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Study Objective To assess the safety of mechanical ventilation and effectiveness of extrinsic positive end-expiratory pressure (PEEP) (PEEPe) in improving peripheral oxygen saturation (SpO2) during direct microlaryngeal laser surgery; to assess the incidence, amount, and nature (dynamic hyperinflation or airflow obstruction) of ensuing intrinsic PEEP (PEEPi); and to find a surrogate PEEPi indicator. Design Quasiexperimental. Setting S. Raffaele Hospital (Milano), November 2009 to December 2010. Patients Fifty-two adults scheduled for direct microlaryngeal laser surgery. Exclusion criterion is pregnancy. Interventions Twenty-one percent O2 mechanical ventilation through 4.5- to 5.5-mm internal diameter endotracheal tubes; in 29 patients, after measurement of PEEPi, an identical amount of PEEPe was added; and PEEPi. Measurements SpO2, peak (Pawpeak) and plateau (Pawplateau) airway pressure, and end-expiratory carbon dioxide were measured every 5 minutes. Respiratory compliance (Crs) was computed. PEEPi was measured (end-expiratory occlusion method). Main Results PEEPi ≥ 5 cm H2O occurred in 14 patients (27%) after intubation, in 16 (30%) at the beginning, and in 14 (27.3%) at the end of surgery. Thirty-one patients (59.4%) exhibited PEEPi ≥ 5 cm H2O on at least 1 time point. PEEPi at the beginning of surgery was positively correlated with Pawplateau, Crs, tidal volume, and body mass index. Body mass index was the only predictor for the occurrence of PEEPi ≥ 5 cm H2O. At the beginning of surgery, the Pawplateau receiver operating characteristic curve predicting PEEPi ≥ 5 cm H2O had area under the receiver operating characteristic curve of 0.85; best cutoff value of 15.5 cm H2O (sensitivity, 88.9%; specificity, 75%; correctly classified cases, 86.1%). When PEEPe was applied, in 23 cases (82.1%), total PEEP equaled PEEPe+ PEEPi; in 3 (10.7%), it was lower; and in 2 (7.1%), it was higher. Application of PEEPe increased SpO2 (P<.05) and Crs (P<.05). Conclusions During vent

Background: The amount of extracorporeal carbon dioxide removal may influence respiratory drive in acute respiratory distress syndrome (ARDS) patients undergoing extracorporeal membrane oxygenation (ECMO). The authors evaluated the effects of different levels of extracorporeal carbon dioxide removal in patients recovering from severe ARDS undergoing pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA). Methods: The authors conducted a prospective, randomized, crossover study on eight spontaneously breathing ARDS patients undergoing venovenous ECMO since 28 ± 20 days. To modulate carbon dioxide extraction, ECMO gas flow (GF) was decreased from baseline resting protective conditions (i.e., GF100%, set to obtain pressure generated in the first 100 ms of inspiration against an occluded airway less than 2 cm H2O, respiratory rate less than or equal to 25 bpm, tidal volume less than 6 ml/kg, and peak airway pressure less than 25 cm H2O) to GF50%-GF25%-GF0% during both PSV and NAVA (random order for ventilation mode). Continuous recordings of airway pressure and flow and esophageal pressure were obtained and analyzed during all study phases. Results: At higher levels of extracorporeal carbon dioxide extraction, pressure generated in the first 100 ms of inspiration against an occluded airway decreased from 2.8 ± 2.7 cm H2O (PSV, GF0%) and 3.0 ± 2.1 cm H2O (NAVA, GF0%) to 0.9 ± 0.5 cm H2O (PSV, GF100%) and 1.0 ± 0.8 cm H2O (NAVA, GF100%; P < 0.001) and patients' inspiratory muscle pressure passed from 8.5 ± 6.3 and 6.5 ± 5.5 cm H2O to 4.5 ± 3.1 and 4.2 ± 3.7 cm H2O (P < 0.001). In time, decreased inspiratory drive and effort determined by higher carbon dioxide extraction led to reduction of tidal volume from 6.6 ± 0.9 and 7.5 ± 1.2 ml/kg to 4.9 ± 0.8 and 5.3 ± 1.3 ml/kg (P < 0.001) and of peak airway pressure from 21 ± 3 and 25 ± 4 cm H2O to 21 ± 3 and 21 ± 5 cm H2O (P < 0.001). Finally, transpulmonary pressure linearly decreased when the amount

Purpose: To investigate the relationship between peak (EAdipeak) and area under the curve (EAdiAUC) of diaphragm electrical activity, and to evaluate the validity of their ratio (P/I index) as a measure of the imbalance between drive and sustainability of effort demand at different support levels. Materials: Prospective physiological study on 18 ready-to-wean patients ventilated with neurally adjusted ventilatory assist (NAVA) undergoing 2 levels of NAVA (NAVA100% and NAVA50%) followed by a weaning trial with continuous positive airway pressure, according to which patients were classified as success or failure. Tidal volume (VT), respiratory rate, EAdipeak, EAdiAUC, rapid shallow breathing index (respiratory rate/VT), neuroventilatory index (VT/EAdipeak), and P/I index were obtained at the end of each step. Results: The slopes of regression line between EAdipeak and EAdiAUC (a mathematical equivalent of P/I index) and P/I index were significantly higher in failures. At variance with other variables, P/I index did not vary with level of support. P/I index was inversely correlated with inspiratory time at all support levels. Conclusions: The relationship between EAdipeak and EAdiAUC and the P/I index may give important information on the balance between respiratory drive and inspiratory demand sustainability.

Rationale: We developed an innovative, minimally invasive, highly efficient extracorporeal CO2 removal (ECCO2R) technique called respiratory electrodialysis (R-ED). Objectives: To evaluate the efficacy of R-ED in controlling ventilation compared with conventional ECCO2R technology. Methods: Five mechanically ventilated swine were connected to a custom-made circuit optimized for R-ED, consisting of a hemofilter, a membrane lung, and an electrodialysis cell. Electrodialysis regionally modulates blood electrolyte concentration to convert bicarbonate to CO2 before entering the membrane lung, enhancing membrane lung CO2 extraction. All animals underwent three repeated experimental sequences, consisting of four steps: baseline (1 h), conventionalECCO2R(2 h), R-ED (2 h), and finalNOECCO2R (1 h). Blood and gas flow were 250 ml/min and 10 L/min, respectively. Tidal volume was set at 8 ml/kg, and respiratory rate was adjusted to maintain arterial PCO2 at 50 mm Hg. Measurements and Main Results: During R-ED, chloride andH1 concentration increased in blood entering the membrane lung, almost doubling CO2 extraction compared with ECCO2R (11266 vs. 6465 ml/min, P,0.001). Compared with baseline, R-ED and ECCO2R reduced minute ventilation by 50% and 27%, respectively. Systemic arterial gas analyses remained stable during the experimental phases. No major complication occurred, but there was an increase in creatinine level. Conclusions: In this first in vivo application, we proved electrodialysis feasible and effective in increasingmembrane lung CO2 extraction. R-ED was more effective than conventional ECCO2R technology in controlling ventilation. Further studies are warranted to assess the safety profile of R-ED, especially regarding kidney function.

Sudden cardiac arrest is a complex, life-threatening event involving a multidisciplinary approach. Despite the use of conventional cardiopulmonary resuscitation, survival rate continues to be low for both in-hospital and out-of-hospital cardiac arrest. In refractory cardiac arrest, defined by the absence of return of spontaneous circulation despite resuscitation manoeuvres, mortality approaches 100%. In the last years, an increasing number of case series, and few propensity-matched cohort studies have reported encouraging results on the use of venoarterial extracorporeal membrane oxygenation for refractory cardiac arrest. Extracorporeal circulation ensures an adequate blood flow, to perform diagnostic and therapeutic interventions even before a return of spontaneous circulation is achieved and to rest the heart by unloading the ventricle while ensuring myocardial perfusion after return of spontaneous circulation. This study reviews the rational, indications, evidence and management of extracorporeal support for cardiac arrest.

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 intratid

Purpose: Prone positioning (PP) improves oxygenation and outcome of patients with acute respiratory distress syndrome undergoing invasive ventilation. We evaluated feasibility and efficacy of PP in awake, non-intubated, spontaneously breathing patients with hypoxemic acute respiratory failure (ARF). Material and Methods: We retrospectively studied non-intubated subjects with hypoxemic ARF treated with PP from January 2009 to December 2014. Data were extracted from medical records. Arterial blood gas analyses, respiratory rate, and hemodynamics were retrieved 1 to 2 hours before pronation (step PRE), during PP (step PRONE), and 6 to 8 hours after resupination (step POST). Results: Fifteen non-intubated ARF patients underwent 43 PP procedures. Nine subjects were immunocompromised. Twelve subjects were discharged from hospital, while 3 died. Only 2 maneuvers were interrupted, owing to patient intolerance. No complications were documented. PP did not alter respiratory rate or hemodynamics. In the subset of procedures during which the same positive end expiratory pressure and Fio2 were utilized throughout the pronation cycle (n = 18), PP improved oxygenation (Pao2/Fio2 124 ± 50 mmHg, 187 ± 72 mmHg, and 140 ± 61 mmHg, during PRE, PRONE, and POST steps, respectively, P < .001), while pH and Paco2 were unchanged. Conclusions: PP was feasible and improved oxygenation in non-intubated, spontaneously breathing patients with ARF.

Background: Auto-positive end-expiratory pressure (auto-PEEP) may substantially increase the inspiratory effort during assisted mechanical ventilation. Purpose of this study was to assess whether the electrical activity of the diaphragm (EAdi) signal can be reliably used to estimate auto-PEEP in patients undergoing pressure support ventilation and neurally adjusted ventilatory assist (NAVA) and whether NAVA was beneficial in comparison with pressure support ventilation in patients affected by auto-PEEP. Methods: In 10 patients with a clinical suspicion of auto-PEEP, the authors simultaneously recorded EAdi, airway, esophageal pressure, and flow during pressure support and NAVA, whereas external PEEP was increased from 2 to 14 cm H2O. Tracings were analyzed to measure apparent "dynamic" auto-PEEP (decrease in esophageal pressure to generate inspiratory flow), auto-EAdi (EAdi value at the onset of inspiratory flow), and IDEAdi (inspiratory delay between the onset of EAdi and the inspiratory flow). Results: The pressure necessary to overcome auto-PEEP, auto-EAdi, and IDEAdi was significantly lower in NAVA as compared with pressure support ventilation, decreased with increase in external PEEP, although the effect of external PEEP was less pronounced in NAVA. Both auto-EAdi and IDEAdi were tightly correlated with auto-PEEP (r2 = 0.94 and r2 = 0.75, respectively). In the presence of auto-PEEP at lower external PEEP levels, NAVA was characterized by a characteristic shape of the airway pressure. Conclusions: In patients with auto-PEEP, NAVA, compared with pressure support ventilation, led to a decrease in the pressure necessary to overcome auto-PEEP, which could be reliably monitored by the electrical activity of the diaphragm before inspiratory flow onset (auto-EAdi)

Extracorporeal (EC) carbon dioxide (CO2) removal (ECCO2R) may be a powerful alternative to ventilation, possibly avoiding the need for mechanical ventilation and endotracheal intubation. We previously reported how an infusion of lactic acid before a membrane lung (ML) effectively enhances ECCO2R. We evaluated an innovative ECCO2R technique based on ventilation of acidified dialysate

BACKGROUND:: Extracorporeal carbon dioxide removal has been proposed to achieve protective ventilation in patients at risk for ventilator-induced lung injury. In an acute study, the authors previously described an extracorporeal carbon dioxide removal technique enhanced by regional extracorporeal blood acidification. The current study evaluates efficacy and feasibility of such technology applied for 48 h. METHODS:: Ten pigs were connected to a low-flow veno-venous extracorporeal circuit (blood flow rate, 0.25 l/min) including a membrane lung. Blood acidification was achieved in eight pigs by continuous infusion of 2.5 mEq/min of lactic acid at the membrane lung inlet. The acid infusion was interrupted for 1 h at the 24 and 48 h. Two control pigs did not receive acidification. At baseline and every 8 h thereafter, the authors measured blood lactate, gases, chemistry, and the amount of carbon dioxide removed by the membrane lung (VCO2ML). The authors also measured erythrocyte metabolites and selected cytokines. Histological and metalloproteinases analyses were performed on selected organs. RESULTS:: Blood acidification consistently increased VCO2ML by 62 to 78%, from 79 ± 13 to 128 ± 22 ml/min at baseline, from 60 ± 8 to 101 ± 16 ml/min at 24 h, and from 54 ± 6 to 96 ± 16 ml/min at 48 h. During regional acidification, arterial pH decreased slightly (average reduction, 0.04), whereas arterial lactate remained lower than 4 mEq/l. No sign of organ and erythrocyte damage was recorded. CONCLUSION:: Infusion of lactic acid at the membrane lung inlet consistently increased VCO2ML providing a safe removal of carbon dioxide from only 250 ml/min extracorporeal blood flow in amounts equivalent to 50% production of an adult man.

This report summarizes current physiological and technical knowledge on esophageal pressure (Pes) measurements in patients receiving mechanical ventilation. The respiratory changes in Pes are representative of changes in pleural pressure. The difference between airway pressure (Paw) and Pes is a valid estimate of transpulmonary pressure. Pes helps determine what fraction of Paw is applied to overcome lung and chest wall elastance. Pes is usually measured via a catheter with an air-filled thin-walled latex balloon inserted nasally or orally. To validate Pes measurement, a dynamic occlusion test measures the ratio of change in Pes to change in Paw during inspiratory efforts against a closed airway. A ratio close to unity indicates that the system provides a valid measurement. Provided transpulmonary pressure is the lung-distending pressure, and that chest wall elastance may vary among individuals, a physiologically based ventilator strategy should take the transpulmonary pressure into account. For monitoring purposes, clinicians rely mostly on Paw and flow waveforms. However, these measurements may mask profound patient-ventilator asynchrony and do not allow respiratory muscle effort assessment. Pes also permits the measurement of transmural vascular pressures during both passive and active breathing. Pes measurements have enhanced our understanding of the pathophysiology of acute lung injury, patient-ventilator interaction, and weaning failure. The use of Pes for positive end-expiratory pressure titration may help improve oxygenation and compliance. Pes measurements make it feasible to individualize the level of muscle effort during mechanical ventilation and weaning. The time is now right to apply the knowledge obtained with Pes to improve the management of critically ill and ventilator-dependent patients.

PURPOSE: Patients with acute respiratory distress syndrome (ARDS) requiring extracorporeal membrane oxygenation (ECMO) usually present very low respiratory system compliance (Cst(rs)) values (i.e., severe restrictive respiratory syndrome patients). As a consequence, they are at high risk of experiencing poor patient-ventilator interaction during assisted breathing. We hypothesized that monitoring of diaphragm electrical activity (EAdi) may enhance asynchrony assessment and that neurally adjusted ventilatory assist (NAVA) may reduce asynchrony, especially in more severely restricted patients. METHODS: We enrolled ten consecutive ARDS patients with very low Cst(rs) values undergoing ECMO after switching from controlled to pressure support ventilation (PSV). We randomly tested (30 min) while recording EAdi: (1) PSV30 (PSV with an expiratory trigger at 30 % of flow peak value); (2) PSV1 (PSV with expiratory trigger at 1 %); (3) NAVA. During each step, we measured the EAdi-based asynchrony index (AI(EAdi)) = flow-, pressure- and EAdi-based asynchrony events/EAdi-based respiratory rate × 100. RESULTS: AI(EAdi) was high during all ventilation modes, and the most represented asynchrony pattern was specific for this population (i.e., premature cycling). NAVA was associated with significantly decreased, although suboptimal, AI(EAdi) values in comparison to PSV30 and PSV1 (p < 0.01 for both). The PSV30-NAVA and PSV1-NAVA differences in AI(EAdi) values were inversely correlated with patients' Cst(rs) (R (2) = 0.545, p = 0.01 and R (2) = 0.425, p < 0.05; respectively). CONCLUSIONS: EAdi allows accurate analysis of asynchrony patterns and magnitude in ARDS patients with very low Cst(rs) undergoing ECMO. In these patients, NAVA is associated with reduced asynchrony.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Blood acidification by lactic acid infusion converts bicarbonate to CO2. This effect can be exploited to increase the transmembrane PCO2 gradient of an extracorporeal membrane lung, resulting in a significant increase of extracorporeal CO2 removal. Lactic acid, however, is an energetic substrate and its metabolism might increase total body CO2 production (VCO2), limiting the potential beneficial effects of this technique. The aim of our study was to compare VCO2 during isocaloric infusion of lactic acid or glucose.

To comprehensively assess published peer-reviewed studies related to extracorporeal membrane oxygenation (ECMO), focusing on outcomes and complications of ECMO in adult patients

INTRODUCTION: H1N1 influenza can cause severe acute lung injury (ALI). Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial. We conducted a systematic review and meta-analysis on ECMO for H1N1-associated ALI. METHODS: CENTRAL, Google Scholar, MEDLINE/PubMed and Scopus (updated 2 January 2012) were systematically searched. Studies reporting on 10 or more patients with H1N1 infection treated with ECMO were included. Baseline, procedural, outcome and validity data were systematically appraised and pooled, when appropriate, with random-effect methods. RESULTS: From 1,196 initial citations, 8 studies were selected, including 1,357 patients with confirmed/suspected H1N1 infection requiring intensive care unit admission, 266 (20%) of whom were treated with ECMO. Patients had a median Sequential Organ Failure Assessment (SOFA) score of 9, and had received mechanical ventilation before ECMO implementation for a median of two days. ECMO was implanted before inter-hospital patient transfer in 72% of cases and in most patients (94%) the veno-venous configuration was used. ECMO was maintained for a median of 10 days. Outcomes were highly variable among the included studies, with in-hospital or short-term mortality ranging between 8% and 65%, mainly depending on baseline patient features. Random-effect pooled estimates suggested an overall in-hospital mortality of 28% (95% confidence interval 18% to 37%; I2 = 64%). CONCLUSIONS: ECMO is feasible and effective in patients with ALI due to H1N1 infection. Despite this, prolonged support (more than one week) is required in most cases, and subjects with severe comorbidities or multiorgan failure remain at high risk of in-hospital death.

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

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.

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.

On November 2009, the Italian health authorities set up a network of selected intensive care unit (ICU) centers (ECMOnet) to prepare for the treatment of the sickest patients of influenza A (H1N1) by means of extracorporeal membrane oxygenation (ECMO). To quickly and efficaciously train all the physicians working in the ICUs of the ECMOnet on ECMO use, we decided to take advantages of the opportunity provided by simulation technology. Simulation proved efficacious in providing adequate training and education to participants as confirmed by the survival results obtained by the group of ICUs of the ECMOnet. Our experience supports the use of simulation as a valuable alternative to animal laboratory sessions proposed by traditional ECMO training programs providing participants with cognitive, technical, and behavioral skills and allowing a proficient transfer of those skills to the real medical domain.

Background: to assess the performance of different expiratory valves and the resistance of helmet outlet ports at increasing gas flow rates. Methods: a gas flow-meter was connected to 10 different expiratory peep valves: 1 water-seal valve, 4 precalibrated fixed PEEP valves and 5 adjustable PEEP valves. Three new valves of each brand, set at different pressure levels (5-7.5-10-12.5-15 cmH2O, if available), were tested at increasing gas flow rates (from 30 to 150 L/min). We measured the pressure generated just before the valves. Three different helmets sealed on a mock head were connected at the inlet port with a gas flow-meter while the outlet was left clear. We measured the pressure generated inside the helmet (due to the flow-resistance of the outlet port) at increasing gas flow rates. Results: Adjustable valves showed a variable degree flow-dependency (increasing difference between the measured and the expected pressure at increasing flow rates), while pre-calibrated valves revealed a flowindependent behavior. Water seal valve showed low degree flow-dependency. The pressures generated by the outlet port of the tested helmets ranged from 0.02 to 2.29 cmH2O at the highest gas flow rate. Conclusions: Adjustable PEEP valves are not suggested for continuous-flow CPAP systems as their flowdependency can lead to pressures higher than expected. Pre-calibrated and water seal valves exhibit the best performance. Different helmet outlet ports do not significantly affect the pressure generated during helmet CPAP. In order to avoid iatrogenic complications gas flow and pressure delivered during helmet CPAP must always be monitored.

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/NO2<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. (Minerva Anestesiol 2012;78:385-9)

Percutaneous dilational tracheostomy (PDT) can potentially lead to hypoxia and alveolar derecruitment. The aim of this prospective study was to evaluate the efficacy of performing a recruitment maneuver (RM) before tracheostomy, in order to improve oxygenation

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, PaO 2 <50 mmHg with FiO 2 >0.6 for >12 hours, PEEP >5 cmH 20, 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. Results: 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 FiO 2 1. Data were recorded 30 minutes before and 60 minutes after initiation of ECMO. ECMO improved PCO 2 (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 cmH 2O, p<0.01). No major clinical or technical complications were observed. Conclusions: ECMO effectively enabled high-risk ground transfer of severely hypoxic patients. © 2011 Wichtig Editore.

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

Introduction: Intensive care is generally regarded as expensive, and as a result beds are limited. This has raised serious questions about rationing when there are insufficient beds for all those referred. However, the evidence for the cost effectiveness of intensive care is weak and the work that does exist usually assumes that those who are not admitted do not survive, which is not always the case. Randomised studies of the effectiveness of intensive care are difficult to justify on ethical grounds; therefore, this observational study examined the cost effectiveness of ICU admission by comparing patients who were accepted into ICU after ICU triage to those who were not accepted, while attempting to adjust such comparison for confounding factors.Methods: This multi-centre observational cohort study involved 11 hospitals in 7 EU countries and was designed to assess the cost effectiveness of admission to intensive care after ICU triage. A total of 7,659 consecutive patients referred to the intensive care unit (ICU) were divided into those accepted for admission and those not accepted. The two groups were compared in terms of cost and mortality using multilevel regression models to account for differences across centres, and after adjusting for age, Karnofsky score and indication for ICU admission. The analyses were also stratified by categories of Simplified Acute Physiology Score (SAPS) II predicted mortality (< 5%, 5% to 40% and >40%). Cost effectiveness was evaluated as cost per life saved and cost per life-year saved.Results: Admission to ICU produced a relative reduction in mortality risk, expressed as odds ratio, of 0.70 (0.52 to 0.94) at 28 days. When stratified by predicted mortality, the odds ratio was 1.49 (0.79 to 2.81), 0.7 (0.51 to 0.97) and 0.55 (0.37 to 0.83) for <5%, 5% to 40% and >40% predicted mortality, respectively. Average cost per life saved for all patients was $103,771 (€82,358) and cost per life-year saved was $7,065 (€5,607). The

Purpose: In view of the expected 2009 influenza A(H1N1) pandemic, the Italian Health Authorities set up a national referral network of selected intensive care units (ICU) able to provide advanced respiratory care up to extracorporeal membrane oxygenation (ECMO) for patients with acute respiratory distress syndrome (ARDS). We describe the organization and results of the network, known as ECMOnet. Methods: The network consisted of 14 ICUs with ECMO capability and a national call center. The network was set up to centralize all severe patients to the ECMOnet centers assuring safe transfer. An ad hoc committee defined criteria for both patient transfer and ECMO institutions. Results: Between August 2009 and March 2010, 153 critically ill patients (53% referred from other hospitals) were admitted to the ECMOnet ICU with suspected H1N1. Sixty patients (48 of the referred patients, 49 with confirmed H1N1 diagnosis) received ECMO according to ECMOnet criteria. All referred patients were successfully transferred to the ECMOnet centers; 28 were transferred while on ECMO. Survival to hospital discharge in patients receiving ECMO was 68%. Survival of patients receiving ECMO within 7 days from the onset of mechanical ventilation was 77%. The length of mechanical ventilation prior to ECMO was an independent predictor of mortality. Conclusions: A network organization based on preemptive patient centralization allowed a high survival rate and provided effective and safe referral of patients with severe H1N1-suspected ARDS. © Copyright jointly held by Springer and ESICM 2011.

Background. The novel influenza A (H1N1) pandemic was associated with an epidemic of critical illness. Methods. 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. Results. 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. Conclusion. 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.

Purpose: Standard polyvinylchloride (PVC) endotracheal tube (ETT) cuffs do not protect from aspiration across the cuff, a leading cause of ventilator-associated pneumonia (VAP). In a long-lasting in vitro study we compared the effect of different cuff materials (PVC, polyurethane, and guayule latex), shapes (cylindrical, conical), and positive end expiratory pressures (PEEP) in reducing fluid leakage across the cuff. Methods: We compared fluid leakage across a cylindrical double-layer guayule latex prototype cuff, three cylindrical PVC cuffs (Mallinckrodt Hi-Lo, Mallinckrodt HighContour, Portex Ivory), one conical PVC cuff (Mallinckrodt TaperGuard), and two polyurethane cuffs (Mallinckrodt SealGuard, conical; Microcuff, cylindrical). Ten centimeters of dyed water was poured above the cuffs inflated (pressure 30 cmH 2O) in a vertical cylinder (diameter 20 mm). A respiratory circuit connected the bottom of the cylinder to a breathing bag inflated at four pressures (PEEP = 0, 5, 10, 15 cmH2O). Pictures were taken every 60 s for 24 h to measure leakage as a reduction in the water column above the cuff. Five new ETTs of each type were tested. Results: The guayule latex cuffs showed no leakage at all the PEEP levels. Both the cylindrical and conical polyurethane cuffs showed limited leakage (2.1 ± 1.8 cm of water) only for PEEP zero. The PVC cuffs showed reduced leakage with increasing PEEP: 8.4 ± 1.5, 7.8 ± 2.2, 2.2 ± 1.0, and 0 cm of water at 0, 5, 10, and 15 cmH2O, respectively. Among all the PVC cuffs, the conical shape ensured higher sealing properties. Conclusions: The guayule latex cuffs always prevented fluid leakage; the polyurethane and PVC cuffs required incremental levels of PEEP to prevent fluid leakage ever-present at zero PEEP. © Copyright jointly held by Springer and ESICM 2010.

Purpose: We assessed the performance of different continuous positive airway pressure (CPAP) helmets equipped with a safety valve during discontinuation of fresh gas flow. Methods: This was a physiological study of five healthy volunteers. We delivered CPAP (fresh gas flow 60 l/min, FiO 2 60%, PEEP 5 cmH2O) with three different helmets in a random sequence: 4Vent (Rüsch), HelmHAR-cp (Harol) and CaStar CP210 (StarMed). For each helmet we randomly applied, for up to 4 min, three disconnections of fresh gas flow: helmet inlet (Dinlet), flowmeter (Dflowmeter) and gas source (Dsource). We continuously recorded from a nostril: end-tidal CO2 (PetCO2), inspiratory CO2 (PiCO2), fraction of inspired oxygen (FiO2) and respiratory rate (RR). Results: During every disconnection we observed an increase in PiCO2 and PetCO2 with a drop in FiO2, while RR did not change. FiO2 decreased more quickly in the CaStar, equipped with the largest safety valve, during D source and Dflowmeter, while FiO2 decreased more quickly during Dinlet in CaStar and in 4Vent. PiCO2 resulted in a lower increase in CaStar during Dsource and D flowmeter compared to 4Vent. PetCO2 in CaStar increases more slowly compared to 4Vent during Dsource and more slowly compared to the other two helmets during Dflowmeter. During Dinlet similar degrees of CO2 rebreathing and PetCO2 were recorded among all the helmets. Conclusions: To minimize CO2 rebreathing during disconnection of the fresh gas supply while performing helmet CPAP, it is desirable to utilize large helmets with a large anti-suffocation valve. Monitoring and alarm systems should be employed for safe application of helmet CPAP. © 2011 jointly held by Springer and ESICM.

Purpose of Review: To describe a physiopathological-based approach to clinical management of severely hypoxemic patients that integrates the most recent findings on the use of rescue therapies. Recent Findings: Several techniques are available to improve oxygenation in severely hypoxemic patients. Survival benefits have not been proved for most of these techniques. In a recent randomized trial, centralization of acute respiratory distress syndrome patients to a specialized center able to provide extracorporeal membrane oxygenation showed better survival as compared to conventional treatment. Randomized trials failed to prove survival benefits with the use of high levels of positive end-expiratory pressure (PEEP) or prone positioning. However, pooled data from two meta-analyses showed significant higher survival in the most severe patients both with the use of higher PEEP and prone positioning. Summary: Treatment of severely hypoxemic patients should aim to improve oxygenation while limiting ventilator-induced lung injury. A physiopathological approach that accounts for the underlying mechanisms of hypoxemia, and physiological and clinical effects of different treatments is likely the best guide we have to treat severely hypoxemic patients. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Introduction. Severe mixed-blocker and calcium channel blocker intoxication presents a significant risk for patient mortality. Although treatment is well-established, it sporadically fails to support the patient through massive overdoses, thus requiring non-conventional treatments. We report the use of extra-corporeal life support in a patient with refractory hemodynamic impairment due to multi-drug intoxication. Although sometimes used in clinical practice, extra-corporeal membrane oxygenation for intoxications has rarely been reported. Case presentation. A 36-year-old Caucasian man presented to our hospital with refractory hypotension, severe cardiac insufficiency and multi-organ failure due to mixed intoxication with atenolol, nifedipine, Lacidipine and sertraline. Together with standard treatment, we performed extra-corporeal membrane oxygenation to overcome refractory cardiogenic shock and lead the patient to achieve a full recovery. Conclusion: Standard of care for -blocker and calcium channel blocker intoxication is well-defined and condensed into protocols of treatment. Although aimed at clearing the noxious agents from the patient's system, standard measures may fail to provide adequate hemodynamic support to allow recovery. In selected cases, extra-corporeal membrane oxygenation could be considered a bridge to drug clearance while preventing multi-organ failure due to profound shock. © 2011 Rona et al; licensee BioMed Central Ltd.

Rationale: During acute lung injury (ALI), mechanical ventilation can aggravate inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an estimate of the intensity of inflammation,metabolic activity can bemeasured by positrone-mission tomography imaging of [18F]fluoro-2-deoxy-D-glucose. Objectives: To assess the relationship between gas volume changes induced by tidal ventilation and pulmonary metabolic activity in patients with ALI. Methods: In 13 mechanically ventilated patients with ALI and relatively high positive end-expiratory pressure, we performed a positron emission tomography scan of the chest and three computed tomography scans: at mean airway pressure, end-expiration, and end-inspiration. Metabolicactivitywasmeasuredfromthe[18F]fluoro-2-deoxy-D-glucose uptake rate. The computed tomography scans were used to classify lung regions as derecruited throughout the respiratory cycle, undergoing recruitment-derecruitment, and normally aerated. Measurements and Main Results: Metabolic activity of normally aerated lung was positively correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm H2O, and with regional VT normalized by end-expiratory lung gas volume. This relationship did not appear to be caused by a higher underlying parenchymal metabolic activity in patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment did not have higher metabolic activity than those collapsed throughout the respiratory cycle. Conclusions: In patients with ALI managed with relatively high end-expiratory pressure, metabolic activity of aerated regions was associated with both plateau pressure and regional VT normalized by end-expiratory lung gas volume, whereas no association was found between cyclic recruitment- derecruitment and increased metabolic activity. Copyright © 2011 American Thoracic Society.