Andrea Coppadoro

A clinical assessment of the Mucus Shaver: A device to keep the endotracheal tube free from secretions

Objective:We evaluated a new device designed to clean the endotracheal tube in mechanically ventilated patients, the Mucus Shaver. Design:Prospective, randomized trial. Setting:University hospital intensive care unit. Patients:We enrolled 24 patients expected to remain ventilated for >72 hrs. Interventions:The Mucus Shaver is a concentric inflatable catheter for the removal of mucus and secretions from the interior surface of the endotracheal tube. The Mucus Shaver is advanced to the distal endotracheal tube tip, inflated, and subsequently withdrawn over a period of 3–5 secs. Patients were prospectively randomized within 2 hrs of intubation to receive standard endotracheal tube suctioning treatment or standard suctioning plus Mucus Shaver use until extubation. Measurements and Main Results:During the study period, demographic data, recent medical history, adverse events, and staff evaluation of the Mucus Shaver were recorded. At extubation, each endotracheal tube was removed, cultured, and analyzed by scanning electron microscopy. Twelve patients were assigned to the study group and 12 were assigned to the control group. No adverse events related to the use of the Mucus Shaver were observed. At extubation, only one endotracheal tube from the Mucus Shaver group was colonized, whereas in the control group ten endotracheal tubes were colonized (8% vs. 83%; p < .001). Scanning electron microscopy showed little secretions on the endotracheal tubes from the study group, whereas thick bacterial deposits were present on all the endotracheal tubes from the control group (p < .001 by Fisher exact test, using a maximum biofilm thickness of 30 &mgr;m as cut-off). The nursing staff was satisfied by the overall safety, feasibility, and efficacy of the Mucus Shaver. Conclusions:The Mucus Shaver is a safe, feasible, and efficient device for endotracheal tube cleaning in the clinical setting. The Mucus Shaver is helpful in preventing endotracheal tube colonization by potentially harmful microorganisms.

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 <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). 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.

Estimation of Patient’s Inspiratory Effort From the Electrical Activity of the Diaphragm*

Objectives:To calculate an index (termed Pmusc/Eadi index) relating the pressure generated by the respiratory muscles (Pmusc) to the electrical activity of the diaphragm (Eadi), during assisted mechanical ventilation and to assess if the Pmusc/Eadi index is affected by the type and level of ventilator assistance. The Pmusc/Eadi index was also used to measure the patient’s inspiratory effort from Eadi without esophageal pressure. Design:Crossover study. Setting:One general ICU. Patients:Ten patients undergoing assisted ventilation. Intervention:Pressure support and neurally adjusted ventilator assist delivered, each, at three levels of ventilatory assistance. Measurement and Main Results:Airways flow and pressure, esophageal pressure, and Eadi were continuously recorded. Sixty tidal volumes for each ventilator settings were analyzed off-line, at three time points during inspiration. For each time point, Pmusc/Eadi index was calculated. Pmusc/Eadi index was also calculated from airway pressure drop during end-expiratory occlusions. Pmusc/Eadi index was very variable among patients, but within one patient it was not affected by type and level of ventilator assistance. Pmusc/Eadi index decreased during the inspiration. Pmusc/Eadi index obtained during an occlusion from airway pressure swing was tightly correlated with that derived from esophageal pressure during tidal ventilation and allowed to estimate pressure time product. Conclusions:Pmusc is tightly related to Eadi, by a proportionality coefficient that we termed Pmusc/Eadi index, stable within each patient under different conditions of ventilator assistance. The derivation of the Pmusc/Eadi index from Eadi and airway pressure during an expiratory occlusion enables a continuous estimate of patient’s inspiratory effort.

Topographic distribution of tidal ventilation in acute respiratory distress syndrome: effects of positive end-expiratory pressure and pressure support.

Objective:Acute respiratory distress syndrome is characterized by collapse of gravitationally dependent lung regions that usually diverts tidal ventilation toward nondependent regions. We hypothesized that higher positive end-expiratory pressure and enhanced spontaneous breathing may increase the proportion of tidal ventilation reaching dependent lung regions in patients with acute respiratory distress syndrome undergoing pressure support ventilation. Design:Prospective, randomized, cross-over study. Setting:General and neurosurgical ICUs of a single university-affiliated hospital. Patients:We enrolled ten intubated patients recovering from acute respiratory distress syndrome, after clinical switch from controlled ventilation to pressure support ventilation. Interventions:We compared, at the same pressure support ventilation level, a lower positive end-expiratory pressure (i.e., clinical positive end-expiratory pressure = 7 ± 2 cm H2O) with a higher one, obtained by adding 5 cm H2O (12 ± 2 cm H2O). Furthermore, a pressure support ventilation level associated with increased respiratory drive (3 ± 2 cm H2O) was tested against resting pressure support ventilation (12 ± 3 cm H2O), at clinical positive end-expiratory pressure. Measurements and Main Results:During all study phases, we measured, by electrical impedance tomography, the proportion of tidal ventilation reaching dependent and nondependent lung regions (Vt%dep and Vt%nondep), regional tidal volumes (Vtdep and Vtnondep), and antero-posterior ventilation homogeneity (Vt%nondep/Vt%dep). We also collected ventilation variables and arterial blood gases. Application of higher positive end-expiratory pressure levels increased Vt%dep and Vtdep values and decreased Vt%nondep/Vt%dep ratio, as compared with lower positive end-expiratory pressure (p < 0.01). Similarly, during lower pressure support ventilation, Vt%dep increased, Vtnondep decreased, and Vtdep did not change, likely indicating a higher efficiency of posterior diaphragm that led to decreased Vt%nondep/Vt%dep (p < 0.01). Finally, PaO2/FIO2 ratios correlated with Vt%dep during all study phases (p < 0.05). Conclusions:In patients with acute respiratory distress syndrome undergoing pressure support ventilation, higher positive end-expiratory pressure and lower support levels increase the fraction of tidal ventilation reaching dependent lung regions, yielding more homogeneous ventilation and, possibly, better ventilation/perfusion coupling.

Transfusion of stored autologous blood does not alter reactive hyperemia index in healthy volunteers

Background: Transfusion of human blood stored for more than 2 weeks is associated with increased mortality and morbidity. During storage, packed erythrocytes progressively release hemoglobin, which avidly binds nitric oxide. We hypothesized that the nitric oxide mediated hyperemic response after ischemia would be reduced after transfusion of packed erythrocytes stored for 40 days. Methods and Results: We conducted a crossover randomized interventional study, enrolling 10 healthy adults. Nine volunteers completed the study. Each volunteer received one unit of 40-day and one of 3-day stored autologous leukoreduced packed erythrocytes, on different study days according to a randomization scheme. Blood withdrawal and reactive hyperemia index measurements were performed before and 10 min, 1 h, 2 h, and 4 h after transfusion. The reactive hyperemia index during the first 4 h after transfusion of 40-day compared with 3-day stored packed erythrocytes was unchanged. Plasma hemoglobin and bilirubin concentrations were higher after transfusion of 40-day than after 3-day stored packed erythrocytes (P = 0.02, [95% CI difference 10–114 mg/l] and 0.001, [95% CI difference 0.6–1.5 mg/dl], respectively). Plasma concentrations of potassium, lactate dehydrogenase, haptoglobin, and cytokines, as well as blood pressure, did not differ between the two transfusions and remained within the normal range. Plasma nitrite concentrations increased after transfusion of 40-day stored packed erythrocytes, but not after transfusion of 3-day stored packed erythrocytes (P = 0.01, [95% CI difference 0.446–0.66 &mgr;M]). Conclusions: Transfusion of autologous packed erythrocytes stored for 40 days is associated with increased hemolysis, an unchanged reactive hyperemia index, and increased concentrations of plasma nitrite.

Novel preventive strategies for ventilator-associated pneumonia

Ventilator-associated pneumonia (VAP) is a complication of mechanical ventilation and is defined as the occurrence of pneumonia in patients undergoing mechanical ventilation for at least 48 hours. Clinical suspicion of VAP arises when new infiltrates are present on chest x-ray, and at least one of the following is present: Fever, leukocytosis, or purulent tracheo-bronchial secretions.

Effects of Sigh on Regional Lung Strain and Ventilation Heterogeneity in Acute Respiratory Failure Patients Undergoing Assisted Mechanical Ventilation

Objective:In acute respiratory failure patients undergoing pressure support ventilation, a short cyclic recruitment maneuver (Sigh) might induce reaeration of collapsed lung regions, possibly decreasing regional lung strain and improving the homogeneity of ventilation distribution. We aimed to describe the regional effects of different Sigh rates on reaeration, strain, and ventilation heterogeneity, as measured by thoracic electrical impedance tomography. Design:Prospective, randomized, cross-over study. Setting:General ICU of a single university-affiliated hospital. Patients:We enrolled 20 critically ill patients intubated and mechanically ventilated with PaO2/FIO2 up to 300 mm Hg and positive end-expiratory pressure at least 5 cm H2O (15 with acute respiratory distress syndrome), undergoing pressure support ventilation as per clinical decision. Interventions:Sigh was added to pressure support ventilation as a 35 cm H2O continuous positive airway pressure period lasting 3–4 seconds at different rates (no-Sigh vs 0.5, 1, and 2 Sigh(s)/min). All study phases were randomly performed and lasted 20 minutes. Measurements and Main Results:In the last minutes of each phase, we measured arterial blood gases, changes in end-expiratory lung volume of nondependent and dependent regions, tidal volume reaching nondependent and dependent lung (Vtnondep and Vtdep), dynamic intratidal ventilation heterogeneity, defined as the average ratio of Vt reaching nondependent/Vt reaching dependent lung regions along inspiration (VtHit). With Sigh, oxygenation improved (p < 0.001 vs no-Sigh), end-expiratory lung volume of nondependent and dependent regions increased (p < 0.01 vs no-Sigh), Vtnondep showed a trend to reduction, and Vtdep significantly decreased (p = 0.11 and p < 0.01 vs no-Sigh, respectively). VtHit decreased only when Sigh was delivered at 0.5/min (p < 0.05 vs no-Sigh), while it did not vary during the other two phases. Conclusions:Sigh decreases regional lung strain and intratidal ventilation heterogeneity. Our study generates the hypothesis that in ventilated acute respiratory failure patients, Sigh may enhance regional lung protection.

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

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 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.MethodsWe 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.ResultsMicrobiologically 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.ConclusionsIn this hypothesis-generating convenience sample, a PTX3 level ≥1 ng/ml in BAL fluid was discriminative of microbiologically confirmed pneumonia in mechanically ventilated patients.

Do spontaneous and mechanical breathing have similar effects on average transpulmonary and alveolar pressure? A clinical crossover study

BackgroundPreservation of spontaneous breathing (SB) is sometimes debated because it has potentially both negative and positive effects on lung injury in comparison with fully controlled mechanical ventilation (CMV). We wanted (1) to verify in mechanically ventilated patients if the change in transpulmonary pressure was similar between pressure support ventilation (PSV) and CMV for a similar tidal volume, (2) to estimate the influence of SB on alveolar pressure (Palv), and (3) to determine whether a reliable plateau pressure could be measured during pressure support ventilation (PSV).MethodsWe studied ten patients equipped with esophageal catheters undergoing three levels of PSV followed by a phase of CMV. For each condition, we calculated the maximal and mean transpulmonary (ΔPL) swings and Palv.ResultsOverall, ΔPL was similar between CMV and PSV, but only loosely correlated. The differences in ΔPL between CMV and PSV were explained largely by different inspiratory flows, indicating that the resistive pressure drop caused this difference. By contrast, the Palv profile was very different between CMV and SB; SB led to progressively more negative Palv during inspiration, and Palv became lower than the set positive end-expiratory pressure in nine of ten patients at low PSV. Finally, inspiratory occlusion holds performed during PSV led to plateau and Δ PL pressures comparable with those measured during CMV.ConclusionsUnder similar conditions of flow and volume, transpulmonary pressure change is similar between CMV and PSV. SB during mechanical ventilation can cause remarkably negative swings in Palv, a mechanism by which SB might potentially induce lung injury.

Modifying endotracheal tubes to prevent ventilator-associated pneumonia.

Purpose of review The endotracheal tube (ETT) is the main avenue leading to airway contamination and subsequent ventilator-associated pneumonia (VAP) during mechanical ventilation. A number of modifications to the ETT are available, aimed at reducing the incidence of VAP. We review here available systems and devices, and clinical data regarding their efficacy. Recent findings Three main modifications of ETTs have been developed: coating with antimicrobials, adding a suction channel for the removal of oro-pharyngeal secretions, and modifying the design of the cuff. Each of these interventions has been shown to limit bacterial colonization of the distal airways and to decrease the incidence of VAP. Data on their ultimate effect on related clinical outcomes are still lacking. Summary Modifications of ETTs aimed at decreasing the onset of VAP show promising results. However, the lack of a significant effect on outcomes prompts us to use caution before recommending their widespread use.