Extracorporeal Respiratory Support Research Articles

PCO 2 Gradient Between Inlet and Outlet Blood of Extracorporeal Respiratory Support Is a Reliable Marker of CO 2 Elimination.

Our objective was to assess the relationship between the pre-/post-oxygenator gradient of the partial pressure of carbon dioxide (∆ EC PCO 2 ; dissolved form) and CO 2 elimination under extracorporeal respiratory support. All patients who were treated with veno-venous extracorporeal membrane oxygenation and high-flow extracorporeal CO 2 removal in our intensive care unit over 18 months were included. Pre-/post-oxygenator blood gases were collected every 12 h and CO 2 elimination was calculated for each pair of samples (pre-/post-oxygenator total carbon dioxide content in blood [ ct CO 2 ] × pump flow [extracorporeal pump flow {Q EC }]). The relationship between ∆ EC PCO 2 and CO 2 elimination, as well as the origin of CO 2 removed. Eighteen patients were analyzed (24 oxygenators and 293 datasets). Each additional unit of ∆ EC PCO 2 × Q EC was associated with an increase in CO 2 elimination of 5.2 ml (95% confidence interval [CI], 4.7-5.6 ml; p < 0.001). Each reduction of 1 ml STPD/dl of CO 2 across the oxygenator was associated with a reduction of 0.63 ml STPD/dl (95% CI, 0.60-0.66) of CO 2 combined with water, 0.08 ml STPD/dl (95% CI, 0.07-0.09) of dissolved CO 2 , and 0.29 ml STPD/dl (95% CI, 0.27-0.31) of CO 2 in erythrocytes. The pre-/post-oxygenator PCO 2 gradient under extracorporeal respiratory support is thus linearly associated with CO 2 elimination; however, most of the CO 2 removed comes from combined CO 2 in plasma, generating bicarbonate.

Pilot Testing of a Lightweight, Pulmonary Assist System in an Ambulatory Sheep Model of Destination Therapy Respiratory Support.

A new, lightweight (2.3 kg), ambulatory pulmonary assist system (PAS) underwent preliminary evaluation in ambulatory sheep. The PAS was purposefully designed for long-term extracorporeal respiratory support for chronic lung disease and utilizes a novel, small (0.9 m 2 surface area) gas exchanger, the pulmonary assist device, with a modified Heart Assist 5 pump fitting in a small wearable pack. Prototype PAS were attached to two sheep in venovenous configuration for 7 and 14 days, evaluating ability to remain thrombus free; maintain gas exchange and blood flow resistance; avoid biocompatibility-related complications while allowing safe ambulation. The PAS achieved 1.56 L/min of flow at 10.8 kRPM with a 24 Fr cannula in sheep one and 2.0 L/min at 10.5 kRPM with a 28 Fr cannula in sheep 2 without significant change. Both sheep walked freely, demonstrating the first application of truly ambulatory ECMO in sheep. While in vitro testing evaluated PAS oxygen transfer rates of 104.6 ml/min at 2 L/min blood flow, oxygen transfer rates averaged 60.6 ml/min and 70.6 ml/min in studies 1 and 2, due to average hemoglobin concentrations lower than humans (8.9 and 10.5 g/dl, respectively). The presented cases support uncomplicated ambulation using the PAS.

Extracorporeal membrane oxygenation (ECMO) and beyond in near fatal asthma: A comprehensive review

The treatment of choice in severe asthma exacerbations with respiratory failure includes ventilatory support, both invasive and/or non-invasive, along with different kinds of asthma medication. Of note, the rate of mortality of patients with asthma has decreased substantially in recent years mainly due to significant advances in pharmacological treatment and other management strategies. However, the risk of death in patients with severe asthma who require invasive mechanical ventilation has been estimated between 6.5% and 10.3%. When conventional measures fail, rescue strategies, such as extracorporeal membrane oxygenation (ECMO) or extracorporeal CO2 removal (ECCO2R) may need to be implemented. While ECMO does not constitute a definitive treatment per se, it can minimize further ventilator associated lung injury (VALI) and can enable diagnostic-therapeutic maneuvers that cannot be performed without ECMO such as bronchoscopy and transfer for diagnostic imaging. Asthma is one of the diseases that is associated with excellent outcomes for patients with refractory respiratory failure requiring ECMO support, as shown by the Extracorporeal Life Support Organization (ELSO) registry. Moreover, in such situations, the use of ECCO2R for rescue has been described and utilized in both children and adults and is more widely spread in different hospitals than ECMO. In this article, we aim to review the evidence for the usefulness of extracorporeal respiratory support measures in the management of severe asthma exacerbations that lead to respiratory failure.

Advances in Extracorporeal Support Technologies in Critically Ill Children.

The field of pediatric heart failure is evolving, and the patient population is growing as survival after complex congenital heart surgeries is improving. Mechanical circulatory support and extracorporeal respiratory support in critically ill children has progressed to a mainstay rescue modality in pediatric intensive care medicine. The need for mechanical circulatory support is growing, since the number of organ donors does not meet the necessity. This article aims to review the current state of available mechanical circulatory and respiratory support systems in acute care pediatrics, with an emphasis on the literature discussing the challenges associated with these complex support modalities.

High- versus Low-Flow Extracorporeal Respiratory Support in Experimental Hypoxemic Acute Lung Injury.

Rationale: In the EOLIA (ECMO to Rescue Lung Injury in Severe ARDS) trial, oxygenation was similar between intervention and conventional groups, whereas [Formula: see text]e was reduced in the intervention group. Comparable reductions in ventilation intensity are theoretically possible with low-flow extracorporeal CO2 removal (ECCO2R), provided oxygenation remains acceptable. Objectives: To compare the effects of ECCO2R and extracorporeal membrane oxygenation (ECMO) on gas exchange, respiratory mechanics, and hemodynamics in animal models of pulmonary (intratracheal hydrochloric acid) and extrapulmonary (intravenous oleic acid) lung injury. Methods: Twenty-four pigs with moderate to severe hypoxemia (PaO2:FiO2 ⩽ 150 mm Hg) were randomized to ECMO (blood flow 50-60 ml/kg/min), ECCO2R (0.4 L/min), or mechanical ventilation alone. Measurements and Main Results: [Formula: see text]o2, [Formula: see text]co2, gas exchange, hemodynamics, and respiratory mechanics were measured and are presented as 24-hour averages. Oleic acid versus hydrochloric acid showed higher extravascular lung water (1,424 ± 419 vs. 574 ± 195 ml; P < 0.001), worse oxygenation (PaO2:FiO2 = 125 ± 14 vs. 151 ± 11 mm Hg; P < 0.001), but better respiratory mechanics (plateau pressure 27 ± 4 vs. 30 ± 3 cm H2O; P = 0.017). Both models led to acute severe pulmonary hypertension. In both models, ECMO (3.7 ± 0.5 L/min), compared with ECCO2R (0.4 L/min), increased mixed venous oxygen saturation and oxygenation, and improved hemodynamics (cardiac output = 6.0 ± 1.4 vs. 5.2 ± 1.4 L/min; P = 0.003). [Formula: see text]o2 and [Formula: see text]co2, irrespective of lung injury model, were lower during ECMO, resulting in lower PaCO2 and [Formula: see text]e but worse respiratory elastance compared with ECCO2R (64 ± 27 vs. 40 ± 8 cm H2O/L; P < 0.001). Conclusions: ECMO was associated with better oxygenation, lower [Formula: see text]o2, and better hemodynamics. ECCO2R may offer a potential alternative to ECMO, but there are concerns regarding its effects on hemodynamics and pulmonary hypertension.

Performance of the decarboxylation index to predict CO2 removal and minute ventilation reduction under extracorporeal respiratory support.

The aim of this study was to assess the interdependence of extracorporeal blood flow (Qec) and gas flow (GF) in predicting CO2 removal and reduction of minute mechanical ventilation under extracorporeal respiratory support. All patients who benefited from V-V ECMO and high-flow ECCO2 R in our intensive care unit over a period of 18 months were included. CO2 removal was calculated from inlet/outlet blood port gases during the first 7 days of oxygenator use. The relationship between the Qec × GF product (named decarboxylation index and expressed in L2 /min2 ) and CO2 removal or expired minute mechanical ventilation reduction (EC MV ratio) was studied using linear regression models. Eighteen patients were analyzed, corresponding to 24 oxygenators and 261 datasets. CO2 removal was 393 ml/min (IQR, 310-526) for 1.8 m2 oxygenators and 179 ml/min (IQR, 165-235) for 1.3 m2 oxygenators. The decarboxylation index was associated linearly with CO2 removal (R2 =0.62 and R2 =0.77 for the two oxygenators, respectively) and EC MV ratio (R2 =0.72 and R2 =0.62, respectively). The 20L2 /min2 value (considering Qec=2 L/min and GF=10 L/min) was associated with an EC MV ratio between 61% and 29% for 1.8 m2 oxygenators, and between 62% and 38% for 1.3 m2 oxygenators. The decarboxylation index is a simple parameter to predict CO2 removal and EC MV ratio under extracorporeal respiratory support.

Too much tolerance for hyperoxemia in mechanically ventilated patients with SARS-CoV-2 pneumonia? Report from an Italian intensive care unit.

BackgroundIn COVID-19 patients requiring mechanical ventilation, the administration of high oxygen (O2) doses for prolonged time periods may be necessary. Although life-saving in most cases, O2 may exert deleterious effects if administered in excessive concentrations. We aimed to describe the prevalence of hyperoxemia and excessive O2 administration in mechanically ventilated patients with SARS-CoV-2 pneumonia and determine whether hyperoxemia is associated with mortality in the Intensive Care Unit (ICU) or the onset of ventilator-associated pneumonia (VAP).Materials and methodsRetrospective single-center study on adult patients with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation for ≥48 h. Patients undergoing extracorporeal respiratory support were excluded. We calculated the excess O2 administered based on the ideal arterial O2 tension (PaO2) target of 55–80 mmHg. We defined hyperoxemia as PaO2 > 100 mmHg and hyperoxia + hyperoxemia as an inspired O2 fraction (FiO2) > 60% + PaO2 > 100 mmHg. Risk factors for ICU-mortality and VAP were assessed through multivariate analyses.ResultsOne hundred thirty-four patients were included. For each day of mechanical ventilation, each patient received a median excess O2 of 1,121 [829–1,449] L. Hyperoxemia was found in 38 [27–55]% of arterial blood gases, hyperoxia + hyperoxemia in 11 [5–18]% of cases. The FiO2 was not reduced in 69 [62–76]% of cases of hyperoxemia. Adjustments were made more frequently with higher PaO2 or initial FiO2 levels. ICU-mortality was 32%. VAP was diagnosed in 48.5% of patients. Hyperoxemia (OR 1.300 95% CI [1.097–1.542]), time of exposure to hyperoxemia (OR 2.758 [1.406–5.411]), hyperoxia + hyperoxemia (OR 1.144 [1.008–1.298]), and daily excess O2 (OR 1.003 [1.001–1.005]) were associated with higher risk for ICU-mortality, independently of age, Sequential Organ failure Assessment score at ICU-admission and mean PaO2/FiO2. Hyperoxemia (OR 1.033 [1.006–1.061]), time of exposure to hyperoxemia (OR 1.108 [1.018–1.206]), hyperoxia + hyperoxemia (OR 1.038 [1.003–1.075]), and daily excess O2 (OR 1.001 [1.000–1.001]) were identified as risk factors for VAP, independently of body mass index, blood transfusions, days of neuromuscular blocking agents (before VAP), prolonged prone positioning and mean PaO2/FiO2 before VAP.ConclusionExcess O2 administration and hyperoxemia were common in mechanically ventilated patients with SARS-CoV-2 pneumonia. The exposure to hyperoxemia may be associated with ICU-mortality and greater risk for VAP.

The physiological underpinnings of life-saving respiratory support.

Treatment of respiratory failure has improved dramatically since the polio epidemic in the 1950s with the use of invasive techniques for respiratory support: mechanical ventilation and extracorporeal respiratory support. However, respiratory support is only a supportive therapy, designed to “buy time” while the disease causing respiratory failure abates. It ensures viable gas exchange and prevents cardiorespiratory collapse in the context of excessive loads. Because the use of invasive modalities of respiratory support is also associated with substantial harm, it remains the responsibility of the clinician to minimize such hazards. Direct iatrogenic consequences of mechanical ventilation include the risk to the lung (ventilator-induced lung injury) and the diaphragm (ventilator-induced diaphragm dysfunction and other forms of myotrauma). Adverse consequences on hemodynamics can also be significant. Indirect consequences (e.g., immobilization, sleep disruption) can have devastating long-term effects. Increasing awareness and understanding of these mechanisms of injury has led to a change in the philosophy of care with a shift from aiming to normalize gases toward minimizing harm. Lung (and more recently also diaphragm) protective ventilation strategies include the use of extracorporeal respiratory support when the risk of ventilation becomes excessive. This review provides an overview of the historical background of respiratory support, pathophysiology of respiratory failure and rationale for respiratory support, iatrogenic consequences from mechanical ventilation, specifics of the implementation of mechanical ventilation, and role of extracorporeal respiratory support. It highlights the need for appropriate monitoring to estimate risks and to individualize ventilation and sedation to provide safe respiratory support to each patient.

Influenza in patients with respiratory failure admitted to intensive care units in Poland and the use of extracorporeal respiratory support: a survey-based multicenter study

BackgroundIn Poland, little is known about the most serious cases of influenza that need admittance to the intensive care unit (ICU), as well as the use of extracorporeal respiratory support.MethodsThis was an electronic survey comprising ICUs in two administrative regions of Poland. The aim of the study was to determine the number of influenza patients with respiratory failure admitted to the ICU in the autumn–winter season of 2018/2019. Furthermore, respiratory support, outcome and other pathogens detected in the airways were investigated.ResultsInfluenza infection was confirmed in 76 patients. The A(H1N1)pdm09 strain was the most common. 34 patients died (44.7%). The median age was 62 years, the median sequential organ failure assessment (SOFA) score was 11 and was higher in patients who died (12 vs. 10, p = 0.017). Mechanical ventilation was used in 75 patients and high flow nasal oxygen therapy in 1 patient. Extracorporeal membrane oxygenation (ECMO) was used in 7 patients (6 survived), and extracorporeal carbon dioxide removal (ECCO2R) in 2 (1 survived). The prone position was used in 16 patients. In addition, other pathogens were detected in the airways on admittance to the ICU.ConclusionA substantial number of influenza infections occurred in the autumn–winter season of 2018/2019 that required costly treatment in the intensive care units. Upon admission to the ICU, influenza patients had a high degree of organ failure as assessed by the SOFA score, and the mortality rate was 44.7%. Advanced extracorporeal respiratory techniques offer real survival opportunities to patients with severe influenza-related ARDS. The presence of coinfection should be considered in patients with influenza and respiratory failure.

Extracorporeal Respiratory Support During the First and Second Waves of the COVID-19 Pandemic in Spain and Portugal: An Observational, Multicenter, Cohort Study Including 334 Patients

Background: The benefits of the use of extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 remain controversial.Methods: In this multicenter cohort study, we analyzed all the adult patients with ARDS due to COVID-19 who received extracorporeal respiratory support at 25 ECMO centers (23 in Spain and two in Portugal) during the first and second waves of the pandemic. Follow-up ended on December 1. Our primary aim was to describe this cohort taking into account its evolution during the pandemic. We also investigated hazard ratios for hospital mortality.Findings: A total of 334 patients were included. Patients supported during the second wave [176 (52.7%)] were older (54.6±9.7 vs 50.9±10.6,p=0.001), had more comorbidities, were more frequently coinfected at the start of ECMO [62 (35.2%) vs 37 (23.3%),p=0.028] and were less likely to be treated at a high-volume center [42 (23.9%) vs 54 (34.2%),p=0.008] than those supported during the first wave [158 (47.3%)]. At December 1, 134 (40.1%) patients had died and 49 (14.6%) were still on ECMO. Among patients supported during the first wave, 93 (58.8%) were discharged and all were alive at six months. Older age [HR 3.49 (1.94-6.28),pInterpretation: ECMO support provided at high volume centers should be considered in selected COVID-19 patients. Age and coinfection, but not mechanical ventilation days, should be taken into account at indication assessment.Funding Statement: No funding.Declaration of Interests: None.Ethics Approval Statement: The study protocol was approved by the local ethics committees at all the participating centers.

The rs738409 G Allele in PNPLA3 Is Associated With a Reduced Risk of COVID-19 Mortality and Hospitalization

The rs738409 G Allele in PNPLA3 Is Associated With a Reduced Risk of COVID-19 Mortality and Hospitalization

Extracorporeal Oxygenation Techniques in Adult Critical Airway Obstruction: A Review.

Extracorporeal life support has been increasingly utilized in different clinical settings to manage either critical respiratory or heart failure. Complex airway surgery with significant or even total perioperative airway obstruction represents an indication for this technique to prevent/overcome a critical period of severe hypoxaemia, hypoventilation, and/or apnea. This review summarizes the current published scientific evidence on the utility of extracorporeal respiratory support in airway obstruction associated with hypoxaemia, describes the available methods, their clinical indications, and possible limitations. Extracorporeal membrane oxygenation using veno-arterial or veno-venous mode is most commonly employed in such scenarios caused by endoluminal, external, or combined obstruction of the trachea and main bronchi.

Key Role of Respiratory Quotient to Reduce the Occurrence of Hypoxemia During Extracorporeal Gas Exchange: A Theoretical Analysis.

Extracorporeal respiratory support, including low blood flow systems providing mainly extracorporeal CO2 removal, are increasingly applied in clinical practice. Gas exchange physiology during extracorporeal respiratory support is complex and differs between full extracorporeal membrane oxygenation and extracorporeal CO2 removal. Aim of the present article is to review pathophysiological aspects which are relevant for the understanding of hypoxemia development during extracorporeal CO2 removal. We will describe the mathematical and physiologic background underlying changes in respiratory quotient and alveolar oxygen tension during venovenous extracorporeal gas exchange and highlight the clinical implications. Theoretical analysis of venovenous extracorporeal gas exchange. Italian university research hospital. None. None. While the effect of extracorporeal CO2 removal on the respiratory quotient of the native lung has long been known, the role of extracorporeal oxygenation in dictating changes in the respiratory quotient has been less addressed. Indeed, both extracorporeal CO2 removal and extracorporeal oxygen delivery affect the respiratory quotient of the native lung and thus influence the alveolar PO2. Indeed, for the same amount of extracorporeal CO2 extraction, it is possible to reduce the FIO2, reduce the risk of absorption atelectasis, and maintain the same alveolar PO2, by increasing the extracorporeal oxygen delivery. Worsening of hypoxemia is frequent during low-flow extracorporeal CO2 removal combined with ultraprotective mechanical ventilation. In this context, increasing extracorporeal oxygen delivery, increases the respiratory quotient of the native lung and could reduce both the occurrence of alveolar hypoxia and absorption atelectasis, thus optimizing the residual lung function.

Extracorporeal Membrane Oxygenation Retrieval in Coronavirus Disease 2019: A Case-Series of 19 Patients Supported at a High-Volume Extracorporeal Membrane Oxygenation Center.

To evaluate the performance of the extracorporeal membrane oxygenation retrieval team at a high-volume extracorporeal membrane oxygenation center during the coronavirus disease 2019 pandemic. Observational study including all adult patients with confirmed infection due to severe acute respiratory syndrome coronavirus-2 cannulated at other centers and transported on extracorporeal membrane oxygenation to the ICU of the Vall d'Hebron University Hospital between 15 March and 10 June 2020. The ICU (capacity expanded to 200 during the pandemic) of the Vall d'Hebron University Hospital (a 1,100-bed public university hospital in Barcelona), the referral center for extracorporeal respiratory support in Catalonia (7.5 million inhabitants). Extracorporeal membrane oxygenation was considered if the Pao2/Fio2 ratio less than 80 mm Hg (refractory to prone position) and/or Paco2 greater than 80 mm Hg and pH less than 7.25 for more than 6 hours, and no contraindications for extracorporeal support were present. Venovenous extracorporeal membrane oxygenation was initiated in the primary center. Then, patients were transferred to the ICU of the Vall d'Hebron University Hospital where they received support until respiratory improvement. After decannulation, patients were discharged for rehabilitation at the primary center. Nineteen patients with severe acute respiratory syndrome coronavirus-2 infection and with a mean Pao2/Fio2 ratio of 71 mm Hg (57-118 mm Hg) despite prone positioning and a mean Paco2 of 70 mm Hg (47-110 mm Hg) were transferred to our center from their primary hospital after cannulation and received venovenous extracorporeal membrane oxygenation support. Prior to cannulation, six patients (31.5%) presented vascular thrombosis, and nine (47.4%) were already receiving anticoagulant therapy. Eighteen transfers were carried out with no significant complications. While on extracorporeal membrane oxygenation, thrombotic events were recorded in nine patients (47.4%) and hemorrhagic events in 13 (68.4%). Thirteen patients (68.4%) were successfully weaned, and 12 (63.1%) were discharged home. Extracorporeal membrane oxygenation retrieval can rescue young, previously healthy patients with severe coronavirus disease 2019 in whom all the conventional respiratory measures have failed. Thrombotic and hemorrhagic complications are frequent in this cohort.

Progress of mechanical power in the intensive care unit.

Mechanical power of ventilation, currently defined as the energy delivered from the ventilator to the respiratory system over a period of time, has been recognized as a promising indicator to evaluate ventilator-induced lung injury and predict the prognosis of ventilated critically ill patients. Mechanical power can be accurately measured by the geometric method, while simplified equations allow an easy estimation of mechanical power at the bedside. There may exist a safety threshold of mechanical power above which lung injury is inevitable, and the assessment of mechanical power might be helpful to determine whether the extracorporeal respiratory support is needed in patients with acute respiratory distress syndrome. It should be noted that relatively low mechanical power does not exclude the possibility of lung injury. Lung size and inhomogeneity should also be taken into consideration. Problems regarding the safety limits of mechanical power and contribution of each component to lung injury have not been determined yet. Whether mechanical power-directed lung-protective ventilation strategy could improve clinical outcomes also needs further investigation. Therefore, this review discusses the algorithms, clinical relevance, optimization, and future directions of mechanical power in critically ill patients.

Extubate Before Venovenous Extracorporeal Membranous Oxygenation Decannulation or Decannulate While Remaining on the Ventilator? The EuroELSO 2019 Weaning Survey.

Extubate Before Venovenous Extracorporeal Membranous Oxygenation Decannulation or Decannulate While Remaining on the Ventilator? The EuroELSO 2019 Weaning Survey.

Evaluating Mortality Risk Adjustment Among Children Receiving Extracorporeal Support for Respiratory Failure.

This study evaluates whether three commonly used pediatric intensive care unit (PICU) severity of illness scores, pediatric risk of mortality score (PRISM) III, pediatric index of mortality (PIM) 2, and pediatric logistic organ dysfunction (PELOD), are the appropriate tools to discriminate mortality risk in children receiving extracorporeal membrane oxygenation (ECMO) support for respiratory failure. This study also evaluates the ability of the Pediatric Risk Estimate Score for Children Using Extracorporeal Respiratory Support (Ped-RESCUERS) to discriminate mortality risk in the same population, and whether Ped-RESCUERS' discrimination of mortality is improved by additional clinical and laboratory measures of renal, hepatic, neurologic, and hematologic dysfunction. A multi-institutional retrospective cohort study was conducted on children aged 29 days to 17 years with respiratory failure requiring respiratory ECMO support. Discrimination of mortality was evaluated with the area under the receiver operating curve (AUC); model calibration was measured by the Hosmer-Lemeshow goodness of fit test and Brier score. Admission PRISM-III, PIM-2, and PELOD were found to have poor ability to discriminate mortality with an AUC of 0.56 [0.46-0.66], 0.53 [0.43-0.62], and 0.57 [0.47-0.67], respectively. Alternatively, Ped-RESCUERS performed better with an AUC of 0.68 [0.59-0.77]. Higher alanine aminotransferase, ratio of the arterial partial pressure of oxygen the fraction of inspired oxygen, and lactic acidosis were independently associated with mortality and, when added to Ped-RESCUERS, resulted in an AUC of 0.75 [0.66-0.82]. Admission PRISM-III, PIM-2, and PELOD should not be used for pre-ECMO risk adjustment because they do not discriminate death. Extracorporeal membrane oxygenation population-derived scores should be used to risk adjust ECMO populations as opposed to general PICU population-derived scores.

Spontaneous breathing during veno-venous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) has started to be applied in awake spontaneously breathing patients as an alternative to invasive mechanical ventilation. As the physiologic cardiorespiratory variability is increased in this condition, the dynamic interaction between patient respiratory activity and extracorporeal system function affects the clinical management. The effect of extracorporeal CO2 removal on patient respiratory drive is variable and not always predictable, with some patients responding to CO2 removal with a decrease in respiratory rate and effort and other patients demonstrating a persistently high work of breathing independent on CO2 unload. While the pathophysiological mechanisms of this different interactions are still to be clarified, improved monitoring ability is needed both to titrate the support in responders and to avoid the risk of ventilation injury in non-responders. Acute changes in patient respiratory patterns may also occur during spontaneous breathing, making it difficult to maintain constant levels of extracorporeal respiratory support, also because changes in the distribution of venous blood volume due to lung-heart interactions affect extracorporeal blood flow. Assessment of native lung function and of its evolution over time is challenging while respiratory gas exchanges are provided by the extracorporeal system, since both oxygenation and decarboxylation capabilities can be fully evaluated only when alveolar ventilation is restored reducing extracorporeal CO2 removal. The rationale for using "awake ECMO" varies across different types of acute respiratory failure: the pathophysiological mechanisms of the underlying disease affect the patient-ECMO interaction and the goal of support. In this review we discuss the pathophysiology, technical challenges and monitoring issues of the use of ECMO in awake spontaneously breathing patients with acute respiratory failure of different etiologies.

Lung Transplantation in Germany Since the Introduction of the Lung Allocation Score.

The allocation of donor lungs for transplantation in Germany was changed on 10 December 2011 to a system based on the Lung Allocation Score (LAS). The aim of the present study is to determine whether this change has prolonged the survival of patients on the transplant waiting list and of those who have undergone lung transplantation (LTx). We retrospectively compared data from the three-year periods before and after the change to an LAS-based allocation system (2009-2011 vs. 2012-2014). The number of patients on the active waiting list declined from 606 on 12/31/2011 to 432 on 12/31/2014, a 29% decrease. The number of patients who died while on the waiting list fell from 306 in 2009-2011 to 226 in 2012-2014 (-26%, p = 0.04). Waiting-list mortality declined across all disease groups. Meanwhile, the number of lung transplantation procedures per year increased by 21% over the period of observation, from 865 to 1045. During the period in which the LAS was used, the proportion of transplant recipients with restrictive lung disease (46% vs. 31%; p<0.001) surpassed the proportion of those with a diagnosis of obstructive lung disease (33% vs. 40%; p = 0.003). The percentage of transplantations in patients treated with mechanical ventilation or extracorporeal respiratory support before transplantation rose from 9% to 13%. The one-year survival rate after lung transplantation was 76% in 2009-2011 and 81% in 2012-2014. The introduction of the LAS in Germany was associated with a decrease in the number of patients on the waiting list, and also in the number of deaths among patients on the waiting list. The distribution of primary diagnoses among transplant recipients shifted away from obstructive and toward restrictive lung diseases. In the future, additional parameters of patients on the waiting list should be considered to enable further improvement of the allocation model.

How best to set the ventilator on extracorporeal membrane lung oxygenation.

Extracorporeal respiratory support in patients with acute respiratory distress syndrome is applied either as rescue maneuver for life-threatening hypoxemia or as a tool to reduce the harm of mechanical ventilation. Depending on the blood and gas flow, extracorporeal support may completely substitute the natural lung as a gas exchanger (high-flow venovenous bypass) or reduce the need for mechanical ventilation, enabling the removal of a fraction of the metabolically produced CO2. Recent studies provide a description on how mechanical ventilation is normally applied in combination with extracorporeal support in acute respiratory distress syndrome. The data show a general trend: a variable decrease of fraction of inspired oxygen (0.9 to 0.7 or 0.4), a consistent decrease in tidal volume (by 2 ml/kg), no change in positive end-expiratory pressure (maintained around 12-13 cmH2O) and a moderate decrease in the respiratory rate (22 to 15 bpm). These ventilatory settings are applied in whatever extracorporeal membrane lung oxygenation modality (venovenous versus venoarterial) and independent from the extent of extracorporeal support (partial or total substitution of gas exchange). Mechanical ventilation and extracorporeal support are marginally integrated. The best environment for lung healing - complete lung collapse or protective ventilation strategy or fully open and immobile lung (all three conditions feasible with extracorporeal support) - remains to be defined.