Anaesth Intensive Care 2018 | 46:6
Cover note
The early history of extracorporeal membrane oxygenation
Cover photo: Theodor Kolobow (left) and Warren Zapol (right), from the
National Heart Institute (later the National Heart, Lung, and Blood Institute),
Bethesda, monitoring a fetal lamb supported by extracorporeal membrane
oxygenation, c. 1969. Image courtesy of Warren Zapol.
“There is a dual purpose in developing a mechanical heart
and lung apparatus. The first is to maintain a part of the
cardiorespiratory functions temporarily in patients with a
failing heart or lung, or both, in the hope that, with such
direct aid for a short time, these organs may be able to
resume their entire function. The second purpose is of
surgical interest.”
Bernard J. Miller, John H. Gibbon Jr and Mary H. Gibbon,
19511.
While the early pioneers of cardiopulmonary bypass (CPB)
hoped the technology could be used as a form of temporary
life support for patients with acute cardiac or respiratory
failure, initial attempts at prolonged “partial perfusion”,
using rotating disc oxygenators (in which blood was directly
exposed to oxygen) proved disappointing2-4. These “direct
contact” oxygenators caused considerable trauma to the
blood, resulting in haemolysis and protein denaturation, and
could rarely be used for more than a few hours before serious
complications occurred5.
During the mid-1950s, George Clowes Jr and colleagues
from the Department of Cardiothoracic Surgery, Cleveland
City Hospital, began to develop a new type of oxygenator to
overcome these difficulties. Reflecting on the structure of
mammalian lungs, and fish gills, it occurred to them “that
membranes ought to play a part in the thing, separating
the blood from either gas or gas containing liquid”6. Clowes
began by assessing the diffusion of oxygen and carbon
dioxide across a range of thin plastic films6,7. Ethylcellulose
Cover note
appeared to be the most promising material on the basis of
its gas permeability, but proved difficult to use in practice,
being brittle, and subject to the formation of pinholes7,8.
Polyethylene films (0.02–0.025 mm thick) were more
robust, and subsequently utilised in the construction of
an experimental membrane oxygenator, in which blood
flowed through short narrow channels between layers of
polyethylene stacked on top of one another8.
Around the same time in the nearby Cleveland Clinic,
a team led by Willem Kolff modified a recently designed
disposable haemodialyser to create an “artificial coil lung”9,10.
The idea behind this was not new. More than a decade
earlier, Kolff had been involved in the development of the
first effective “artificial kidney”11. This comprised 30 metres
of cellophane tubing wound around a rotating aluminium
cylinder, suspended over a tank of dialysis fluid. As the drum
was rotated and blood within the cellophane tubing came into
contact with aerated dialysate, Kolff observed that “oxygen is
resorbed very rapidly: already after a few windings one sees
the blue blood get red”11.
Both prototype membrane oxygenators were subject to
extensive testing on animals7-10, and by 1957, had been
trialled in the CPB circuits of adults and children undergoing
open-heart procedures in Ohio8,12. In addition, Clowes
attempted the prolonged perfusion of two adults who
could not be revived from cardiac arrest. The first patient
received central venoarterial (VA) extracorporeal membrane
oxygenation (ECMO) for a total of 63 minutes and “resumed a
normal heartbeat, but ultimately died from cerebral damage
incurred as a result of the arrest”8. The second underwent
98 minutes of perfusion, but failed to regain a spontaneous
cardiac output8.
Subsequent advances in bioengineering, including the
development of dimethylpolysiloxane (silicone rubber)
membranes13, facilitated the development of oxygenators
that could be used for days, rather than hours14-17. During
the mid–late 1960s, Theodor Kolobow and Warren Zapol,
from the National Heart Institute (later the National
Heart, Lung, and Blood Institute), Bethesda, demonstrated
prolonged survival of full-term lambs exposed to one week of
venovenous (VV) ECMO17, and the successful employment of
ECMO and parenteral nutrition to provide 55 hours of total
extrauterine support to a premature lamb fetus suspended in
a bath of synthetic amniotic fluid18.
Concomitantly, doctors at the Pacific Medical Center, San
Francisco, began using a Bramson membrane14 heart-lung
machine to provide partial VA and VV ECMO to adults with
cardiogenic shock19, or hypoxic respiratory failure refractory
555

to mechanical ventilation with 100% oxygen19,20. The
individuals treated were universally moribund at the initiation
of extracorporeal therapy, and between 1966 and 1970, there
were no long-term survivors.
In 1971, a 24-year old man was admitted to Santa
Barbara Cottage Hospital with subadventitial transection
of his thoracic aorta, as well multiple pelvic and lower limb
fractures, after being struck by a motor vehicle21. The patient
was intubated, and the aortic injury repaired through a left
thoracotomy. Both legs were placed in traction. Four days
later he developed worsening acute respiratory distress
syndrome (ARDS), and a team from the Pacific Medical Center
was flown down to assess his suitability for ECMO. On the
morning of the sixth postoperative day “it was the consensus
of the attending physicians and surgeons that conventional
therapy had been exhausted and that the patient was
dying”21. Peripheral VA ECMO was initiated using a Bramson
membrane heart-lung machine and continued for a total of 75
hours. The patient was subsequently weaned off mechanical
ventilation, and eight weeks after admission, transferred to an
orthopaedic rehabilitation unit.
The following year at the University of California, Irvine,
CA, Robert Bartlett and Alan Gazzaniga utilised partial VA
ECMO to support a two-year-old boy with cardiogenic shock
following a Mustard procedure for transposition of the great
vessels22. Three years later, the child was reported to be well,
“with no cardiac, neurologic, or renal problems”23.
Bartlett and Gazzaniga were also responsible for the first
successful use of ECMO for neonatal respiratory failure,
which was undertaken in 197523. By the end of the decade,
survival among newborns receiving extracorporeal therapy for
refractory meconium aspiration syndrome, infant respiratory
distress syndrome and persistent fetal circulation approached
50%24, and ECMO became an accepted therapy in this patient
group.
1979 saw the publication of a multicentre randomised
controlled trial comparing conventional mechanical
ventilation plus partial VA ECMO, to conventional mechanical
ventilation alone, in patients aged 12–65 years, with severe
acute respiratory failure25. Survival rates were poor in both
groups (9.5% and 8.3% respectively). As a result, interest in
ECMO for adult respiratory failure diminished, and it would be
almost a decade before significant research resumed26.
P. J. Featherstone
Addenbrooke’s Hospital, Cambridge, UK
C. M. Ball
Department of Anaesthesia and Perioperative Medicine,
Alfred Hospital, and Monash University, Melbourne, Victoria
References
1. Miller BJ, Gibbon JH, Gibbon MH. Recent advances in the
development of a mechanical heart and lung apparatus. Ann
Surg 1951; 134:694-708.
556
Anaesth Intensive Care 2018 | 46:6
2. Melrose DG, Bassett JW, Beaconsfield P, Graber IG, Shackman R.
Experimental physiology of a heart-lung machine in parallel with
normal circulation. Br Med J 1953; 2:62-66.
3. Newman MH, Stuckey JH, Levowitz BS, Young LA, Dennis C,
Fries C et al. Complete and partial perfusion of animal and
human subjects with the pump-oxygenator; a study of factors
yielding consistent survival. Successful application to one case.
Surgery 1955; 38:30-37.
4. Stuckey JH, Newman MM, Dennis C, Berg E, Goodman SE,
Fries CC et al. Partial perfusion in the treatment of selected
cases of myocardial infarction. ASAIO J 1957; 3:30-32.
5. Lim MW. The history of extracorporeal oxygenators. Anaesthesia
2006; 61:984-995.
6. Clowes GHA, Hopkins AL, Kolobow T. Oxygen diffusion through
plastic films. ASAIO J 1955; 1:23-24.
7. Clowes GHA, Hopkins AL. Further studies with plastic films and
their use in oxygenating blood. ASAIO J 1956; 2:6-12.
8. Clowes GHA, Neville WE. Further development of a blood
oxygenator dependent upon the diffusion of gases through
plastic membranes. ASAIO J 1957; 3:52-58.
9. Kolff WJ, Balzer R. The artificial coil lung. ASAIO J 1955; 1:39-42.
10. Kolff WJ, Effler DB, Groves LK, Peereboom G, Moraca PP.
Disposable membrane oxygenator (heart-lung machine) and its
use in experimental surgery. Cleve Clin J Med 1956; 23:69-97.
11. Kolff WJ, Berk HTJ, ter Welle M, van der Ley AJW, van Dijk EC,
van Noordwijk J. The artificial kidney: a dialyser with a great
area. Acta Med Scan 1944; 117:121-134.
12. Kolff WJ, Effler DB. Disposable membrane oxygenator (heart-
lung machine) and its use in experimental and clinical surgery
while the heart is arrested with potassium citrate according to
Melrose technic. ASAIO J 1956; 2:13-17.
13. Kammermeyer K. Silicone rubber as a selective barrier. Ind Eng
Chem 1957; 49:1685-1686.
14. Bramson ML, Osbourn JJ, Main FB, O’Brien MF, Wright JS,
Gerbode F. A new disposable membrane oxygenator with
integral heat exchanger. J Thorac Cardiovasc Surg 1965; 50:
391-400.
15. Landé A, Dos S, Carlson R, Porsche R, Lange R, Sonstegard L,
Lillehei CW. A new membrane oxygen-dialyzer. Surg Clin North
Am 1967; 47:1461-1466.
16. Dorson W, Baker E, Cohen ML, Meyer B, Molthan M, Trump D,
Elgas R. A perfusion system for infants. ASAIO J 1969; 15:155-160.
17. Kolobow T, Zapol W, Pierce J. High survival and minimal blood
damage in lambs exposed to long term (1 week) veno-venous
pumping with a polyurethane chamber roller pump with and
without a membrane blood oxygenator. ASAIO J 1969; 15:
172-177.
18. Zapol WM, Kolobow T, Pierce JE, Vurek GG, Bowman RL. Artificial
placenta: two days of total extrauterine support of the isolated
premature lamb fetus. Science 1969; 166:617-618.
19. Hill JD, Bramson ML, Rapaport E, Scheinman M, Osbourn JJ,
Gerbode F. Experimental and clinical experiences with prolonged
oxygenation and assisted circulation. Ann Surg 1969; 170:
448-459.
20. Hill JD, Fallat R, Cohn K, Eberhart R, Dontigny L, Bramson ML
et al. Clinical cardiopulmonary dynamics during prolonged
extracorporeal circulation for acute respiratory insufficiency.
ASAIO J 1971; 17:355-361.
Anaesth Intensive Care 2018 | 46:6 Cover note

21. Hill JD, O’Brien TG, Murray JJ, Dontigny L, Bramson ML,
Osborn JJ, Gerbode F. Prolonged extracorporeal oxygenation for
acute post-traumatic respiratory failure (shock-lung syndrome).
Use of the Bramson membrane lung. N Engl J Med 1972;
286:629-634.
22. Bartlett RH, Gazzaniga AB, Fong SW, Burns NE. Prolonged
extracorporeal cardiopulmonary support in man. J Thorac
Cardiovasc Surg 1974; 68:918-932.
23. Bartlett RH, Gazzaniga AB, Jefferies MR, Huxtable RF, Haiduc NJ,
Fong SW. Extracorporeal membrane oxygenation (ECMO)
cardiopulmonary support in infancy. ASAIO J 1976; 22:80-92.
24. Bartlett RH, Gazzaniga AB, Huxtable RH, Worcester C, Rucker R,
Wetmore N, Haiduc N. Extracorporeal membrane oxygenation
(ECMO) in newborn respiratory failure: technical consideration.
ASAIO J 1979; 25:473-475.
25. Zapol WM, Snider MT, Hill JD, Fallat RJ, Bartlett RH, Edmunds LH
et al. Extracorporeal membrane oxygenation in severe acute
respiratory failure; a randomised prospective study. JAMA 1979;
242:2193-2196.
26. Bartlett RH. ECMO Symposium; an introduction. ASAIO J 1988;
34:29-30.

557