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Effectiveness of Extracorporeal Membrane Oxygenation When Conventional Ventilation Fails: Valuable Option or Vague Remedy?
... For more than 40 years, veno-venous extracorporeal membrane oxygenation (vvECMO) has been used in critically ill patients with reversible acute lung failure (ALF). Following major improvements in ECMO technology and safety, the survival benefit shown in the CESAR trial [1], the usefulness of ECMO support during the influenza-A/H1N1-virus epidemic in 2009 to 2010 [2] and the increasing evidence that early ECMO may help to avoid substantial lung and consecutive organ injury [3][4][5], ECMO is now implemented more frequently and in a broader spectrum of patients. ...
... Recent results indicate that patients receiving ECMO due to influenza-A virus infection have a lower mortality than patients presenting with other causes of ALF [13]. In addition, the ECMOnet study excluded patients with pre-ECMO mechanical ventilation >7 days, leaving a patient population that may have a more favorable risk profile [4]. Although a more homogenous study population improves performance and stability of a risk prediction model, this may also limit its general applicability. ...
... The improved performance with Model 2 indicates that ECMO relieves patients from acute respiratory and hemodynamic stress and provides time to recover already within the first 24 hours. In patients with severe hypoxemia or high cardiac output, where ECMO may not improve gas exchange sufficiently to decrease aggressiveness of mechanical ventilation, continued invasive ventilation with high volume and FiO 2 may bring about a vicious cycle with ventilator-induced lung injury [4]. Thus, sparse reduction or continued need for a high FiO 2 and norepinephrine on day 1 may indicate patients with unresponsive respiratory failure despite ECMO. ...
Veno-venous extracorporeal membrane oxygenation (vvECMO) can be a life-saving therapy in patients with severe acute lung failure refractory to conventional therapy. Nevertheless, vvECMO is a procedure associated with high costs and resource utilization. The aim of this study was to assess published models for prediction of mortality following vvECMO and optimize an alternative model.
Established mortality risk scores were validated to assess their usefulness in 304 adult patients undergoing vvECMO for refractory lung failure at the University Medical Center Regensburg from 2008 to 2013. A parsimonious prediction model was developed based on variables available before ECMO initiation using logistic regression modelling. We then assessed whether addition of variables available one day after ECMO implementation enhanced mortality prediction. Models were internally validated and calibrated by bootstrapping (400 runs). Predictive ability, goodness-of-fit and model discrimination were compared across the different models.
In the present study population, existing mortality prediction tools for vvECMO patients showed suboptimal performance. Evaluated before vvECMO initiation, a logistic prediction model comprising age, immunocompromised state, artificial minute ventilation, pre-ECMO serum lactate and haemoglobin concentrations showed best mortality prediction in our patients (area under curve, AUC: 0.75). Additional information about norepinephrine dosage, fraction of inspired oxygen, C-reactive protein and fibrinogen concentrations the first day following ECMO initiation further improved discrimination (AUC: 0.79, P = 0.03) and predictive ability (likelihood ratio test, P < 0.001). When classifying patients as lower (<40%) or higher (>80%) risk based on their predicted mortality, the pre-ECMO and day1-on-ECMO models had negative/positive predictive values of 76%/82% and 82%/81%, respectively.
While pre-ECMO mortality prediction remains a challenge due to large patient heterogeneity, evaluation one day after ECMO initiation may improve the ability to separate lower- and higher-risk patients. Our findings support the clinical perception that chronic health condition, high comorbidity and reduced functional reserves are strongly related to survival during and following ECMO support. Renewed evaluation the first day after ECMO initiation may provide enhanced guidance for further handling of ECMO patients. Despite the usefulness of prediction models, thorough clinical evaluation should always represent the cornerstone in decision for ECMO.
... Extracorporeal life support (ECLS) has proven to be effective in shock status and pulmonary failure, even when standard therapies have failed. [9][10][11] ECLS can provide full hemodynamic support (in venoarterial [VA] configuration) in cases of refractory shock unresponsive to conventional treatment, allowing time for diagnosis and heart recovery. Moreover, even in cases of refractory pulmonary failure, complete gas exchange is ensured by ECLS (in venovenous [VV] configuration), improving blood oxygenation and carbon dioxide removal, allowing time for lung recovery, and reducing mechanical ventilation invasiveness. ...
... Since the first use of ECLS in a patient with trauma, performed by Donald Hill in 1972, 12 many changes and improvements in devices and materials biocompatibility have made the deployment of ECLS safer and easier even in complex and polytraumatized patients. [9][10][11]13 Heparin-coated circuits decrease blood coagulation activation and allow starting heparin-free ECLS, delaying heparin administration for just 48/72 hours. 5,13 Percutaneous cannulation and double-lumen catheters (for VV-ECLS) enable less-invasive and faster procedures that are suitable for emergency situations. ...
... Since the first pioneering experience of ECLS used in a patient with trauma in 1971, 12 many advances in technology, materials, and intensive care have occurred. 10,11 The use of ECLS in cardiogenic shock and pulmonary failure of different causes has been accepted, and a new group of indications is being considered. ...
Objectives:
Major trauma is a leading cause of death, particularly among young patients. New strategies in management are needed to improve poor outcomes in cases of severe trauma. Extracorporeal life support (ECLS) has proven to be effective in acute cardiopulmonary failure of different causes, even when conventional therapies fail. We report our initial experience with ECLS as a rescue therapy in severely polytraumatized patients in a refractory clinical setting. This study identifies the pre-ECLS characteristics of patients to predict the appropriateness of ECLS treatment.
Methods:
From December 2008 to May 2012, 375 patients with polytrauma were treated in the Careggi Teaching Hospital, a tertiary-level referral trauma center. Our ECLS team was alerted on 30 patients and applied ECLS in 18 adult patients with trauma. We adopted venoarterial ECLS in 14 patients with cardiopulmonary failure with refractory shock and venovenous ECLS in 4 patients with isolated refractory acute respiratory failure.
Results:
ECLS was initiated at a mean of 359.176 ± 216.606 (145-950) minutes from trauma. In 4 patients, the ECLS treatment failed because of an incapability to maintain adequate ECLS flow and perfusion. In 14 patients, efficiently supported by ECLS, the cardiac index, mean arterial pressure, blood lactate concentration, arterial oxygen tension, arterial carbon dioxide tension, and pH showed significant improvement, with normal values reached at 3.5 ± 1.5 hours.
Conclusions:
From our data, ECLS seems to be a valuable option to resuscitate patients with severe trauma when conventional therapies are insufficient. ECLS is safe, feasible, and effective in providing hemodynamic support and blood gas exchange.
... 2 Over the past decade, technological advances in ECLS equipment have rendered its use outside the operating room more clinically viable. 3,4 Devices have become much more dependable, portable, and easier to manage. Enhanced biocompatibility and better understanding of anticoagulants have enhanced performance and improved patient safety. ...
... The risk associated with VA-ECLS is high; its use should be limited to patients with refractory shock, as serious complications still occur frequently. 4,9,13,[16][17][18][19][20][21] Not surprisingly, the most common adverse effect of ECLS is bleeding, in part due to the need for anticoagulation. Overall bleeding complications occur in 10 to 36% of patients, 6,8,20,22 most often at cannulation entry sites. ...
... The mortality predicted with this syndrome can be as high as 100% [1]. VA-ECMO has been previously used to support patients with severe HVCPS, but historically only as a "rescue" therapy after conventional strategies to treat shock and ARDS have failed [2,3]. There is no clear guide in the literature as to the optimal timing to pursue this invasive strategy for HVCPS [4]. ...
... Renzo Arauco Brown, 1 Jay Murthy, 1,2 Prasad Manian, 1,2 Becky Rumbaoa, 3 and Timothy Connolly 1,2 Figure 1. A, Initial portable chest film obtained after intubation with evidence of dense bilateral alveolar opacities consistent with a combination of acute respiratory distress syndrome and cardiogenic pulmonary edema. ...
... Se ha descrito el uso de la oxigenación con membrana para circulación extracorpórea en pacientes con traumas traqueales, y se han reportado casos con manejo conservador o quirúrgico. Esto abre una puerta para el tratamiento de este tipo de pacientes, ya que permite disminuir al máximo la presión utilizada en la asistencia respiratoria mecánica sin comprometer la oxigenación tisular y, además, usar asistencia respiratoria espontánea, disminuyendo la sedación al máximo, lo que conlleva un despertar temprano del paciente y una mejoría clínica más rápida 17,18 . ...
Introducción.
El traumatismo traqueal es una condición poco frecuente que puede ser ocasionada por traumas abiertos, cerrados o iatrogénicos; su presentación clínica es variable y el diagnóstico suele ser clínico, apoyándose en la radiografía de tórax, la tomografía cérvico-torácica y la fibrobroncoscopia.
Su manejo representa todo un reto médico y quirúrgico, y se requieren múltiples herramientas para su adecuado tratamiento. La terapia con oxigenación con membrana para circulación extracorpórea ha sido ampliamente utilizada en el manejo de pacientes con falla respiratoria aguda, en los cuales los métodos convencionales de asistencia respiratoria mecánica no son suficientes para garantizar una adecuada oxigenación.
Caso clínico.
Se presenta el caso de una paciente con una lesión traqueal iatrogénica reparada quirúrgicamente, bajo asistencia con oxigenación con membrana para circulación extracorpórea, para garantizar la oxigenación tisular y la adecuada recuperación y supervivencia de la paciente.
Conclusiones.
La terapia con oxigenación con membrana para circulación extracorpórea es una excelente alternativa para el manejo quirúrgico de las lesiones traqueales complejas que amenazan la vida del paciente, ya que permite brindar un soporte vital y un adecuado intercambio gaseoso durante el procedimiento.
... The recruitment of activated neutrophils into the lung can cause endothelial damage and further enhance permeability of the alveolar-capillary barrier in ALI or acute respiratory distress syndrome [7,8]. Mortality in ALI patients remains high despite several treatment strategies [9,10]. ...
Formyl peptide receptor 1 (FPR1) is an emerging therapeutic target for the discovery of drugs to treat neutrophilic inflammatory diseases. However, development of FPR1 antagonists for clinical use is still inadequate. The purpose of this study was to identify a synthetic dipeptide N-(N-benzoyl-L-tryptophanyl)-D-phenylanlanine methyl ester (HCH6-1) as a FPR1 inhibitor and to investigate its protective effects against acute lung injury (ALI). HCH6-1 inhibited superoxide anion generation, elastase release, and chemotaxis in human neutrophils specifically activated by formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF), an FPR1 agonist. HCH6-1 produced right shifts in the concentration-response curves of fMLF, suggesting that HCH6-1 was a competitive antagonist of FPR1. Indeed, HCH6-1 bound to FPR1 in human neutrophils and neutrophil-like THP-1 as well as hFPR1-transfected HEK293 cells. Also, the FPR1 downstream signaling pathways were competitively inhibited by HCH6-1. Furthermore, HCH6-1 prevented pulmonary neutrophil infiltration and edema along with alveolar damage in LPS-induced ALI in mice. Our findings suggest that HCH6-1, a FPR1 antagonist, may have potential as a new therapeutic agent for treating FPR1-involved inflammatory lung diseases.
... ventilation. [1] Since ECMO therapy might increase resource requirements and increase hospital costs and can be complicated by a high risk of physical impairments, [2] an accurate survival prediction model to candidates is crucial. Survival prediction models have been developed for bedside use by clinicians, [3][4][5][6][7] to guide the selection of appropriate candidates for treatment, provide prognosis information to the patient's family members, and to facilitate risk-adjusted comparison of individual center outcomes. ...
Background: There has been no external validation of survival prediction models for severe adult respiratory distress syndrome (ARDS) with extracorporeal membrane oxygenation (ECMO) therapy in China. The aim of study was to compare the performance of multiple models recently developed for patients with ARDS undergoing ECMO based on Chinese single-center data.
Methods: A retrospective case study was performed, including twenty-three severe ARDS patients who received ECMO from January 2009 to July 2015. The PRESERVE (Predicting death for severe ARDS on VV-ECMO), ECMOnet, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score, a center-specific model developed for inter-hospital transfers receiving ECMO, and the classical risk-prediction scores of Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) were calculated. In-hospital and six-month mortality were regarded as the endpoints and model performance was evaluated by comparing the area under the receiver operating characteristic curve (AUC).
Results: The RESP and APACHE II scores showed excellent discriminate performance in predicting survival with AUC of 0.835 (95% confidence interval [CI], 0.659–1.010, P = 0.007) and 0.762 (95% CI, 0.558–0.965, P = 0.035), respectively. The optimal cutoff values were risk class 3.5 for RESP and 35.5 for APACHE II score, and both showed 70.0% sensitivity and 84.6% specificity. The excellent performance of these models was also evident for the pneumonia etiological subgroup, for which the SOFA score was also shown to be predictive, with an AUC of 0.790 (95% CI, 0.571–1.009, P = 0.038). However, the ECMOnet and the score developed for externally retrieved ECMO patients failed to demonstrate significant discriminate power for the overall cohort. The PRESERVE model was unable to be evaluated fully since only one patient died six months postdischarge.
Conclusions: The RESP, APCHAE II, and SOFA scorings systems show good predictive value for intra-hospital survival of ARDS patients treated with ECMO in our single-center evaluation. Future validation should include a larger study with either more patients' data at single-center or by integration of domestic multi-center data. Development of a scoring system with national characteristics might be warranted.
... In prior studies, successful respiratory ECMO has been reported in the context of the listed relative contraindications, including severely immunocompromised hosts, contraindications to anticoagulation (such as massive diffuse alveolar hemorrhage), and advanced age [14][15][16][17][18][19][20]. Based on previously published observational data and selection criteria used in recent major ECMO trials, pre-ECMO mechanical ventilation duration greater than or equal to 7 days was an absolute contraindication for the purposes of this study [5,9,10,21,22]. ...
... Intratracheal (i.t.) and i.p. instillation of LPS, a bacterial cell wall component, to rodents is a well-accepted and common experimental model for ALI from pulmonary and extrapulmonary origin (24,25) featuring key pathological components of the disease such as profound neutrophilic lung recruitment, vascular leakage/lung edema, and subsequent systemic inflammation (20,26). Unfortunately, despite marked efforts and multiple therapeutic strategies, the mortality rate of patients suffering from ALI remains high (21,(27)(28)(29). ...
Recently, ceramide-1-phosphate (C1P) has been shown to modulate acute inflammatory events. Acute lung injury (Arnalich et al. 2000. Infect. Immun. 68: 1942-1945) is characterized by rapid alveolar injury, lung inflammation, induced cytokine production, neutrophil accumulation, and vascular leakage leading to lung edema. The aim of this study was to investigate the role of C1P during LPS-induced acute lung injury in mice. To evaluate the effect of C1P, we used a prophylactic and therapeutic LPS-induced ALI model in C57BL/6 male mice. Our studies revealed that intrapulmonary application of C1P before (prophylactic) or 24 h after (therapeutic) LPS instillation decreased neutrophil trafficking to the lung, proinflammatory cytokine levels in bronchoalveolar lavage, and alveolar capillary leakage. Mechanistically, C1P inhibited the LPS-triggered NF-κB levels in lung tissue in vivo. In addition, ex vivo experiments revealed that C1P also attenuates LPS-induced NF-κB phosphorylation and IL-8 production in human neutrophils. These results indicate C1P playing a role in dampening LPS-induced acute lung inflammation and suggest that C1P could be a valuable candidate for treatment of ALI.
... Circuitry, management, and cannulation procedures have evolved considerably since earlier studies of a few decades ago [2,3]. At the same time, outcomes associated with the use of ECMO as a therapy for these patients have improved [6]. The largest and most recent published randomized trial to date found that patients who were referred to receive ECMO had increased survival at 6 months without disability compared to those who received conventional treatment in non-ECMO centers [4]. ...
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 extracorporeal membrane oxygenation (ECMO) as an adjunct to mechanical ventilation, to those in patients who received conventional mechanical ventilation alone.
Materials and methods:
This is a multicenter, retrospective unmatched and matched cohort study of patients admitted between April 2006 and December 2013. Generalized logistic mixed-effects models and Cox proportional hazards models were used to determine the association between treatment with ECMO that 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 etiologies were included, 46 who received early veno-venous ECMO and 2394 unmatched and 398 matched controls who received conventional ventilation alone. Compared to matched controls, ECMO was associated with a lower odds of ICU (odds ratio [95% confidence interval], 0.30 [0.13-0.67]) and inhospital death (odds ratio 0.30 [0.14-0.67]). In addition, ECMO was associated with longer times to discharge from ICU and hospital (hazard ratio, 0.42 [0.37-0.47] and 0.53 [0.38-0.73], 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.
... In the early years of membrane oxygenation, relatively impermeable polyethylene or Teflon homogeneous membranes were the mainstay [13]. These have since been replaced by silicone rubber membrane oxygenators and the newer polymethylpentene membranes which offer lower resistance, lower consumption of blood products and resulting thrombocytopenia, and offer better gas exchange [14]. Microporus hollow fiber oxygenators, in which gas flows through microfibers around which blood flows, offer some advantages to membrane oxygenators such as lower resistance and higher efficiency, but currently have a limited lifespan, making them less than ideal in a VV-ECMO circuit that may have to last days to weeks. ...
In the 1970s, the use of cardiopulmonary bypass at the bedside for critically ill patients with respiratory failure began and was termed extracorporeal membrane oxygenation (ECMO). Later, in the 1980s, applications for extracorporeal technology expanded, and included oxygenation, CO2 removal, and hemodynamic support. However, early studies regarding the use of ECMO for acute lung failure provided less than optimistic results. Today, recent research has created a renewed interest in such technology. There have been progressive advancements in artificial lung technology, and ECMO serves as a form of life support and as a bridge to transplantation for critically ill patients when traditional supportive care is no longer effective. These progressive advancements in artificial lung technology provide another tool in the critical care physician’s arsenal to combat this often fatal injury.
... Pulmonary infectious disease can lead to a severe pathological state called acute respiratory distress syndrome (ARDS) (Dreyfuss & Ricard, 2005). Treatment of this acute disease consists of lung-protective mechanical ventilation (Moloney & Griffiths, 2004) and, in the most severe cases, of extra-corporeal membrane oxygenation (ECMO) (Bonacchi et al., 2012;Combes et al., 2012a,b;Davies et al., 2009;Lewandowski, 2000;Tiruvoipati et al., 2012). Effective treatment requires regular adjustments to the anti-infectious therapy (File, 2009;Frei et al., 2010;Mandell et al., 2007). ...
... vent iatrogenic lung damage from high-pressure and high-FiO2 ventilation. 20 Surprisingly, a 94% survival rate (15 of 16 patients) was achieved in our trauma patients among those who received a short pre-ECMO ventilation interval of 1.0 days. This result was superior to survival rates reported in previous studies. ...
The objective of this study was to evaluate our institutional experience with veno-venous (VV) extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory failure (ARF).
From January 2007 to August 2013, 31 patients with severe ARF that was due to various causes and refractory to mechanical ventilation with conventional therapy were supported with VV ECMO. A partial pressure of arterial oxygen (PaO₂)/inspired fraction of oxygen (FiO₂) <100 mm Hg at an FiO₂ of 1.0 or a pH <7.25 due to CO₂ retention were set as criteria for VV ECMO.
Overall, 68% of patients survived among those who had received VV ECMO with a mean PaO₂/FiO₂ of 56.8 mm Hg. Furthermore, in trauma patients, early use of ECMO had the best outcome with a 94% survival rate.
VV ECMO is an excellent, life-saving treatment option in patients suffering from acute and life-threatening respiratory failure due to various causes, especially trauma, and early use of VV ECMO therapy improved outcomes in these patients.
... Extracorporeal membrane oxygenation (ECMO) may have been beneficial in this patient, and several reports have confirmed the use of ECMO in managing severe hypercapnic respiratory failure (2,8,9). Furthermore, the use of ECMO is increasing, and the complications associated with the use of ECMO is reduced with modern ECMO cannulae and circuts (10). Nevertheless, the use of ECMO is still limited to specialised centres and requires a multidisciplinary approach for a successful outcome. ...
Status asthmaticus is a life threatening condition that requires intensive care management. Most of these patients have severe hypercapnic acidosis that requires lung protective mechanical ventilation. A small proportion of these patients do not respond to conventional lung protective mechanical ventilation or pharmacotherapy. Such patients have an increased mortality and morbidity. Successful use of extracorporeal membrane oxygenation (ECMO) is reported in such patients. However the use of ECMO is invasive with its associated morbidity and is limited to specialised centres. In this report we report the use of a novel, minimally invasive, low flow extracorporeal carbon dioxide removal device in management of severe hypercapnic acidosis in a patient with life threatening status asthmaticus.
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... Venovenous extracorporeal membrane oxygenation (VV ECMO) is a life-saving treatment for severe respiratory failure patient refractory to conventional therapy. VV ECMO maintains sufficient tissue oxygenation and carbon dioxide elimination, so that ventilator settings can be reduced which minimizes ventilator-induced lung injury, and provides time for lung to rest and recovery [1,2]. The improved survival of patients randomized to the ECMO arm in the CESAR research [3] and the successful use of ECMO in the 2009 H1N1 pandemic [4] brought ECMO into the spotlight of the world, and VV ECMO is coming into wider use [5]. ...
Cardiac function is important for patients treated by venovenous extracorporeal membrane oxygenation (VV ECMO), but data about the effect of VV ECMO on the heart in nonneonates is absent. We studied the effect of VV ECMO on cardiac performance, cardiomyocyte and mitochondria in an animal model.
Twelve farm piglets were randomly assigned into two groups: control group and ECMO group. In the ECMO group, ECMO cannulaes were placed and ECMO was instituted. Hemodynamics was recorded at baseline, 1 hour after induction, and every 4 hours thereafter, to assess the cardiac performance. All animals were monitored for 24 hours and were euthanized and myocardium was harvested. Myocardial histology, ultrastructure of cardiomyocyte and mitochondria were observed, and activities of mitochondrial complexes I-V were measured, to assess the effect to cardiomyocyte and mitochondria.
Hemodynamics were stable in each group of animals throughout the experiment. Interstitial edema, disorderd and dissolved of focal myofilament, morphological deformations of mitochondria were observed in the ECMO group. The activities of mitochondrial complexes were decreased in the ECMO group, and complex I and IV reached significance.
VV ECMO therapy is associated with changes of ultrastructure and function of cardiomyocyte and mitochondria, inducing myocardium injury. However, the injury was mild and had no effect on the cardiac performance for healthy piglets.
... It is therefore desirable to start ECMO treatment at an earlier stage, which gives the lungs a better chance to recover since protective lung ventilation can be instituted. [11][12][13] The goal of interhospital transfer is to offer patients better treatment options at high volume centers with specialized know-how. [8,14] Interhospital transfer may be dangerous for a patient in a critical condition. ...
Extracorporeal membrane oxygenation (ECMO) therapy constitutes the last option for patients with acute respiratory distress syndrome (ARDS) refractory to conservative treatment. Since primary care centers are unable to provide this therapy, such patients need a transfer to a tertiary care center, which may be life-threatening without extracorporeal support.
An ECMO transport team implanted an ECMO at the site of the primary care center with subsequent transport of the patient to the tertiary care center. Between September 2009 and March 2011, six patients with ARDS were treated by our ECMO transport team. Mean age was 39.5±12.0 years. All implantations were done percutaneously in a veno-venous configuration.
No complications occurred during the implant procedure and the subsequent transport. Four patients (67%) were successfully weaned from ECMO-therapy, and discharged from hospital.
With a specialized ECMO transport team, ECMO-implantation can be achieved successfully in a peripheral hospital, and patients can be transported safely.
Context:
Although extracorporeal membrane oxygenation (ECMO) was used in many patients following its introduction in 1972, most hospitals had abandoned this experimental treatment for adult patients. Recently, improvements in the ECMO circuitry rendered it more biocompatible. The surprisingly low mortality in patients with severe acute respiratory distress syndrome who were treated with ECMO in the influenza A/H1N1 pandemic of 2009 resurrected interest in ECMO in many intensive care units around the world.
Objectives:
This article reviews the different techniques of ECMO, the indications, contraindications and complications of its use, its role in poisoned patients and the ethics of its use.
Methods:
We searched Pubmed, Toxnet, Cochrane database and Embase from 1966 to September 2012 using the search terms (''extracorporeal membrane oxygenation'', 'extracorporeal life support', 'ECMO', 'ECLS', 'assist-device', and 'intox*' or 'poison*'). These searches identified 242 papers of which 116 described ECMO in conditions other than intoxications or were reviews. In total 46 publications selected for this manuscript were case reports or case series involving poisoned patients. ECMO TECHNIQUES: Two types of ECMO are used: veno-venous ECMO (VV-ECMO) or veno-arterial ECMO (VA-ECMO). VV-ECMO is used for patients with severe ARDS to secure adequate oxygenation of the organs while protecting the lungs from harmful ventilation pressures or prolonged inspiratory fraction of oxygen. VA-ECMO can be used whenever the patient remains in shock despite adequate fluid resuscitation and is refractory to administration of inotropes and vasopressors.
Indications:
The organ support that can be applied with ECMO makes it especially useful in patients with severe poisoning as the clinical impact of the intoxication is often temporary; ECMO can be used as a 'bridge to recovery'.
Contraindications:
Absolute contraindications are uncontrolled coagulopathy and severe intracranial bleeding, which precludes the use of anticoagulation therapy. Relative contraindications to ECMO include advanced age, severe irreversible brain injury, untreatable metastatic cancer, severe organ dysfunction (some suggest a Sequential Organ Failure Assessment (SOFA) score > 15), and high pressure positive pressure ventilation for more than 7 days.
Complications:
The most common complication of ECMO is either bleeding at the cannulation site (in VV-ECMO) or bleeding at the surgical entry site (in VA-ECMO). Overall bleeding complications currently occur in 10-36% patients, and intracranial haemorrhage is seen in up to 6% of patients. ECMO should be reserved, therefore, for the most severely ill poisoned patients with a high risk of death. ECMO in poisoned patients. There are no randomised trials of ECMO in poisoned patients with refractory shock or who have ARDS caused by an intoxication. VV-ECMO can be considered in patients with type l and ll respiratory failure. In patients with life-threatening haemodynamic instability, VA-ECMO can be considered when shock persists despite volume administration, inotropes and vasoconstrictors, and (sometimes) intra-aortic balloon counterpulsation. Typical examples include poisoning due to calcium channel antagonists, beta-blockers, tricyclic antidepressants, chloroquine and colchicine. ETHICS OF ECMO USE: It is only ethical to use such a costly intervention (£19,252 and US$ 31,000 per quality-adjusted life year) if the treatment has a real purpose such as a 'bridge to recovery', a 'bridge to transplant', or a 'bridge to permanent assist device' (in the case of persistent cardiac failure).
Conclusions:
In the last decade, ECMO equipment has improved considerably, rendering it more biocompatible, and it has been used more frequently as an assist device for patients needing oxygenation as well as circulatory support. ECMO is considered a good salvage therapy for patients who are severely poisoned with ARDS or refractory circulatory shock.
Intrathoracic calcifications occur in a wide variety of disorders. Although they are usually harmless sequelae of remote processes, calcifications provide important information for establishing the diagnosis or for evaluating the progression of known disease. They may arise in the pulmonary parenchyma, mediastinum, hilar and mediastinal lymph nodes, pleura, chest wall, or any combination of these structures. The cause of the calcification may be determined by means of the location and pattern of the calcifications within the lung parenchyma and knowledge of the associated clinical features. Calcifications in the thorax are frequently manifestations of previous infectious processes. Less often, they may be due to neoplasms, metabolic disorders, occupational exposure, or previous medical therapy. Large intrathoracid calcifications are usually identified on conventional chest radiographs; detection of smaller calcifications may require use of other imaging modalities, such as dual-energy digital radiography, fluoroscopy, radionuclide scanning, computed tomography (CT), and high-resolution CT.
The intratracheal administration of a perfluorocarbon liquid during continuous positive-pressure ventilation (partial liquid ventilation) improves lung function in animals with surfactant deficiency. Whether partial liquid ventilation is effective in the treatment of infants with severe respiratory distress syndrome is not known.
We studied the efficacy of partial liquid ventilation with perflubron in 13 premature infants with severe respiratory distress syndrome in whom conventional treatment, including surfactant therapy, had failed. Partial liquid ventilation was initiated by instilling perflubron during conventional mechanical ventilation to a volume approximating the functional residual capacity. Infants were considered to have completed the study if they received partial liquid ventilation for at least 24 hours.
Ten infants received partial liquid ventilation for 24 to 76 hours. In the other three infants, partial liquid ventilation was discontinued within four hours in favor of high-frequency ventilation, which was not permitted by the protocol, and the data from these infants were excluded from the analysis. Within one hour after the instillation of perflubron, the arterial oxygen tension increased by 138 percent and the dynamic compliance increased by 61 percent; the mean (+/- SD) oxygenation index was reduced from 49 +/- 60 to 17 +/- 16. Chest radiographs showed symmetric filling, with patchy clearing during the return from partial liquid to gas ventilation. There were no adverse events clearly attributable to partial liquid ventilation. Infants were weaned from partial liquid to gas ventilation without complications. Eight infants survived to 36 weeks' corrected gestational age.
Partial liquid ventilation leads to clinical improvement and survival in some infants with severe respiratory distress syndrome who are not predicted to survive.
We investigated whether the survival of patients with inhospital cardiac arrest could be extended by extracorporeal cardiopulmonary resuscitation supported with extracorporeal membrane oxygenation compared with those of conventional cardiopulmonary resuscitation.
: A retrospective, single-center, observational study.
A tertiary care university hospital.
We retrospectively analyzed a total of 406 adult patients with witnessed inhospital cardiac arrest receiving cardiopulmonary resuscitation for >10 mins from January 2003 to June 2009 (85 in the extracorporeal cardiopulmonary resuscitation group and 321 in the conventional cardiopulmonary resuscitation group).
None.
The primary end point was a survival discharge with minimal neurologic impairment. Propensity score matching was used to balance the baseline characteristics and cardiopulmonary resuscitation variables that could potentially affect prognosis. In the matched population (n = 120), the survival discharge rate with minimal neurologic impairment in the extracorporeal cardiopulmonary resuscitation group was significantly higher than that in the conventional cardiopulmonary resuscitation group (odds ratio of mortality or significant neurologic deficit, 0.17; 95% confidence interval, 0.04-0.68; p = .012). In addition, there was a significant difference in the 6-month survival rates with minimal neurologic impairment (hazard ratio, 0.48; 95% confidence interval, 0.29-0.77; p = .003; p <.001 by stratified log-rank test). In the subgroup based on cardiac origin, extracorporeal cardiopulmonary resuscitation also showed benefits for survival discharge (odds ratio, 0.19; 95% confidence interval, 0.04-0.82; p = .026) and 6-month survival with minimal neurologic impairment (hazard ratio, 0.56; 95% confidence interval, 0.33-0.97; p = .038; p = .013 by stratified log-rank test).
Extracorporeal cardiopulmonary resuscitation showed a survival benefit over conventional cardiopulmonary resuscitation in patients who received cardiopulmonary resuscitation for >10 mins after witnessed inhospital arrest, especially in cases with cardiac origins.
Severe acute respiratory failure in adults causes high mortality despite improvements in ventilation techniques and other treatments (eg, steroids, prone positioning, bronchoscopy, and inhaled nitric oxide). We aimed to delineate the safety, clinical efficacy, and cost-effectiveness of extracorporeal membrane oxygenation (ECMO) compared with conventional ventilation support.
In this UK-based multicentre trial, we used an independent central randomisation service to randomly assign 180 adults in a 1:1 ratio to receive continued conventional management or referral to consideration for treatment by ECMO. Eligible patients were aged 18-65 years and had severe (Murray score >3.0 or pH <7.20) but potentially reversible respiratory failure. Exclusion criteria were: high pressure (>30 cm H(2)O of peak inspiratory pressure) or high FiO(2) (>0.8) ventilation for more than 7 days; intracranial bleeding; any other contraindication to limited heparinisation; or any contraindication to continuation of active treatment. The primary outcome was death or severe disability at 6 months after randomisation or before discharge from hospital. Primary analysis was by intention to treat. Only researchers who did the 6-month follow-up were masked to treatment assignment. Data about resource use and economic outcomes (quality-adjusted life-years) were collected. Studies of the key cost generating events were undertaken, and we did analyses of cost-utility at 6 months after randomisation and modelled lifetime cost-utility. This study is registered, number ISRCTN47279827.
766 patients were screened; 180 were enrolled and randomly allocated to consideration for treatment by ECMO (n=90 patients) or to receive conventional management (n=90). 68 (75%) patients actually received ECMO; 63% (57/90) of patients allocated to consideration for treatment by ECMO survived to 6 months without disability compared with 47% (41/87) of those allocated to conventional management (relative risk 0.69; 95% CI 0.05-0.97, p=0.03). Referral to consideration for treatment by ECMO led to a gain of 0.03 quality-adjusted life-years (QALYs) at 6-month follow-up [corrected]. A lifetime model predicted the cost per QALY of ECMO to be pound19 252 (95% CI 7622-59 200) at a discount rate of 3.5%.
We recommend transferring of adult patients with severe but potentially reversible respiratory failure, whose Murray score exceeds 3.0 or who have a pH of less than 7.20 on optimum conventional management, to a centre with an ECMO-based management protocol to significantly improve survival without severe disability. This strategy is also likely to be cost effective in settings with similar services to those in the UK.
UK NHS Health Technology Assessment, English National Specialist Commissioning Advisory Group, Scottish Department of Health, and Welsh Department of Health.
Certain perfluorocarbon (PFC) compounds, commonly used as the oxygen transport components of "blood substitutes," may be breathed as neat liquids with survival because of their chemical inertness and their high solubility for oxygen and carbon dioxide. In addition, the paramagnetism of oxygen reduces the fluorine T1 value according to an inverse relationship allowing a potential method of monitoring PO2 gradients in vivo. This article presents the results of magnetic resonance (MR) imaging of the lungs of mice and rats following breathing of four PFC liquids (FC-43, FC-75, PFOB, APF-215). The images presented were obtained at two magnetic field strengths (0.66 and 0.14 T) under conditions of breathing either ambient air or pure oxygen. Spin-lattice relaxation times (T1) for the PFCs are measured both in vitro and in vivo (in the lungs) as a function of the state of oxygenation. A MR image signal strength enhancement of up to 90% is demonstrated in vivo under conditions of pure oxygen breathing.
We evaluated the safety and efficacy of partial liquid ventilation in a series of 19 adults, children, and neonates who were in respiratory failure and on extracorporeal life support. During partial liquid ventilation, the alveolar-arterial oxygen difference decreased from 590 (SE 25) to 471 (42) mm Hg (p = 0.0002) and static pulmonary compliance increased from 0.18 (0.04) to 0.29 (0.04) mL cm H2O-1 kg-1 (p = 0.0002). 11 patients (58%) survived. These preliminary data suggest that partial liquid ventilation can be safely used in patients with severe respiratory failure and may improve lung function.
The use of perfluoroctylbromide (PFOB), a liquid ventilatory agent, was evaluated as a computed tomographic contrast agent to visualize small airway anatomy to the level of the centrilobular bronchiole, normally not visible on high-resolution computed tomography (HRCT). A freshly excised neonatal lamb heart-lung preparation was tracheally intubated, suspended in a saline bath, and mechanically ventilated with gas. After obtaining HRCT control images with suspended respiration using continuous positive airway pressure, 30 ml of perfluorocytlbromide was instilled into the trachea and repeat scans were obtained. These images demonstrated PFOB filling and distending the airways to the level of the centrilobular bronchioles and their first order branches. There was only minimal spillage into air spaces, allowing excellent anatomic detail of the bronchiolar structures. A liquid ventilatory agent, PFOB is a superb candidate as a bronchographic contrast agent due to its promotion of gas exchange, low toxicity, low surface tension, radiopacity, and vaporized excretion via the lung. It has great potential to evaluate small airway disease when used in conjunction with HRCT.
To describe the radiographic appearance of perflubron-filled lungs during partial liquid ventilation (PLV).
Supine chest radiographs (391 anteroposterior, 154 lateral radiographs) were obtained before and after daily perflubron instillation in 13 adults undergoing PLV who were receiving extracorporeal life support. Perflubron distribution, barotrauma, and inability to discern catheters were evaluated.
Immediately after instillation of perflubron, opacification of more than two-thirds of the lungs was shown in 12 of 13 patients. A gravity-dependent distribution of perflubron was shown on 146 (95%) of 154 lateral radiographs. Perflubron gradually cleared until it filled less than one-third of the lungs 6.8 days later (range, 2-20 days). In the five survivors, minimal perflubron was visible up to 138 days. In five patients, perflubron increased the visibility of small pneumothoraces present before PLV. Location of intrathoracic catheters was obscured on 44 radiographs.
Perflubron symmetrically opacifies the lungs in a gravity-dependent distribution during PLV and clears to minimal levels within 3 weeks.
Liquid ventilation with perfluorocarbon previously has not been reported in pediatric patients with respiratory failure beyond the neonatal period. We evaluated the technique of partial liquid ventilation in six pediatric patients with the acute respiratory distress syndrome of sufficient severity to require extracorporeal life support (ECLS).
This study was a noncontrolled, phase I/II experimental study with a single group pretest/posttest design.
All studies were performed at a tertiary, pediatric referral hospital at the University of Michigan Medical School.
Six pediatric patients, from 8 wks to 5 1/2 yrs of age, with severe respiratory failure requiring ECLS to support gas exchange.
After 2 to 9 days on ECLS, perfluorocarbon was administered into the trachea until the dependent zone of each lung was filled. The initial administered was 12.9 +/- 2.3 mL/kg (range 5 to 20). Gas ventilation of the perfluorocarbon-filled lungs (partial liquid ventilation) was then performed. The perfluorocarbon dose was repeated daily for a total of 3 to 7 days, with a cumulative dose of 45.2 +/- 6.1 mL/kg (range 30 to 72.5).
All measurements of native gas exchange were made during brief periods of discontinuation of ECLS and include PaO2 and the alveolar-arterial oxygen gradient, P(A-a)O2. Static pulmonary compliance, corrected for weight, was also measured directly. The mean PaO2 increased from 39 +/- 6 to 92 +/- 29 torr (5.2 +/- 0.8 to 12.2 +/- 3.9 kPa) over the 96 hrs after the initial dose (p = .021 by repeated-measures analysis of variance). The average P(A-a)O2 decreased from 635 +/- 10 to 499 +/- 77 torr (84.7 +/- 1.3 to 66.5 +/- 10.3 kPa) over the same time period (p = .059), while the mean static pulmonary compliance (normalized for patient weight) increased from 0.12 +/- 0.02 to 0.28 +/- 0.08 mL/cm H2O/kg (p = .01). All six patients survived. Complications potentially associated with partial liquid ventilation were limited to pneumothoraces in two of six patients.
Perfluorocarbon may be safely administered into the lungs of pediatric patients with severe respiratory failure on ECLS and may be associated with improvement in gas exchange and pulmonary compliance.
To evaluate the safety and efficacy of partial liquid ventilation (PLV).
Before-after trial.
The surgical intensive care unit at the University of Michigan, Ann Arbor, from April to December 1994.
A consecutive sample of 10 patients aged 19 to 55 years with the acute respiratory distress syndrome who were receiving extracorporeal life support.
Perflubron was administered into the trachea until the dependent zone of the lung was filled. Gas ventilation of the perflubron-filled lung was then performed (PLV). Volatilized perflubron replacement was repeated daily for from 1 to 7 days with a median cumulative dose of 38 mL/kg (range, 15 to 62 mL/kg).
Physiologic shunt and static pulmonary compliance.
Physiologic shunt decreased from a median of 0.72 (range, 0.37 to 1.0) to 0.46 (range, 0.21 to 0.96) over the 72 hours following initiation of PLV (P = .01 by repeated measures analysis of variance). Static pulmonary compliance corrected for patient weight increased from a median of 0.16 mL/cm H2O per kilogram (range, 0.01 to 0.48 mL/cm H2O per kilogram) to 0.27 mL/cm H2O per kilogram (range, 0.05 to 1.11 mL/cm H2O per kilogram) over the same time period (P = .04 by repeated measures analysis of variance). Overall survival was five (50%) of 10 patients. Complications that were potentially associated with PLV included pneumothorax development in one patient and mucus plug formation in one patient.
Perflubron may be safely administered into the lungs of patients with severe respiratory failure receiving extracorporeal life support and may be associated with improvement in gas exchange and pulmonary compliance.
Therapeutic management of respiratory distress syndrome, pneumonia, and pulmonary hypertension includes delivery of biologically active agents to the neonatal lung. However, mechanical abnormalities of the lung, intrapulmonary shunting, ventilation-perfusion mismatching, and elevated surface tension impede effective systemic or intratracheal delivery of agents to the lung during conventional gas ventilation. The objective of this study was to test the hypothesis that perfluorochemical (PFC) liquid ventilation can be used for pulmonary administration of vasoactive drugs (PAD) and to compare these responses to those elicited with intravascular (IV) administration during tidal liquid ventilation.
Cardiovascular responses of 16 preterm and neonatal lambs to randomized doses of acetylcholine, epinephrine, and priscoline were studied. Physiologic gas exchanged and acid-base balance were maintained using previously described tidal liquid ventilation techniques. In subgroups of animals, the distribution pattern of carbon 1- and choline 14-labeled dipalmitoylphosphatidylcholine (14C-DPPC) in saline and the responses to priscoline after hypoxia-induced pulmonary hypertension and hypoxemia administered during liquid ventilation were studied.
Dose-response curves for PAD and IV administration demonstrated progressive, dose-dependent, cholinergic responses to acetylcholine (decreased mean systemic arterial pressure [MAP] and heart rate), sympathomimetic responses to epinephrine (increased MAP and heart rate), and alpha-adrenergic blockade responses to priscoline (decreased MAP and mean pulmonary arterial pressure). Compared with IV administration, PAD of priscoline resulted in a significantly greater decrease in pulmonary relative to systemic arterial pressure; this response was potentiated by hypoxia, reduced pulmonary pressures to near normal values, and improved oxygenation. The 14C-DPPC in saline was distributed relatively homogeneously throughout the lung by PAD, with 80% of the lung pieces receiving amounts of 14C-DPPC with +/-20% of the mean value.
This study demonstrates that vasoactive agents can be delivered to the lung directly by PAD during PFC liquid ventilation. The inherent advantages of this method relate to the physical properties of PFC liquid ventilation as a vehicle (respiratory gas solubility, low surface tension-enhancing distribution, and inertness precluding interaction) and physiological properties of the lung as an exchanger.
Perfluorochemical (PFC) liquids are biologically inert and nonbiotransformable substances that, when used as breathing medium, may be transported across the lung epithelium in small quantities, distributed throughout the body, and ultimately vapourized through the lungs and transpired through the skin. To further evaluate the uptake, biodistribution and elimination of a PFC liquid (perfluorodecalin) in the neonatal population, arterial blood, tissue and expired gas samples were obtained from preterm lambs (105-114 days gestation). Two groups of premature lambs were studied: Group I (n = 4) lambs were liquid ventilated from birth for 1 h and killed without exposure to gas ventilation (GV) and Group II (n = 5) lambs were liquid ventilated for 1 h followed by up to 2 h of GV. Samples were analysed by electron-capture gas chromatography and data were expressed in nl of PFC/ml of blood or gas and nl of PFC/gm tissue. During liquid ventilation and subsequent GV, PFC blood levels significantly increased (P < 0.001) from baseline control levels (0.007 +/- 0.001 SE nl PFC/ml blood) to a high of 2.95 +/- 1.03 SE nl PFC/ml blood. Perfluorochemical levels measured in expired gas (Group II) demonstrated a rapid decrease as a function of time of GV. Tissue levels of PFC indicated that uptake of PFC in Group I was significantly different (P < 0.001) than baseline levels and organ dependent; the highest levels were in the lungs (221 +/- 26.2 SE nl PFC/g tissue) and the lowest in the liver (2.24 +/- 1.6 SE nl PFC/g tissue). Comparison of tissue levels of PFC between groups indicated a 34.8% mean decrease across organs in Group II compared with Group I. These data indicate that PFC uptake and elimination is organ dependent and that PFC liquids can be eliminated through the lungs upon return to GV. Sustained PFC blood levels may be related to residual PFC in the organs and lung as well as regional variation in ventilation-perfusion matching upon return to GV.
Pulmonary absorption of aminoglycosides is poor with intravenous administration, but may be enhanced by direct intratracheal administration of these drugs using perfluorochemical liquid ventilation (LV). To test this hypothesis, gentamicin sulfate was administered to two groups of newborn lambs during LV. Serum and lung tissue levels of gentamicin were compared after either pulmonary intratracheal (IT) or intravenous (IV) routes of administration. Serial serum levels of gentamicin were obtained every 15 min for the 1st h, every 30 min for the 2nd h, and then hourly until sacrifice (maximum 6 h). At sacrifice, representative samples of each lung lobe were homogenized and analyzed for tissue gentamicin content. At 1 h, serum gentamicin levels were similar in both groups: IT administration levels were 3.7 ± 0.55 SE μg/ml and IV levels were 3.5 ± 0.85 SE μg/ml. The peak serum gentamicin level of 4.8 ± 0.8 SE μg/ml for the pulmonary administration group occurred 1.5 h after administration. Lung tissue levels of gentamicin for IT administration (4.04 ± 0.62 SE μg/g) were significantly greater than for IV administration (1.75 ± 0.33 SE μg/g; P < 0.05). There were no significant differences in interlobar gentamicin distribution for either mode of administration.
Conclusion Perfluorochemical can be used as a vehicle for intratracheal delivery of antimicrobials. This route provides equivalent serum levels at 1 h, higher lung tissue levels, and uniform interlobar distribution relative to intravenous administration of gentamicin. We speculate that pulmonary administered gentamicin during LV may provide an effective alternative treatment modality in the management of severe neonatal pneumonia.
To assess the pulmonary and systemic distribution and elimination of perflubron (C(8)F(17)Br(1); LiquiVent; Alliance Pharmaceutical; San Diego, CA) during and following the period of partial liquid ventilation.
Prospective phase I and II clinical trial.
Adult surgical ICU.
Eighteen adult patients (mean +/- SEM age, 37.9 +/- 3.4 years) with severe respiratory failure, some of whom required extracorporeal life support (72%), and who were managed with partial liquid ventilation with perflubron.
Perflubron was administered into the trachea, and gas ventilation of the perfluorocarbon-filled lung (partial liquid ventilation) was then performed. Additional doses were administered daily for from 1 to 7 days, with a median cumulative dose of 31 mL/kg (range, 3 to 60 mL/kg). Measurements and main results: Patient blood samples were evaluated by gas chromatography for serum perflubron levels. Sequential lateral and anteroposterior radiographs were assessed, using a 5-point rating scale, for the degree of perflubron fill following the final dose. Samples of expired gas were collected, and the rate of loss of perflubron in the expired gas was measured by gas chromatography. Mean serum perflubron levels increased to 0.16 +/- 0.05 mg/dL at 24 h following administration of the initial dose. A mean maximum level of 0.26 +/- 0.05 mg/dL of perflubron was present in the serum 24 h following the administration of the last dose. This level slowly trended downward to 0.18 +/- 0.06 mg/dL over the ensuing 7 days (p = 0.281). Perflubron elimination via expired gas occurred at a mean rate of 9.4 +/- 3.0 mL/h at 1 h, and 1.0 +/- 0.4 mL/h at 48 h after the last dose (p = 0.012). By radiologic evaluation, perflubron was eliminated from the lungs progressively from 4.2 +/- 0.2 at the time of administration of the last dose, to 2.8 +/- 0.3 at 4 days later (p < 0.001). Perflubron tended to distribute and remain for longer periods in the dependent regions of the lung when compared to the nondependent regions (96-h perflubron fill score: posterior, 3.8 +/- 0.5; anterior, 1.9 +/- 0.4; p = 0.004).
Perflubron is eliminated at a maximum rate of 9.4 +/- 3.0 mL/h by evaporative loss from the airways and is retained in greater amounts in the dependent lung regions when compared to the nondependent lung regions. There is a low but measurable maximum blood concentration of 0.26 +/- 0.05 mg/dL in patients after perflubron administration, which did not decrease significantly after cessation of partial liquid ventilation.