# Evolution of ECMO

Suneel Kumar Pooboni

Received on: 30 January 2023; Accepted on: 19 February 2023; Published on: 09 March 2023

## ABSTRACT

ECMO (Extra Corporeal Membrane Oxygenation), synonymously known as ECLS (Extra Corporeal Life Assist) has been proven to be helpful in saving the lives of patients who have been critically unwell due to reversible, cardio-pulmonary failure. The knowledge and the scientific discoveries leading to the successful trials of ECMO happened over centuries. It is interesting to note how the beliefs and superstitions were replaced by proven, scientific data over millennia before we reached the latest era of working with bio-compatible materials.

Medical History has always been interesting. In this review article, I will briefly summarise the evolution of Medicine in different periods as the foundations were laid in this period.

I will narrate further concepts about the development of ECMO technology over a period of four centuries in part 2. Lastly, in Part 3, I will describe the birth and evolution of ECMO as a science and the perfection of the components of ECMO.

**Keywords:** Extra Corporeal Membrane Oxygenation, Evolution, Galen, History, Hippocrates, Sushruta.

Indian Journal of ECMO (2023): 10.5005/jaypee-journals-11011-0006

ECMO (Extra Corporeal Membrane Oxygenation), synonymously known as ECLS (Extra Corporeal Life Assist) has been proven to be helpful in saving lives of patients who have been critically unwell due to reversible, cardio-pulmonary failure. As it happens in most scientific discoveries, innumerable people put their thoughts together and worked hard for centuries. We are standing on the shoulders of great pioneers to reap the benefits of their hard work.

As we know, once the lungs or heart fails to perform it's intended function of gas exchange and perfusion to the vital organs, it is implied that the organs need rest. Nature has created the living being in an innovative way as it becomes nearly impossible to mimic. Hence researchers have been trying to find ways to understand physiology, pathology and pathophysiology to recreate the mechanisms that can be of help during this process of repair to the damaged organs. As some of the measures we use are against the mechanisms Nature has devised for us (for example, positive pressure ventilation against negative pressure ventilation) and it's subsequent ill effects inducing fibrotic changes as a result of high-pressure ventilation, researchers are continuing with their efforts in finding the best possible ways in mimicking the Nature.

Much of the understanding and development of extracorporeal support happened in the last century. Physicians and researchers have been thinking about a way forward to solve the problems concerning respiratory failure or cardiorespiratory failure. These thoughts developed over a few centuries. We shall review the histories of these pioneers contributing to the success of cardiopulmonary bypass.

Medical History has always been interesting. I would like to put forward a brief synopsis of the evolution of Medicine in different periods with a brief note on comparison to understanding the concepts of medicine in a few important cultures in part 1. I will narrate further concepts about the development of ECMO technology in part 2. Lastly, in part 3, we will talk about the birth and evolution of ECMO as a science and its components.

* Evolution of concepts and knowledge of Medicine prior to the 20th century

Consultant, Pediatric Critical Care, Mediclinic City Hospital, Dubai, UAE

**Corresponding Author:** Suneel Kumar Pooboni, Consultant, Pediatric Critical Care, Mediclinic City Hospital, Dubai, UAE, Phone: +00919642562218, e-mail: poobonisk@gmail.com

**How to cite this article:** Pooboni SK. Evolution of ECMO. Indian J ECMO 2023;1(1):5-14.

**Source of support:** Nil

**Conflict of interest:** None

* Evolution of concepts of ECMO

* Birth and Evolution of ECMO

## Part 1 – Foundations to the understanding of Human anatomy, physiology and practice of Medicine

It is amazing to learn the beliefs of physicians over centuries regarding the structure and function of the Human body. I will briefly describe the attributes of a few of the important scholars who contributed to the field of medicine till the beginning of the last century.

According to the allopathic system of medicine, we consider Hippocrates the father of modern medicine. His era dates back to 460 BC – 370 BC. His father was Hippocrates first and he was three second. Greek medicine existed before him as well. From the source of information from Soranus, it looks like Hippocrates learned the practice of medicine from his father. He was presumed to have been trained at the Asklepieion of Kos, the prestigious medical school in Greece in his time. The concepts of medicine in ancient times used to consist of beliefs regarding bad air, witchcraft, evil powers etc. Hippocrates seems to be the torch bearer to change the concepts causing illnesses as, not due to gods getting angry but attribution to some natural processes. It is possible that he thought about clinical observations and devised a classification of diseases. The Hippocratic oath is still taken by generations of physicians at the time of graduation.¹ Surprisingly, Hippocrates seems to have worked on the same principles of ancient Indian medicine, namely,
<figure><img src="image_1.png" /><figcaption>Fig. 1: Hippocrates by unidentified engraver – 1881 young persons cycloedia of persons and places. Upload by RedWolf 05:45, Jan 10, 2005 (UTC), public domain, https://commons.wikimedia.org/w/index.php?curid=164808</figcaption></figure>

black bile, yellow bile, phlegm and blood, prevalent at that time. Western medicine at the time of Hippocrates wasn't aware of the structure and function of the Human body, which happened after few centuries (Fig 1).

A brief review of the Indian literature (Ayurveda) shows some of the concepts from the Susruta Samhita, containing the information about the knowledge shared by Susruta, which appears to be before 600 BCE. This was as per the Rudolf Hoernle.² The humors, as stated above, are still part of ayurveda theory as it is being practised from ancient times. The physicians from later centuries, such as Drdhabala seems to be aware of Sushrut a Samhita. Drdhabala compiled the works of Gurus (teachers) prior to him and wrote one chapter by himself between the fourth and fifth centuries CE.³ We also knew many subjects were learnt as slokas, which were passed on from Guru (teacher) to Shishya (disciple) during these times. Sushrut a taught a number of young physicians the art of medicine for a period up to 6 years before taking up surgical training. Before commencing their training (in the period much before Hippocrates), they took a solemn oath to devote themselves to the care of humanity and to do no harm to others. It seems to be similar to Hippocratic Oath, which we adopted into our practice in current times (Fig. 2).

The students under Sushrut a seem to have learnt their surgical techniques by experimenting on vegetables and dead animals. Next step used to be, preceptorship by watching senior physicians doing the procedures. At this time they used to establish their own surgeries.⁴,⁵ Sushrut a is famous for his methods on rhinoplasty. Even in ancient days, his medical knowledge is exhibited through his writings on rhinoplasty surgery, involving nasal reconstructions using skin from the patient's forehead or cheek. From the literature, it seems that Indian medicine was at a much-advanced stage than Greek Medicine in the contemporary period (Figs 3–5).

Exchange of information and studying overseas might explain some of the similarities. It is also possible that assumptions, hypotheses and independent research might have happened at the same time in different regions of the World for the solution of medical problems. Unfortunately, an important treasure cove of knowledge, the library of Alexandria which housed close to 200000 to 700000 books from multiple countries on various subjects was

burnt around 48 BCE in the war between Ptolemy XIII and Caesar. The library was destroyed in the fire set to engulf the enemy's fleet by Caeser's army.⁶ Another important source of ancient knowledge, the library of Nalanda university, India considered by historians to be the world's first residential university⁷ and among the greatest centres of learning in the ancient world, which existed from 427 until 1197 CE was burnt down by Muhammad Bakhtiyār Khalji in 1200 CE.⁸

Reviewing the Hippocratic period shows that during his period, he brought the concept of classification of diseases as acute, chronic, epidemic and pandemic (etc.). As an evidence, we can see his description of empyema chest in terms of clinical presentation, measures that can be taken and the outcomes. If the documentation matters for the historians as evidence, his methodology stays alive even in contemporary clinical practice.⁹ Hippocrates was the first documented chest surgeon and his findings and techniques, while crude, such as the use of lead pipes to drain chest wall abscesses, were documented.¹⁰

Reviewing the Egyptian medicine with regards to the medical knowledge they have acquired is interesting. As it is evident from the mummification process, the texts described on the papyri found in various excavations besides the inscriptions on the temples stand as testimony for their knowledge about human anatomy and the treatment methodology they adopted for treating various ailments. This period dates back to approximately 3500 BC. Like Ayurveda, the Egyptian medicine describes the effects of various plants. They believed in animal products and minerals too. (Figs 6 and 7).¹¹

As per the inscriptions and the documented evidence, probably it was the ancient Egyptian medicine (3300 BCE–525 BCE) where the first principles of modern medical care have been found, including orthopaedic principles of healing fractures, simple surgical methods, setting the teeth, and the use of different sets of medicinal plants.¹² Ancient Egyptians believed in evil spirits as the cause of the ill health. They also considered other animals and people responsible for keeping humans healthy or causing disease.¹³ Egyptians had access to human dissection for the purpose of mummification. They had knowledge about the human anatomy. The papyri hold the evidence of their knowledge concerning different systems. They identified the heart function. They knew about cerebro spinal fluid too.¹⁴ They presumed that the heart was
<figure><img src="image_2.png" /><figcaption>**Fig. 2:** Susrutahhttps://wellcomeimages.org/indexplus/obf_images/d0/45/c210860bff03f531e5b1a2d4ce08.jpgGallery: https://wellcomeimages.org/indexplus/image/V0006619.htmlWellcome Collection gallery (2018-04-03): https://wellcomecollection.org/works/zqhc6qjz CC-BY-4.0, https://commons.wikimedia.org/w/index.php?curid=36422819</figcaption></figure>

originating centre for all body fluids such as blood, tears and urine.¹⁵ Unfortunately, those details couldn't be decoded until the discovery of the Rosetta stone in July 1799 and further translational work to decode hieroglyphic language was done. Much of the knowledge was understood from the papyrus, stones, clay and carvings on the walls of the temples.

Coming back to the understanding and practice of Medicine in ancient Greece, Galen was the next physician who influenced medical science. His time period was from 129 AD to 216 AD. He was considered to be one of the most accomplished of all medical researchers of antiquity. Galen persuaded the development of various scientific disciplines concerning human organ systems such as anatomy, physiology, pathology, study of medicines and neurology. Additional disciplines such as philosophy and logic as separate disciplines. Galen continued to have belief in the four humors theory as proposed by Hippocrates. Surprisingly, in the western world, Galen's views were followed as authority on

medical practice for the next 1,300 years. Human dissection was still a taboo at his time and for the next few centuries after him. His knowledge of anatomy was mainly based on dissecting Barbary apes. He dissected other animals such as pigs as well as studying humans and animals resembling humans (for dissection purpose) was forbidden. Galen's description of the human anatomy based on the dissection of animals stayed uncontested until 1543, till Vesalius published refined information based on dissections of human bodies of executed criminals in his book "De humani corporis fabrica". Galen's physiological concepts stayed the same until c. 1242 when Ibn al-Nafis published his book Sharh tashrih al-qanun li' Ibn Sina (Commentary on Anatomy in Avicenna's Canon), in which he reported the details about pulmonary circulation (Figs 8 and 9).¹⁶

## Andres Veselius

Andreas Vesalius (1514–1564) was a new era in our understanding of human anatomy. He is regarded as the great anatomist of the
<figure><img src="image_3.png" /><figcaption>**Fig. 3:** Ancient poster by Shushrutu, given in Sushrutu Samhita showing surgical instruments, in which most of them still continue to exist today. By Kaviraj Kunja Lal Bhishagratna - https://archive.org/stream/englishtranslati01susruoft#page/n5/mode/2up, Public Domain, https://commons.wikimedia.org/w/index.php?curid=46924580</figcaption></figure>
<figure><img src="image_4.png" /><figcaption>**Fig. 4:** Sushrutna operating on a patient.
Source: Painting from Anatomy department, Kurnool Medical College, Kurnool, India</figcaption></figure>

<figure><img src="image_5.png" /><figcaption>**Fig. 5:** Charak monument in yog peeth campus, Father of Medicine and Surgery by Alokprasad, Balajijagadesh - CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8124213</figcaption></figure>

16th centur. He was the author of one of the most influential books with illustrations on human anatomy, "De Humani Corporis Fabrica Libri Septem". It is based on studying human anatomy via dissections. Vesaleus got the support of rulers of his time for the supply for human cadavers for dissection purposes. This was a tremendous advance in overcoming the taboos of Galen's time. Vesalius encouraged his students to study Medicine by dissecting human bodies (Fig. 10).

The changes in the social-cultural circumstances helped Vasalius. In 1539, a judge at the Padua criminal court had been interested in Vesalius' work and sanctioned the dissection of human bodies. Hence forth, he had access to regular supply of the dead bodies of executed criminals for human dissection.¹⁷

In understanding the basics of human physiology, Galen interpreted that the arteries transported the purest blood to some of the organs such as the brain and lungs from the left ventricle of the heart, while veins passed blood to organs situated below the level of the heart such as the stomach from the right ventricle. So dominant was Galen's authority that for the next 1400 years, the physicians supported the finding of holes between the two chambers of the heart. Vesalius self-confessed

<figure><img src="image_6.png" /><figcaption>**Fig. 6:** The above inscription from Ptolemaic times was seen on the temple walls of the Temple of Kom Ombo. The inscription mentions the types of diverse medical instruments used for surgery besides the mummification process. https://commons.wikimedia.org/wiki/File:Ancient_Egyptian_medical_instruments.jpg
Jeff Dahl, CC BY-SA 3.0 https://creativecommons.org/licenses/by-sa/3.0, via Wikimedia</figcaption></figure>

that he could not find these inter-connecting holes. Nonetheless, he did not venture to dispute Galen on the distribution of blood, as he couldn't offer any other explanation. He suggested that it diffused through the unbroken partition between the two ventricles.¹⁸⁻²⁰

Then came the period of William Harvey (1578–1657). He was responsible for bringing new knowledge to the understanding of Human anatomy and physiology. He was the first known physician to describe completely, and in detail, the systemic circulation and properties of blood being pumped to the brain and the rest of the body by the heart (Fig 11).

Part 2 will follow with further concepts on evolution of ECMO.
<figure><img src="image_7.png" /><figcaption>Fig. 7: The Papyrus documents collected by Edwin Smith show ancient Egyptian awareness about the diagnostic methodology and the approach they used for treatment of various cases of traumatic injuries. This period dates to c. 1500 BC. It is unclear if it could be dated back to 3000–2500 BC as well. Jeff Dahl - EdSmPaPlateVlandVIIPrintsx.jpg</figcaption></figure>
<figure><img src="image_8.png" /><figcaption>**Fig. 8:** Portrait of Galen. (September 129 AD – c. AD 216). His teachings were uncontested in the Western Medicine for the next millennium. By Georg Paul Busch (engraver) – The Lancet, public domain, https://commons.wikimedia.org/w/index.php?curid=40855568In</figcaption></figure>
<figure><img src="image_9.png" /><figcaption>**Fig. 9:** Interpretation of Galen's understanding of human physiology by https://wellcomeimages.org/indexplus/obf_images/e4/ea/3b3191a5df9013f3a607cf06a756.jpg
Gallery: https://wellcomeimages.org/indexplus/image/M0000376.html
Wellcome Collection gallery (2018-03-29): https://wellcomecollection.org/works/sa2dbj78 CC-BY-4.0, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=36308717</figcaption></figure>
<figure><img src="image_10.png" /><figcaption>**Fig. 10:** Illustration showing the teachings of Andreas Vesalius, from the title page of the first edition of De humani corporis fabrica libri septem (AD 1543). https://www.britannica.com/biography/Andreas-Vesalius#/media/1/626818/198189</figcaption></figure>
<figure><img src="image_11.png" /><figcaption>**Fig. 11:** An illustration showing the blood circulation in Harvey's "de Motu Cordis"</figcaption></figure>

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Continues as Evolution of ECMO-Part 2 in next issue