|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)
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Experts have already discussed the basic principles and history of development of pulse oximeters in other sections. So, in this chapter, I provide an overview of the history of introduction of pulse oximeters in neonatal care in Japan. explain the significance of development of blood oxygen level monitors dedicated to neonates, particularly premature infants, in the context of their clinical significance in reducing the risk of retinopathy of prematurity and hypoxic brain damage.
Characteristics of medical care of neonates, particularly premature infants
Human babies, even full-term (40 weeks) infants, are born with physiological immaturity, in compensation for the large brain supporting the high level of human intelligence. This can be easily imagined from the fact that while other large mammals begin to walk independently almost immediately after birth, human neonates can just begin to hold their heads up by 3 months after birth and begin to walk alone by around the age of 1 year. In particular, in regard to respiration, gas exchange between the fetus and the maternal placenta occurs through the umbilical cord and fetuses make breathing-like movements in the womb, but pulmonary function only begins to be established at birth. Infants easily become apneic due to pulmonary immaturity, and sudden infant death syndrome (SIDS), which occurs due to delayed recovery from sleep apnea, is a well-known entity 1).
For this reason, in the history of medical care of premature infants, apnea monitors are counted as the medical devices that have contributed the most to preventing SIDS and brain damage due to hypoxia. In 1972, when I became a neonatologist, I remember that young residents, equivalent to human monitors, used to be stationed near the incubators for premature infants all day long; at present, however, the world of medical care has changed dramatically, and premature infants are monitored by pulse oximetry in every neonatal intensive care unit (NICU).
Retinopathy of prematurity and blood oxygen levels
Retinopathy of prematurity (ROP) is thought to be caused by the toxicity exerted by high concentrations of oxygen. At one time in the United States, instituting the limitation of the oxygen concentration that could be administered to premature infants to 40% decreased the incidence of ROP, but increased the frequency of brain damage occurrence, which triggered a discussion on whether it was more important to protect the eyes or the brain 2). Since, it has been revealed that ROP is caused not by high oxygen concentrations per se, but by retinal tissue ischemia induced by constriction of the retinal arteries caused by oxygen supplementation at high concentrations, which has led to a focus on the necessity of adequate measurement of the arterial blood oxygen levels. However, the partial pressure of oxygen in arterial blood, specimens of which are difficult to obtain, was not found to be correlated with the incidence of ROP. This suggests that an accurate assessment cannot be made by a single measured value of the partial pressure of oxygen, which changes continuously, but by continuous monitoring of the arterial oxygen tension. Namely, it became clear that devices that allow continuous, not intermittent, monitoring and recording of the arterial blood oxygen levels are required to prevent ROP, which has led to the development of transcutaneous partial pressure of oxygen monitors and pulse oximeters.
Widespread use of these medical devices has greatly decreased the incidence of acquired blindness in premature infants. However, at present, while many very preterm infants with a birth weight of 500 g or less (approximately 23 weeks of gestation) grow normally, ROP is encountered even in infants managed with adequate blood oxygen levels. Therefore, immaturity is at the root of the pathogenesis, and I would like to add that further studies are ongoing. ☆
From transcutaneous partial pressure of oxygen monitors to pulse oximeters
Transcutaneous partial pressure of oxygen monitors were initially developed to continuously monitor the blood oxygen levels in neonatal care, and there is the late Dr. Itsuro Yamanouchi’s interesting episode of their introduction in Japan 3). He believed that noninvasive care is important in the medical care of premature infants and developed a transcutaneous bilirubin measurement method, which has also spread from Japan to the world, together with Akio Yamanishi of Minolta Co., Ltd (who also invented the fingertip pulse oximeter, the currently commonly used type of pulse oximeter around the world).
In transcutaneous partial pressure of oxygen measurement, the skin is warmed to arterialize the capillaries and the blood partial pressure of oxygen is measured using the principle of polarography. At first, a German obstetrician, Prof. Huch, developed this device to measure fetal scalp partial pressure of oxygen, and it was Dr. Itsuro Yamanouchi who demonstrated that the device is also clinically useful for neonates, which led to its commercialization by German and Swiss companies. Thus, in contrast to pulse oximeters, transcutaneous partial pressure of oxygen monitors were developed in Europe, while their usefulness in neonates was demonstrated by Dr. Yamanouchi in Japan. However, the sensors of transcutaneous partial pressure of oxygen monitors must be replaced every 2 to 3 hours, because they could get hot (heated up to 43.5°C), and when the skin of the premature infants begins to thicken with age, the accuracy of the measurement would decrease; therefore, transcutaneous partial pressure of oxygen monitors began to be replaced by pulse oximeters of oxygen saturation monitoring. At that time, Dr. Yamanouchi was concerned that the use of pulse oximeters in neonates might be associated with a gradual increase in the incidence of ROP because, as shown in Figure, in the measurement of high blood oxygen levels, a slight difference in the arterial oxygen saturation corresponds to a large difference in the arterial partial pressure of oxygen 4). Fortunately, however, the incidence of ROP did not increase with the introduction of pulse oximeters, due to the improvement in the accuracy of pulse oximetry measurements and the careful management by nurses and other staff working in NICUs across Japan.
History of appropriate dissemination of pulse oximeters in Japanese neonatal care
As mentioned in other chapters, the principle of pulse oximetry was discovered in Japan, but Japan lagged far behind the United States in allowing its clinical application to spread as a monitor. In neonates, in particular, this is partly because transcutaneous partial pressure of oxygen monitors had already been widely introduced, and furthermore, because not only medical device manufacturers, but also medical professionals did not yet fully understand the usefulness of pulse oximeters in neonatal care.
In those days, pulse oximeters were very unpopular; physicians and nurses working in Japanese NICUs felt that pulse oximeters were useless because they were too sensitive to body motions and generated too many false alarms, and that they were unreliable as compared to transcutaneous oxygen monitors. In addition, the manufacturers themselves also had insufficient knowledge, and I remember once when I complained that I was having trouble with the breakage of the wires of the sensors attached to the hands and legs of the neonates, the electrical engineers who visited the NICU in response to my complaint, who had previously exclusively observed only anesthetized, immobilized adult patients, were astonished to observe the continuous body motions of the neonates in incubators. Furthermore, low temperature burns due to pulse oximeters, which they had bluntly said were unbelievable, were considered to result from local heat retention caused by slight wire breakage in the light-emitting part and inhibition of perfusion due to compression. Subsequently, various technical improvements have been made, and pulse oximeters have evolved to sufficiently withstand daily use in NICUs; however, the experiences with early models left a strong impression on the users, which could explain why the use of pulse oximeters has spread rather slowly in Japanese neonatal care.
Dr. Katsuyuki Miyasaka took up the mission to remove this unfavorable impression and disseminate the clinical importance of pulse oximeters in NICUs throughout Japan. Dr. Miyasaka organized the “Hakone workshop on neonatal pulse oximeters” at the Fujiya Hotel, Miyanoshita, Hakone, which is famous as one of the three major classic Japanese hotels, on July 11, 1987, to which he invited the chiefs of major NICUs across Japan. The original purpose of the workshop was to determine whether the algorithms of foreign pulse oximeter manufacturers for calculating the arterial oxygen saturation were also applicable to Japanese neonates, by comparing pulse oximeter (Omeda Biox 3700) measurements with measurements of the arterial oxygen levels made in samples collected via an arterial line, as part of the research projects of the Psychosomatic Disorder Research Neonatal Management Group of the Ministry of Health and Welfare (leader: Kazuo Okuyama, co-investigator: Hiroshi Nishida). Another purpose was to have Dr. Joyce Peabody, a neonatologist from Loma Linda University, provide a thorough explanation about the principles of blood oxygen monitors and discuss the actual status of use of pulse oximeters in NICUs in the United States, so that Japanese neonatologists could clearly understand the principles and show greater interest in the use of pulse oximeters. At that time, Dr. Miyasaka mentioned differences between functional oxygen saturation (So2) and fractional So2, from the point of view of neonatal care: methemoglobin levels increase when nitric oxide (NO) inhalation therapy is provided for persistent pulmonary hypertension of the neonate (PPHN) and the carbon monoxide (CO)-hemoglobin concentration increases with bilirubin production.
This, along with advances in the functioning of pulse oximeters, such as improvements of the measurement accuracy and simplicity of use, led to improvements in the reliability of pulse oximeters. As a result, pulse oximeters are currently used routinely to monitor the blood oxygen levels even in neonates.
In the chapter entitled “Japan’s contribution to the world in the development of blood oxygen monitors that protect the brain and eyes” in my book entitled “Trajectory of the Development of Japanese Neonatal Care (In Japanese), Medicus Shuppan Publishers, Co., Ltd., 2015,” I stated that “the historic achievements of Dr. Itsuro Yamanouchi in demonstrating the efficacy of transcutaneous partial pressure of oxygen monitors in neonates and of Dr. Takuo Aoyagi in discovering the principles of pulse oximetry, are the pride of Japan, worthy of special mention, as they have contributed to saving the lives of many neonates and preventing blindness due to ROP worldwide.” In particular, pulse oximeters are used for medical purposes in wide areas not limited to neonatal care, and Lindahl from Sweden, who was a member of the Nobel Committee and gave a keynote speech at the 1997 Annual Meeting of the Japanese Society of Pediatric Anesthesiology stated that Dr. Aoyagi’s contribution to humanity deserves a Nobel Prize. Dr. Aoyagi stated, in his letter to me (September 2017), that he was trying to obtain theoretical pulse oximetry values based on the theory of scattered light to leave his footprints as a researcher deserving it. He accomplished this task before his demise, and his achievements went down in history, although he missed the Nobel Prize.
Hiroshi Nishida, MD, PhD
Professor Emeritus, Tokyo Women’s Medical University
- Nishida, H. Why human babies sleep on their backs -What did we find from Sudden Infant Death Syndrome research and anthropological considerations?, Perinatal Medicine; 2021 , 51(1): 137-140, (in Japanese)
- Nishida, H. Scientific Basis of Clinical Neonatology, 5th ed. Japan, IGAKUSHOIN; 2019. 456p. (in Japanese)
- Nishida, H.: Dr. Yamanouchi, the person with rebellious spirit in the history of modernizing Japanese neonatal medicine, Medica Publishing Co., LTD, Osaka Japan 2015, Page 4-9 ( in Japanese)
- Delivoria-Papadopoulos M, Roncevic NP, Oski FA: Postnatal changes in oxygen transport of term, preterm and sick infants: role of red call 2,3-diphosphglicerate and adult hemoglobin. Pediatric Research 5: 235, 1971
- Miyasaka K (ed): Application of pulse oximeters in neonatal and pediatric medicine. Nihon Igakukan 1988.171p. (in Japanese)
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