Lung replacement therapies for acute respiratory failure

Acute respiratory failure is one of the critical conditions with an increased mortality. In order to reverse lung injury and reduce the mortality rate, several lung replacement therapies have been developed, including the extracorporeal membrane oxygenation, the intravascular oxygenator and carbon dioxide removal device, the intravenous membrane oxygenator and the thoracic artificial lung. This article aims to present the properties, indications and advantages of these devices.


INTRODUCTION
Acute respiratory failure is one of the critical conditions that endangers patients' lives and hence is associated with an increased mortality.In recent years, people have been endeavoring to explore new approaches for the effective treatment of this critical condition in the hope of reversing lung injury and reducing mortality.(1) Currently, several lung replacement therapies are in use, including the extracorporeal membrane oxygenation (ECMO), the intravascular oxygenator and carbon dioxide (CO2) removal device (IVOX), the intravenous membrane oxygenator (IMO) and the thoracic artificial lung (TAL).The oxygenator is the central component of the cardiopulmonary bypass (CPB) or ECMO circuit.The oxygenators provide gas exchange by contact between blood and the gas phase, either with hollow fibers or a folded silicone membrane.(2) An oxygenrich gas mixture is passed through the oxygenator in an opposite direction to blood flow, promoting oxygen diffusion into the blood.(3) This article will briefly present the clinical application of the devices as well as patients' outcomes.

ECMO
ECMO is a mechanical support system used to aid heart and lung function in patients with severe respiratory or cardiac failure aiming at promoting oxygenation and later also at carbon dioxide removal.The technology is similar to CPB, as used during cardiac surgery, but modified for prolonged use at the bedside in the intensive care unit.The differences between ECMO and CPB are shown in table 1.
Since 1885, when Frey and Gruber developed the first extracorporeal blood oxygenation device, until early 1970's when Hill et al. successfully treated a patient with prolonged extracorporeal oxygenation (Bramson membrane lung) for acute posttraumatic respiratory failure (shock-lung syndrome), oxygenators have undergone sustained technical modifications, which brought about the emergence of the membrane oxygenator and surface-heparinized extracorporeal circulation technique.(4) ECMO currently is divided into two types: venoarterial (VA) and venovenous (VV).VA ECMO, support blood circulation by improving cardiac output, while VV ECMO is a type of extracorporeal CO2 removal system (ECCO2R).(5) In 1978, Gattinoni et al. (6) reported their results of mechanical pulmonary ventilation with low-frequency positive pressure ventilation and extracorporeal CO2 removal (LFPPV-ECCO2R) in five lambs, where cannulations were performed via the subclavian artery-external jugular vein, and blood was pumped through an extracorporeal carbon dioxide membrane lung (CDML), with a surface area of 1.6 m2.The CO2 elimination function with this device seemed to be good.Subsequently, they reported their clinical application of LFPPV-ECCO2R in 19 acute respiratory distress syndrome (ARDS) patients with an overall mortality rate of 23%.(7) Recent studies showed that reduction in tidal volumes to 4 mL/kg and concomitant use of ECCO2R were more effective for permissive hypercapnia in ARDS patients.(8) Table 1.The differences between ECMO and cardiopulmonary bypass.

IMO
The current IMO device uses a constrained fiber bundle made by wrapping hollow fiber fabric around a concentrically located polyurethane balloon.The constrained fiber bundle is intentionally smaller than vessel lumen size, which allows for shunt flow of blood past the device to reduce flow resistance.( 26) Like IVOX, IMO consists of a bundle of manifolded hollow fibers, and is intended for intravenous placement within the superior and inferior vena cava.( 27) An IMO with a design goal of 50% of basal oxygen and CO2 exchange requirements has been successfully used for treatment of end-stage ARDS.However, it was considered that IVOX and IMO are surface-limited and may provide inadequate gas exchange.( 28)

TAL
TALs are an alternative device for bridging patients with respiratory failure to lung transplantation.TALs are attached to the pulmonary circulation, and thus their blood flow is provided by the right ventricle.Current TALs possess blood flow impedances greater than the natural lungs, resulting in low cardiac output when implanted in series with the natural lung or in parallel under exercise conditions.( A compliant TAL has been developed for acute respiratory failure or as a bridge to transplantation.The device uses microporous, hollow fiber bundles.
The complexity, risk potential and cost of ECMO significantly prohibit its wide use in clinical practice.IVOX is a novel therapeutic approach for respiratory failure.It is a good choice in hospitals that cannot establish ECMO for critical patients.IVOX does not need an additional bypass circuit, thereby protecting blood components, reducing energy loss and decreasing the infective opportunity.IVOX is free of blood priming, maintenance becomes simple, and the costs are significantly decreased.Pumpfree TAL is now in the process of manufacture.An ideal implantable artificial lung should be flexible, with good gas exchange function and good biological compatibility.Modifications on structure and physical and chemical stability of the medical membranes, arrangements of hollow fibers and prevention of membranous pollution are being undertaken to enhance the properties of the artificial devices.Further research should be concentrated on the improvement of its properties including gas exchange, blood compatibility, hemodynamic compatibility and configuration of the device.