Extracorporeal Support Techniques for Sepsis and Multi-Organ Failure

Extracorporeal Support Techniques for Sepsis and Multi-Organ Failure
Keith Wille, MD 2016 CRRT Highlights Hyderabad, India

Outline The burden of disease Consequences of mechanical ventilation
ARDS Consequences of mechanical ventilation Studies of ECMO in Sepsis Future directions

The Burden of Disease for which ECMO is Considered
Abstract Despite expensive life-sustaining interventions delivered in the ICU, mortality and morbidity in patients with acute respiratory failure (ARF) remain unacceptably high. Extracorporeal membrane oxygenation (ECMO) has emerged as a promising intervention that may provide more efficacious supportive care to these patients. Improvements in technology have made ECMO safer and easier to use, allowing for the potential of more widespread application in patients with ARF. A greater appreciation of the complications associated with the placement of an artificial airway and mechanical ventilation has led clinicians and researchers to seek viable alternatives to providing supportive care in these patients. Thus, this review will summarize the current knowledge regarding the use of venovenous (VV)- ECMO for ARF and describe some of the recent controversies in the field, such as mechanical ventilation, anticoagulation and transfusion therapy, and ethical concerns in patients supported with VV-ECMO. Keywords: Critical care, Extracorporeal membrane oxygenation,

ARDS >400,000 cases annually worldwide
High mortality, and significant potential for disability in survivors 27-45% mortality Sepsis, pneumonia, trauma, inhalation injury are a few of many recognized causes Acute respiratory distress syndrome presents as hypoxia and bilateral pulmonary infi ltrates on chest imaging in the absence of heart failure suffi cient to account for this clinical state. Management is largely supportive, and is focused on protective mechanical ventilation and the avoidance of fl uid overload. Patients with severe hypoxaemia can be managed with early short-term use of neuromuscular blockade, prone position ventilation, or extracorporeal membrane oxygenation. The use of inhaled nitric oxide is rarely indicated and both β2 agonists and late corticosteroids should be avoided. M ortality remains at approximately 30%. Epidemiology The landmark ARMA study,28 which was published in 2000, demonstrated the benefi ts of a low-tidal-volume, low-airway-pressure ventilatory strategy in acute respiratory distress syndrome and marked the establishment of lung protective ventilation as the standard of care. Despite this advance, the syndrome remains highly prevalent, with, in the lung-protective era, estimated incidences per patients per year of 34 in the USA29 and approximately fi ve to seven in Europe.30–32 Its epidemiology is probably under-reported in less developed health-care systems, in which, as a result of resource limitations, few patients meet the current defi nition for diagnosis, despite 4% of all hospital admissions having a clinical state similar to that of acute respiratory distress syndrome.33 7% of patients in the intensive-care unit (ICU), and 16% of those receiving mechanical ventilation, have acute respiratory distress syndrome.

Hospital Survival by ARDS Severity
IMPORTANCE Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts—for example prone positioning—in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES The primary outcomewas ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS Of patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0%(95%CI, 28.2%-31.9%); of moderate ARDS, 46.6%(95%CI, 44.5%-48.6%); and of severe ARDS, 23.4%(95%CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4%(95%CI, 10.0%-10.7%) of ICU admissions and 23.4%of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95%CI, 47.5%-55.0%) in mild to 78.5%(95%CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1%(95%CI, ), whereas 82.6%(95%CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3%(95%CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9%(95%CI, 31.4%-38.5%) for those with mild, 40.3%(95%CI, 37.4%-43.3%) for those with moderate, and 46.1%(95%CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE Among ICUs in 50 countries, the period prevalence of ARDS was 10.4%of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT JAMA. 2016;315(8): doi: /jama Observational data from 459 ICUs from 50 countries across 5 continents

Poor Adherence to ARDS guidelines
A, Cumulative frequency distribution of tidal volume was similar in patients in each severity category, with 65%of patients with acute respiratory distress syndrome (ARDS) receiving a tidal volume of 8 mL/kg of predicted body weight or less. B, In contrast, a right shift of the cumulative frequency distribution curves of plateau pressures was seen for increasing ARDS severity category, with plateau pressure of more than 30 cm H2O in 8.5%of patients for which these data are available. C, Represents the distribution of day-1 tidal volume vs plateau pressure for each patient for which these data are available. Two-thirds of the patients fell within the limits for protective ventilation, defined as plateau pressure less than or equal to 30 cm H2O and tidal volume of less than or equal to 8 mL/kg of predicted body weight. Data refer to the first day of ARDS. A minority of patients maintained Vt in the 4-6 cc/ kg IBW range; nearly two-thirds of patients with severe ARDS kept Pplat < 30 cm H2O

n=109 ARDS Survivors, Sedation, paralytics, corticosteroids, prolonged immobility, and co-morbidities increased disability risk Findings: exercise limitation, reduced physical and psychological function, lower quality of life, and increased costs and use of health care services

Distribution of ECMO Use
Single Center

Consequences of Conventional Mechanical Ventilation

Probability of Discontinuing MV Support by ARDS Severity
IMPORTANCE Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts—for example prone positioning—in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES The primary outcomewas ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS Of patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0%(95%CI, 28.2%-31.9%); of moderate ARDS, 46.6%(95%CI, 44.5%-48.6%); and of severe ARDS, 23.4%(95%CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4%(95%CI, 10.0%-10.7%) of ICU admissions and 23.4%of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95%CI, 47.5%-55.0%) in mild to 78.5%(95%CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1%(95%CI, ), whereas 82.6%(95%CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3%(95%CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9%(95%CI, 31.4%-38.5%) for those with mild, 40.3%(95%CI, 37.4%-43.3%) for those with moderate, and 46.1%(95%CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE Among ICUs in 50 countries, the period prevalence of ARDS was 10.4%of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT JAMA. 2016;315(8): doi: /jama

Complications of Mechanical Ventilation
Intubation complications Sedation Immobility Deconditioning Nutritional impairment Ventilator-associated pneumonia DVT / PE Dynamic hyperinflation (obstructive diseases) Ventilator dependency

Lung Injury and Diaphragm Dysfunction with MV Support
Mechanical ventilation supports gas exchange and alleviates the work of breathing when the respiratory muscles are overwhelmed by an acute pulmonary or systemic insult. Although mechanical ventilation is not generally considered a treatment for acute respiratory failure per se, ventilator management warrants close attention because inappropriate ventilation can result in injury to the lungs or respiratory muscles and worsen morbidity and mortality. Key clinical challenges include averting intubation in patients with respiratory failure with non-invasive techniques for respiratory support; delivering lung-protective ventilation to prevent ventilator-induced lung injury; maintaining adequate gas exchange in severely hypoxaemic patients; avoiding the development of ventilator-induced diaphragm dysfunction; and diagnosing and treating the many pathophysiological mechanisms that impair liberation from mechanical ventilation. Personalisation of mechanical ventilation based on individual physiological characteristics and responses to therapy can further improve outcomes. Lancet 2016; 387: 1856–66. Figure 2: Mechanisms of ventilator-mediated injury to the lungs and respiratory muscles Representative tracings of flow, volume (Vt), transpulmonary pressure (PL), and oesophageal pressure (Pes) are given to support bedside identifi cation of the various injury mechanisms. (A) Ventilator-induced lung injury results when passive infl ation of open (uncollapsed) lung regions exceeds the stress-bearing capacity of the lung, resulting in excess mechanical stress and strain (indicated by large swings in PL). (B) In patients with lung injury, vigorous diaphragm contraction during spontaneous breathing (indicated by negative swings in Pes) can result in regional heterogeneity in mechanical strain (indicated by varying ΔPL), where ΔPL might exceed safe limits in some regions but not others. (C) Parenchymal inhomogeneities scattered throughout the injured lung locally amplify mechanical stresses resulting in large local ΔPL. (D) Passive mechanical ventilation in the absence of diaphragm activity (indicated by positive swings in Pes) mediates rapid disuse atrophy and myofi bril injury. (E) However, excess inspiratory eff ort (indicated by relatively large swings in Pes) risks respiratory muscle injury from excess loading and fatigue. (F) When pressure and fl ow delivered by the ventilator are not synchronous with the patient’s respiratory cycle (easily detected on the Pes tracing), the diaphragm might be forced to contract eccentrically, resulting in acute injury and weakness. The clinical signifi cance of mechanisms E and F remains uncertain, as suggested by the question marks.

ECMO is Uncommonly Utilized in ARDS
Table 4. Abbreviations: ARDS, acute respiratory distress syndrome; ECMO, extracorporeal membrane oxygenation; HFOV, high-frequency oscillatory ventilation; PEEP, positive end-expiratory pressure. a For this analysis, ARDS severity was defined based on the patients’ worst severity category over the course of their ICU stay in patients who developed ARDS on day 1 or 2. b P value represents comparisons across the ARDS severity categories for each variable. c High-dose corticosteroids was defined as doses that were equal to or greater than the equivalent of 1mg/kg of methylprednisolone. IMPORTANCE Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts—for example prone positioning—in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES The primary outcomewas ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS Of patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0%(95%CI, 28.2%-31.9%); of moderate ARDS, 46.6%(95%CI, 44.5%-48.6%); and of severe ARDS, 23.4%(95%CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4%(95%CI, 10.0%-10.7%) of ICU admissions and 23.4%of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95%CI, 47.5%-55.0%) in mild to 78.5%(95%CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1%(95%CI, ), whereas 82.6%(95%CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3%(95%CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9%(95%CI, 31.4%-38.5%) for those with mild, 40.3%(95%CI, 37.4%-43.3%) for those with moderate, and 46.1%(95%CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE Among ICUs in 50 countries, the period prevalence of ARDS was 10.4%of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT 459 ICUs from 50 countries across 5 continents

Abstract Rationale: The management of severe and refractory hypoxemia in critically ill adult patients is practice-based. Variability across individual practitioners and institutions is not well documented. Objectives: To conduct a nationwide survey of critical care physicians in the United States regarding accepted definitions and management strategies for severe and refractory hypoxemia. Methods: A web-based survey was distributed to a stratified random sample of adult intensivists listed in the American Medical Association physician masterfile. The survey was generated by a mixed-methods approach. Measurements and Main Results: In the survey, s were sent and 791 (16.3%) were opened. Among those who opened the message, 50% (396) responded, representing 8.1% of total surveys sent. Seventy-two percent stated that their institutions lacked a protocol for identification and management of severe or refractory hypoxemia in the setting of acute respiratory failure. While the majority of respondents use low-tidal-volume ventilation (81%), high positive end-expiratory pressure (86%), recruitment maneuvers (89%), and either bolus or infusion neuromuscular blockade (94%), there is marked variability in the use of specific rescue strategies as tier 1 or 2 interventions, respectively: prone position (27.8% and 47.8%), extracorporeal membrane oxygenation (2.3% and 51.2%), airway pressure release ventilation (49% and 34.5%), inhaled vasodilators (30.1% and 40%), and high-frequency oscillatory ventilation (7.8% and 40%). The variability was partly explained by provider’s expertise with Page 2 of 59 ANNALSATS Articles in Press. Published on 29-April-2016 as /AnnalsATS OC Copyright © 2016 by the American Thoracic Society particular rescue strategies (77.7%), advance directives (70.1%), the training of allied health staff (62.3%), and institutional availability (53.8%). Conclusions: US adult critical care physicians predominantly employ lung protective ventilation for severe hypoxemia. A wide variation in other rescue strategies is noted, partly explained by user expertise and availability. Less than 30% institutions have formal protocols for management of refractory hypoxemia.

Multicenter, retrospective study 2006-2013 N=46 with early VV-ECMO
N=398 matched controls (MV) ECMO use was associated with: - lower mortality - greater ICU LOS and time to hospital discharge Purpose: The purpose of the study is to compare outcomes in patients who had severe hypoxemic respiratory failure (PaO2/fraction of inspired oxygen <100)who received early veno-venous extracorporealmembrane oxygenation (ECMO) as an adjunct to mechanical ventilation, to those in patientswho received conventionalmechanical ventilation alone. Materials and methods: This is a multicenter, retrospective unmatched and matched cohort study of patients admitted between April 2006 and December Generalized logisticmixed-effects models and Cox proportional hazardsmodelswere used to determine the association between treatmentwith ECMOthat was started within 3 days of intensive care unit (ICU) admission and ICU and hospital mortality and length of stay, respectively. Results: A total of 2440 patients who had severe hypoxemic respiratory failure due to various etiologieswere included, 46who received early veno-venous ECMOand 2394 unmatched and 398 matched controlswho received conventional ventilation alone. Compared to matched controls, ECMO was associated with a lower odds of ICU (odds ratio [95% confidence interval], 0.30 [ ]) and inhospital death (odds ratio 0.30 [ ]). In addition, ECMOwas associatedwith longer times to discharge fromICU and hospital (hazard ratio, 0.42 [ ] and 0.53 [ ], respectively). Conclusions: In this observational study, use of early ECMO compared to conventional mechanical ventilation alone in patients who had severe hypoxemic respiratory failure was associated with a lower risk of mortality and a longer length of stay. © 2016 Elsevier Inc. All rights reserved.

Role for ECMO / ECCO2R combined with MV Support in ARDS?
Figure 1: Management of hypoxaemia in mechanically ventilated patients In acute respiratory distress syndrome, hypoxaemia results from the combination of ventilation–perfusion mismatch and marked intrapulmonary shunt. Hypoxaemia can be ameliorated by a variety of manoeuvres aimed at redirecting blood fl ow to ventilated regions, increasing mixed venous oxygen tension, or recruiting collapsed lung regions to participate in ventilation. PEEP=positive end-expiratory pressure. *Increasing cardiac output may also increase perfusion to non-ventilated lung regions, so that the overall eff ect of increased cardiac output on oxygenation can vary.

Rationale for Use of ECMO
Bridge to recovery Moratorium of decision Bridge to transplant or device therapy

Goals of ECMO for Sepsis and Acute Respiratory Failure
Avoid the complications of mechanical ventilation Provide time for recovery from the acute injury Limit progression to multi-organ dysfunction Limit sedation, allow for spontaneous breathing and communication Early mobilization / physical therapy Minimize the risk of ventilator dependence

Abstract Purpose: The evolution of the epidemiology and mortality of extracorporeal membrane oxygenation (ECMO) remains unclear. The present study investigates the evolving epidemiology and mortality of various ECMO techniques in Germany over time, used for both severe respiratory and cardiac failure. Methods: Data on all patients receiving venovenous (vv-ECMO) and venoarterial (va-ECMO) ECMO as well as pumpless extracorporeal lung assist/interventional lung assist (PECLA/ILA) outside the operating room in Germany from 1 January 2007 through 31 December 2014 were obtained from the Federal Statistical Office of Germany and analyzed. Results: The incidence of vv-ECMO and va-ECMO in the population increased threefold from 1.0:100,000 inhabitants/ year in 2007 to a maximum of 3.0:100,000 in 2012, and from 0.1:100,000 in 2007 to 0.7:100,000 in 2012 and to a maximum of 3.5:100,000 in 2014, respectively. The incidence of arteriovenous PECLA/ILA also increased from 0.4:100,000 to a maximum of 0.6:100,000 in 2011, but decreased thereafter to 0.3:100,000 in The relative proportion of older patients receiving ECMO is steadily increasing. In-hospital mortality decreased over time and reached 58 and 66 % for vv-ECMO and va-ECMO in 2014, respectively. In addition, mortality steadily increased with age and was especially high in the first 48 h of ECMO use. Conclusions: In a high-income country like Germany, the use of ECMO has been rapidly increasing since 2007 for both respiratory and cardiac support, with a recent plateau in vv-ECMO use. In-hospital mortality decreased with increasing ECMO utilization, but remains high, especially in older patients and in the first 48 h of use. Keywords: Extracorporeal membrane oxygenation, Extracorporeal carbon dioxide removal, Epidemiology, Indication, Technical development. Intensive Care Med (2016) 42:889–896

Available ECLS Technologies

Using Extracorporeal Technologies for Acute Respiratory Failure

Summary: In modernintensivecaremedicine,lungsandkidneysfrequentlyareinvolvedinthecontextof multiorgan failure.Whenorgandysfunctionoccurs,theprimaryclinicalmanagementofcriticallyillpatientsisbased on support/replacementoforganfunctionuntilrecovery.Mechanicalventilationisthefirst-lineinterventionincase of respiratoryfailure,butinmostseverecasesmay,itself,causeventilator-inducedlunginjury.Thesame inflammatorymechanismalsomayharmthekidneythroughmediatorspilloverfromtheinjuredlungsintothe bloodstream.Tolimitthedeleteriouseffectsofmechanicalventilationandavoidexcessivecarbondioxide accumulation,devicesforextracorporealCO2 removal(ECCO2R),havebeendeveloped.Someconsistentclinical experiencecurrentlyhasbeenreachedinpatientswith obstructivepulmonarydiseaseandacuterespiratory distress syndrome.Interestingly,ECCO2R recentlyhasbeencoupledwithcontinuousrenalreplacementtherapy systems intospecificlung-renalsupport.Theresultsfrom the firstexperimentalandclinicalapplicationsare encouraging:itisexpectedthatasystemincludingcontinuousrenalreplacementtherapyandECCO2R will developfromthecurrentpioneeringattemptsintoafeasible multiple-organsupportplatformtobecomecommonly used asaroutinetoolinintensivecareunits.Thisreviewfocusesonrecentliteratureandclinicalapplicationsof renal-pulmonarysupportwithspecificattentiontotechnicalaspectsofthemostrecentmaterialsanddevices. Semin Nephrol36:71-77 C 2016 ElsevierInc.Allrightsreserved.

n=15 patients with moderate ARDS
Hemolung Respiratory Assist System (ALung Technologies) n=2 adverse events – hemolysis and catheter kinking 28-day mortality was 47% Abstract Background: Mechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R). Methods: In fifteen patients with moderate ARDS, VT was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure – (Pplat) between 23 and 25 cmH2O. Low-flow ECCO2R was initiated when respiratory acidosis developed (pH < 7.25, PaCO2 > 60 mmHg). Ventilation parameters (VT, respiratory rate, PEEP), respiratory compliance (CRS), driving pressure (DeltaP = VT/CRS), arterial blood gases, and ECCO2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO2R when PaO2/FiO2 was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO2R were also collected. Results: During the 2 h run in phase, VT reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO2 to within 10 % of baseline values. PEEP values tended to increase at VT of 4 mL/kg from 12.2 to 14.5 cmH2O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH2O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking). Conclusions: The low-flow ECCO2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS. (Continued on next page) * Correspondence: 1Department of Anesthesia and Critical Care - AOU Città della Salute e della Scienza di Torino, University of Turin, Corso Dogliotti 14, Torino, Italy Full list of author information is available at the end of the article

Addressing ECLS Complications in Acute Respiratory Failure
Cannulation issues Up to 6% with complications (ELSO Registry Data) Circuit issues Oxygenator failure in up to 10% PMP membranes and centrifugal pumps have reduced complications Thrombosis and bleeding Up to 4% with intracranial bleeding while on VV-ECMO Poly-methyl pentene oxygenators have improved gas exchange

Bleeding We assessed the incidence and predictors of intracranial hemorrhage (ICH) occurring during ECMO support. Out of 154 patients who received ECMO, 12 (7.8%) developed ICH. Patients with ICH had a longer ECMO duration (10.3 vs. 5.3days, P=0.029), higher activated clotting time (ACT,P=0.027), higher frequency of central ECMO cannulation (P=0.039) and a trend towards higher in-hospital mortality(92% vs. 65%,P=0.091). Multivariate analysis showed that a longer ECMO duration(OR=1.079,95%CI= ,P=0.020) and central ECMO cannulation (OR=5.177,95%CI= ,P=0.018) are independently associated with risk of ICH. We recommend routine neurological checks, monitoring of coagulation parameters and to attempt earlier rather than late weaning from ECMO whenever feasible. (PMID: )

N=61, enoxaparin 40 mg SC daily N=1, heparin 5000 u SC every 8 hr
Abstract: Extracorporeal lung support and therapeutic anticoagulation are dogmatically linked for most clinicians in fear of clotting of the extracorporeal circuit. In the last decade, however, we have learned that bleeding complications in the course of extracorporeal membrane oxygenation (ECMO) therapy are common and not occasionally limiting or fatal. Even though international guidelines lowered the PTT-target values, ECMO therapy without anticoagulation has only been reported sporadically in case reports heretofore. This monocentric, observational study was designed to evaluate a protocol for venovenous ECMO therapy without additional anticoagulation. Patients without former thrombotic events solely received thrombosis prophylaxis with 40 mg subcutaneous enoxaparin per day like every critical care patient. After approval by the local ethics committee (Albert-Ludwigs- University Freiburg ethics committee, EK 513/14) all consecutive patients treated with venovenous ECMO therapy since introduction of the protocol have been identified. Digital charts of the patients have been evaluated with special regard to bleeding and thrombotic or embolic events or breakdown of the extracorporeal circuit. Sixty-one patients received venovenous ECMO therapy with prophylactic subcutaneous enoxaparin only. Median duration of ECMO therapy was 7 days (2–32). Overall 560 ECMO days have been observed. No system exchange because of thrombotic occlusion was necessary within the permitted 5 days run time of the centrifugal pump. Overall we identified thrombotic complications in four patients. In three of them centrifugal pump after a runtime of more than 5 days unexpectedly stopped completely because of thrombotic occlusion. In all cases pump exchange was performed promptly and patients did not incur hypoxic deficit. One other patient received substitution of blood products and coagulation factor concentrates because of severe bleeding and sustained myocardial infarction the day after. Only 18% of patients presented with essential clinical bleeding after 7 days of therapy. No fatal bleeding event and no intracranial hemorrhage was observed. Patients required only a third of blood product transfusion compared to published data. Venovenous ECMO therapy with prophylactic anticoagulation only was feasible in this study. It was not associated with an increased rate of system exchanges compared to regimes with therapeutic anticoagulation in registry data. It provides the potential to relevantly decrease the incidence of severe bleeding events and blood transfusion requirements. The apodictic adherence to anticoagulation in therapeutic dosage should be critically scrutinized in every patient. Artificial Organs 2016,

Use of ECMO for Sepsis

Context The novel influenza A(H1N1) pandemic affected Australia and New Zealand
during the 2009 southern hemisphere winter. It caused an epidemic of critical illness and some patients developed severe acute respiratory distress syndrome (ARDS) and were treated with extracorporeal membrane oxygenation (ECMO). Objectives To describe the characteristics of all patients with 2009 influenza A(H1N1)– associated ARDS treated with ECMO and to report incidence, resource utilization, and patient outcomes. Design, Setting, and Patients An observational study of all patients (n=68) with 2009 influenza A(H1N1)–associated ARDS treated with ECMO in 15 intensive care units (ICUs) in Australia and New Zealand between June 1 and August 31, 2009. Main Outcome Measures Incidence, clinical features, degree of pulmonary dysfunction, technical characteristics, duration of ECMO, complications, and survival. Results Sixty-eight patients with severe influenza-associated ARDS were treated with ECMO, of whom 61 had either confirmed 2009 influenza A(H1N1) (n=53) or influenza A not subtyped (n=8), representing an incidence rate of 2.6 ECMO cases per million population. An additional 133 patients with influenza A received mechanical ventilation but no ECMO in the same ICUs. The 68 patients who received ECMO had a median (interquartile range [IQR]) age of 34.4 ( ) years and 34 patients (50%) were men. Before ECMO, patients had severe respiratory failure despite advanced mechanical ventilatory support with a median (IQR) PaO2/fraction of inspired oxygen (FIO2) ratio of 56 (48-63), positive end-expiratory pressure of 18 (15-20) cm H2O, and an acute lung injury score of 3.8 ( ). The median (IQR) duration of ECMO support was 10 (7-15) days. At the time of reporting, 48 of the 68 patients (71%; 95% confidence interval [CI], 60%-82%) had survived to ICU discharge, of whom 32 had survived to hospital discharge and 16 remained as hospital inpatients. Fourteen patients (21%; 95% CI, 11%-30%) had died and 6 remained in the ICU, 2 of whom were still receiving ECMO. Conclusions During June to August 2009 in Australia and New Zealand, the ICUs at regional referral centers provided mechanical ventilation for many patients with 2009 influenza A(H1N1)–associated respiratory failure, one-third of whom received ECMO. These ECMO-treated patients were often young adults with severe hypoxemia and had a 21% mortality rate at the end of the study period. JAMA. 2009;302(17):

N=216 Sepsis and VA ECMO Abstract
Purpose: Limited data on the outcomes of adults with active sepsis undergoing extracorporeal membrane oxygenation (ECMO) exist. Materials and Methods: Weanalyzed our prospective database for adults undergoing their firstECMOfrom 2001 to Patients with preexisting sepsis had newly emerging or uncontrolled infections precipitating refractory respiratory and/or circulatory failure within 7 days preceding ECMO. Propensity score matching was performed to equalize potential prognostic factors between patients with and patients without sepsis. Results: Of the 514 adults receiving their first ECMO, 108 with preexisting sepsis were matched with 108 without sepsis by propensity score. Overall survival to discharge did not differ between those with (28.7%) and those without sepsis (37.0%; P = .192). When venovenous ECMO and venoarterial ECMO were considered separately, survival tended to be worse for septic patients on venoarterial ECMO (24.4%) compared with nonseptic adults on venoarterial ECMO (34.9%; P = .147). After adjustments for age, stroke, acutemyocarditis, inter-extracorporeal cardiopulmonary resuscitation, and post-ECMO renal and neurologic deficits by multivariate analysis, the increased risk of mortality persisted for septic adults receiving venoarterial ECMO (hazard ratio, 2.54; 95% confidence intervals, ; P b .01). Patients on venovenous ECMO had similar outcomes regardless of preexisting sepsis. Conclusions: Preexisting sepsis is not a contraindication for ECMO.However, venoarterial ECMOshould be used with caution, given active sepsis. © 2013 Elsevier Inc. All rights reserved. Sepsis and VA ECMO

Except for infection, septic and non-septic groups were well matched.

No survivors when ECMO use delayed
, Single Center Abstract OBJECTIVES: The role of extracorporeal membrane oxygenation (ECMO) remains controversial in adult patients with refractory septic shock. We sought to describe the clinical outcomes of adult patients supported by ECMO during septic shock refractory to conventional treatment. METHODS: We analysed consecutive adult patients with refractory septic shock, assisted by an ECMO system between January 2005 and December 2013 in a single-centre registry. The primary outcome was survival to hospital discharge. RESULTS: A total of 32 patients (21 males) received ECMO support for refractory septic shock. Of these, 14 patients (43.8%) had undergone cardiopulmonary resuscitation (CPR) and 7 patients (21.9%) did not achieve the return of spontaneous circulation until initiation of ECMO flow. ECMO was weaned off successfully in 13 patients (40.6%) and 7 patients (21.9%) survived to hospital discharge. The survivors had lower peak lactate (4.5 vs 15.1 mmol/l, P = 0.03), lower Sepsis-related Organ Failure Assessment day 3 score (15 vs 18, P = 0.01) and higher peak troponin I (32.8 vs 3.7 ng/ml, P = 0.02) than the non-survivors. None of the patients (31.3%) in whom ECMO was initiated more than 30.5 h after onset of septic shock, survived. In multivariable-adjusted models, CPR [adjusted hazard ratio (HR), 4.61; 95% confidence interval (CI), 1.55–13.69; P = 0.006] was an independent predictor of in-hospital mortality after ECMO in patients with refractory septic shock. Higher peak troponin I > 15 ng/ml (adjusted HR, 0.34; 95% CI, 0.12–0.97; P = 0.04) was associated with a lower risk of in-hospital mortality. CONCLUSIONS: Survival to hospital discharge remained low in adult patients with refractory septic shock despite ECMO support. Our findings suggest that implantation of ECMO during refractory septic shock could be considered in patients with severe myocardial injury but should be avoided in patients who have received CPR. No survivors when ECMO use delayed beyond 30.5 hours

ECMO for Refractory Septic Shock
Non-survivors had significant increases in serum lactate and SOFA score at day 3

Cytokine hemoadsorption column added to the ECMO circuit
Case report 33 yo patient Cytokine hemoadsorption column added to the ECMO circuit ? Toxin adsorption Abstract Sepsis-induced cardiogenic shock in combination with severe acute respiratory failure represents a lifethreatening combination that is often refractory to the conventional methods of treatment. We describe the case of a 33-year-old patient who developed acute cardiovascular collapse and ARDS secondary to superinfection of Panton–Valentine leukocidin—positive Staphylococcus aureus and H1N1 pneumonia who underwent successful combination therapy for severe sepsis-related cardiomyopathy and respiratory failure using extracorporeal membrane oxygenation and cytokine adsorption therapy.

ECMO patients exhibit high pharmacokinetic variability.
Standard meropenem dosing (1 g IV 8 hourly) during ECMO may not achieve higher target MICs (>8 mg/L), especially in preserved renal function Therapeutic drug monitoring recommended where possible 500 mg 8hr 1000 mg 8hr Abstract Introduction: The scope of extracorporeal membrane oxygenation (ECMO) is expanding; however, optimal drug prescription during ECMO remains a developing science. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This open-label, descriptive, matched-cohort pharmacokinetics (PK) study aimed to compare the PK of meropenem in ECMO patients to critically ill patients with sepsis not receiving ECMO (controls). Methods: Eleven adult patients on ECMO (venovenous (VV) ECMO, n = 6; venoarterial (VA) ECMO, n = 5) receiving intravenous (IV) meropenem were included. Meropenem plasma concentrations were determined using validated chromatography. Population PK analysis was performed using non-linear mixed effects modelling. This data was compared with previously published meropenem PK data from 10 critically ill adult patients not on ECMO (preserved renal function (n = 5) or receiving renal replacement therapy (RRT) (n = 5). Using these data, we then performed Monte Carlo simulations (n = 1,000) to describe the effect of creatinine clearance on meropenem plasma concentrations. Results: In total, five (two VV, three VA) out of eleven ECMO patients received RRT. The other six patients (four VV, two VA) had no significant impairment in renal function. A two-compartment model adequately described the data. ECMO patients had numerically higher volume of distribution (0.45 ± 0.17 versus 0.41 ± 0.13 L/kg, P = 0.21) and lower clearance compared to controls (7.9 ± 5.9 versus 11.7 ± 6.5 L/h, P = 0.18). Variability in meropenem clearance was correlated with creatinine clearance or the presence of RRT. The observed median trough concentrations in the controls were 4.2 (0.0 to 5.7) mg/L. In ECMO patients, while trough meropenem concentrations >2 mg/L were achieved in all patients, a more aggressive target of >8 mg/L for less susceptible microorganisms was observed in only eight out of eleven patients, with five of them being on RRT. Conclusions: ECMO patients exhibit high PK variability. Decreased meropenem CL on ECMO appears to compensate for ECMO and critical illness-related increases in volume of distribution. Routine target concentrations >2 mg/L are maintained with standard dosing (1 g IV 8-hourly). However, an increase in dose may be necessary when targeting higher concentrations or in patients with elevated creatinine clearance.

Questions / Future Directions
Anticoagulation Low-dose vs. no-dose Thresholds for monitoring / replacement of blood products Reducing Infection Risk Impact of Mechanical Ventilation Strategy / Extubation Atelectasis Better predictive models for ECLS initiation and outcome / refinement of indications Pharmacokinetics Optimizing Rehabilitation Improved Device Portability and Safety

Summary Select patients with sepsis and acute respiratory failure (hypercapnic and / or hypoxemic) or shock may benefit from extracorporeal support Several questions remain regarding optimal ECLS support for patients with sepsis and respiratory failure, and further research is warranted

NEED FOR BETTER PREDICTIVE MODELS FOR INITIATION AND OUTCOMES
Rationale: Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Better prediction of survival in these patients may improve resource use, allow risk-adjusted comparison of center-specific outcomes, and help clinicians to target patients most likely to benefit from ECMO. Objectives: To create a model for predicting hospital survival at initiation of ECMO for respiratory failure. Methods: Adult patients with severe acute respiratory failure treated by ECMO from 2000 to 2012 were extracted from the Extracorporeal Life Support Organization (ELSO) international registry. Multivariable logistic regression was used to create the Respiratory ECMO Survival Prediction (RESP) score using bootstrapping methodology with internal and external validation. Measurements and Main Results: Of the 2,355 patients included in the study, 1,338 patients (57%) were discharged alive from hospital. The RESP score was developed using pre-ECMO variables independently associated with hospital survival on logistic regression, which included age, immunocompromised status, duration of mechanical ventilation before ECMO, diagnosis, central nervous system dysfunction, acute associated nonpulmonary infection, neuromuscular blockade agents or nitric oxide use, bicarbonate infusion, cardiac arrest, PaCO2, and peak inspiratory pressure. The receiver operating characteristics curve analysis of the RESP score was c = 0.74 (95% confidence interval, 0.72–0.76). External validation, performed on 140 patients, exhibited excellent discrimination (c = 0.92; 95% confidence interval, 0.89–0.97). Conclusions: The RESP score is a relevant and validated tool to predict survival for patients receiving ECMO for respiratory failure. Copyright © 2014 by the American Thoracic Society Originally Published in Press as DOI: /rccm OC on April 2, 2014 Internet address: 1374 American Journal of Respiratory and Critical Care Medicine Volume 189 Number 11 | June cases during the influenza A(H1N1) pandemic (3, 4) and a positive randomized controlled trial (5) have increased the practice of this salvage therapy over the past decade (6). Despite major technologic advances in design, increasing simplicity of implementation, and devices (1, 2, 7, 8), this therapy is still burdened with a high rate of complications (e.g., bleeding [5, 9–12], infection [13], mechanical complications [11]). In addition, these patients still exhibit a high mortality (5, 9) and are prone to significant long-term physical and neuropsychological impairment (9, 14). Increased use of ECMO, with its associated needs for training expertise and resources, may also increase hospital costs (5). Thus, in the modern era of ECMO support (8), it is necessary to define risk factors for death in these patients prior ECMO initiation, which will in turn allow institutions to appropriately allocate resources and benchmark mortality outcomes. Predictive mortality scores have been recently proposed (9, 15). However, these have several limitations that impede their widespread applicability: the small size of the population used to derive the model (9, 15, 16), restriction to specific groups (e.g., influenza A(H1N1)–induced ARDS, or patients transferred to a referral center) (15, 16), lack of external validation (9), and unknown suitability for patients in other centers (17). The Extracorporeal Life Support Organization (ELSO) has prospectively maintained a registry of ECMO use in active ELSO centers since Currently, data from 160 US and 120 other international centers are collected on standardized ELSO forms. Based on the currently collected pre-ECMO assessment data in this large international database, we hypothesized that predictors of hospital survival for patients with adult respiratory failure treated with ECMO could be identified. These would then allow construction of a robust survival prediction model that would have widespread applicability, namely the Respiratory ECMO Survival Prediction (RESP) score. Methods Data Collection We queried the ELSO registry for adult patients who received ECMO primarily for acute respiratory failure from 2000 through 2012. Only data from the primary ECMO run were analyzed including demographic data, pre-ECMO variables, International Classification of Diseases-9 diagnosis codes, procedure and complication codes, year of ECMO run, and hospital outcome. No patient or hospital identifying information was extracted. The pre-ECMO variables included cardiopulmonary resuscitation, blood gases, ventilator settings, and pre- ECMO rescue therapies. High-frequency oscillatory ventilation, nitric oxide neuromuscular blocker agent use, and steroid use before ECMO were reported. Prone positioning is not collected in the ELSO registry. ECMO modes were reported as venoarterial, venovenous including a dual-lumen venovenous cannula (AvalonElite, Maquet, Sweden), or mixed modes (i.e., combinations of venoarterial and venovenous). Two researchers (D.P. and M.S.) independently reviewed all International Classification of Diseases-9 codes. Any discrepancies between the two reviewers were resolved by discussion. Diagnoses for severe acute respiratory failure were collapsed into the following groups: “bacterial pneumonia,” “viral pneumonia,” “aspiration pneumonitis,” “asthma,” “trauma/burn,” and “others acute respiratory diagnoses.” “Obesity” was defined as a body mass index greater than 30 kg/m2. “Renal dysfunction” included chronic or acute renal insufficiency (e.g., creatinine .1.5 mg/dl) with or without renal-replacement therapy. Similarly “heart dysfunction” was defined by chronic or acute heart failure. “Acute associated infection” was defined as a bacterial, viral, parasitic, or fungal infection that did not involve the lung (e.g., intraabdominal sepsis). “Central nervous system (CNS) dysfunction” combined neurotrauma, stroke, encephalopathy, cerebral embolism, and seizure and epileptic syndromes. “Immunocompromised” was defined as hematologic malignancies, solid tumor, solid organ transplantation, human immunodeficiency virus, or cirrhosis. This analysis of deidentified data was approved by the ECMO Registry Committee of ELSO. Statistical Analysis Analyses were performed with STATA (StataCorp. 2011, Stata Statistical Software: Release 12; StataCorp LP, College Station, TX). Continuous variables were compared with Student t test or the Wilcoxon signed rank test, as appropriate. Categorical variables were compared using the chi-square test for equal proportion. The RESP score was constructed using the following steps: Step 1: Identification of candidate variable. Variables relating to patient or treatment factors before initiation of ECMO were considered. Candidate variables for inclusion in the RESP score were identified using logistic regression applied on 2,355 patients with complete data with hospital mortality as the dependent variable. All potential explanatory variables included in the multivariable analyses were subjected to a correlation matrix for analysis of collinearity. Continuous variables were explored for linearity by considering as both quartiles and deciles before being converted into categorical variables for practical purposes. At a Glance Commentary Figure 2. Individual observed survival regarding the Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score within 95% confidence interval. Each dot represents the observed survival percentage in the study population (n = 2,355) used to derive the RESP score. Curved dotted gray lines and curved black lines represent 95 and 99% confidence intervals, respectively, for predicted survival at each score level. Subject: Increasing use of extracorporeal membrane oxygenation (ECMO) for acute respiratory failure may increase resource requirements and hospital costs. Better prediction of survival in these patients may improve resource use, allow risk-adjusted comparison of center-specific outcomes, and help clinicians to target patients most likely to benefit from ECMO. What This Study Adds to the Field: Derived from a population of 2,355 international patients, the (RESP) score is a robust prediction tool comprising 12 simple pre-ECMO variables that predict survival after initiation of ECMO for respiratory support. It is the first validated international predictive mortality model based on a large population of patients with acute respiratory failure requiring ECMO. In light of the growing use of ECMO, the RESP score is a clinically relevant tool to predict survival for patients receiving ECMO for respiratory failure. ORIGINAL ARTIC

Objective: Acute clinical deterioration preceding death is a common observation in patients with advanced interstitial lung disease and secondary pulmonary hypertension. Patients with pulmonary arterial hypertension refractory to medical therapy are also at risk of sudden cardiac death (cor pulmonale). The treatment of these patients remains complex, and the findings from retrospective studies have suggested that intubation and mechanical ventilation are inappropriate given the universally poor outcomes. Extracorporeal support technologies have received limited attention because of the presumed inability to either recover cardiopulmonary function in the patient with end-stage disease or the presumed inability to proceed to definitive therapy with transplantation. Methods: A retrospective review was performed of 31 patients from 2 institutions placed on extracorporeal membrane oxygenation as a bridge to lung transplantation compared with similar patients without extracorporeal membrane oxygenation at the same institutions and comparison groups queried from the United Network for Organ Sharing database. Results:We have transplanted 31 patients with refractory lung disease frommechanical artificial lung support. Of the 31 patients, 19 were ambulatory at transplantation. Pulmonary fibrosis (42%), cystic fibrosis (20%), and pulmonary hypertension (16%) were the most common diagnostic codes and acute cor pulmonale (48%) and hypoxia (39%) were the most common indications for device deployment. The average duration of extracorporeal membrane oxygenation support was 13.7 days (range, 2-53 days), and the mean survival of all patients bridged to pulmonary transplantation was 26 months (range, 54 days to 95 months). The 1-, 3-, and 5-year survival was 93%, 80%, and 66%, respectively. The duration of in-house postoperative transplant care ranged from 12 to 86 days (mean, 31 days). Patients requiring an extracorporeal membrane oxygenation bridge had comparable survival to that of the high acuity patients transplanted without extracorporeal membrane oxygenation support in the Scientific Registry of Transplant Recipients database but were at a survival disadvantage compared with the high-acuity patients (lung allocation score,>50) transplanted at the same center who did not require mechanical support (P<.001). Conclusions: These observations challenge current assumptions about the treatment of selected patients with end-stage lung disease and suggest that ‘‘salvage transplant’’ is both technically feasible and logistically viable. Widespread adoption of artificial lung technology in lung transplant will require the design of clinical trials that establish the most effective circumstances in which to use these technologies. A discussion of a clinical trial and reconsideration of current allocation policy is warranted. (J Thorac Cardiovasc Surg 2013;145:862-8)

Mean percentages of our ARDS survivors treated by
ECMO (evaluated after a median follow-up of 17 months after ICU discharge) with clinically significant anxiety and/or depression (HAD-A/D subscale scores C8/21) compared with those of 156 conventionally treated ARDS patients [35], 26 myocarditis survivors treated by MCA [25], 153 trauma patients [36] and 194 ICU survivors [37]. b Mean percentages of our ECMO-treated ARDS survivors at risk of post-traumatic stress disorder compared with those of 80 conventionally treated ARDS patients [38], 26 myocarditis survivors [25] and 194 ICU survivors [37]. ARDS acute respiratory distress syndrome, ECMO extracorporeal membrane oxygenation, HAD Hospital Anxiety and Depression, ICU intensive care unit, MCA mechanical circulatory assistance

Figure 1. (A) Hospital survival percentage in original cohort according to the Respiratory
Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score at extracorporeal membrane oxygenation initiation for severe acute respiratory failure. (B) Hospital survival percentage in the external validation cohort according to the RESP score. n = number of patients in the study who had particular RESP score values. Survival percentage is expressed as mean and 95% confidence interval. The external validation cohort was extracted from Reference 9.

ECMO Can Allow For Physical Activity
Abstract Background: Following the 2009 H1N1 Influenza pandemic, extracorporeal membrane oxygenation (ECMO) emerged as a viable alternative in selected, severe cases of ARDS. Acute Respiratory Distress Syndrome (ARDS) is a major public health problem. Average medical costs for ARDS survivors on an annual basis are multiple times those dedicated to a healthy individual. Advances in medical and ventilatory management of severe lung injury and ARDS have improved outcomes in some patients, but these advances fail to consistently “rescue” a significant proportion of those affected. Discussion: Here we present a synopsis of the challenges, considerations, and potential controversies regarding veno-venous ECMO that will be of benefit to anesthesiologists, surgeons, and intensivists, especially those newly confronted with care of the ECMO patient. We outline a number of points related to ECMO, particularly regarding cannulation, pump/oxygenator design, anticoagulation, and intravascular fluid management of patients. We then address these challenges/considerations/controversies in the context of their potential future implications on clinical approaches to ECMO patients, focusing on the development and advancement of standardized ECMO clinical practices. Summary: Since the 2009 H1N1 pandemic ECMO has gained a wider acceptance. There are challenges that still must be overcome. Further investigations of the benefits and effects of ECMO need to be undertaken in order to facilitate the implementation of this technology on a larger scale. Keywords: ECMO, Respiratory distress syndrome, Adult,

ECLS Future Directions
Earlier ECLS deployment for severe hypoxemic and/ or hypercapnic respiratory failure Shift from ECMO as salvage therapy Broader availability and improved expertise Newer technologies Increased portability Prolonged circuit maintenance

COPD Prevalence Has Increased Globally

IMPORTANCE Limited information exists about the epidemiology, recognition, management,
and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts—for example prone positioning—in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES The primary outcomewas ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS Of patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0%(95%CI, 28.2%-31.9%); of moderate ARDS, 46.6%(95%CI, 44.5%-48.6%); and of severe ARDS, 23.4%(95%CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4%(95%CI, 10.0%-10.7%) of ICU admissions and 23.4%of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95%CI, 47.5%-55.0%) in mild to 78.5%(95%CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1%(95%CI, ), whereas 82.6%(95%CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3%(95%CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9%(95%CI, 31.4%-38.5%) for those with mild, 40.3%(95%CI, 37.4%-43.3%) for those with moderate, and 46.1%(95%CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE Among ICUs in 50 countries, the period prevalence of ARDS was 10.4%of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT JAMA. 2016;315(8): doi: /jama Mortality increased with increasing quintiles of driving pressure (day 1)

ARDS: Radiographic Presentation

Abstract Rationale: Existing studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size. Objectives: To evaluate risk factors for three measures of physical impairments commonly experienced by survivors of ALI in the first year after hospitalization. Methods: A prospective, longitudinal study of 6- and 12-month physical outcomes (muscle strength, 6-minute-walk distance, and Short Form [SF]-36 Physical Function score) for 203 survivors of ALI enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness–related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status. Measurements and Main Results: At 6 and 12 months, respectively, mean (6 SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (6 8%) and 93% (6 9%), 6-minute-walk distance (as percent-predicted) was 64% (622%) and 67% (626%), and SF-36 Physical Function score (as percent-predicted) was 61% (6 36%) and 67% (6 37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and intensive care unit length of stay with impairments in physical outcomes. Conclusions: Patients had substantial impairments, from predicted values, for 6-minute-walk distance and SF-36 Physical Function outcomemeasures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of intensive care unit stay and associated patient immobilization may be important interventions for improving ALI survivors’ physical outcomes. Keywords: acute lung injury; exercise test; muscle strength; risk factors; follow-up studies ( Implementing strategies to reduce ICU LOS and associated bedrest may be important changes for improving physical impairments

Cannula Migration RA Displacement of Cannula Hepatic Vein Displacement

Oxygenator Clotting Normal Abnormal

Rationale Extracorporeal membrane oxygenation (ECMO) may provide mechanical pulmonary and circulatory support for patients with cardiogenic shock refractory to conventional medical therapy. Prediction of survival in these patients may assist in management of these patients and comparison of results from different centers. Aims To identify pre-ECMO factors which predict survival from refractory cardiogenic shock requiring ECMO and create the survival after veno-arterial-ECMO (SAVE)-score. Methods and results Patients with refractory cardiogenic shock treated with veno-arterialECMObetween January 2003 and December 2013 were extracted fromthe international Extracorporeal Life Support Organization registry. Multivariable logistic regression was performed using bootstrapping methodology with internal and external validation to identify factors independently associated with in-hospital survival. Of 3846 patients with cardiogenic shock treated with ECMO, 1601 (42%) patients were alive at hospital discharge. Chronic renal failure, longer duration of ventilation prior to ECMO initiation, pre-ECMO organ failures, pre-ECMO cardiac arrest, congenital heart disease, lower pulse pressure, and lower serum bicarbonate (HCO3) were risk factors associated with mortality. Younger age, lower weight, acute myocarditis, heart transplant, refractory ventricular tachycardia or fibrillation, higher diastolic blood pressure, and lower peak inspiratory pressure were protective. The SAVE-score (area under the receiver operating characteristics [ROC] curve [AUROC] 0.68 [95%CI 0.64–0.71]) was created. External validation of the SAVE-score in an Australian population of 161 patients showed excellent discrimination with AUROC ¼ 0.90 (95%CI 0.85–0.95). Conclusions The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock (www. save-score.com

Figure 1. (A) Hospital survival percentage in original cohort according to the Respiratory
Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score at extracorporeal membrane oxygenation initiation for severe acute respiratory failure. (B) Hospital survival percentage in the external validation cohort according to the RESP score. n = number of patients in the study who had particular RESP score values. Survival percentage is expressed as mean and 95% confidence interval. The external validation cohort was extracted from Reference 9.

Figure 3. Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score
calculated for the 1,021 patients who had incomplete data and had not initially been included in the score development. Observed survival is expressed as mean and standard deviation. Missing RESP score variables were allocated zero score. Dark gray = 2,355 patients used to develop score; light gray = 1,021 patients (i.e., remainder who have one or more missing values for the score).

Complications of DLC Cannula
Arrhythmias Malposition Cardiac rupture Hepatic vein cannulation Difficult to maintain return port toward the tricuspid valve Bleeding / Thrombosis Site bleeding DVT Blood flow / hemodynamic changes

Low Flow VV Extracorporeal CO2 Removal
ASAIO J May 18. [Epub ahead of print] A retrospective observational case series of low flow veno-venous extracorporeal carbon dioxide removal use in patients with respiratory failure. Moss CE1, Galtrey EJ, Camporota L, Meadows C, Gillon S, Ioannou N, Barrett NA. Author information 1*Intensive Care Unit, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom. Abstract We aimed to describe the use of veno-venous extracorporeal carbon dioxide removal (ECCO2R) in patients with hypercapnic respiratory failure. We performed a retrospective case note review of patients admitted to our tertiary regional intensive care unit and commenced on ECCO2R from August 2013 to February patients received ECCO2R. Demographic data, physiologic data (including pH and partial pressure of carbon dioxide in arterial blood (PaCO2)) when starting ECCO2R (t=0), at 4 hourly intervals for the first 24 hours, then at 24 hour intervals until cessation of ECCO2R, and overall outcome were recorded.Patients are reported separately depending on whether the indication for ECCO2R was an exacerbation of chronic obstructive pulmonary disease (COPD) (n=5), or acute respiratory distress syndrome (ARDS) and persisting hypercapnoea (n=9).Patients were managed with ECCO2R (Hemolung, ALung Inc). Median duration of ECCO2R was five days. Four complications related to ECCO2R were reported, none resulting in serious adverse outcomes. Ten patients were discharged from ICU alive. A statistically significant improvement in pH (p=0.012) was demonstrated.Our observational series of ECCO2R shows this technique can be safely used to achieve therapeutic goals in patients requiring lung protection, and in COPD, in line with current publications in this area.

Automated ECLA maintained SaO2>90% and PCO2 40-49 mmHg more than 96% of the time
Abstract: Veno-venous extracorporeal lung assist (ECLA) can provide sufficient gas exchange even in most severe cases of acute respiratory distress syndrome. Commercially available systems are manually controlled, although an automatically controlled ECLA could allow individualized and continuous adaption to clinical requirements. Therefore, we developed a demonstrator with an integrated control algorithm to keep continuously measured peripheral oxygen saturation and partial pressure of carbon dioxide constant by automatically adjusting extracorporeal blood and gas flow. The “SmartECLA” system was tested in six animal experiments with increasing pulmonary hypoventilation and hypoxic inspiratory gas mixture to simulate progressive acute respiratory failure. During a cumulative evaluation time of 32 h for all experiments, automatic ECLA control resulted in a peripheral oxygen saturation ≥90% for 98% of the time with the lowest value of 82% for 15 s. Partial pressure of venous carbon dioxide was between 40 and 49 mm Hg for 97% of the time with no value <35 mm Hg or >49 mm Hg. With decreasing inspiratory oxygen concentration, extracorporeal oxygen uptake increased from 68- to 154 ― and reducing respiratory rate resulted in increasing extracorporeal carbon dioxide elimination from 71 ― to 92 ― The “SmartECLA” demonstrator allowed reliable automatic control of the extracorporeal circuit. Proof of concept could be demonstrated for this novel automatically controlled veno-venous ECLA circuit. Artificial Organs 2016

31% - circuit changes Abstract
Objectives: Technical complications are a known hazard in veno-venous extracorporeal membrane oxygenation (vvECMO). Identifying these complications and predictive factors indicating a developing system-exchange was the goal of the study. Methods: Retrospective study on prospectively collected data of technical complications including 265 adult patients (Regensburg ECMO Registry, 2009- 2013) with acute respiratory failure treated with vvECMO. Alterations in blood flow resistance, gas transfer capability, hemolysis, coagulation and hemostasis parameters were evaluated in conjunction with a system-exchange in all patients with at least one exchange (n583). Results: Values presented as median (interquartile range). Patient age was 50(36– 60) years, the SOFA score 11(8–14.3) and the Murray lung injury Score 3.33(3.3– 3.7). Cumulative ECMO support time 3411 days, 9(6–15) days per patient. Mechanical failure of the blood pump (n55), MO (n52) or cannula (n51) accounted for 10% of the exchanges. Acute clot formation within the pump head (visible clots, increase in plasma free hemoglobin (frHb), serum lactate dehydrogenase (LDH), n513) and MO (increase in pressure drop across the MO, n516) required an urgent system-exchange, of which nearly 50% could be foreseen by measuring the parameters mentioned below. Reasons for an elective system-exchange were worsening of gas transfer capability (n510) and device-related coagulation disorders (n532), either local fibrinolysis in the MO due to clot formation (increased D-dimers [DD]), decreased platelet count; n524), or device-induced hyperfibrinolysis (increased DD, decreased fibrinogen [FG], decreased platelet count, diffuse bleeding tendency; n58), which could be reversed after systemexchange. Four MOs were exchanged due to suspicion of infection. Conclusions: The majority of ECMO system-exchanges could be predicted by regular inspection of the complete ECMO circuit, evaluation of gas exchange, pressure drop across the MO and laboratory parameters (DD, FG, platelets, LDH, frHb). These parameters should be monitored in the daily routine to reduce the risk of unexpected ECMO failure.

Survival Following Transplant in Bridged Patients

We would love for you to present a talk regarding your thoughts on extracorporeal support (ECMO/ECCO2R) from a pulmonologists perspective, and your vision for the future of the field (e.g. can extracorporeal pulmonary support be moved out of the ICU?, interaction between ECLS and IMV, etc.)

NO – it seems to work in adults
ELSO Registry, Jan 2016

Some Unanswered Questions in ECMO Management
Background In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. Methods In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. Results The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P = 0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P = 0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P = 0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. Conclusions In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique–Hopitaux de Marseille and the Programme Hospitalier de Recherche Clinique Regional of the French Ministry of Health; ClinicalTrials.gov number, NCT ) N Engl J Med 2010;363: Previous trials involving patients with the acute respiratory distress syndrome (ARDS) have failed to show a beneficial effect of prone positioning during mechanical ventilatory support on outcomes. We evaluated the effect of early application of prone positioning on outcomes in patients with severe ARDS. In this multicenter, prospective, randomized, controlled trial, we randomly assigned 466 patients with severe ARDS to undergo prone-positioning sessions of at least 16 hours or to be left in the supine position. Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (Fio2) of less than 150 mm Hg, with an Fio2 of at least 0.6, a positive end-expiratory pressure of at least 5 cm of water, and a tidal volume close to 6 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died from any cause within 28 days after inclusion. A total of 237 patients were assigned to the prone group, and 229 patients were assigned to the supine group. The 28-day mortality was 16.0% in the prone group and 32.8% in the supine group (P<0.001). The hazard ratio for death with prone positioning was 0.39 (95% confidence interval [CI], 0.25 to 0.63). Unadjusted 90-day mortality was 23.6% in the prone group versus 41.0% in the supine group (P<0.001), with a hazard ratio of 0.44 (95% CI, 0.29 to 0.67). The incidence of complications did not differ significantly between the groups, except for the incidence of cardiac arrests, which was higher in the supine group. In patients with severe ARDS, early application of prolonged prone-positioning sessions significantly decreased 28-day and 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique National 2006 and 2010 of the French Ministry of Health; PROSEVA ClinicalTrials.gov number, NCT ) N Engl J Med 2013;368: N=340, severe ARDS PaO2/ FiO2 < 150 mmHg Cisatracurium for 48 hours N=466, severe ARDS PaO2/ FiO2 < 150 mmHg Prone for > 16 hours/ day

ARDS Therapies

Background Given substantial advances in venovenous extracorporeal membrane oxygenation (ECMO) technology, long-term support is increasingly feasible. Although the benefits of short-term ECMO as a bridge to recovery in acute respiratory distress syndrome (ARDS) are well described, the utility and outcomes of long-term support remain unclear. Methods Patients requiring ECMO for ARDS between January 2009 and November 2012 were retrospectively reviewed and analyzed separately for those requiring ECMO support for less than 3 weeks or for 3 weeks or longer. Demographic factors, ECMO variables, and outcomes were assessed. Results Fifty-five patients with ARDS received ECMO during the study period, with 11 patients requiring long-term ECMO support and a median duration of 36 (interquartile range: 24 to 68) days. Recovery was the initial goal in all patients. Pre-ECMO mechanical ventilatory support, indices of disease severity, and the ECMO cannulation strategy were similar between the two groups. Eight (73%) patients receiving long-term support were bridged to recovery, and 1 patient was bridged to transplantation after a refractory course. Eight (73%) patients receiving long-term support and 25 (57%) patients receiving short-term support survived to 30 days and hospital discharge. Conclusions Previously, long-term ECMO support was thought to be associated with unfavorable outcomes. This study, however, may provide support for the efficacy of ECMO support even for 3 weeks or more as a bridge to recovery or transplantation.

Purpose: Appropriately identifying and triaging patients with newly diagnosed acute respiratory distress syndrome (ARDS) who may progress to severe ARDS is a common clinical challenge without any existing tools for assistance. Materials and methods: Using a retrospective cohort, a simple prediction score was developed to improve early identification of ARDS patients who were likely to progress to severe ARDS within 7 days. A broad array of comorbidities and physiologic variables were collected for the 12-hour period starting from intubation for ARDS. Extracorporeal membrane oxygenation (ECMO) eligibility was determined based on published criteria from recent ECMO guidelines and clinical trials. Separate data-driven and expert opinion approaches to prediction score creation were completed. Results: The study included 767 patientswithmoderate or severe ARDSwho were admitted to the intensive care unit between January 1, 2005, and December 31, In the data-driven approach, incorporating the ARDS index (a novel variable incorporating oxygenation index and estimated dead space), aspiration, and change of PaO2/fraction of inspired oxygen ratio into a simple predictionmodel yielded a c-statistic (area under the receiver operating characteristic curve) of 0.71 in the validation cohort. The expert opinion–based prediction score (including oxygenation index, change of PaO2/fraction of inspired oxygen ratio, obesity, aspiration, and immunocompromised state) yielded a c-statistic of 0.61 in the validation cohort. Conclusions: The data-driven early prediction ECMO eligibility for severe ARDS score uses commonly measured variables of ARDS patients within 12 hours of intubation and could be used to identify those patients who may merit early transfer to an ECMO-capable medical center.

Abstract Purpose: This study
was designed to identify factors associated with death by 6 months post-intensive care unit (ICU) discharge and to develop a practical mortality risk score for extracorporeal membrane oxygenation (ECMO)- treated acute respiratory distress syndrome (ARDS) patients. We also assessed long-term survivors’ healthrelated quality of life (HRQL), respiratory symptoms, and anxiety, depression and post-traumatic stress disorder (PTSD) frequencies. Methods: Data from 140 ECMO-treated ARDS patients admitted to three French ICUs (2008–2012) were analyzed. ICU survivors contacted [6 months post-ICU discharge were assessed for HRQL, psychological and PTSD status. Results: Main ARDS etiologies were bacterial (45 %), influenza A[H1N1] (26 %) and post-operative (17 %) pneumonias. Six months post-ICU discharge, 84 (60 %) patients were still alive. Based on multivariable logistic regression analysis, the PRESERVE (PRedicting dEath for SEvere ARDS on VV-ECMO) score (0–14 points) was constructed with eight pre- ECMO parameters, i.e. age, body mass index, immunocompromised status, prone positioning, days of mechanical ventilation, sepsis-related organ failure assessment, plateau pressure andpositive end-expiratory pressure. Six-month post-ECMO initiation cumulative probabilities of survival were 97, 79, 54 and 16 % for PRESERVE classes 0–2, 3–4, 5–6 and C7 (p\0.001), respectively. HRQL evaluation in 80 % of the 6-month survivors revealed satisfactory mental health but persistent physical and emotional-related difficulties, with anxiety, depression or PTSD symptoms reported, by 34, 25 or 16 %, respectively. Conclusions: The PRESERVE score might help ICU physicians select appropriate candidates for ECMO among severe ARDS patients. Future studies should also focus on physical and psychosocial rehabilitation that could lead to improved HRQL in this population. Intensive Care Med (2013) 39:1704–1713

See comment in PubMed Commons belowASAIO J. 2016 Jan-Feb;62(1):80-6
See comment in PubMed Commons belowASAIO J Jan-Feb;62(1):80-6. doi: /MAT The objective is to assess the influence of infections and the microbiological spectrum on the general outcome of patients undergoing therapy with extracorporeal devices (ECDs), extracorporeal membrane oxygenation, extracorporeal life support, and pumpless extracorporeal lung assist. We performed a single-center, retrospective analysis of 99 patients receiving ECD. Infections requiring ECD, nosocomial infections occurring during treatment, the use of guideline-based antiinfective therapies, and patient outcomes were described and statistically analyzed. We analyzed 88 patients-survivors and nonsurvivors-and subdivided the infections into primary and nosocomial infections. The median patient age was 54.0 years, 85.2% were men, and 45 (51.1%) survived. Surviving ECD patients had a higher risk of nosocomial infection because of their prolonged hospital stay. Our results indicated that early, focused, antiinfective therapy was important to avoid severe infection complications. Infections causing sepsis and multiorgan dysfunction were negatively associated with outcome and successful weaning of ECD. The percentages and types of pathogens in the ECD cohort did not differ from the general colonization of intensive care units. Because a significant correlation between pathogens, infections, and outcome was not detected, we recommend focusing on clinical parameters to decide whether patients will benefit from ECD support.

The acute respiratory distress syndrome (ARDS) was defined in 1994 by the
American-European Consensus Conference (AECC); since then, issues regarding the reliability and validity of this definition have emerged. Using a consensus process, a panel of experts convened in 2011 (an initiative of the European Society of Intensive Care Medicine endorsed by the American Thoracic Society and the Society of Critical Care Medicine) developed the Berlin Definition, focusing on feasibility, reliability, validity, and objective evaluation of its performance. A draft definition proposed 3 mutually exclusive categories of ARDS based on degree of hypoxemia: mild (200 mm HgPaO2/FIO2300 mmHg), moderate (100mmHgPaO2/FIO2200mmHg), and severe (PaO2/ FIO2100mmHg) and 4 ancillary variables for severe ARDS: radiographic severity, respiratory system compliance (40 mL/cm H2O), positive endexpiratory pressure (10 cm H2O), and corrected expired volume per minute (10 L/min). The draft Berlin Definition was empirically evaluated using patientlevel meta-analysis of 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets containing physiologic information. The 4 ancillary variables did not contribute to the predictive validity of severe ARDS for mortality and were removed from the definition. Using the Berlin Definition, stages of mild, moderate, and severe ARDS were associated with increased mortality (27%;95%CI, 24%-30%; 32%;95% CI, 29%-34%; and 45%; 95% CI, 42%-48%, respectively; P.001) and increased median duration of mechanical ventilation in survivors (5 days; interquartile [IQR], 2-11; 7 days; IQR, 4-14; and 9 days; IQR, 5-17, respectively; P.001). Compared with the AECC definition, the final Berlin Definition had better predictive validity for mortality, with an area under the receiver operating curve of (95% CI, ) vs (95% CI, ; P.001). This updated and revised Berlin Definition for ARDS addresses a number of the limitations of the AECC definition. The approach of combining consensus discussions with empirical evaluation may serve as a model to create more accurate, evidence-based, critical illness syndrome definitions and to better inform clinical care, research, and health services planning. JAMA. 2012;307(23): Published online May 21, doi: /jama

Source: The American Surgeon, Volume 81, Number 3, March 2015, pp
No study describes the use of extracorporeal membrane oxygenation (ECMO) in pediatric patients with abdominal sepsis (AS) requiring surgery. A description of outcomes in this patient population would assist clinical decision-making and provide a context for discussions with patients and families. The Extracorporeal Life Support Organization database was queried for pediatric patients (30 days to 18 years) with AS requiring surgery. Forty-five of 61 patients survived (73.8%). Reported bleeding complications (57.1 vs 48.8%), the number of pre-ECMO ventilator hours (208.1 vs 178.9), and the timing of surgery before (50 vs 66.7%) and on-ECMO (50 vs 26.7%) were similar in survivors and nonsurvivors. Decreased pre-ECMO mean pH (7.1 vs 7.3) was associated with increased mortality (odds ratio, 1.49; 95% confidence interval, 1.04 to 2.14). ECMO use for pediatric patients with AS requiring surgery is associated with increased mortality and an increased rate of bleeding complications compared with all pediatric patients receiving ECMO support. Acidemia predicts mortality and provides a potential target of examination for future studies.

Infect Control Hosp Epidemiol. 2013 Jan;34(1):24-30. doi: 10
Infect Control Hosp Epidemiol Jan;34(1): doi: / Epub 2012 Nov 21. Infections acquired by adults who receive extracorporeal membrane oxygenation: risk factors and outcome Abstract OBJECTIVES: To analyze infectious complications that occur in patients who receive extracorporeal membrane oxygenation (ECMO), associated risk factors, and consequences on patient outcome. DESIGN: Retrospective observational survey from 2005 through 2011. PARTICIPANTS AND SETTING: Patients who required ECMO in an Australian referral center. METHODS: Cases of bloodstream infection (BSI), catheter-associated urinary tract infection (CAUTI), and ventilator-associated pneumonia (VAP) that occurred in patients who received ECMO were analyzed. RESULTS: A total of 146 ECMO procedures were performed for more than 48 hours in 139 patients, and 36 patients had a total of 46 infections (30.1 infectious episodes per 1,000 days of ECMO). They included 24 cases of BSI, 6 of them secondary to VAP; 23 cases of VAP; and 5 cases of CAUTI. The most frequent pathogens were Enterobacteriaceae (found in 16 of 46 cases), and Candida was the most common cause of BSI (in 9 of 24 cases). The Sequential Organ Failure Assessment score before ECMO initiation and the number of days of support were independently associated with a risk of BSI, with odds ratios of 1.23 (95% confidence interval [CI], ; [Formula: see text]) and 1.08 (95% CI, ]; [Formula: see text]), respectively. Infected patients did not have a significantly higher mortality compared with uninfected patients (41.7% vs 32%; [Formula: see text]), but intensive care unit length of stay (16 days [interquartile range, 8-26 days] vs 11 days [IQR, 4-19 days]; [Formula: see text]) and hospital length of stay (33.5 days [interquartile range, ] vs 24 days [interquartile range, 9-42 days]; [Formula: see text]) were longer. CONCLUSION: The probability of infection increased with the duration of support and the severity of illness before initiation of ECMO. Infections affected length of stay but did not have an impact on mortality. PMID: DOI: /668439

2007-2012, tertiary care hospital
Case-control design n=45 ECMO matched with 45 non-ECMO , tertiary care hospital Background. Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for patients with ARDS and refractory hypoxia. This study compared the characteristics and outcomes of ARDS patients who did or did not receive ECMO matched with Acute Physiology and Chronic Health Evaluation II (APACHE II) score and age. Methods. This retrospective, case-control study enrolled patients with ARDS admitted to the intensive care unit of a tertiary referral hospital between January 2007 and December Overall, 216 patients with ARDS—81 receiving ECMO (ECMO group) and 135 not receiving ECMO (non-ECMO group)—were enrolled in this study. Patients were paired when the difference in their APACHE II scores was within 3 points and their age difference was 3 years. In total, 126 patients could not be matched and were thus excluded. Eventually, of the 90 patients with ARDS enrolled in this study, 45 ECMO group patients were matched with 45 non-ECMO group patients. The demographic data, reasons for intensive care unit admission, and laboratory variables were evaluated. Results. The primary etiology of ARDS was infection (72.2%). The APACHE II score and age-matched group receiving ECMO therapy had higher inhospital survival rates. Moreover, the patients receiving ECMO therapy had significantly lower 6-month mortality rates than did the non-ECMO group. Conclusions. Patients with ARDS who received ECMO treatment had higher inhospital survival rates than did those with a similar disease severity and at a similar age who did not receive ECMO.

Extracorporeal Support Techniques for Sepsis and Multi-Organ Failure

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Extracorporeal Support Techniques for Sepsis and Multi-Organ Failure

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