A[H1N1] flu and refractory hypoxaemia: is extracorporeal lung support the holy grail?

There is a call for methodologically robust randomised clinical trials in adult extracorporeal membrane oxygenation for its routine implementation for patients with "failing" conventional ventilation. Adherence to lung protective ventilation strategies, along with fluid balance [if required early renal replacement therapy] and inotropes to support the circulation to minimise ventilator-induced lung injury, may mitigate deterioration requiring extracorporeal lung support. Currently there is no convincing evidence to routinely advocate extracorporeal lung support in failed conventional ventilation, and a prospective trial is needed to define standard best practice and to tailor extracorporeal lung support referral criteria in young patient cohort with severe refractory respiratory failure.     

Mechanical ventilation in acute respiratory distress syndrome

The acute respiratory distress syndrome occurs commonly in critical care. There is an increasing volume of clinical and experimental evidence that poor ventilatory technique that is injurious to the lungs can propagate the systemic inflammatory response and adversely affect mortality. Many ventilatory techniques have been hypothesized to 'protect' the lungs during mechanical ventilation, including tidal volume limitation, high positive end-expiratory pressure, pressure-controlled inverse ratio ventilation, and prone positioning. Experimental techniques include liquid ventilation, surfactant administration and extracorporeal gas exchange. Despite excellent rationale for their use, few techniques, apart from tidal volume limitation, have been shown to improve survival in randomized controlled trials.     

Extracorporeal Lung Assist in Severe Respiratory Failure and ARDS. Current Situation and Clinical Applications

Despite improvements in ventilation support techniques, lung protection strategies and the application of new support treatment, acute respiratory distress syndrome continues to have a high mortality rate. Many strategies and treatments for this syndrome have been investigated over the last few years. However, the only therapeutic measure that has systematically shown to be able to improve survival is that of low volume lung protective ventilation. Thus, using a low tidal volume prevents added lung damage by the same mechanical ventilation that is essential for life support. In this context, the use of extracorporeal lung assist systems is considered as a salvage treatment for use in extreme cases. On the other hand, it could be a potentially useful complementary method for an ultra-protective ventilation strategy, that is, by using even lower tidal volumes. The currently available extracorporeal lung assist systems are described in this article, including high flow systems such as traditional extracorporeal membrane oxygenation, CO₂ removal systems (interventional lung assist or iLA, with or without associated centrifugal pumps), and the new low flow and less invasive systems under development. The aim of this review is to update the latest available clinical and experimental data, the indications for these devices in adult respiratory distress syndrome (ARDS), and their potential indications in other clinical situations, such as the bridge to lung transplantation, multiple organ dysfunction syndrome, and COPD.     

Evidence-based medicine of the acute respiratory distress syndrome

Different therapeutic approaches have recently been developed for treatment of acute respiratory distress syndrome (ARDS) with the aim of improving the outcome. The clinical significance and success of these therapies is variable with respect to evidence based medicine. Lung protective ventilation is accepted as a proven therapy and the use of positive end-expiratory pressure as well as spontaneous breathing during controlled ventilation are common therapies. High frequency ventilation, partial liquid ventilation and pulmonary surfactant application are still in the experimental stage. The prone position is recommended for severe cases of ARDS and the application of inhaled nitric oxide and of extracorporeal membrane oxygenation is established in specialized centers for patients with imminent hypoxia. But for the routine use of these three therapies a clear improvement in outcome could not demonstrated. Recommended drug therapy is limited to the administration of stress doses of corticosteroids and a special anti-inflammatory enteral diet.     

Extracorporeal lung support for advanced lung failure: a new era in thoracic surgery and translational science

For the patients with progressively decompensating acute or acute-on-chronic respiratory failure, the first-choice treatment remains as mechanical ventilation. Despite the consistent value of mechanical ventilation, the majority of lung specialists are aware of its limitations, in particular for the patients with advanced lung failure, and inherent drawbacks that augment disease progression. More recently, the concept of allowing the lungs to ‘rest and recover’ has been supported by quite a few clinical studies. The pressure and volume of gas delivered to the lungs are reduced compared with mechanical ventilation. Based on recent remarkable evidence and experiences using extracorporeal lung support (ECLS) before, during and after lung transplant, there is growing interest in and expectations for the use of ECLS beyond lung transplant to encompass the entire field of pulmonary medicine. The purpose of this review article is to provide an update on evolving ECLS technologies and their effectiveness and discuss the future of ECLS for advanced lung failure as a new subspecialty in cardiothoracic surgery.     

Experience with high frequency oscillation ventilation during the 2009 H1N1 influenza pandemic in Australia and New Zealand

During the 2009 H1N1 pandemic, large numbers of patients had severe respiratory failure. High frequency oscillation ventilation was used as a salvage technique for profound hypoxaemia. Our aim was to compare this experience with high frequency oscillation ventilation during the 2009 H1N1 pandemic with the same period in 2008 by performing a three-month period prevalence study in Australian and New Zealand intensive care units. The main study end-points were clinical demographics, care delivery and survival. Nine intensive care units contributed data. During 2009 there were 22 H1N1 patients (17 adults, five children) and 10 non-H1N1 patients (five adults, five children), while in 2008, 18 patients (two adults, 16 children) received high frequency oscillation ventilation. The principal non-H1N1 high frequency oscillation ventilation indication was bacterial or viral pneumonia (56%). For H1N1 patients, the median duration of high frequency oscillation ventilation was 3.7 days (interquartile range 1.8 to 5) with concomitant therapies including recruitment manoeuvres (22%), prone ventilation (41%), inhaled prostacyclins (18%) and inhaled nitric oxide (36%). Seven patients received extracorporeal membrane oxygenation, six having H1N1. Three patients had extracorporeal membrane oxygenation concurrently, two as salvage therapy following the commencement of high frequency oscillation ventilation. In 2008, no high frequency oscillation ventilation patient received extracorporeal membrane oxygenation. Overall hospital survival was 77% in H1N1 patients, while survival in patients having adjunctive extracorporeal membrane oxygenation was similar to those receiving high frequency oscillation ventilation alone (65% compared to 71%, P = 1.00). Survival rates were comparable to published extracorporeal membrane oxygenation outcomes. High frequency oscillation ventilation was used successfully as a rescue therapy for severe respiratory failure. High frequency oscillation ventilation was only available in a limited number of intensive care units during the H1N1 pandemic.     

Extrakorporale Herz- und Lungenersatzverfahren

The use of extracorporeal support systems in cardiac and/or pulmonary failure is an established treatment option. Although scientific evidence is limited there is an increasing amount of data from individual studies, e.g. Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) trial 2010, suggesting that extracorporeal membrane oxygenation (ECMO) as a veno-venous pump-driven system is a life-saving procedure in severe respiratory failure. Initially established as a rescue option for postcardiotomy cardiac failure extracorporeal life support (ECLS) as a pump-driven veno-arterial cardiovascular support system is increasingly being used in cardiogenic shock after myocardial infarction, as bridging to transplantation or as part of extended cardiopulmonary resuscitation. The pumpless extracorporeal lung assist (pECLA) as an arterio-venous pumpless system is technically easier to handle but only ensures sufficient decarboxylation and not oxygenation. Therefore, this method is mainly applied in primarily hypercapnic respiratory failure to allow lung protective ventilation. Enormous technical improvements, e.g. extreme miniaturization of the extracorporeal assist devices must not obscure the fact that this therapeutic option represents an invasive procedure frequently associated with major complications. With this in mind a widespread use of this technology cannot be recommended and the use of extracorporeal systems should be restricted to centers with high levels of expertise and experience.     

Single site venovenous extracorporeal membrane oxygenation as an alternative to invasive ventilation in post-pneumonectomy fistula with acute respiratory failure

We report the use of venovenous extracorporeal membrane oxygenation with a single dual lumen cannula in a 42-year-old patient suffering from a post-pneumonectomy fistula and severe respiratory insufficiency, avoiding the classical approach of invasive mechanical ventilation. We discussed the potential advantages of extracorporeal oxygenation as the main support in this particular clinical setting.     

Three controversial issues in extracorporeal toxin removal

The optimal method of extracorporeal removal of many toxic compounds is often a matter of debate. Due to the lack of well‐designed studies, we are often left with circumstantial evidence, and we must exercise our best clinical judgment as to whether extracorporeal drug removal is beneficial and if so, by what method. It is clear, however, that rapidity in toxin removal is beneficial. We present three issues dealing with extracorporeal removal of toxins for which there is no definitive answer but which may arise in clinical practice. The first is whether continuous renal replacement therapy (CRRT) is better at removing dialyzable toxins than classic hemodialysis. The second is whether charcoal hemoperfusion is at all useful in treating paraquat poisoning. Finally, is any modality of extracorporeal treatment useful in the treatment of amatoxin poisoning? After a thorough literature review, it is evident that definitive answers are not strikingly apparent. However, extracorporeal treatment in the latter two instances may have potential benefit and may be the only hope for patient survival. Due to the urgent nature of treatment for poisoning, as well as the somewhat obscure nature of these issues, there may never be well‐designed evidence‐based studies to help guide us. In the meantime, we must continue to use less than ideal evidence and our own experience in dealing with these controversial issues to guide our decision‐making process.     

Acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a devastating clinical condition characterized by poor gas exchange and bilateral interstitial opacification demonstrated on chest imaging. Despite years of research, the mortality associated with ARDS remains high. Early recognition and treatment of the underlying cause, combined with strategies to reduce ventilator-induced lung injury are key to optimising the likelihood of survival. This article will provide an update on the most recent evidence base on clinical practice, including the use of acute severe respiratory failure bundles and extracorporeal techniques to support lung protective ventilation.     

pH-stat ventilation management: a simple method of achieving this regimen

Since the advent of extracorporeal circulation for life support during cardiac surgery, there have been varied opinions as to the best method of ventilating an oxygenator to achieve the optimum arterial blood gas. With respect to the optimum pCO2, clinical investigators have focused primarily on the pros and cons of the alpha-stat and pH-stat ventilation schemes. pH-stat is a ventilation scheme that attempts to maintain the temperature corrected pH of the arterial blood at 7.40, no matter what the actual temperature of the blood. This paper does not attempt to elucidate the benefits of one scheme over the other, but is offered to provide perfusionists with a simple method of achieving pH-stat ventilation, using a CO2 source and materials readily available in any operating room. Strict adherence to a few cautionary notes should enable any perfusionist to safely deliver pH-stat ventilation when indicated. This technique of providing pH-stat ventilation has been used at our institution for over three years. It has proven to be easy to accomplish, adjust and maintain.     

Control of breathing using an extracorporeal membrane lung.

Various amounts of carbon dioxide were removed through an extracorporeal membrane lung in spontaneously breathing lambs. The decrease in alveolar ventilation was proportional to the fraction of total carbon dioxide removed by the membrane lung. When extracorporeal CO2 removal approximated CO2 production (VCO2), alveolar ventilation almost ceased. Pulmonary ventilation can be controlled by extracorporeal carbon dioxide removal.     

Extrakorporale Membranoxygenierung beim akuten Lungenversagen

After various observational studies demonstrated a benefit of extracorporeal membrane oxygenation (ECMO) in the therapy of severe acute respiratory distress syndrome (ARDS), ECMO now represents an important contribution for ARDS therapy using clinical algorithms despite a lack of positive controlled studies. In specialized centers patients with severe ARDS and imminent hypoxia despite intensive conventional therapy, are treated with ECMO using blood pumps and artificial membrane lungs (oxygenators) for extracorporeal lung assist. The development of new surface modifications, optimized oxygenators and miniaturized blood pumps should increase hemocompatibility and lead to simplified treatment as well as less complications. New oxygenators with significantly decreased blood resistance allow the clinical application of pumpless arteriovenous extracorporeal lung assist (ECLA). After these new developments indications for ECMO could be extended from use not only as ultimate ratio but to less severe ARDS to enable lung protective, less invasive mechanical ventilation.     

Clinical efficacy of high frequency jet ventilation during extracorporeal shock wave lithotripsy of renal and ureteral calculi: a comparison with conventional mechanical ventilation

The use of high frequency jet ventilation compared to conventional mechanical ventilation during general anesthesia for extracorporeal shock wave lithotripsy of renal or ureteral calculi can reduce stone movement. This decrease in stone movement theoretically lessens the total shock and energy requirements for stone fragmentation and perirenal tissue damage. To assess these theoretical advantages of high frequency jet ventilation, we studied patients undergoing extracorporeal shock wave lithotripsy to determine differences in stone movement during high frequency jet and conventional mechanical ventilation (30 patients), and in total shock requirements (1,174 patients). Mean stone movement in the 30 patients was 34.3 +/- 4.3 mm. during conventional mechanical ventilation compared to 4.1 +/- 1.9 mm. during high frequency jet ventilation (p less than 0.001). Mean total shocks were 1,542 +/- 212 (452 patients) during conventional mechanical ventilation compared to 1,217 +/- 165 (722 patients) during high frequency jet ventilation (p less than 0.001). Only 1 patient in the study had clinically significant perirenal tissue damage. We conclude that high frequency jet ventilation when compared to conventional mechanical ventilation results in clinically and economically beneficial decreases in total shocks for extracorporeal shock wave lithotripsy fragmentation of renal or ureteral calculi.     

Protective and ultra-protective ventilation: using pumpless interventional lung assist (iLA)

Acute lung failure is associated with high mortality and usually requires mechanical ventilation to ensure adequate gas exchange. However, mechanical ventilation itself can be associated with major complications and can aggravate pre-existing lung disease, thus contributing to morbidity and mortality. Extracorporeal gas exchange is increasingly used when conventional mechanical ventilation has failed. In contrast to veno-venous extracorporeal membrane oxygenation (ECMO), pumpless extracorporeal interventional lung assist (iLA) is applied via an arterio-venous bypass into which a gas exchange membrane is integrated. iLA allows for efficient carbon dioxide removal, which allows for a significant reduction in ventilator settings. iLA may be a useful tool in protective or even 'ultraprotective' ventilation, enabling the application of very low tidal volumes in patients with acute respiratory failure of different etiologies. This article reviews the current status and the potential role of interventional (pumpless) lung-assist iLA within the context of lung-protective ventilation strategies.     

Colonic mucosal ecchymoses after extracorporeal shock wave lithotripsy for upper ureteral calculus

Bright red blood was found in stool immediately following extracorporeal shock wave lithotripsy with 2,700 shock waves to a right upper ureteral calculus beside an indwelling Double-J stent. The vital signs remained stable and bleeding did not recur. Colonoscopy revealed small areas of mucosal ecchymoses in the ascending colon. To our knowledge this effect of extracorporeal shock wave lithotripsy has not been reported previously. There is no evidence as yet that these ecchymoses are of any clinical significance for most patients.     

A New Perfusion Circuit for the Newborn with Lung Immaturity: Extracorporeal CO2 Removal via an Umbilical Arteriovenous Shunt During Apneic O2 Diffusion

In spite of improved prophylaxis and therapy, the respiratory distress syndrome is still a major cause of morbidity and mortality in premature babies. Owing to the fact that a number of patients are unresponsive to other methods of neonatal care, an increasing number of perinatal centers have started to treat this group of patients with extracorporeal membrane oxygenation successfully. To make the extracorporeal gas exchange more practicable for the neonate directly after birth, a modification of this method using an umbilical arteriovenous shunt for CO2 removal in apneic premature lambs as an animal model was evaluated. A miniaturized low-resistance extracorporeal circuit that is totally incorporated in a regular intensive care baby incubator was developed. The benefit of using extracorporeal CO2 removal in very low birth weight newborns could be a conditioning of the premature lung during a short period of bypass, after which ventilation at nontraumatic pressures and nontoxic O2 concentrations would become possible.     

Techniques of ventilatory therapy in the adult respiratory distress syndrome (ARDS)

Techniques of respiratory support in ARDS are becoming more and more complex. New modes of ventilatory therapy like continuous positive airway pressure (CPAP), appeared during the last years and became popular; other ones are now under investigation, high frequency ventilation and extracorporeal CO2 removal, for instance. A lot of abbreviations are actually commonly used by physicians involved in intensive care as well as by ventilator industries. The purpose of this article is to review these different modes of respiratory assistance in ARDS, as well as their indications. They are grouped into four categories: mechanical ventilation, spontaneous breathing with positive pressure, a "mature" of both, also called intermittent mandatory ventilation (IMV) and finally extracorporeal support. The respective use of these different modes in our Center of Intensive Care at the University of Liège during recent years is analysed. It appears that mechanical ventilation, especially with positive end expiratory pressure (PEEP) keeps a place of choice and that spontaneous breathing with positive pressure (CPAP) represents one of the best improvements of the late years in respiratory intensive care. Last but not least is the absolute necessity to start respiratory assistance with positive pressure as soon as possible, once the diagnosis of ARDS is suspected.     

Protektive Beatmungstherapie

General anesthesia and mechanical ventilation affect gas exchange, ventilation and pulmonary perfusion and there is an increasing body of evidence that mechanical ventilation itself promotes lung injury. Lung protective mechanical ventilation in patients suffering from acute lung injury or acute respiratory distress syndrome by means of reduced tidal volumes and limited plateau pressures has been shown to result in reduction of systemic inflammatory mediators, increased ventilator-free days and reduction in mortality. Experimental studies suggest that mechanical ventilation of uninjured lungs may also induce lung damage; however, the clinical relevance remains unknown. Human prospective studies comparing mechanical ventilation strategies during general anesthesia have shown inconsistent results with respect to inflammatory mediators. There is a lack of clinical evidence that lung protective ventilation strategies as used in patients with lung injury may improve clinical outcome of patients with uninjured lungs. The question of which ventilatory strategy will best protect normal human lungs remains unanswered.     

NeonatOx: a pumpless extracorporeal lung support for premature neonates

Gas exchange in premature neonates is regularly impaired by structural and functional immaturity of the lung. Mechanical ventilation, which is vitally important to sustain oxygenation and CO(2) elimination, causes, at the same time, mechanical and inflammatory destruction of lung tissue. To date, extracorporeal oxygenation is not a treatment option, one reason among others being the size of available oxygenators and cannulas. We hypothesized that a substantial improvement in gas exchange can be achieved by maintenance of the fetal cardiopulmonary bypass and interposition of a suitable passively driven (arteriovenous) membrane oxygenator. In close cooperation between engineers and neonatologists, we developed a miniaturized oxygenator and adapted cannulas to be used as a pumpless extracorporeal lung support that is connected to the circulation via cannulation of the umbilical cord vessels. First in vitro and in vivo studies show promising results. We regard this as one step on the way to clinical application of the artificial placenta.