Lung Injury Score (LIS) ≥3 or respiratory acidosis with pH <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.
Sixteen patients were possible candidates for ECMO transfer. Two patients were excluded while 14 (mean±SD, age 35.4±18.6, SOFA 8.4±3.7, Oxygenation Index 43.7±13.4) were transported to our institution (distance covered 102±114 km, global duration of transport 589±186 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±1 L·min⁻¹, gas flow 3.8±1.8 L·min⁻¹, and FiO₂ 1. Data were recorded 30 minutes before and 60 minutes after initiation of ECMO. ECMO improved PCO₂ (75±23 vs. 53±9 mmHg, p<0.01) thus improving pH (7.28±0.13 vs. 7.39±0.05, p<0.01) and allowing a reduction in respiratory rate (35±14 vs. 10±4 breaths/min, p<0.01), minute ventilation (10.1±3.8 vs. 3.7±1.7 L·min⁻¹, p<0.01), and mean airway pressure (26±6.5 vs. 22±5 cmH₂O, p<0.01). No major clinical or technical complications were observed.
ECMO effectively enabled high-risk ground transfer of severely hypoxic patients.
The International journal of artificial organs 11/2011; 34(11):1052-60. · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The novel influenza A (H1N1) pandemic was associated with an epidemic of critical illness.
We describe the clinical profiles of critically ill patients with severe complications due to microbiologically confirmed pandemic influenza A (H1N1) infection admitted to a medical ICU in Monza, Italy, over a 6-month period.
From August 2009 to January 2010, 19 patients (13 adults and 6 children) required ICU admission. Nine subjects were referred to our hospital from other ICUs. In all patients, with the exception of a case of severe septic shock, the cause of ICU admission was acute respiratory failure. Other nonpulmonary organ failures were common. A trial of non-invasive ventilation was attempted in 13 cases and was successful in four of them. The majority of the patients required invasive mechanical ventilation. In the 7 most severely hypoxemic patients, we applied veno-venous ECLS, with a very high rate of success. The median ICU stay was 9 days (range 1-78 days). Sixteen out of 19 (84%) patients survived.
In the majority of our patients, critical illness caused by pandemic influenza A (H1N1) was associated with severe hypoxemia, multiple organ failure, requirement for mechanical ventilation and frequent use of rescue therapies and ECLS support.
[Show abstract][Hide abstract] ABSTRACT: Pulmonary tuberculosis can lead to acute respiratory distress syndrome (ARDS) which is associated with high mortality. We report the case of a patient with pulmonary tuberculosis and severe ARDS (PaO2/FiO2<100 mmHg) who was initially managed with advanced up-to-date treatments (protective ventilation and extracorporeal membrane oxygenation, ECMO) but failed to improve. After a month of failure and the development of bilateral pneumothoraces, we drastically changed our therapeutic strategy: we maximized ECMO support to maintain oxygenation, we greatly reduced ventilation pressures and we left the pneumothoraces undrained. From then on, the patient improved and he eventually survived. This case suggests that ECMO permits large reductions in lung inflation and ventilation to rest the lungs, while maintaining acceptable oxygenation. The combination of ECMO and markedly attenuated ventilation strategy may be effective in cases of severe ARDS.
[Show abstract][Hide abstract] ABSTRACT: 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.
ASAIO journal (American Society for Artificial Internal Organs: 1992) 01/2011; 57(4):336-40. · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
The Tohoku Journal of Experimental Medicine 01/2010; 222(2):105-12. · 1.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
One university medical center general intensive care unit.
The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria).
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 <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 < 0.001) and number of organ failures (p < 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 < 0.05).
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.
Critical care medicine 07/2008; 36(8):2302-8. · 6.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a case in which life support for cardiogenic shock was achieved by a nonpulsatile venoarterial bypass, and left ventricular decompression was obtained by a catheter placed percutaneously through the aortic valve into the left ventricle. The blood drained from the left ventricle was pumped into the femoral artery. The normalization of left heart filling pressures allowed the resolution of pulmonary edema, and the patient underwent a successful heart transplantation following 7 days of mechanical cardiocirculatory support.
The International journal of artificial organs 06/2004; 27(5):410-3. · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Plasma leakage has been regarded as the main technical problem during prolonged extracorporeal circulation (ECC) with microporous membrane oxygenators (MMOs). We report the case of a 15 year old male who underwent long term ECC for ARDS and in whom, by using new MMOs with reduced pore size, we were able to achieve prolonged artificial gas exchange efficiency with minimal plasma leakage. We conclude that reduced pore size MMOs might represent a valuable technical advance in extracorporeal oxygenation therapy.
The International journal of artificial organs 04/1996; 19(3):177-80. · 1.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the clinical consequences of duration of adult respiratory distress syndrome (ARDS) on lung structure and function.
A university hospital referral center for extracorporeal support.
A total of 84 patients with severe ARDS (Murray score > 2.5) recruited from 48 intensive care units (1979 to 1992), who suffered ARDS and underwent mechanical ventilation for up to 1 week (37 patients with early ARDS), between 1 and 2 weeks (24 patients with intermediate ARDS), or more than 2 weeks (23 patients with late ARDS) and subsequently underwent extracorporeal support.
Before beginning extracorporeal support, we measured gas exchange, pulmonary mechanics, hemodynamics, oxygen transport and delivery, incidence of barotrauma (presence of one or more thoracic tubes for pneumothorax drainage), and organ dysfunctions. In a subgroup of 16 patients, we studied lung structure by computed tomographic scan, scoring the densities and quantifying the emphysemalike lesions (bullae).
Late ARDS showed lower respiratory compliance, higher dead space, higher PaCO2, lower venous admixture, and lower positive end-expiratory pressure requirement compared with early ARDS (P < .01). The incidence of pneumothorax (48.8% of the entire population) was significantly (P < .01) higher in late ARDS (87%) vs intermediate ARDS (46%) and early ARDS (30%). The mortality of patients with pneumothorax (66%) was significantly (P < .01) higher compared with patients without pneumothorax (46%). The number of bullae per lung was significantly higher in late ARDS vs intermediate and early ARDS (mean [SD], 8 , 4.3 , and 1.9 [3.9], respectively; P < .01), and they were preferentially distributed in the dependent lung regions. The number of bullae per lung was significantly higher in patients with pneumothorax vs those without pneumothorax (mean [SD], 13.6 [9.8] vs 1.4 [2.1]; P = .007). The mean (SD) duration of ARDS in patients with pneumothorax was 15.3 (10.0) days vs 7.0 (6.6) days in those without pneumothorax (P = .0001). No differences within the three groups were found in computed tomographic scan densities, hemodynamics, and number of organ system dysfunctions.
The lung structure and function changes markedly with ARDS duration, and the late stages may be described as restrictive lung disease with superimposed emphysemalike lesions. Presence of pneumothorax affects survival and appears to be related to the lung structural changes occurring with time.
JAMA The Journal of the American Medical Association 06/1994; 271(22):1772-9. · 29.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Long-term extracorporeal support for acute lung failure was introduced in 1972. In the 1970s, much effort was concentrated on technical improvements. However, a multicenter study comparing continuous positive-pressure ventilation and continuous positive-pressure ventilation plus extracorporeal circulation failed to show improvement in survival rates. In the 1980s, new physiopathologic concepts were developed, such as extracorporeal CO2 removal coupled with lung rest. The main complication of the technique was bleeding due to systemic heparinization. However, the technology used in that period was the same as in the 1970s. Recently, technological improvement--such as percutaneous cannulation and surface-heparinized artificial lungs--has allowed clinical performances to improve substantially. "Lung rest" philosophy, coupled with safe technology, may provide a rational basis to test this technique in a randomized fashion for widespread use.
New horizons (Baltimore, Md.) 12/1993; 1(4):603-12.