**2. History of ECMO**

Pioneering animal research on extracorporeal oxygenation began in the seventeenth century. Early experiments that included perfusion were initially limited by coagulation/thrombosis and only became possible with the development of anticoagulants. Direct contact oxygenation became available in the nineteenth century with agitated oxygenators and motorized oxygenators. Bubble-type and surface-type oxygenators were described by Hooker in the early twentieth century [2]. Following the discovery of anticoagulation, stationary screen oxygenators were developed, and subsequently modified pump oxygenators became commercially available. Rotating disc film oxygenators, which were initially developed for animal use and then adapted to human use was made possible in the mid-twentieth century. With the development of the DeWall bubble oxygenator, concerns about optimum bubble size arose. Small bubble sizes achieved a higher surface area for direct contact with blood and allowed better oxygenation; however, they had a longer transit time through the oxygenating column predisposing patients to air embolism. The best compromise was achieved with bubble sizes between 2 and 7 mm in diameter, a mixture of large- and small-sized bubbles and optimizing the rate of fresh gas flow. The use of these bubble oxygenators resulted in blood shearing with resultant hemolysis, activation of the inflammatory response, platelet activation, and increased thrombogenicity.

Technological advances that ushered in the era of contemporary ECMO began with the oxygenation of blood as it flowed through an artificial cistern. Kolf and Berk observed that the gas contents of blood approximated those of aerated dialysate across a cellophane tube [3]. This led to research on biomaterials with the hope of identifying materials with optimum gas exchange and mechanical properties. Initial materials that were tested include ethylcellulose and polyethylene, but these materials were limited by mechanical strength and presence of pinholes. The development of the membrane exchange system, the membrane lung, was made possible using polysiloxane or silicon polymers.

The development of hydrophobic, microporous membranes with pore sizes less than 1 micron, allowed direct contact of blood and air while plasmatic leak across the micropores limited by surface tension forces. These membranes allowed highperformance membrane oxygenators capable of being used for long ECMO runs.

Gibbon reported the first successful use of a mechanical extracorporeal lung and heart bypass during cardiac surgery in 1954 [4], and Hill et al. reported the first use of prolonged extracorporeal bypass in the context of post-traumatic respiratory failure in 1972 [5]. Extracorporeal support lasted for 75 hours in this case. In 1975, Bartlett went on to describe the first successful ECMO in a neonatal patient [6]. Following a premature termination of a multicenter trial of ECMO for ARDS, the development of ECMO was stalled for 20 years [7]. Thereafter, significant progress has been made in the circuit, management, indications and outcomes [8].
