Oxygenator History

OXYGENATION

The historical development of oxygenators is summarized in Fig. 1.1.Many methods of oxygenating the blood have been investigated over the years. Early experiments involved actually injecting oxygen directly into the blood stream, whilst other equally inventive techniques of oxygenation
were attempted and soon abandoned. These early experiments focused purely on artificial oxygenation, without concerning themselves with the need for carbon dioxide removal. It seemed that what was actually needed was in fact a lung, either natural or artificial.
The lungs
In 1956, Campbell reported successful cardiac surgical procedures in humans on bypass, by use of dog lungs (Campbell et al., 1956), and Mustard and co-workers reported the use of scrupulously washed monkey lungs for oxygenation in human cardiac surgery in 1954. These experiments, although seemingly moderately successful, were extremely complicated and soon abandoned
(Mustard et al., 1954; Mustard and Thomson, 1957). In 1958 Drew used patients’ own lungs as the oxygenator, with a combination of right and left heart bypass and profound hypothermia (Drew and Anderson, 1959).With this technique, the time available for surgical repair was increased and more complex abnormalities could be addressed (Westaby and Bosher, 1997).
Cross-circulation
Andreasen and Watson conducted some canine experiments in Kent, England and published their results in 1952. If the superior vena caval entry into the heart was snared at the cavo-atrial junction, no dog survived beyond 10 minutes. If the snare was distal to azygos vein, allowing azygos venous flow into the right atrium, there was adequate flow to prevent cerebral damage for up to 40 minutes. This finding challenged the existing notion that flows equivalent to normal cardiac output were necessary to prevent damage to vital centres, and suggested that in fact only eight to nine per cent of normal flow was needed (Andreasen and Watson, 1952).
                               Lillehei, at the University of Minnesota, recognized the significance of these findings for cardiac surgery (Lillehei, 2000). After a series of careful experiments (Cohen and Lillehei, 1954), he introduced the technique of ‘controlled cross-circulation’. As the name suggests, the technique used an adult whose circulation was connected to a child patient, the adult subject acting as the oxygenator. In Lillehei’s own words, ‘controlled’ refers to the use of a pump to precisely control the balance of the volume of blood flowing into and out of the donor and the patient.
                   This was a daring and innovative idea. These operations carried a theoretical 200 per cent mortality. In fact, there was no donor mortality in 45 operations. Of 45 patients, 28 survived and were discharged from hospital, many surviving for as long as 30 years (Lillehei et al.,1986). Controlled cross-circulation, however, was limited in its use and could not fully support the circulation. At
the same time,more conventional forms of extracorporeal circulation were being developed, and before long Lillihei himself went on to develop a new pump oxygenator.
Bubble oxygenators
Simple measures to bubble oxygen into the blood met with disastrous results because of air embolism. Clark and co-workers had a breakthrough in 1950, when they started to use small glass beads or rods coated with DC Antifoam A, made by the Dow Corning Company in Michigan
(Clark et al., 1950). This concept was further developed by Lillehei and DeWall, who used a spiral settling tube with a helical system that largely eliminated bubbles. The initial models were sterilized and re-used. Later on, disposable bubble oxygenators were developed. The first clinical use of the DeWall–Lillehei bubble oxygenator was on 13 May 1955, for a three-year-old child with a ventricular septal defect and pulmonary hypertension. By use of normothermia, a Sigmamotor pump and flows of 25–30 mL/kg, Lillehei reported the first success story with the bubble oxygenator (Lillehei et al., 1956).
               Bubble oxygenators were later refined to serve adult patients. The Rygg–Kyvsgaard bag (Rygg and Kyvsgaard, 1956) combined the bubbling and settling chambers with a reservoir, all in one plastic bag. Sponges made of polyethylene and coated with antifoam agent were used for bubble removal. This model was manufactured in Denmark. Up to 3 L/min flows were possible. Gott and
co-workers developed a self-contained unitized plastic sheet oxygenator, and improved the DeWall–Lillehei bubble oxygenator further, which meant that the bubble oxygenator became available as a sterile sealed unit. This development played a significant role in expanding cardiac surgery beyond Minnesota (Gott et al., 1957a,b).
Naef (1990) wrote:
the home made helix reservoir bubble oxygenator of DeWall and Lillehei, first used clinically on May 13, 1955, went to conquer the world and helped many teams to embark on the correction of malformations inside the heart in a precise and unhurried manner. The road to openheart surgery had been opened.
DeWall went on to develop the bubble oxygenator further and introduced the oxygenator and omnithermic heat exchanger in a disposable and pre-sterilized polycarbonate unit (DeWall et al., 1966).With the advent of better technology, and safer operations under more controlled circumstances, surgeons were, for the first time, appreciating the intricacies of pathologic anatomy in
congenital and acquired heart disease, and leading to the development of surgical techniques in the present form.
Film oxygenators
Gibbon developed a film oxygenator with a rapidly revolving vertical cylinder. The film itself was a thin film of blood on the metal plate, where the oxygenation took place. In the first model, there was no reservoir. Gas flow included a 95 per cent oxygen and five per cent carbon dioxide mixture at 5 L/min. The venous and arterial sides of the oxygenators had roller pumps and blood passed
through tubing, which was immersed in a waterbath to maintain a constant temperature throughout the perfusion. Flows of up to 500 mL/min were generated with the initial model (Gibbon, 1937). Next, a wire mesh was introduced to produce a turbulent blood–gas interface to improve oxygenation (Gibbon, 1954). This was further improvised at the Mayo Clinic, with 14 wire meshes enclosed in a lucite case. Blood flowed onto the screens through a series of 0.6 micron slots. Gas flow was 10 L of
oxygen, and the carbon dioxide flow was varied depending on the pH of the blood (Kirklin et al., 1955).However, compared with the DeWall–Lillehei bubble oxygenator, the Mayo Clinic Gibbon film oxygenator, although impressive, was handcrafted and expensive, and difficult to use and maintain.
             Kay and Cross developed a rotating disk film oxygenator in Cleveland, USA. Although this device did become commercially available, it had serious drawbacks in terms of ease of use, massive priming volumes, and difficulty in cleaning and sterilizing (Cross et al., 1956; Kay et al., 1956).
Membrane oxygenators
By 1944,Kolff had refined a cellophane membrane apparatus for dialysis as an artificial kidney. He later tried to use this as a membrane oxygenator, but found it to be inefficient (Kolff and Berk, 1944; Kolff and Balzer, 1955). However, Clowes and Neville developed a teflon membrane oxygenator for human usage in 1957. The membrane area was 25m2, but the oxygenator was bulky with problems of sterilization and assembly (Clowes and Neville, 1957). Once silicone became available as a membrane with satisfactory permeability to both oxygen and carbon dioxide, Bramson and colleagues (Bramson et al., 1965) reported a new disposable membrane oxygenator with integral heat exchanger. This model had 14 cells, each having a silicone rubber membrane across which diffusion took place. Bodell et al. (1963) proposed the use of tubular capillary membranes instead of film, and
this notion led to the hollow-fibre membrane oxygenators. Not to be outdone, Lillehei was also associated with the availability of the first compact, disposable and commercially manufactured membrane oxygenator for clinical use (Lande et al., 1967).