Between Issues

Adoption of Pulse Oximetry into the JSA Anesthesia Safety Guidelines – The Brilliance of Aoyagi’s Intellectual Legacy – Talk of Nobel Prize

June 10, 2021

Shosuke Takahashi, MD
Adapted from Special Feature on Pulse Oximeters: The invention that changed the paradigm of patient safety around the world. (LiSA (1340-8836) vol28 No3 Page237-308, 2021.03 (in Japanese)

View more articles from this special collection hosted by the APSF on Pulse Oximetry and the Legacy of Dr. Takuo Aoyagi.

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When the concept of anesthesia for surgery was first introduced half a century ago, only one cardiograph was available at the operating theater, and we were checking for signs of crisis using this device in combination with visual inspection, palpation, percussion, auscultation, intermittent manual measurement of the blood pressure, and also clinical intuition. After pulse oximetry was introduced, it became possible to evaluate the status of oxygenation, ventilation, circulation, body temperature and muscle relaxation using scientific indicators, on the basis of the principle of vigilance. For example, it became possible to detect imminent cardiac arrest about 1 minute before its occurrence if arterial blood oxygen saturation (SpO2) monitoring was performed, and several minutes before its occurrence if end-tidal carbon dioxide (ETCO2) monitoring was performed, whereas the time from the detection of signs of cardiac arrest to the occurrence of cardiac arrest was only 10 seconds when electrocardiogram (ECG) monitoring was performed.


For us anesthesiologists whose mission is to protect the life of patients under conditions of body invasion, in which there may be only seconds or minutes left until the onset of a critical condition, introduction of the pulse oximeter enabling non-invasive measurement of SpO2 was a great relief, as if we had met Buddha in hell. This was a brilliant achievement which later triggered advances in the monitoring of vital signs as well. Discovery by Dr. Takuo Aoyagi, in 1974, of the principle of measurement of the arterial oxygen saturation using cardiac pulsations by pulse oximetry has contributed greatly to mankind. At first, an ear oximeter was manufactured on a trial basis for clinical application of this principle, but the device was not commercialized, and research for its commercialization suffered a setback and delay.

Nearly 10 years later, pulse oximeters with fingertip sensors were developed in the USA, followed by the rapid spread of these devices. Japan hastily introduced the devices made in the USA without laying claim to the fact that the pulse oximeter principle was first invented in Japan (by Dr. Aoyagi), until Prof. Severinghaus (University of California, San Francisco [UCSF]) publicized the fact in 1986.

I was shocked when I was informed by Prof. Michiaki Yamakage (Chief Secretary, Japan Association for Clinical Monitoring) of the death of Dr. Takuo Aoyagi on April 18, 2020. At that time, my memory of him ran like a revolving lantern, including my seeing Dr. Aoyagi while he was alive, and events related to him during the days when I was involved in spreading the clinical application of pulse oximeters. On this occasion, I would like to present some of those scenes in memory of Dr. Aoyagi, while dedicating my deep respect and gratitude to him.

Before Creation of Guidance on Monitoring for Safe Anesthesia

Tragedy of accidental erroneous inhalation of pure nitrous oxide

Surgeon: “Now, skin suturing has started. The operation will be completed in 5 minutes.”

Anesthesiologist: “So, I will initiate procedures to let the patient emerge from anesthesia.”

Nurse: “Blood pressure is 120/80, pulse rate 80, good tension.”

Anesthesiologist: “OK”

Surgeon: “Doctor, the patient looks a little pale —?”

Anesthesiologist: “Is that so? Isn’t it an effect of the light? How about the vital signs?”

Nurse: “Blood pressure is 180/100, pulse rate is 110.”

Anesthesiologist: “It’s strange. Is the patient feeling pain while emerging from anesthesia?”

Surgeon: “Finished. — Is the patient OK?”

Nurse: “Blood pressure 200/120, pulse rate 130.”

Anesthesiologist: “The patient is cyanotic! Chest motions are normal and no abnormality heard on auscultation. Strange, something is abnormal.”

Nurse: “Blood pressure is dropping – it is 60/30. Pulse rate is 40.”

Anesthesiologist: “Vasopressors! Ephedrine 1 ampule intravenous injection, also atropine – Hurry up!”

Nurse: “ECG pattern is abnormal.”

Anesthesiologist: “Xylocaine!”

Nurse: “Doctor, no pulse palpable.”

Anesthesiologist: “Pupils are dilated. Why? Cardiac massage! Infuse adrenaline! All anesthetic lines have been turned off and only oxygen is being supplied. It’s strange! Is oxygen really being supplied? — Ach!!!”

This is a conversation during a simulation of a miserable accident involving nitrous oxide. This served as a driving force for the creation of guidance on monitoring for safe anesthesia.

Operating Room Safety Management Committee (Japanese Society of Anesthesiologists)

It was in 1976 that the Operating Room Safety Management Committee was constituted within the Japanese Society of Anesthesiologists. Prof. Hideo Yamamura (University of Tokyo) served as the first chairman of this committee. Later, the role of the chairman was passed on to Professors Toyohisa Arai, Keizo Takahashi, Keninchi Kobayashi and Masahiro Suzuki in that order, and the baton was also handed at one time to the author. In those days, anesthesia was viewed unfavorably by people, and there prevailed a negative attitude about anesthesia itself being a risk factor for operation. For example, when the patient died as a result of a poor operative outcome, explanation like the following was often offered without hesitation: “The operative procedure itself was successful, but the patient failed to wake from anesthesia,” etc.

On the occasion of the 31st Conference of the Japanese Society of Anesthesiologists in 1984, a symposium titled “Towards Safer Anesthesia” was organized. This was the first meeting focusing on the safety of anesthesia in the setting of an academic conference. Around that time, I began to place great importance to the activities within the framework of the Operating Room Safety Management Committee, which eventually led to the publication of “Guidance on Monitoring for Safe Anesthesia” on April 21, 1993. The process until preparation of this guidance is described in the published monograph “Guidebook – Guidance on Monitoring for Safe Anesthesia by the Japanese Society of Anesthesiologists” (edited by Masahiro Suzuki and Toyohisa Arai, published by Kokuseido Co., Ltd., 1995). This guidance has been revised 4 times and provides easily understandable guidance while avoiding ambiguous expressions.

A survey of accident cases related to anesthesia was conducted in parallel with the creation of this guidance. At some point of time, some of the survey staff proposed that the survey be discontinued, because data collection and entry were labor-intensive. However, our definitive determination to continue with the survey was understood by successive members of the committee and the staff in charge of the survey at each leader hospital, so that the survey has been continued to date, without interruption. Analysis of the data collected during this survey have yielded significant outcomes, such as the creation of the guidance for countermeasures against massive bleeding and guidance for prevention of pulmonary embolism.

Why Was the Guidance Created So Rapidly?

Development of a concrete guidance was started at a time when standards on intraoperative monitoring were being published one after another in European countries, modeled after the standard published in 1986 by the American Society of Anesthesiologists (ASA). Needless to say, the introduction of pulse oximetry served as a driving force for these actions.

Another factor which prompted rapid creation of the guidance was the death of 2 patients caused by accidental erroneous inhalation of pure nitrous oxide at an influential national hospital in Kyushu in 1987. The episode was attributed to an error in the arrangement of the supply pipes for oxygen and nitrous oxide made during the construction of the hospital. Although the anesthesiologists involved in the care of the victims were exempted from legal responsibility, a tense atmosphere prevailed in those days at the mention of anesthesia, and we resolved to never have such accidents recur.

Preparation for Wiping out the Demon: Monitored Anesthesia Care (MAC)

In recent years, it has become mandatory for the guidance on monitoring to be followed if a test or treatment requiring anesthesia is undertaken even outside the operating room. Introduction of such a regulation is also being debated now in Japan, under the so-called MAC. If anesthesia provided without the MAC results in an adverse event, the healthcare provider concerned will be judged as “having been negligent, i.e., there is a default obligation on experts to predict the possible risks associated with a given medical act and to take steps to avoid the risks.” Simply said, invasive medical acts under environments that lack preparation for risk management are unacceptable. MAC is “a preparatory step for wiping out the demon” hidden behind medical acts. In Japan, however, reimbursement for MAC is not provided by the national health insurance system to the physicians in charge of vigilance, putting a considerably heavy burden on the healthcare providers.

Japan Association for Clinical Monitoring

When talking about Dr. Aoyagi, I cannot omit to referring to the Japan Association for Clinical Monitoring founded under the initiative of Prof. Akira Okuaki (Fukushima Prefectural Medical University). At the meetings of this association, Dr. Aoyagi often presented research data aimed at improving the precision of pulse oximeters and optimizing the cost of this device. He also made a presentation at the 7th conference of this association held in Fukuoka and was awarded the Okuaki Memorial Prize in the following year. In those days, Prof. Katsuyuki Miyasaka (National Children’s Hospital) was also actively involved as a co-researcher in the research conducted by Dr. Aoyagi. Prof. Okuaki invited researchers from varied specialties to this association to allow multidisciplinary wisdoms to debate an issue, and Dr. Aoyagi was a very valuable asset for this association. It was also impressive that Prof. Kunio Suwa (University of Tokyo), who was the best speaker on oxygen-related topics among Japanese researchers, enthusiastically suggested that the performance of Dr. Aoyagi was worthy of a Nobel Prize.

Talk of Nobel Prize

Awarded to the research on hypoxia-inducible factor (HIF)

The year 2001 was the 100th anniversary of awards of the Nobel Prize. In those days, Prof. Lindahl (Department of Anesthesiology, Karolinska Institute) was the chairman of the Nobel Committee for Physiology or Medicine. I became acquainted with him in those days and we became reasonably good friends as we were around the same age (born in 1943). Prof. Lindahl always talked passionately about the beauty and novelty of science.

We asked him to deliver a special speech at the 49th Conference of the Japanese Society of Anesthesiologists in 2002. We asked him to refer to the (1) criteria for selection of a Nobel Prize winner and (2) introduction of the research in our field that would be the worthiest of this prize, when delivering the special speech. He immediately responded to this request, saying that the answer to (1) was “good for mankind” i.e., great contribution to mankind, and to (2) was the research on biological reactions to hypoxia from the standpoint of molecular genetics. On that day at the Conference, his audience was fascinated by his smart and appealing special speech.

The Nobel Prize in Physiology or Medicine 2019 was awarded to 3 researchers, including Prof. Semenza (Johns Hopkins University), for their contribution to elucidation of the mechanism of cellular sensing and responses related to oxygen utilization. We were excited much by the Nobel Prize having been awarded for a field of research that was of interest to us. According to the special article by Prof. Kiichi Hirota (Kansai Medical University), published in the November issue of LiSA, 2019 in Japanese, these three researchers were awarded the prize for their detection and isolation of HIF as a factor, a component of the molecular mechanism involved in the induction and maintenance of erythropoietin expression, as well as elucidation of the molecular mechanism for oxygen tension-dependent HIF activity modulation. I hear that Prof. Hirota was involved in isolating the gene encoding the HIF molecule as a member of the laboratory led by Prof. Semenza.

Very broadly speaking perhaps, the connection between SpO2 and HIF can be viewed as a dialogue between oxygen and the living body during the course of external and internal respiration closely involved in homeostasis and evolution.

Criteria for Award of the Nobel Prize

During the 75 years after World War II, slightly more than 25 Japanese have been awarded the Nobel Prize. Why was Dr. Aoyagi not awarded the Nobel Prize? Prof. Kunio Suwa had pointed out on several occasions that Dr. Aoyagi deserved this prize, and Prof. Katsuyuki Miyasaka had also provided strong support for the awarding of this prize to Dr. Aoyagi. I also tried to use the best of my limited abilities for this purpose, advising Prof. Lindahl (Chairman of the Nobel Committee) that the performance of Dr. Aoyagi satisfied the criterion “good for mankind” for award of the Nobel Prize. At that time, I thought the chairman subtly told me that while his work was great, it was still some distance from deserving the Nobel Prize. However, because of my poor language abilities, I am not confident that I understood his response completely. He did seem, though, to suggest the weak points of Dr. Aoyagi, i.e., the fact that his first paper was written in Japanese and that the intellectual proprietorship of the outcome of his research had not been established by a globally valid method. It has been pointed out for many years that the basis for the protection of intellectual proprietorship is weak in Japan and that Japanese enterprises show poor capability for translating advanced technologies. I think that these shortcomings remain open issues even until date.

Despite such limitations, the greatness of Dr. Aoyagi’s performance has been steadily enriched. His research has led to submission of many applications for patent registration (linked to US patent registration), publication of papers in journals, such as Anesthesiology and Anesth Analg, and awards of many professional society prizes such as the Patent Agency Director’s Encouraging Prize, the Science and Technology Director Award, the Medal with Purple Ribbon, Gravenstein Lifetime Achievement Award of the Society for Technology in Anesthesia (USA), the Institute of Electrical and Electronic Engineers (IEEE) Medal For Innovations In Healthcare Technology, and so on. Thus, global recognition of the performance of Dr. Aoyagi has been deepening. Although not satisfying the criteria for the Nobel Prize, the intellectual relics left by Dr. Aoyagi will remain brilliant forever.


I immediately accepted the offer for writing on this topic from the LiSA Editorial Office, because I have been paying close attention to this journal since its Issue No. 0 in 1994, and because Prof. Miyasaka advised me to accept it. Soon, however, I became aware that I had disposed of the documents needed for writing on this topic during a previous attempt at decluttering that I was engaged in, in preparation for the end of my life. Nevertheless, I made efforts to delve deep into my memory, which has become somewhat unreliable, and to refer to the documents kept at Nihon Kohden Corporation, to make up for my inadequate memory, and managed this piece in memory of Dr. Aoyagi. Under these circumstances, please bear in mind that memory of some of the events may be slightly skewed. I regret that I could not refer to the activities of the Pulse Oximeter Study Group and the Vital Sign Discussion Group, both of which I had been involved with closely. However, when I completed the writing, I was confident that the magnitude of respect and gratitude that I had for Dr. Takuo Aoyagi was second to none. Although this topic deals with a short history spanning only half a century, I would be happy if young readers can learn at least something through “taking lessons from history.”

Joining my hands together in prayer for late Dr. Aoyagi


Shosuke Takahashi, MD
Professor Emeritus, Kyushu University
Medical corporation, Soseikai

Read more articles from this special collection hosted by the APSF on Pulse Oximetry and the Legacy of Dr. Takuo Aoyagi.