Western medical historians tend to place the origin of anesthesia with the use of volatile organic solvents such as diethyl ether and chloroform, in concert with nitrous oxide, following the demonstration of diethyl ether anesthesia at Massachusetts General Hospital in 1846. While “Ether Day” (the first successful public demonstration of surgical anesthesia) is an epochal moment in surgical history, surgeons had, for centuries, sought a means to induce a pain-free state that would allow them to operate without causing excessive suffering.
Historical records indicate the use of various medicinal plants as anesthetics stretching back nearly to the beginning of recorded time, though accounts describing their efficacy are rare. There is an exception, however, in the tradition of plant-based anesthetics beginning in ancient China but finding its apotheosis in early 19th-century Japan. There are published formulae for anesthetic concoctions (a liquid mixture of various ground plants used as a medicine) from the Islamic and European medieval periods, best exemplified by “The Great Rest,” whose lengthy recipe contains mandrake and henbane, as well as opium.1
Mandrake and henbane are rich in tropane alkaloids, including recognizable pharmaceuticals such as hyoscyamine, scopolamine, and atropine. These biopharmaceuticals account for the pharmacologic effects of these potions. While such anesthetic formulae abound, there is little evidence of the clinical utility of these brews in Europe, the Middle East, or Central Asia. From the influential The Canon of Medicine by the Islamic philosopher-physician Ibn Sina (also known as Avicenna), to the influential medieval medical school of Salerno’s Antidotarium Nicolai, there are many similar recipes, but no accounts of their actual use in surgery.
Anesthesia Use in Ancient China
In Asia, however, there is evidence that herbal concoctions induced surgical anesthesia. Tradition holds that between 140 and 208 CE, corresponding to the time of Galen, Hua Tuo, a surgeon practicing in eastern China, performed visceral surgery under anesthesia using an herbal preparation he called Mafeisan.2
Recent efforts to reconstruct Hua Tuo’s recipe from medieval chronicles suggest that the difference between Hua Tuo’s concoction and those from the West was the addition of aconitum (also known as monkshood and wolfsbane). This plant contains aconite, a powerful inhibitor of voltage-dependent sodium channels, responsible for the propagation of membrane depolarization. Aconite is a powerful neurotoxin and cardiotoxin. The lethal dose of purified aconite may be as little as 1–2 mg. This risk was well-known in ancient China, with The Masters of Huainan—a second-century CE historical chronical—stating: “For all things under heaven, nothing is more vicious than the poison of aconite,” and “Yet, a good doctor packs and stores it.”3 Though limited to Asia, Mafeisan was quietly employed by Chinese surgeons for centuries. It is in modern Japan where its use is best documented.
Seishu Hanaoka, a surgeon who had studied under both European and Japanese master surgeons, knew of the Chinese tradition of Mafeisan, and in the late 18th century, set out to develop a safe and effective formula for it.4 Experimenting first on his wife and mother, Dr. Hanaoka perfected the dosing of his herbs, reprising the work of Hua Tuo nearly 2 millennia before. Once he was able to anesthetize his family members safely in clinical trials in his kitchen, he was brought the mixture to his clinic. On October 13, 1804, Dr. Hanaoka performed a partial mastectomy on a 60-year-old woman under a state of general anesthesia produced by a cocktail he called Mafutsusan. Subsequently, he and his student Gendai Kamada performed numerous procedures with Mafutsusan, though limiting themselves to mastectomy, plastic surgery, management of fractures, and amputations. Dr. Kamada would eventually publish a textbook describing the use of Mafutsusan in 1840, 6 years before “Ether Day” and 2 years before Crawford Long, MD, anesthetized James Venable in Jefferson, Georgia. In addition to describing a general anesthetic technique for the first time, this text includes a list of risk factors for poor outcomes—an early risk stratification system that was years ahead of its time.
Dr. Kamada’s illustrations of surgery featuring Mafutsusan, in some cases, suggest the successful induction of surgical anesthesia on an apparently unconscious patient (see Figure 1). But others that depict blindfolded patients restrained by large men, suggest that this technique may have had inconsistent efficacy (see Figure 2). Differences in potency of various crops of monkshood and datura flower no doubt led to variations in clinical efficacy of the mixture. The narrow therapeutic margin for aconite, where a small overdose would lead to cardiac arrest, must have made the use of Mafutsusan a difficult act of titration. This supposition is supported by Mafutsusan’s complete disappearance from Japanese surgery after the introduction of diethyl ether and chloroform in the 1840s.
However, reports of the end of Mafutsusan may have been premature. During the Cultural Revolution in China, shortages of ether led Yan Tau Wang, a surgeon at Xu Zhou Medical University, to use an herbal anesthetic recipe based on Mafutsusan. After first experimenting on himself to determine the correct ingredients and dosing, he used the herbal anesthetic in more than 46,000 surgeries, often in conjunction with the antipsychotic neuroleptic drug, Thorazine.5
Although, it is true that the greater safety and ease of administration of diethyl ether and other volatile organic substances would come to define surgical anesthesia for nearly 2 centuries, our surgical ancestors in Asia were able to induce surgical anesthesia using high-risk medicinal plants long ago, possibly as far back as the age of Galen at the beginning of the common era.
Dr. Frederick Millham is surgeon-in-chief at the South Shore Hospital in Weymouth, MA, and an associate professor of surgery at Harvard Medical School in Boston.
References
- Everett N, Gabra M, The pharmacology of medieval
sedatives: The “Great Rest” of the Antidotarium Nicoliai. J Ethnopharmacol. 2014;155(1):443-449.
- Wai FK. On Hua Tuo’s position in the history of Chinese medicine. Am J Chin Med. 2004;32(2):313-320.
- Liu Y. Poisonous medicine in ancient China. In: Wexler P, ed. History of Toxicology and Environmental Health: Toxicology in Antiquity II. London, UK: Elsevier; 2019:431-439.
- Dote K, Ikemune K, et al. Mafutsuto-Ron: The first anesthesia textbook in the world. Bibliographic review and English translation. J Anesth Hist. 2015;1(4):102-110.
- Zhao P, Yu X, Kagemoto Y. Was Mafeisan an anesthetic in ancient China? J Anesth Hist. 2018;4(3):177-181.
