Was Mafeisan an Anesthetic in Ancient China?

According to the Chinese historical books, Records of the Three Kingdoms () and Book of the Later Han (), Hua Tuo (, 140 - 208), a Traditional Chinese medicine (TCM) physician invented Mafeisan, an oral herbal general anesthetic, more than 1800 years ago during Eastern Han Dynasty. However, no written record of ingredients of the original Mafeisan has been found anywhere so far although there have been several similar anesthetic prescriptions published in TCM books later. There has been controversy over the existence of Mafeisan and even Hua Tuo in Chinese literature. We did extensive literature search and analysis, and believe that there indeed was Mafeisan in Hua Tuo's time.

Recent History of Publication-Based Academic Interest in General Anesthetics.

PURPOSE: The aim of this study was to determine how interest in various general anesthetics among the authors of academic publications changed over the past 50 years. METHODS: Publication-based academic interest were analyzed using specific scientometric indices: popularity index (PI), top journal selectivity index (TJSI), and index of change (IC). Terms used for searches were the names of drugs belonging to two pharmacological classes of general anesthetics - inhaled and intravenous. Only those that had a PI value > 2.0 during at least one of the 10 five-year periods, from 1967 to 2016, were selected. RESULTS: The PI, an index of comparative popularity, reflects a consistent decline in academic interest over time in both classes of general anesthetics. Over the past 25 years, the PI of inhaled anesthetics decreased by 52 %, and that of intravenous anesthetics fell by 32%. At the same time, the PI of anesthesia management increased by 167%. Among individual anesthetics, the most impressive change was a profound decline in halothane's PI, from 22.9 in 1972-1976 to 0.5 in 2012-2016. The interest in halothane was gradually supplanted by that in new agents, initially by enflurane, followed by isoflurane and finally, sevoflurane. The next meaningful change was the gradual rise in sevoflurane's PI to surpass that of isoflurane. The most dramatic change among the PIs of intravenous anesthetics was associated with the introduction of propofol: an increase from 1.8 to its maximum of 13.6. CONCLUSIONS: The study revealed a constant decline over time in academic interest in the pharmacological basis of general anesthesia relative to all fields of anesthesia combined.

Three Newly-Discovered Copies of the Manuscript Mayaku Ko, Written by Shutei Nakagawa, with Special Reference to their Appearance and Genealogy.

Seishu Hanaoka's greatest achievement was the anesthetic Mafutsusan. He developed it and then used it successfully for various operations, primarily breast cancer tumor excisions. The developmental process can be traced in Mayaku Ko, a memorandum written and edited in 1796 by Hanaoka's close friend Shutei Nakagawa. Contained in this document is a list of fourteen prescriptions for earlier attempts by other doctors to create-a general anesthetic. These prescriptions, which Nakagawa had passed along to Hanaoka, were the foundation for the scientific breakthrough. The preface suggests that Hanaoka had nearly perfected Mafutsusan by 1796. Nakagawa's original manuscript has been lost, but copies of it are extant. Until recently, we knew of four, all of them in Japan. I have discovered three more: one in the University of Tokyo Library (Gakken Collection), another in the Keio University Shinanomachi Media Center, and the third in the Asahikawa Medical University Library (Sekiba-Samejima Collection). After carefully examiiing the new ones, I put the seven known copies of Mayaku Ko into four groups, A to D, according to the order in which they were likely transcribed. One of the copies in Group A, which is from the Matsuki Collection, appears to have been the first.

Development of Mafutsusan by Seishu Hanaoka and General Anesthetics in the Very Early Part of the 19th Century in Japan.

Seishu Hanaoka's medicine is famed for its breast cancer surgery. Hanaoka, who,was motivated by Dokushoan Nagatomi's Man-yu zakki, published in 1771, had the idea to excise a breast cancer tumor and not to perform a breast amputation. Because he recognized that general anesthesia was indispensable for performing a surgical operation of the breast, he developed a general anesthetic and surmounted various difficulties: selection of an anesthetic method, anesthetic ingredients, determination of the opti- mal dosage, administration methods, indications and contra-indications, evaluation of the depth of anesthesia, facilitation of the smooth emergence from anesthesia, and postoperative care. I reviewed previous articles on these subjects and, using several unpublished manuscripts, provided new information on disseminated general anesthetics in Japan during the decade after the first general anesthesia for Kan Aiya in 1804.

Anaesthetic mechanisms: update on the challenge of unravelling the mystery of anaesthesia.

General anaesthesia is administered each day to thousands of patients worldwide. Although more than 160 years have passed since the first successful public demonstration of anaesthesia, a detailed understanding of the anaesthetic mechanism of action of these drugs is still lacking. An important early observation was the Meyer-Overton correlation, which associated the potency of an anaesthetic with its lipid solubility. This work focuses attention on the lipid membrane as a likely location for anaesthetic action. With the advent of cellular electrophysiology and molecular biology techniques, tools to dissect the components of the lipid membrane have led, in recent years, to the widespread acceptance of proteins, namely receptors and ion channels, as more likely targets for the anaesthetic effect. Yet these accumulated data have not produced a comprehensive explanation for how these drugs produce central nervous system depression. In this review, we follow the story of anaesthesia mechanisms research from its historical roots to the intensely neurophysiological research regarding it today. We will also describe recent findings that identify specific neuroanatomical locations mediating the actions of some anaesthetic agents.

Molecular targets underlying general anaesthesia.

The discovery of general anaesthesia, over 150 years ago, revolutionised medicine. The ability to render a patient unconscious and insensible to pain made modern surgery possible and general anaesthetics have become both indispensible as well as one of the most widely used class of drugs. Their extraordinary chemical diversity, ranging from simple chemically inert gases to complex barbiturates, has baffled pharmacologists, and ideas about how they might work have been equally diverse. Until relatively recently, thinking was dominated by the notion that anaesthetics acted 'nonspecifically' by dissolving in the lipid bilayer portions of nerve membranes. While this simple idea could account for the chemical diversity of general anaesthetics, it has proven to be false and it is now generally accepted that anaesthetics act by binding directly to sensitive target proteins. For certain intravenous anaesthetics, such as propofol and etomidate, the target has been identified as the GABA(A) receptor, with particular subunits playing a crucial role. For the less potent inhalational agents, the picture is less clear, although a relatively small number of targets have been identified as being the most likely candidates. In this review, I will describe the work that led up to the identification of the GABA(A) receptor as the key target for etomidate and propofol and contrast this with current progress that has been made in identifying the relevant targets for other anaesthetics, particularly the inhalational agents.

Medieval anesthesia--the spongia somnifera.

The author reviews in detail the literature concerning medieval general anesthesia in general and the so-called spongia somnifera in particular. In spite of claims to the contrary, he concludes that there is no evidence that medieval physicians had at their disposal general anesthesia for their patients undergoing surgery. On the contrary, there is evidence that the spongia somnifera was ineffective and that what kept the tradition of its effectiveness in the literature may have been the everlasting hope for surgical analgesia.

[Robert R. Macintosh and Spain: a productive relationship]. / Robert R. Macintosh y España: una relación fecunda.

Through his visit to Spain in 1946, Robert R. Macintosh exercised considerable influence on the introduction and development of modern anesthesia in this country. This paper reviews the technical advances Mackintosh introduced and considers how his visit was one of the most important factors in unleashing the development of the profession here. Also reviewed are the other visits Mackintosh made in the course of his career. Those trips were less important, with the exception of a 1937 visit that inspired the design of the Oxford vaporizer, a technical concept based on simplicity, safety and the anesthesiologist's experience.