Attempts at producing a state of general anesthesia can be traced throughout recorded history

Recorded history

Recorded history is the period in history of the world after prehistory. It has been written down using language, or recorded using other means of communication. It starts around the 4th millennium BC, with the invention of writing.-Historical accounts:...

 in the writings of the ancient Sumer

Sumer

Sumer was a civilization and historical region in southern Mesopotamia, modern Iraq during the Chalcolithic and Early Bronze Age....

ians, Babylonia

Babylonia

Babylonia was an ancient cultural region in central-southern Mesopotamia , with Babylon as its capital. Babylonia emerged as a major power when Hammurabi Babylonia was an ancient cultural region in central-southern Mesopotamia (present-day Iraq), with Babylon as its capital. Babylonia emerged as...

ns, Assyria

Assyria

Assyria was a Semitic Akkadian kingdom, extant as a nation state from the mid–23rd century BC to 608 BC centred on the Upper Tigris river, in northern Mesopotamia , that came to rule regional empires a number of times through history. It was named for its original capital, the ancient city of Assur...

ns, Egyptians

Ancient Egypt

Ancient Egypt was an ancient civilization of Northeastern Africa, concentrated along the lower reaches of the Nile River in what is now the modern country of Egypt. Egyptian civilization coalesced around 3150 BC with the political unification of Upper and Lower Egypt under the first pharaoh...

, Greeks

Ancient Greece

Ancient Greece is a civilization belonging to a period of Greek history that lasted from the Archaic period of the 8th to 6th centuries BC to the end of antiquity. Immediately following this period was the beginning of the Early Middle Ages and the Byzantine era. Included in Ancient Greece is the...

, Romans

Ancient Rome

Ancient Rome was a thriving civilization that grew on the Italian Peninsula as early as the 8th century BC. Located along the Mediterranean Sea and centered on the city of Rome, it expanded to one of the largest empires in the ancient world....

, Indians

Indus Valley Civilization

The Indus Valley Civilization was a Bronze Age civilization that was located in the northwestern region of the Indian subcontinent, consisting of what is now mainly modern-day Pakistan and northwest India...

, and Chinese. During the Middle Ages

Middle Ages

The Middle Ages is a periodization of European history from the 5th century to the 15th century. The Middle Ages follows the fall of the Western Roman Empire in 476 and precedes the Early Modern Era. It is the middle period of a three-period division of Western history: Classic, Medieval and Modern...

, which correspond roughly to what is sometimes referred to as the Islamic Golden Age

Islamic Golden Age

During the Islamic Golden Age philosophers, scientists and engineers of the Islamic world contributed enormously to technology and culture, both by preserving earlier traditions and by adding their own inventions and innovations...

, scientists and other scholars made significant advances in science and medicine in the Muslim world

Muslim world

The term Muslim world has several meanings. In a religious sense, it refers to those who adhere to the teachings of Islam, referred to as Muslims. In a cultural sense, it refers to Islamic civilization, inclusive of non-Muslims living in that civilization...

 and Eastern world

Eastern world

__FORCETOC__The term Eastern world refers very broadly to the various cultures or social structures and philosophical systems of Eastern Asia or geographically the Eastern Culture...

, while their European counterparts also made important advances.

The European Renaissance

Renaissance

The Renaissance was a cultural movement that spanned roughly the 14th to the 17th century, beginning in Italy in the Late Middle Ages and later spreading to the rest of Europe. The term is also used more loosely to refer to the historical era, but since the changes of the Renaissance were not...

 saw significant advances in anatomy

Anatomy

Anatomy is a branch of biology and medicine that is the consideration of the structure of living things. It is a general term that includes human anatomy, animal anatomy , and plant anatomy...

 and surgical technique

Surgery

Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

. However, despite all this progress, surgery remained a treatment of last resort. Largely because of the associated pain

Pain

Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

, many patients with surgical disorders chose certain death rather than undergo surgery. Although there has been a great deal of debate as to who deserves the most credit for the discovery of general anesthesia, it is generally agreed that certain scientific discoveries in the late 18th and early 19th centuries were critical to the eventual introduction and development of modern anesthetic techniques.

Two "quantum leaps" occurred in the late 19th century, which together allowed the transition to modern

Modernity

Modernity typically refers to a post-traditional, post-medieval historical period, one marked by the move from feudalism toward capitalism, industrialization, secularization, rationalization, the nation-state and its constituent institutions and forms of surveillance...

 surgery. An appreciation of the germ theory of disease

Germ theory of disease

The germ theory of disease, also called the pathogenic theory of medicine, is a theory that proposes that microorganisms are the cause of many diseases...

 led rapidly to the development and application of antiseptic

Antiseptic

Antiseptics are antimicrobial substances that are applied to living tissue/skin to reduce the possibility of infection, sepsis, or putrefaction...

 techniques in surgery. Antisepsis, which soon gave way to asepsis

Asepsis

Asepsis is the state of being free from disease-causing contaminants or, preventing contact with microorganisms. The term asepsis often refers to those practices used to promote or induce asepsis in an operative field in surgery or medicine to prevent infection...

, reduced the overall morbidity and mortality

Mortality rate

Mortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...

 of surgery to a far more acceptable rate than in previous eras. Concurrent with these developments were the significant advances in pharmacology

Pharmacology

Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...

 and physiology

Physiology

Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...

 which led to the development of general anesthesia and the control of pain.

In the 20th century, the safety and efficacy of general anesthesia was improved by the routine use of tracheal intubation

Tracheal intubation

Tracheal intubation, usually simply referred to as intubation, is the placement of a flexible plastic or rubber tube into the trachea to maintain an open airway or to serve as a conduit through which to administer certain drugs...

 and other advanced airway management

Airway management

In cardiopulmonary resuscitation, anaesthesia, emergency medicine, intensive care medicine and first aid, airway management is the process of ensuring that:# there is an open pathway between a patient’s lungs and the outside world, and...

 techniques. Significant advances in monitoring

Medical monitor

A medical monitor or physiological monitor or display, is an electronic medical device used in medical monitoring that displays the monitored data, and may or may not have the ability to transmit the data on a monitoring network...

 and new anesthetic agents with improved pharmacokinetic

Pharmacokinetics

Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...

 and pharmacodynamic

Pharmacodynamics

Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect...

 characteristics also contributed to this trend. Finally, standardized training programs for anesthesiologist

Anesthesiologist

An anesthesiologist or anaesthetist is a physician trained in anesthesia and peri-operative medicine....

s and nurse anesthetist

Nurse anesthetist

A nurse anesthetist is a nurse who specializes in the administration of anesthesia.In the United States, a Certified Registered Nurse Anesthetist is an advanced practice registered nurse who has acquired graduate-level education and board certification in anesthesia...

s emerged during this period.

Etymology of "anesthesia"

The word "anesthesia", coined by Oliver Wendell Holmes, Sr.

Oliver Wendell Holmes, Sr.

Oliver Wendell Holmes, Sr. was an American physician, professor, lecturer, and author. Regarded by his peers as one of the best writers of the 19th century, he is considered a member of the Fireside Poets. His most famous prose works are the "Breakfast-Table" series, which began with The Autocrat...

 (1809–1894) in 1846 from the Greek

Greek language

Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...

 , an-, "without"; and , aisthēsis, "sensation"), refers to the inhibition of sensation.

Antiquity

The first attempts at general anesthesia were probably herbal remedies

Herbalism

Herbalism is a traditional medicinal or folk medicine practice based on the use of plants and plant extracts. Herbalism is also known as botanical medicine, medical herbalism, herbal medicine, herbology, herblore, and phytotherapy...

 administered in prehistory

Prehistory

Prehistory is the span of time before recorded history. Prehistory can refer to the period of human existence before the availability of those written records with which recorded history begins. More broadly, it refers to all the time preceding human existence and the invention of writing...

. Alcohol

Ethanol

Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

 is the oldest known sedative

Sedative

A sedative or tranquilizer is a substance that induces sedation by reducing irritability or excitement....

; it was used in ancient Mesopotamia

Mesopotamia

Mesopotamia is a toponym for the area of the Tigris–Euphrates river system, largely corresponding to modern-day Iraq, northeastern Syria, southeastern Turkey and southwestern Iran.Widely considered to be the cradle of civilization, Bronze Age Mesopotamia included Sumer and the...

 thousands of years ago.

Opium

It has long been written that the Sumerians cultivated and harvested the opium

Opium

Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...

 poppy (Papaver somniferum) in lower Mesopotamia as early as 3400 BC, though this has been disputed. The most ancient testimony concerning the opium poppy found to date was inscribed in cuneiform script

Cuneiform script

Cuneiform script )) is one of the earliest known forms of written expression. Emerging in Sumer around the 30th century BC, with predecessors reaching into the late 4th millennium , cuneiform writing began as a system of pictographs...

 on a small white clay tablet at the end of the third millennium BC. This tablet was discovered in 1954 during excavations at Nippur

Nippur

Nippur was one of the most ancient of all the Sumerian cities. It was the special seat of the worship of the Sumerian god Enlil, the "Lord Wind," ruler of the cosmos subject to An alone...

, and is currently kept at the University of Pennsylvania Museum of Archaeology and Anthropology

University of Pennsylvania Museum of Archaeology and Anthropology

The University of Pennsylvania Museum of Archaeology and Anthropology, commonly called The Penn Museum, is an archaeology and anthropology museum that is part of the University of Pennsylvania in the University City neighborhood of Philadelphia, Pennsylvania.-History:An internationally renowned...

. Deciphered by Samuel Noah Kramer

Samuel Noah Kramer

Samuel Noah Kramer was one of the world's leading Assyriologists and a world renowned expert in Sumerian history and Sumerian language.-Biography:...

 and Martin Leve, it is considered to be the most ancient pharmacopoeia

Pharmacopoeia

Pharmacopoeia, pharmacopeia, or pharmacopoea, , in its modern technical sense, is a book containing directions for the identification of samples and the preparation of compound medicines, and published by the authority of a government or a medical or pharmaceutical society.In a broader sense it is...

 in existence. Some Sumerian tablets of this era have an ideogram

Ideogram

An ideogram or ideograph is a graphic symbol that represents an idea or concept. Some ideograms are comprehensible only by familiarity with prior convention; others convey their meaning through pictorial resemblance to a physical object, and thus may also be referred to as pictograms.Examples of...

 inscribed upon them, "hul gil", which translates to "plant of joy", believed by some authors to refer to opium. The term gil is still used for opium in certain parts of the world. The Sumerian goddess Nidaba

Nidaba

Nanibgal , also Nisaba or Nidaba was the Sumerian goddess of writing, learning, and the harvest. Her sanctuaries were E-zagin at Eresh and at Umma. On a depiction found in Lagash, she appears with flowing hair, crowned with horned tiara bearing supporting ears of corn and a crescent moon...

 is often depicted with poppies growing out of her shoulders. About 2225 BC, the Sumerian territory became a part of the Babylonian empire. Knowledge and use of the opium poppy and its euphoric

Euphoria

Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...

 effects thus passed to the Babylonians, who expanded their empire eastwards to Persia

Iran

Iran , officially the Islamic Republic of Iran , is a country in Southern and Western Asia. The name "Iran" has been in use natively since the Sassanian era and came into use internationally in 1935, before which the country was known to the Western world as Persia...

 and westwards to Egypt, thereby extending its range to these civilizations. British archaeologist and cuneiformist Reginald Campbell Thompson

Reginald Campbell Thompson

Reginald Campbell Thompson was a British archaeologist, assyriologist, and cuneiformist. He excavated at Nineveh, Ur, Nebo and Carchemish among many other sites.He was born in Kensington, and educated at Colet Court, St...

 writes that opium was known to the Assyrians in the 7th century BC. The term "Arat Pa Pa" occurs in the Assyrian Herbal

Herbal

AThe use of a or an depends on whether or not herbal is pronounced with a silent h. herbal is "a collection of descriptions of plants put together for medicinal purposes." Expressed more elaborately — it is a book containing the names and descriptions of plants, usually with information on their...

, a collection of inscribed Assyrian tablets dated to c. 650 BC. According to Thompson, this term is the Assyrian name for the juice of the poppy and it may be the etymological

Etymology

Etymology is the study of the history of words, their origins, and how their form and meaning have changed over time.For languages with a long written history, etymologists make use of texts in these languages and texts about the languages to gather knowledge about how words were used during...

 origin of the Latin "papaver

Papaver

Papaver is a genus of 70-100 species of frost-tolerant annuals, biennials, and perennials native to temperate and cold regions of Eurasia, Africa and North America. It is the type genus of the poppy family, Papaveraceae.-Description:...

".

The ancient Egyptians were known to have had some surgical instruments, as well as certain crude analgesics and sedatives, including possibly an extract prepared from the mandrake

Mandrake (plant)

Mandrake is the common name for members of the plant genus Mandragora, particularly the species Mandragora officinarum, belonging to the nightshades family...

 fruit. The use of preparations similar to opium in surgery is recorded in the Ebers Papyrus

Ebers papyrus

The Ebers Papyrus, also known as Papyrus Ebers, is an Egyptian medical papyrus dating to circa 1550 BC. Among the oldest and most important medical papyri of ancient Egypt, it was purchased at Luxor, in the winter of 1873–74 by Georg Ebers...

, an Egyptian medical papyrus written in the Eighteenth dynasty

Eighteenth dynasty of Egypt

The eighteenth dynasty of ancient Egypt is perhaps the best known of all the dynasties of ancient Egypt...

. However, it is questionable whether opium itself was known in ancient Egypt at that time. The Greek gods Hypnos

Hypnos

In Greek mythology, Hypnos was the personification of sleep; the Roman equivalent was known as Somnus. His twin was Thánatos ; their mother was the primordial goddess Nyx . His palace was a dark cave where the sun never shines. At the entrance were a number of poppies and other hypnogogic plants...

 (Sleep), Nyx

Nyx

In Greek mythology, Nyx was the primordial goddess of the night. A shadowy figure, Nyx stood at or near the beginning of creation, and was the mother of personified gods such as Hypnos and Thánatos...

 (Night), and Thanatos

Thanatos

In Greek mythology, Thanatos was the daemon personification of death. He was a minor figure in Greek mythology, often referred to but rarely appearing in person...

 (Death) were often depicted holding poppies.

Prior to the introduction of opium to ancient India

Indus Valley Civilization

The Indus Valley Civilization was a Bronze Age civilization that was located in the northwestern region of the Indian subcontinent, consisting of what is now mainly modern-day Pakistan and northwest India...

 and China, these civilizations pioneered the use of cannabis

Cannabis

Cannabis is a genus of flowering plants that includes three putative species, Cannabis sativa, Cannabis indica, and Cannabis ruderalis. These three taxa are indigenous to Central Asia, and South Asia. Cannabis has long been used for fibre , for seed and seed oils, for medicinal purposes, and as a...

 incense

Incense

Incense is composed of aromatic biotic materials, which release fragrant smoke when burned. The term "incense" refers to the substance itself, rather than to the odor that it produces. It is used in religious ceremonies, ritual purification, aromatherapy, meditation, for creating a mood, and for...

 and aconitum

Aconitum

Aconitum , known as aconite, monkshood, wolfsbane, leopard's bane, women's bane, Devil's helmet or blue rocket, is a genus of over 250 species of flowering plants belonging to the buttercup family .-Overview:These herbaceous perennial plants are chiefly natives of the mountainous parts of the...

. c. 400 BC, the Sushruta Samhita

Sushruta Samhita

The Sushruta Samhita is a Sanskrit text, attributed to one Sushruta, foundational to Ayurvedic medicine , with innovative chapters on surgery....

 (a text from the Indian subcontinent

Indian subcontinent

The Indian subcontinent, also Indian Subcontinent, Indo-Pak Subcontinent or South Asian Subcontinent is a region of the Asian continent on the Indian tectonic plate from the Hindu Kush or Hindu Koh, Himalayas and including the Kuen Lun and Karakoram ranges, forming a land mass which extends...

 on ayurvedic medicine

Ayurveda

Ayurveda or ayurvedic medicine is a system of traditional medicine native to India and a form of alternative medicine. In Sanskrit, words , meaning "longevity", and , meaning "knowledge" or "science". The earliest literature on Indian medical practice appeared during the Vedic period in India,...

 and surgery) advocates the use of wine

Wine

Wine is an alcoholic beverage, made of fermented fruit juice, usually from grapes. The natural chemical balance of grapes lets them ferment without the addition of sugars, acids, enzymes, or other nutrients. Grape wine is produced by fermenting crushed grapes using various types of yeast. Yeast...

 with incense of cannabis for anesthesia. By the 8th century AD, Arab traders had brought opium to India and China.

China

Bian Que (Chinese

Chinese character

Chinese characters are logograms used in the writing of Chinese and Japanese , less frequently Korean , formerly Vietnamese , or other languages...

: 扁鹊, Wade–Giles: Pien Ch'iao, c. 300 BC) was a legendary Chinese internist

Internal medicine

Internal medicine is the medical specialty dealing with the prevention, diagnosis, and treatment of adult diseases. Physicians specializing in internal medicine are called internists. They are especially skilled in the management of patients who have undifferentiated or multi-system disease processes...

 and surgeon who reportedly used general anesthesia for surgical procedures. It is recorded in the Book of Master Han Fei

Han Feizi (book)

The Han Feizi is a work written by Han Feizi at the end of the Warring States Period in China, detailing his political philosophy. It belongs to the Legalist school of thought....

(c. 250 BC), the Records of the Grand Historian

Records of the Grand Historian

The Records of the Grand Historian, also known in English by the Chinese name Shiji , written from 109 BC to 91 BC, was the Magnum opus of Sima Qian, in which he recounted Chinese history from the time of the Yellow Emperor until his own time...

(c. 100 BC), and the Book of Master Lie

Liezi

The Liezi is a Daoist text attributed to Lie Yukou, a circa 5th century BCE Hundred Schools of Thought philosopher, but Chinese and Western scholars believe it was compiled around the 4th century CE.-Textual history:...

(c. AD 300) that Bian Que gave two men, named "Lu" and "Chao", a toxic drink which rendered them unconscious for three days, during which time he performed a gastrostomy

Gastrostomy

Gastrostomy refers to a surgical opening into the stomach. Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression....

 upon them.

Hua Tuo

Hua Tuo

Hua Tuo was an ancient Chinese physician who lived during the late Han Dynasty and Three Kingdoms era of Chinese history. The Records of Three Kingdoms and Book of Later Han record Hua as the first person in China to use anesthesia during surgery. He used a general anesthetic combining wine with a...

 (Chinese

Chinese character

Chinese characters are logograms used in the writing of Chinese and Japanese , less frequently Korean , formerly Vietnamese , or other languages...

:华佗， c. AD 145-220) was a Chinese surgeon

Surgeon

In medicine, a surgeon is a specialist in surgery. Surgery is a broad category of invasive medical treatment that involves the cutting of a body, whether human or animal, for a specific reason such as the removal of diseased tissue or to repair a tear or breakage...

 of the 2nd century AD. According to the Records of Three Kingdoms

Records of Three Kingdoms

Records of Three Kingdoms , is regarded as the official and authoritative historical text on the Three Kingdoms period of Chinese history covering the years 184-280 CE. Written by Chen Shou in the 3rd century, the work combines the smaller histories of the rival states of Cao Wei , Shu Han and...

(c. AD 270) and the Book of the Later Han (c. AD 430), Hua Tuo performed surgery under general anesthesia using a formula he had developed by mixing wine with a mixture of herbal extract

Herbal extract

Tincture is a liquid solution of herbs and a fluid menstruum, usually ethanol. The dried or fresh herbs are combined with alcohol, then the solid matter is removed leaving only the oils of the herbs mixed with the alcohol...

s he called mafeisan (麻沸散). Hua Tuo reportedly used mafeisan to perform even major operations such as resection

Segmental resection

Segmental resection is a surgical procedure to remove part of an organ or gland. It may also be used to remove a tumor and normal tissue around it. In lung cancer surgery, segmental resection refers to removing a section of a lobe of the lung.- External links :* entry in the public domain NCI...

 of gangrenous

Gangrene

Gangrene is a serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies . This may occur after an injury or infection, or in people suffering from any chronic health problem affecting blood circulation. The primary cause of gangrene is reduced blood...

 intestines. Before the surgery, he administered an oral anesthetic potion

Potion

A potion is a consumable medicine or poison.In mythology and literature, a potion is usually made by a magician, sorcerer, dragon, fairy or witch and has magical properties. It might be used to heal, bewitch or poison people...

, probably dissolved in wine, in order to induce a state of unconsciousness

Unconsciousness

Unconsciousness is the condition of being not conscious—in a mental state that involves complete or near-complete lack of responsiveness to people and other environmental stimuli. Being in a comatose state or coma is a type of unconsciousness. Fainting due to a drop in blood pressure and a...

 and partial neuromuscular blockade

Neuromuscular-blocking drug

Neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished either by acting presynaptically via the inhibition of acetylcholine synthesis or release or by acting postsynaptically at the...

.

The exact composition of mafeisan, similar to all of Hua Tuo's clinical knowledge, was lost when he burned his manuscripts, just before his death. The composition of the anesthetic powder was not mentioned in either the Records of Three Kingdoms or the Book of the Later Han. Because Confucian

Confucianism

Confucianism is a Chinese ethical and philosophical system developed from the teachings of the Chinese philosopher Confucius . Confucianism originated as an "ethical-sociopolitical teaching" during the Spring and Autumn Period, but later developed metaphysical and cosmological elements in the Han...

 teachings regarded the body as sacred

Sacred

Holiness, or sanctity, is in general the state of being holy or sacred...

 and surgery was considered a form of body mutilation, surgery was strongly discouraged in ancient China. Because of this, despite Hua Tuo's reported success with general anesthesia, the practice of surgery in ancient China ended with his death.

The name mafeisan combines ma (麻, meaning "cannabis, hemp

Hemp

Hemp is mostly used as a name for low tetrahydrocannabinol strains of the plant Cannabis sativa, of fiber and/or oilseed varieties. In modern times, hemp has been used for industrial purposes including paper, textiles, biodegradable plastics, construction, health food and fuel with modest...

, numbed

Anesthesia

Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...

 or tingling

Paresthesia

Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...

"), fei (沸, meaning "boiling

Boiling

Boiling is the rapid vaporization of a liquid, which occurs when a liquid is heated to its boiling point, the temperature at which the vapor pressure of the liquid is equal to the pressure exerted on the liquid by the surrounding environmental pressure. While below the boiling point a liquid...

 or bubbling"), and san (散, meaning "to break up or scatter", or "medicine in powder form"). Therefore, the word mafeisan probably means something like "cannabis boil powder". Many sinologist

Sinology

Sinology in general use is the study of China and things related to China, but, especially in the American academic context, refers more strictly to the study of classical language and literature, and the philological approach...

s and scholars of traditional Chinese medicine

Traditional Chinese medicine

Traditional Chinese Medicine refers to a broad range of medicine practices sharing common theoretical concepts which have been developed in China and are based on a tradition of more than 2,000 years, including various forms of herbal medicine, acupuncture, massage , exercise , and dietary therapy...

 have guessed at the composition of Hua Tuo's mafeisan powder, but the exact components still remain unclear. His formula is believed to have contained some combination of:

• bai zhi (Chinese
  Chinese character
  Chinese characters are logograms used in the writing of Chinese and Japanese , less frequently Korean , formerly Vietnamese , or other languages...
  
  :白芷，Angelica dahurica
  Angelica
  Angelica is a genus of about 60 species of tall biennial and perennial herbs in the family Apiaceae, native to temperate and subarctic regions of the Northern Hemisphere, reaching as far North as Iceland and Lapland...
  
  ),
• cao wu (Chinese
  Chinese character
  Chinese characters are logograms used in the writing of Chinese and Japanese , less frequently Korean , formerly Vietnamese , or other languages...
  
  :草烏, Aconitum kusnezoffii, Aconitum kusnezoffii
  Aconitum
  Aconitum , known as aconite, monkshood, wolfsbane, leopard's bane, women's bane, Devil's helmet or blue rocket, is a genus of over 250 species of flowering plants belonging to the buttercup family .-Overview:These herbaceous perennial plants are chiefly natives of the mountainous parts of the...
  
  , Kusnezoff's monkshood, or wolfsbane root),
• chuān xiōng (Chinese
  Chinese character
  Chinese characters are logograms used in the writing of Chinese and Japanese , less frequently Korean , formerly Vietnamese , or other languages...
  
  :川芎，Ligusticum wallichii
  Ligusticum wallichii
  Ligusticum wallichii is a flowering plant in the carrot family best known for its use in traditional Chinese medicine where it is considered one of the 50 fundamental herbs. It is known by the common names chuānxiōng and Szechuan lovage....
  
  , or Szechuan lovage),
• dong quai (Chinese
  Chinese character
  Chinese characters are logograms used in the writing of Chinese and Japanese , less frequently Korean , formerly Vietnamese , or other languages...
  
  :当归,Angelica sinensis
  Angelica sinensis
  Angelica sinensis, commonly known as "dong quai" or "female ginseng" is a herb from the family Apiaceae, indigenous to China.-Chinese:...
  
  , or "female ginseng
  Ginseng
  Ginseng is any one of eleven species of slow-growing perennial plants with fleshy roots, belonging to the genus Panax of the family Araliaceae....
  
  "),
• wu tou (烏頭, Aconitum carmichaelii
  Aconitum carmichaelii
  Aconitum carmichaelii is a flowering plant species native to East Asia, particularly in China and Japan. It is commonly known as Chinese Aconite, Carmichael's Monkshood and Chinese Wolfsbane...
  
  , rhizome of Aconitum, or Chinese monkshood"),
• yang jin hua (洋金花, Flos Daturae metelis, or Datura stramonium
  Datura stramonium
  Datura stramonium, known by the common names Jimson weed, devil's trumpet, devil's weed, thorn apple, tolguacha, Jamestown weed, stinkweed, locoweed, datura, pricklyburr, devil's cucumber, Hell's Bells, moonflower and, in South Africa, malpitte and mad seeds, is a common weed in the...
  
  , jimson weed, devil's trumpet, thorn apple, locoweed, moonflower),
• ya pu lu (Mandragora officinarum
  Mandragora officinarum
  Mandragora officinarum is a species of the plant genus mandrake. It has a variety of medicinal uses, especially anodyne and soporific, though in the past much of the use was due to superstition.-Physical characteristics:...
  
  )
• rhododendron
  Rhododendron
  Rhododendron is a genus of over 1 000 species of woody plants in the heath family, most with showy flowers...
  
   flower, and
• jasmine
  Jasmine
  Jasminum , commonly known as jasmines, is a genus of shrubs and vines in the olive family . It contains around 200 species native to tropical and warm temperate regions of the Old World...
  
   root.

Others have suggested the potion may have also contained hashish

Hashish

Hashish is a cannabis preparation composed of compressed stalked resin glands, called trichomes, collected from the unfertilized buds of the cannabis plant. It contains the same active ingredients but in higher concentrations than unsifted buds or leaves...

, bhang

Bhang

Bhang is a preparation from the leaves and flowers of the female cannabis plant, smoked or consumed as a beverage in the Indian subcontinent.- India:...

, shang-luh, or opium. Victor H. Mair

Victor H. Mair

Victor Henry Mair is a Philologist specializing in Sinitic and Indo-European languages, and holds the position of Professor of Chinese Language and Literature in the Department of East Asian Languages and Civilizations at the University of Pennsylvania, Philadelphia, United States...

 wrote that mafei "appears to be a transcription of some Indo-European

Indo-European languages

The Indo-European languages are a family of several hundred related languages and dialects, including most major current languages of Europe, the Iranian plateau, and South Asia and also historically predominant in Anatolia...

 word related to "morphine"." Some authors believe that Hua Tuo may have discovered surgical analgesia by acupuncture

Acupuncture

Acupuncture is a type of alternative medicine that treats patients by insertion and manipulation of solid, generally thin needles in the body....

, and that mafeisan either had nothing to do with or was simply an adjunct to his strategy for anesthesia. Many physicians have attempted to re-create the same formulation based on historical records but none have achieved the same clinical efficacy as Hua Tuo's. In any event, Hua Tuo's formula did not appear to be effective for major operations.

Other substances used from antiquity for anesthetic purposes include extracts of juniper

Juniper

Junipers are coniferous plants in the genus Juniperus of the cypress family Cupressaceae. Depending on taxonomic viewpoint, there are between 50-67 species of juniper, widely distributed throughout the northern hemisphere, from the Arctic, south to tropical Africa in the Old World, and to the...

 and coca

Coca

Coca, Erythroxylum coca, is a plant in the family Erythroxylaceae, native to western South America. The plant plays a significant role in many traditional Andean cultures...

.

Middle Ages and Renaissance

Arabic and Persian physicians may have been among the first to utilize oral as well as inhaled anesthetics

Inhalational anaesthetic

An inhalational anaesthetic is a chemical compound possessing general anaesthetic properties that can be delivered via inhalation. They are administered by anaesthetists through an anaesthesia mask, laryngeal mask airway or tracheal tube connected to some type of anaesthetic vaporiser and an...

. Ferdowsi

Ferdowsi

Ferdowsi was a highly revered Persian poet. He was the author of the Shahnameh, the national epic of Iran and related societies.The Shahnameh was originally composed by Ferdowsi for the princes of the Samanid dynasty, who were responsible for a revival of Persian cultural traditions after the...

 (940–1020) was a Persian

Persian people

The Persian people are part of the Iranian peoples who speak the modern Persian language and closely akin Iranian dialects and languages. The origin of the ethnic Iranian/Persian peoples are traced to the Ancient Iranian peoples, who were part of the ancient Indo-Iranians and themselves part of...

 poet

Poet

A poet is a person who writes poetry. A poet's work can be literal, meaning that his work is derived from a specific event, or metaphorical, meaning that his work can take on many meanings and forms. Poets have existed since antiquity, in nearly all languages, and have produced works that vary...

 who lived in the Abbasid Caliphate. In Shahnameh

Shahnameh

The Shahnameh or Shah-nama is a long epic poem written by the Persian poet Ferdowsi between c.977 and 1010 AD and is the national epic of Iran and related societies...

, his national epic

National epic

A national epic is an epic poem or a literary work of epic scope which seeks or is believed to capture and express the essence or spirit of a particular nation; not necessarily a nation-state, but at least an ethnic or linguistic group with aspirations to independence or autonomy...

 poem, Ferdowsi described a caesarean section

Caesarean section

A Caesarean section, is a surgical procedure in which one or more incisions are made through a mother's abdomen and uterus to deliver one or more babies, or, rarely, to remove a dead fetus...

 performed on Rudaba

Rudaba

Rūdāba or Roodabeh is a Persian mythological female figure in Ferdowsi's epic Shahnameh. She is the princess of Kabul, daughter of Mehrab Kaboli, and later she becomes married to Zal, as they become lovers. They had two children, including Rostam, the main hero of the Shahnama.-Etymology:The word...

. A special wine prepared by a Zoroastrian

Zoroastrianism

Zoroastrianism is a religion and philosophy based on the teachings of prophet Zoroaster and was formerly among the world's largest religions. It was probably founded some time before the 6th century BCE in Greater Iran.In Zoroastrianism, the Creator Ahura Mazda is all good, and no evil...

 priest was used as an anesthetic for this operation. Although Shahnameh is fictional, the passage nevertheless supports the idea that general anesthesia had at least been described in ancient Persia, even if not successfully implemented.

In 1000, Abu al-Qasim al-Zahrawi (936-1013), an Arab physician who lived in Al-Andalus

Al-Andalus

Al-Andalus was the Arabic name given to a nation and territorial region also commonly referred to as Moorish Iberia. The name describes parts of the Iberian Peninsula and Septimania governed by Muslims , at various times in the period between 711 and 1492, although the territorial boundaries...

, published the 30-volume Kitab al-Tasrif

Al-Tasrif

The Kitab al-Tasrif was an Arabic encyclopedia on medicine and surgery, written near the year 1000 by Abu al-Qasim al-Zahrawi...

, the first illustrated work on surgery. In this book, he wrote about the use of general anesthesia for surgery. c. 1020, Ibn Sīnā

Avicenna

Abū ʿAlī al-Ḥusayn ibn ʿAbd Allāh ibn Sīnā , commonly known as Ibn Sīnā or by his Latinized name Avicenna, was a Persian polymath, who wrote almost 450 treatises on a wide range of subjects, of which around 240 have survived...

 (980–1037) described the use of inhaled anesthesia in The Canon of Medicine

The Canon of Medicine

The Canon of Medicine is an encyclopedia of Galenic medicine in five books compiled by Ibn Sīnā and completed in 1025. It presents a clear and organized summary of all the medical knowledge of the time...

. The Canon described the "soporific sponge", a sponge imbued with aromatics

Aromaticity

In organic chemistry, Aromaticity is a chemical property in which a conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibit a stabilization stronger than would be expected by the stabilization of conjugation alone. The earliest use of the term was in an article by August...

 and narcotic

Narcotic

The term narcotic originally referred medically to any psychoactive compound with any sleep-inducing properties. In the United States of America it has since become associated with opioids, commonly morphine and heroin and their derivatives, such as hydrocodone. The term is, today, imprecisely...

s, which was to be placed under a patient's nose during surgical operations. Ibn Zuhr

Ibn Zuhr

Abū Merwān ’Abdal-Malik ibn Zuhr was a Muslim physician, surgeon and teacher in Al-Andalus.He was born at Seville...

 (1091–1161) was another Arab physician from Al-Andalus. In his 12th century medical textbook Al-Taisir, Ibn Zuhr describes the use of general anesthesia. These three physicians were among many who performed operations under inhaled anesthesia with the use of narcotic-soaked sponges. Opium made its way from Asia Minor to all parts of Europe between the 10th and 13th centuries.

Alchemist

Alchemy

Alchemy is an influential philosophical tradition whose early practitioners’ claims to profound powers were known from antiquity. The defining objectives of alchemy are varied; these include the creation of the fabled philosopher's stone possessing powers including the capability of turning base...

 Ramon Llull

Ramon Llull

Ramon Llull was a Majorcan writer and philosopher, logician and tertiary Franciscan. He wrote the first major work of Catalan literature. Recently-surfaced manuscripts show him to have anticipated by several centuries prominent work on elections theory...

 has been credited with discovering diethyl ether

Diethyl ether

Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...

 in 1275. Aureolus Theophrastus Bombastus von Hohenheim (1493–1541), better known as Paracelsus

Paracelsus

Paracelsus was a German-Swiss Renaissance physician, botanist, alchemist, astrologer, and general occultist....

, discovered the analgesic

Analgesic

An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....

 properties of diethyl ether around 1525. It was first synthesized in 1540 by Valerius Cordus

Valerius Cordus

Valerius Cordus was a German physician and botanist who authored one of the greatest pharmacopoeias and one of the most celebrated herbals in history...

, who noted some of its medicinal properties. He called it oleum dulce vitrioli, a name that reflects the fact that it is synthesized by distilling a mixture of ethanol and sulfuric acid

Sulfuric acid

Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...

 (known at that time as oil of vitriol). August Sigmund Frobenius

August Sigmund Frobenius

August Sigmund Frobenius , FRS, also known as Sigismond Augustus Frobenius, Joannes Sigismundus Augustus Frobenius, and Johann Sigismund August Froben, was a German-born chemist in the 18th century who is known for the first detailed description of the properties of diethyl ether and the naming of...

 gave the name aether to the substance in 1730.

18th century

Joseph Priestley

Joseph Priestley

Joseph Priestley, FRS was an 18th-century English theologian, Dissenting clergyman, natural philosopher, chemist, educator, and political theorist who published over 150 works...

 (1733–1804) was an English polymath

Polymath

A polymath is a person whose expertise spans a significant number of different subject areas. In less formal terms, a polymath may simply be someone who is very knowledgeable...

 who discovered nitrous oxide

Nitrous oxide

Nitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula . It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...

, nitric oxide

Nitric oxide

Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...

, ammonia

Ammonia

Ammonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...

, hydrogen chloride

Hydrogen chloride

The compound hydrogen chloride has the formula HCl. At room temperature, it is a colorless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric humidity. Hydrogen chloride gas and hydrochloric acid are important in technology and industry...

 and (along with Carl Wilhelm Scheele

Carl Wilhelm Scheele

Carl Wilhelm Scheele was a German-Swedish pharmaceutical chemist. Isaac Asimov called him "hard-luck Scheele" because he made a number of chemical discoveries before others who are generally given the credit...

 and Antoine Lavoisier

Antoine Lavoisier

Antoine-Laurent de Lavoisier , the "father of modern chemistry", was a French nobleman prominent in the histories of chemistry and biology...

) oxygen

Oxygen

Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...

. Beginning in 1775, Priestley published his research in Experiments and Observations on Different Kinds of Air

Experiments and Observations on Different Kinds of Air

Experiments and Observations on Different Kinds of Air is a six-volume work published by 18th-century British polymath Joseph Priestley which reports a series of his experiments on "airs" or gases, most notably his discovery of oxygen gas .-Airs:While working as a companion for Lord Shelburne,...

, a six-volume work. The recent discoveries about these and other gas

Gas

Gas is one of the three classical states of matter . Near absolute zero, a substance exists as a solid. As heat is added to this substance it melts into a liquid at its melting point , boils into a gas at its boiling point, and if heated high enough would enter a plasma state in which the electrons...

es stimulated a great deal of interest in the European scientific community. Thomas Beddoes

Thomas Beddoes

Thomas Beddoes , English physician and scientific writer, was born at Shifnal in Shropshire. He was a reforming practitioner and teacher of medicine, and an associate of leading scientific figures. Beddoes was a friend of Samuel Taylor Coleridge, and, according to E. S...

 (1760–1808) was an English philosopher

Philosophy

Philosophy is the study of general and fundamental problems, such as those connected with existence, knowledge, values, reason, mind, and language. Philosophy is distinguished from other ways of addressing such problems by its critical, generally systematic approach and its reliance on rational...

, physician and teacher of medicine, and like his older colleague Priestley, was also a member of the Lunar Society of Birmingham. With an eye toward making further advances in this new science as well as offering treatment for diseases previously thought to be untreatable (such as asthma

Asthma

Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

 and tuberculosis

Tuberculosis

Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

), Beddoes founded the Pneumatic Institution

Pneumatic Institution

The Pneumatic Institution was a medical research facility in Bristol, England, in 1799–1802. It was established by physician and science writer Thomas Beddoes to study the medical effects of the gases that had recently been discovered...

for inhalation gas therapy in 1798 at Dowry Square

Dowry Square

Dowry Square is in the Hotwells area of Bristol.It was laid out in 1727 by George Tully and building continued until 1750. The houses are three-storeyed with attics, simply detailed and with channelled pilasters to the party walls....

 in Clifton, Bristol

Clifton, Bristol

Clifton is a suburb of the City of Bristol in England, and the name of both one of the city's thirty-five council wards. The Clifton ward also includes the areas of Cliftonwood and Hotwells...

. Beddoes employed chemist

Chemist

A chemist is a scientist trained in the study of chemistry. Chemists study the composition of matter and its properties such as density and acidity. Chemists carefully describe the properties they study in terms of quantities, with detail on the level of molecules and their component atoms...

 and physicist Humphry Davy

Humphry Davy

Sir Humphry Davy, 1st Baronet FRS MRIA was a British chemist and inventor. He is probably best remembered today for his discoveries of several alkali and alkaline earth metals, as well as contributions to the discoveries of the elemental nature of chlorine and iodine...

 (1778–1829) as superintendent of the institute, and engineer

Engineer

An engineer is a professional practitioner of engineering, concerned with applying scientific knowledge, mathematics and ingenuity to develop solutions for technical problems. Engineers design materials, structures, machines and systems while considering the limitations imposed by practicality,...

 James Watt

James Watt

James Watt, FRS, FRSE was a Scottish inventor and mechanical engineer whose improvements to the Newcomen steam engine were fundamental to the changes brought by the Industrial Revolution in both his native Great Britain and the rest of the world.While working as an instrument maker at the...

 (1736–1819) to help manufacture the gases. Other members of the Lunar Society such as Erasmus Darwin

Erasmus Darwin

Erasmus Darwin was an English physician who turned down George III's invitation to be a physician to the King. One of the key thinkers of the Midlands Enlightenment, he was also a natural philosopher, physiologist, slave trade abolitionist,inventor and poet...

 and Josiah Wedgwood

Josiah Wedgwood

Josiah Wedgwood was an English potter, founder of the Wedgwood company, credited with the industrialization of the manufacture of pottery. A prominent abolitionist, Wedgwood is remembered for his "Am I Not A Man And A Brother?" anti-slavery medallion. He was a member of the Darwin–Wedgwood family...

 were also actively involved with the institute.

During the course of his research at the Pneumatic Institution, Davy discovered the anesthetic properties of nitrous oxide. Davy, who coined the term "laughing gas" for nitrous oxide, published his findings the following year in the now-classic treatise

Treatise

A treatise is a formal and systematic written discourse on some subject, generally longer and treating it in greater depth than an essay, and more concerned with investigating or exposing the principles of the subject.-Noteworthy treatises:...

, Researches, chemical and philosophical–chiefly concerning nitrous oxide or dephlogisticated nitrous air, and its respiration. Davy was not a physician, and he never administered nitrous oxide during a surgical procedure. He was however the first to document the analgesic effects of nitrous oxide, as well as its potential benefits in relieving pain during surgery:

Eastern hemisphere

Hanaoka Seishū

Hanaoka Seishu

was a Japanese surgeon of the Edo period with a knowledge of Chinese herbal medicine, as well as Western surgical techniques he had learned through Rangaku...

 (華岡 青洲, 1760–1835) of Osaka

Osaka

is a city in the Kansai region of Japan's main island of Honshu, a designated city under the Local Autonomy Law, the capital city of Osaka Prefecture and also the biggest part of Keihanshin area, which is represented by three major cities of Japan, Kyoto, Osaka and Kobe...

 was a Japanese surgeon of the Edo period

Edo period

The , or , is a division of Japanese history which was ruled by the shoguns of the Tokugawa family, running from 1603 to 1868. The political entity of this period was the Tokugawa shogunate....

 with a knowledge of Chinese herbal medicine

Chinese herbology

Chinese Herbology is the theory of Traditional Chinese herbal therapy, which accounts for the majority of treatments in Traditional Chinese medicine ....

, as well as Western surgical techniques he had learned through Rangaku

Rangaku

Rangaku is a body of knowledge developed by Japan through its contacts with the Dutch enclave of Dejima, which allowed Japan to keep abreast of Western technology and medicine in the period when the country was closed to foreigners, 1641–1853, because of the Tokugawa shogunate’s policy of national...

(literally "Dutch learning", and by extension "Western learning"). Beginning in about 1785, Hanaoka embarked on a quest to re-create a compound that would have pharmacologic properties similar to Hua Tuo's mafeisan. After years of research and experimentation, he finally developed a formula which he named tsūsensan (also known as mafutsu-san). Like that of Hua Tuo, this compound was composed of extracts of several different plants, including:

• 2 parts bai zhi (Chinese
  Chinese character
  Chinese characters are logograms used in the writing of Chinese and Japanese , less frequently Korean , formerly Vietnamese , or other languages...
  
  :白芷，Angelica dahurica);
• 2 parts cao wu (Chinese
  Chinese character
  Chinese characters are logograms used in the writing of Chinese and Japanese , less frequently Korean , formerly Vietnamese , or other languages...
  
  :草烏，Aconitum sp., monkshood or wolfsbane);
• 2 parts chuān ban xia (Pinellia ternata
  Pinellia ternata
  Pinellia ternata , crow-dipper, is a plant native to China, but also grows as an invasive weed in parts of North America. The leaves are trifoliate, while the flowers are of the spathe and spadix form typical of plants in Araceae.-Characteristics:The plant spreads by rhizomes, and there are also...
  
  );
• 2 parts chuān xiōng (Ligusticum wallichii, Cnidium rhizome, Cnidium officinale or Szechuan lovage);
• 2 parts dong quai (Angelica sinensis or female ginseng
  Ginseng
  Ginseng is any one of eleven species of slow-growing perennial plants with fleshy roots, belonging to the genus Panax of the family Araliaceae....
  
  );
• 1 part tian nan xing (Arisaema rhizomatum
  Arisaema
  Arisaema is a genus of about 150 species in the flowering plant family Araceae, native to eastern and central Africa, Asia and eastern North America. Its species are often called Cobra lilies, particularly the Asiatic species...
  
  or cobra lily)
• 8 parts yang jin hua (Datura stramonium, Korean morning glory, thorn apple, jimson weed, devil's trumpet, stinkweed, or locoweed).

The reader will note that five of these seven ingredients were thought to be elements of Hua Tuo's anesthetic potion, 1600 years earlier. Some sources claim that Angelica archangelica

Garden Angelica

Angelica archangelica, commonly known as Garden Angelica, Holy Ghost, Wild Celery, and Norwegian angelica, is a biennial plant from the Apiaceae family Apiaceae family, formerly known as Umbelleferae...

(often referred to as garden angelica, holy ghost, or wild celery) was also an ingredient.

The active ingredients in tsūsensan are scopolamine

Scopolamine

Scopolamine, also known as levo-duboisine, and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects. It is among the secondary metabolites of plants from Solanaceae family of plants, such as henbane, jimson weed and Angel's Trumpets , and corkwood...

, hyoscyamine

Hyoscyamine

Hyoscyamine is a tropane alkaloid. It is a secondary metabolite found in certain plants of the Solanaceae family, including henbane , mandrake , jimsonweed , tomato and deadly nightshade...

, atropine

Atropine

Atropine is a naturally occurring tropane alkaloid extracted from deadly nightshade , Jimson weed , mandrake and other plants of the family Solanaceae. It is a secondary metabolite of these plants and serves as a drug with a wide variety of effects...

, aconitine

Aconitine

Aconitine is a highly poisonous alkaloid derived from various aconite species.-Uses:...

 and angelicotoxin. When consumed in sufficient quantity, tsūsensan produces a state of general anesthesia and skeletal muscle

Skeletal muscle

Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

 paralysis

Paralysis

Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...

. Shutei Nakagawa (1773–1850), a close friend of Hanaoka, wrote a small pamphlet entitled "Mayaku-ko" ("narcotic powder") in 1796. Although the original manuscript was lost in a fire in 1867, this brochure described the current state of Hanaoka's research on general anesthesia.

On 13 October 1804, Hanaoka performed a partial mastectomy

Mastectomy

Mastectomy is the medical term for the surgical removal of one or both breasts, partially or completely. Mastectomy is usually done to treat breast cancer; in some cases, women and some men believed to be at high risk of breast cancer have the operation prophylactically, that is, to prevent cancer...

 for breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

 on a 60 year old woman named Kan Aiya, using tsūsensan as a general anesthetic. This is generally regarded today as the first reliable documentation of an operation to be performed under general anesthesia. Hanaoka went on to perform many operations using tsūsensan, including resection of malignant tumor

Tumor

A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...

s, extraction of bladder stones

Urolithiasis

A bladder stone is a solid concretion or crystal aggregation found in the urinary bladder...

, and extremity amputation

Amputation

Amputation is the removal of a body extremity by trauma, prolonged constriction, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on individuals as a preventative surgery for...

s. Before his death in 1835, Hanaoka performed more than 150 operations for breast cancer.

Western hemisphere

Friedrich Sertürner

Friedrich Sertürner

Friedrich Wilhelm Adam Sertürner was a German pharmacist, who discovered morphine in 1804.-Biography:He was born on 19 June 1783 in Neuhaus ....

 (1783–1841) first isolated morphine

Morphine

Morphine is a potent opiate analgesic medication and is considered to be the prototypical opioid. It was first isolated in 1804 by Friedrich Sertürner, first distributed by same in 1817, and first commercially sold by Merck in 1827, which at the time was a single small chemists' shop. It was more...

 from opium

Opium

Opium is the dried latex obtained from the opium poppy . Opium contains up to 12% morphine, an alkaloid, which is frequently processed chemically to produce heroin for the illegal drug trade. The latex also includes codeine and non-narcotic alkaloids such as papaverine, thebaine and noscapine...

 in 1806; he named it morphine after Morpheus, the Greek god of dreams.

Henry Hill Hickman

Henry Hill Hickman

Henry Hill Hickman was born to tenant farmers at Lady Halton, . He was the seventh of thirteen children....

 (1800–1830) experimented with the use of carbon dioxide

Carbon dioxide

Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

 as an anesthetic in the 1820s. He would make the animal insensible, effectively via almost suffocating it with carbon dioxide, then determine the effects of the gas by amputating one of its limbs. In 1824, Hickman submitted his the results of his research to the Royal Society

Royal Society

The Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...

 in a short treatise entitled Letter on suspended animation: with the view of ascertaining its probable utility in surgical operations on human subjects. The response was an 1826 article in The Lancet

The Lancet

The Lancet is a weekly peer-reviewed general medical journal. It is one of the world's best known, oldest, and most respected general medical journals...

 titled 'Surgical Humbug' that ruthlessly criticised his work. Hickman died four years later at age 30. Though he was unappreciated at the time of his death, his work has since been positively reappraised and he is now recognised as one of the fathers of anesthesia.

By the late 1830s, Humphry Davy's experiments had become widely publicized within academic circles in the northeastern United States. Wandering lecturers would hold public gatherings, referred to as "ether frolics", where members of the audience were encouraged to inhale diethyl ether or nitrous oxide to demonstrate the mind-altering properties of these agents while providing much entertainment to on­lookers. Four notable men participated in these events and witnessed the use of ether in this manner. They were William Edward Clarke (1819–1898), Crawford Long

Crawford Long

Crawford Williamson Long was an American surgeon and pharmacist best known for his first use of inhaled diethyl ether as an anesthetic...

 (1815–1878), Horace Wells

Horace Wells

Horace Wells was an American dentist who pioneered the use of anaesthesia in dentistry, specifically nitrous oxide .-Life:...

 (1815–1848), and William T. G. Morton (1819–1868).

While attending undergraduate school in Rochester, New York in 1839, classmates Clarke and Morton apparently participated in ether frolics with some regularity. In January 1842, by now a medical student at Berkshire Medical College

University of Vermont College of Medicine

The University of Vermont College of Medicine is an American medical school located in Burlington, Vermont and associated with the University of Vermont . Established in 1822, it is the nation's seventh oldest medical school...

, Clarke administered ether to a Miss Hobbie, while Elijah Pope performed a dental extraction. In so doing, he became the first to administer an inhaled anesthetic to facilitate the performance of a surgical procedure. Clarke apparently thought little of his accomplishment, and chose neither to publish nor to pursue this technique any further. Indeed, this event is not even mentioned in Clarke's biography.

Crawford Long was a physician and pharmacist practicing in Jefferson, Georgia

Jefferson, Georgia

Jefferson is a city in Jackson County, Georgia, United States. The population was 3,825 at the 2000 census. The city is the county seat of Jackson County. Jefferson is known for its superior recreation department...

 in the mid-19th century. During his time as a student at the University of Pennsylvania School of Medicine

University of Pennsylvania School of Medicine

The Perelman School of Medicine , formerly the University of Pennsylvania School of Medicine, was founded in 1765, making it the oldest American medical school. As part of the University of Pennsylvania, it is located in the University City section of Philadelphia, Pennsylvania. It is widely...

 in the late 1830s, he had observed and probably participated in the ether frolics that had become popular at that time. At these gatherings, Long observed that some participants experienced bumps and bruises, but afterward had no recall of what had happened. He postulated that that diethyl ether produced pharmacologic effects similar to those of nitrous oxide. On 30 March 1842, he administered diethyl ether by inhalation to a man named James Venable, in order to remove a tumor from the man's neck. Long later removed a second tumor from Venable, under ether anesthesia. He went on to employ ether as a general anesthetic for limb amputations and parturition

Childbirth

Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...

. Long however did not publish his experience until 1849, thereby denying himself much of the credit he deserved.

On 10 December 1844, Gardner Quincy Colton

Gardner Quincy Colton

Gardner Quincy Colton was an American showman, lecturer, and former medical student who pioneered the use of nitrous oxide in dentistry....

 held a public demonstration of nitrous oxide in Hartford, Connecticut. One of the participants, Samuel A. Cooley, sustained a significant injury to his leg while under the influence of nitrous oxide without noticing the injury. Horace Wells, a Connecticut dentist present in the audience that day, immediately seized upon the significance of this apparent analgesic effect of nitrous oxide. The following day, Wells underwent a painless dental extraction while under the influence of nitrous oxide administered by Colton. Wells then began to administer nitrous oxide to his patients, successfully performing several dental extractions over the next couple of weeks.

William T. G. Morton, another New England

New England

New England is a region in the northeastern corner of the United States consisting of the six states of Maine, New Hampshire, Vermont, Massachusetts, Rhode Island, and Connecticut...

 dentist, was a former student and then-current business partner of Wells. He was also a former acquaintance and classmate of William Edward Clarke (the two had attended undergraduate school together in Rochester, New York). Morton arranged for Wells to demonstrate his technique for dental extraction under nitrous oxide general anesthesia at Massachusetts General Hospital

Massachusetts General Hospital

Massachusetts General Hospital is a teaching hospital and biomedical research facility in the West End neighborhood of Boston, Massachusetts...

, in conjunction with the prominent surgeon John Collins Warren

John Collins Warren

John Collins Warren , of Boston, was one of the most renowned American surgeons of the 19th century. In 1846 he gave permission to William T.G. Morton to provide ether anesthesia while Warren performed a minor surgical procedure...

. This demonstration, which took place on 20 January 1845, ended in failure when the patient cried out in pain in the middle of the operation.

On 30 September 1846, Morton administered diethyl ether to Eben Frost, a music teacher from Boston

Boston

Boston is the capital of and largest city in Massachusetts, and is one of the oldest cities in the United States. The largest city in New England, Boston is regarded as the unofficial "Capital of New England" for its economic and cultural impact on the entire New England region. The city proper had...

, for a dental extraction. Two weeks later, Morton became the first to publicly demonstrate the use of diethyl ether as a general anesthetic at Massachusetts General Hospital, in what is known today as the Ether Dome

Ether Dome

The Ether Dome is an amphitheater in the Bulfinch Building at Massachusetts General Hospital in Boston. It served as the hospital's operating room from its opening in 1821 until 1867. It was the site of the first use of inhaled ether as a surgical anesthetic on 16 October 1846. William Thomas...

. On 16 October 1846, John Collins Warren removed a tumor from the neck of a local printer, Edward Gilbert Abbott

Edward Gilbert Abbott

Edward Gilbert Abbott was the patient upon whom William TG Morton first publicly demonstrated the use of ether as a surgical anesthetic. The operation was done in an amphitheater at the Massachusetts General Hospital now known as the Ether Dome on 16 October 1846. After Morton administered the...

. Upon completion of the procedure, Warren reportedly quipped, "Gentlemen, this is no humbug." News of this event rapidly traveled around the world. Morton published his experience that year. Harvard University

Harvard University

Harvard University is a private Ivy League university located in Cambridge, Massachusetts, United States, established in 1636 by the Massachusetts legislature. Harvard is the oldest institution of higher learning in the United States and the first corporation chartered in the country...

 professor Charles Thomas Jackson

Charles Thomas Jackson

Charles Thomas Jackson was an American physician and scientist who was active in medicine, chemistry, mineralogy, and geology.- Life and work :...

 (1805–1880) later claimed that Morton stole his idea; Morton disagreed and a lifelong dispute began. For many years, Morton was credited as being the pioneer of general anesthesia in the Western hemisphere, despite the fact that his demonstration occurred four years after Long's initial experience. Long later petitioned William Crosby Dawson

William Crosby Dawson

William Crosby Dawson was a lawyer, judge, politician, and soldier from Georgia.-Early life, education and legal career:...

 (1798–1856), a United States Senator from Georgia at that time, to support his claim on the floor of the United States Senate

United States Senate

The United States Senate is the upper house of the bicameral legislature of the United States, and together with the United States House of Representatives comprises the United States Congress. The composition and powers of the Senate are established in Article One of the U.S. Constitution. Each...

 as the first to use ether anesthesia.

In 1847, Scottish obstetrician

Obstetrics

Obstetrics is the medical specialty dealing with the care of all women's reproductive tracts and their children during pregnancy , childbirth and the postnatal period...

 James Young Simpson

James Young Simpson

Sir James Young Simpson was a Scottish doctor and an important figure in the history of medicine. Simpson discovered the anaesthetic properties of chloroform and successfully introduced it for general medical use....

 (1811–1870) of Edinburgh

Edinburgh

Edinburgh is the capital city of Scotland, the second largest city in Scotland, and the eighth most populous in the United Kingdom. The City of Edinburgh Council governs one of Scotland's 32 local government council areas. The council area includes urban Edinburgh and a rural area...

 was the first to use chloroform

Chloroform

Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...

 as a general anesthetic. The use of chloroform anesthesia expanded rapidly thereafter in Europe. Chloroform began to replace ether as an anesthetic in the United States at the beginning of the 20th century. It was soon abandoned in favor of ether when its hepatic

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 and cardiac

Heart

The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

 toxicity

Toxicity

Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...

, especially its tendency to cause potentially fatal cardiac dysrhythmia

Cardiac dysrhythmia

Cardiac dysrhythmia is any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow, and may be regular or irregular.Some arrhythmias are life-threatening medical emergencies that can result in cardiac...

s, became apparent.

In 1871, the German surgeon Friedrich Trendelenburg

Friedrich Trendelenburg

Friedrich Trendelenburg was a German surgeon. He was son of the philosopher Friedrich Adolf Trendelenburg, father of the pharmacologist Paul Trendelenburg and grandfather of the pharmacologist Ullrich Georg Trendelenburg.Trendelenburg was born in Berlin and studied medicine at the University of...

 (1844–1924) published a paper describing the first successful elective

Choice

Choice consists of the mental process of judging the merits of multiple options and selecting one of them. While a choice can be made between imagined options , often a choice is made between real options, and followed by the corresponding action...

 human tracheotomy

Tracheotomy

Among the oldest described surgical procedures, tracheotomy consists of making an incision on the anterior aspect of the neck and opening a direct airway through an incision in the trachea...

 to be performed for the purpose of administration of general anesthesia.

In 1880, the Scottish surgeon William Macewen

William Macewen

Sir William Macewen, CB, FRS, was a Scottish surgeon. He was a pioneer in modern brain surgery and contributed to the development of bone graft surgery, the surgical treatment of hernia and of pneumonectomy .-Career:Macewen was born near Port Bannatyne, Isle of Bute, Scotland in 1848 and studied...

 (1848–1924) reported on his use of orotracheal intubation as an alternative to tracheotomy to allow a patient with glottic edema to breathe, as well as in the setting of general anesthesia with chloroform

Chloroform

Chloroform is an organic compound with formula CHCl3. It is one of the four chloromethanes. The colorless, sweet-smelling, dense liquid is a trihalomethane, and is considered somewhat hazardous...

. All previous observations of the glottis and larynx (including those of Manuel García

Manuel Patricio Rodríguez García

Manuel Patricio Rodríguez García , was a Spanish singer, music educator, and vocal pedagogue.-Biography:García was born on 17 March 1805 in the town of Zafra in Badajoz Province, Spain. His father was singer and teacher Manuel del Pópulo Vicente Rodriguez García...

, Wilhelm Hack and Macewen) had been performed under indirect vision (using mirrors) until 23 April 1895, when Alfred Kirstein (1863–1922) of Germany first described direct visualization of the vocal cords. Kirstein performed the first direct laryngoscopy in Berlin, using an esophagoscope he had modified for this purpose; he called this device an autoscope. The death of Emperor Frederick III

Frederick III, German Emperor

Frederick III was German Emperor and King of Prussia for 99 days in 1888, the Year of the Three Emperors. Friedrich Wilhelm Nikolaus Karl known informally as Fritz, was the only son of Emperor William I and was raised in his family's tradition of military service...

 (1831–1888) may have motivated Kirstein to develop the autoscope.

20th century

The 20th century saw the transformation of the practices of tracheotomy, endoscopy

Endoscopy

Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...

 and non-surgical tracheal intubation from rarely employed procedures to essential components of the practices of anesthesia, critical care medicine, emergency medicine

Emergency medicine

Emergency medicine is a medical specialty in which physicians care for patients with acute illnesses or injuries which require immediate medical attention. While not usually providing long-term or continuing care, emergency medicine physicians diagnose a variety of illnesses and undertake acute...

, gastroenterology

Gastroenterology

Gastroenterology is the branch of medicine whereby the digestive system and its disorders are studied. The name is a combination of three Ancient Greek words gaster , enteron , and logos...

, pulmonology and surgery.

In 1902, Hermann Emil Fischer

Hermann Emil Fischer

Hermann Emil Fischer, Emil Fischer was a German chemist and 1902 recipient of the Nobel Prize in Chemistry. He discovered the Fischer esterification. He developed the Fischer projection, a symbolic way of drawing asymmetric carbon atoms.-Early years:Fischer was born in Euskirchen, near Cologne,...

 (1852–1919) and Joseph von Mering

Joseph von Mering

Josef, Baron von Mering was a German physician.Working at the University of Strasbourg, Mering was the first person to discover that one of the pancreatic functions is the production of insulin, a hormone which controls blood sugar levels.Mering was curious about the...

 (1849–1908) discovered that diethylbarbituric acid

Barbital

Barbital , also called barbitone, was the first commercially marketed barbiturate. It was used as a sleeping aid from 1903 until the mid-1950s. The chemical names for barbital are diethylmalonyl urea or diethylbarbituric acid...

 was an effective hypnotic

Hypnotic

Hypnotic drugs are a class of psychoactives whose primary function is to induce sleep and to be used in the treatment of insomnia and in surgical anesthesia...

 agent. Also called barbital or Veronal (the trade name

Trade name

A trade name, also known as a trading name or a business name, is the name which a business trades under for commercial purposes, although its registered, legal name, used for contracts and other formal situations, may be another....

 assigned to it by Bayer Pharmaceuticals

Bayer

Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...

), this new drug became the first commercially marketed barbiturate

Barbiturate

Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...

; it was used as a treatment for insomnia

Insomnia

Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...

 from 1903 until the mid-1950s.

Until 1913, oral and maxillofacial surgery

Oral and maxillofacial surgery

Oral and maxillofacial surgery is surgery to correct a wide spectrum of diseases, injuries and defects in the head, neck, face, jaws and the hard and soft tissues of the oral and maxillofacial region. It is an internationally recognized surgical specialty...

 was performed by mask inhalation anesthesia

Inhalational anaesthetic

An inhalational anaesthetic is a chemical compound possessing general anaesthetic properties that can be delivered via inhalation. They are administered by anaesthetists through an anaesthesia mask, laryngeal mask airway or tracheal tube connected to some type of anaesthetic vaporiser and an...

, topical application of local anesthetic

Local anesthetic

A local anesthetic is a drug that causes reversible local anesthesia, generally for the aim of having local analgesic effect, that is, inducing absence of pain sensation, although other local senses are often affected as well...

s to the mucosa

Mucous membrane

The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

, rectal anesthesia, or intravenous

Intravenous therapy

Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...

 anesthesia. While otherwise effective, these techniques did not protect the airway from obstruction and also exposed patients to the risk of pulmonary aspiration of blood and mucus

Mucus

In vertebrates, mucus is a slippery secretion produced by, and covering, mucous membranes. Mucous fluid is typically produced from mucous cells found in mucous glands. Mucous cells secrete products that are rich in glycoproteins and water. Mucous fluid may also originate from mixed glands, which...

 into the tracheobronchial tree. In 1913, Chevalier Jackson

Chevalier Jackson

Chevalier Jackson was a laryngologist.Jackson was born in Pittsburgh, Pennsylvania. He went to school at the Western University of Pennsylvania from 1879 to 1883, and received his MD from Jefferson Medical College. He also studied laryngology in England.His work reduced the risks involved in a...

 (1865–1958) was the first to report a high rate of success for the use of direct laryngoscopy as a means to intubate the trachea. Jackson introduced a new laryngoscope blade that had a light source at the distal tip, rather than the proximal light source used by Kirstein. This new blade incorporated a component that the operator could slide out to allow room for passage of an endotracheal tube or bronchoscope.

Also in 1913, Henry H. Janeway (1873–1921) published results he had achieved using a laryngoscope he had recently developed. An American anesthesiologist practicing at Bellevue Hospital

Bellevue Hospital Center

Bellevue Hospital Center, most often referred to as "Bellevue", was founded on March 31, 1736 and is the oldest public hospital in the United States. Located on First Avenue in the Kips Bay neighborhood of Manhattan, New York City, Bellevue is famous from many literary, film and television...

 in New York City

New York City

New York is the most populous city in the United States and the center of the New York Metropolitan Area, one of the most populous metropolitan areas in the world. New York exerts a significant impact upon global commerce, finance, media, art, fashion, research, technology, education, and...

, Janeway was of the opinion that direct intratracheal insufflation

Insufflation (medicine)

Insufflation is the practice of inhaling a substance. Insufflation has limited medical use, but is a common route of administration with many respiratory drugs used to treat conditions in the lungs and paranasal sinus .The technique is common for many recreational drugs and is also used for some...

 of volatile anesthetics would provide improved conditions for otolaryngologic

Otolaryngology

Otolaryngology or ENT is the branch of medicine and surgery that specializes in the diagnosis and treatment of ear, nose, throat, and head and neck disorders....

 surgery. With this in mind, he developed a laryngoscope designed for the sole purpose of tracheal intubation. Similar to Jackson's device, Janeway's instrument incorporated a distal light source. Unique however was the inclusion of batteries

Battery (electricity)

An electrical battery is one or more electrochemical cells that convert stored chemical energy into electrical energy. Since the invention of the first battery in 1800 by Alessandro Volta and especially since the technically improved Daniell cell in 1836, batteries have become a common power...

 within the handle, a central notch in the blade for maintaining the tracheal tube in the midline of the oropharynx during intubation and a slight curve to the distal tip of the blade to help guide the tube through the glottis. The success of this design led to its subsequent use in other types of surgery. Janeway was thus instrumental in popularizing the widespread use of direct laryngoscopy and tracheal intubation in the practice of anesthesiology.

Sodium thiopental

Sodium thiopental

Sodium thiopental, better known as Sodium Pentothal , thiopental, thiopentone sodium, or Trapanal , is a rapid-onset short-acting barbiturate general anaesthetic...

, the first intravenous anesthetic, was synthesized in 1934 by Ernest H. Volwiler

Ernest H. Volwiler

Ernest Henry Volwiler spent his entire career at Abbott Laboratories working his way from staff chemist to CEO....

 (1893–1992) and Donalee L. Tabern (1900–1974), working for Abbott Laboratories

Abbott Laboratories

Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....

. It was first used in humans on 8 March 1934 by Ralph M. Waters in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia. Three months later, John Silas Lundy

John Silas Lundy

John Silas Lundy was an American physician and anesthesiologist who established the first post-anesthesia recovery room and the first blood bank in the United States.-References:...

 started a clinical trial of thiopental at the Mayo Clinic

Mayo Clinic

Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...

 at the request of Abbott Laboratories. Volwiler and Tabern were awarded U.S. Patent No. 2,153,729 in 1939 for the discovery of thiopental, and they were inducted into the National Inventors Hall of Fame in 1986.

In 1939, the search for a synthetic substitute for atropine culminated serendipitously in the discovery of meperidine, the first opiate with a structure altogether different from that of morphine. This was followed in 1946 by the synthesis of methadone, another structurally unrelated compound with pharmacological properties similar to those of morphine.

After World War I

World War I

World War I , which was predominantly called the World War or the Great War from its occurrence until 1939, and the First World War or World War I thereafter, was a major war centred in Europe that began on 28 July 1914 and lasted until 11 November 1918...

, further advances were made in the field of intratracheal anesthesia. Among these were those made by Sir Ivan Whiteside Magill

Ivan Magill

Sir Ivan Whiteside Magill was an Irish born anaesthetist who is famous for his involvement in much of the innovation and development in modern anaesthesia....

 (1888–1986). Working at the Queen's Hospital for Facial and Jaw Injuries

Frognal House

Frognal House, in Foots Cray near Sidcup, Greater London, England, was built in the early 18th century.-History:Frognal House was purchased by Thomas Townshend in 1752 and became the residence of his son, Thomas Townshend, 1st Viscount Sydney, after whom Sydney, Australia was named...

 in Sidcup

Sidcup

Sidcup is a district in South East London in the London Borough of Bexley and small parts of the district in the London Borough of Greenwich.Located south east of Charing Cross, Sidcup is bordered by the London Boroughs of Greenwich and Bromley and Kent County Council, and whilst now part of...

 with plastic surgeon Sir Harold Gillies

Harold Gillies

Sir Harold Delf Gillies was a New Zealand-born, and later London based, otolaryngologist who is widely considered as the father of plastic surgery.-Personal life:Gillies was born in Dunedin, New Zealand...

 (1882–1960) and anesthetist E. Stanley Rowbotham (1890–1979), Magill developed the technique of awake blind nasotracheal intubation. Magill devised a new type of angulated forceps (the Magill forceps) that are still used today to facilitate nasotracheal intubation in a manner that is little changed from Magill's original technique. Other devices invented by Magill include the Magill laryngoscope blade, as well as several apparati for the administration of volatile anesthetic agents. The Magill curve of an endotracheal tube is also named for Magill.

The first hospital anesthesia department was established at the Massachusetts General Hospital in 1936, under the leadership of Henry K. Beecher

Henry K. Beecher

Henry Knowles Beecher was an important figure in the history of anesthesiology and medicine, receiving awards and honors during his career. His 1966 article on unethical practices in medical experimentation within the New England Journal of Medicine was instrumental in the implementation of...

 (1904–1976).

Sir Robert Reynolds Macintosh

Robert Reynolds Macintosh

Sir Robert Reynolds Macintosh was a New Zealand-born anaesthetist. He was the first Professor of Anaesthetics outside United States.-Early life:...

 (1897–1989) achieved significant advances in techniques for tracheal intubation when he introduced his new curved laryngoscope blade in 1943. The Macintosh blade remains to this day the most widely used laryngoscope blade for orotracheal intubation. In 1949, Macintosh published a case report describing the novel use of a gum elastic urinary catheter as an endotracheal tube introducer to facilitate difficult tracheal intubation. Inspired by Macintosh's report, P. Hex Venn (who was at that time the anesthetic advisor to the British firm Eschmann Bros. & Walsh, Ltd.) set about developing an endotracheal tube introducer based on this concept. Venn's design was accepted in March 1973, and what became known as the Eschmann endotracheal tube introducer went into production later that year. The material of Venn's design was different from that of a gum elastic bougie in that it had two layers: a core of tube woven from polyester

Polyester

Polyester is a category of polymers which contain the ester functional group in their main chain. Although there are many polyesters, the term "polyester" as a specific material most commonly refers to polyethylene terephthalate...

 threads and an outer resin

Resin

Resin in the most specific use of the term is a hydrocarbon secretion of many plants, particularly coniferous trees. Resins are valued for their chemical properties and associated uses, such as the production of varnishes, adhesives, and food glazing agents; as an important source of raw materials...

 layer. This provided more stiffness but maintained the flexibility and the slippery surface. Other differences were the length (the new introducer was 60 cm (23.6 in), which is much longer than the gum elastic bougie) and the presence of a 35° curved tip, permitting it to be steered around obstacles.

Many new intravenous and inhalational anesthetics were developed and brought into clinical use during the second half of the 20th century. Paul Janssen

Paul Janssen

Paul Adriaan Jan, Baron Janssen was the founder of Janssen Pharmaceutica, a pharmaceutical company with over 20,000 employees. In 2005 he finished as runner up, after Father Damien, in the poll for The Greatest Belgian organized by the regional Flemish television...

 (1926–2003), the founder of Janssen Pharmaceutica

Janssen Pharmaceutica

Janssen Pharmaceutica is pharmaceutical company, established in Belgium in 1953 by Paul Janssen. Its headquarters are located in Beerse, in the Campine region of the province of Antwerp, Belgium. It was created not as a subsidiary of a chemical factory but solely with the aim of conducting...

, is credited with the development of over 80 pharmaceutical compounds. Janssen synthesized nearly all of the butyrophenone

Butyrophenone

Butyrophenone is a chemical compound ; some of its derivatives are used to treat various psychiatric disorders such as schizophrenia, as well as acting as antiemetics....

 class of antipsychotic

Antipsychotic

An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...

 agents, beginning with haloperidol

Haloperidol

Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....

 (1958) and droperidol

Droperidol

Droperidol is an antidopaminergic drug used as an antiemetic and antipsychotic...

 (1961). These agents were rapidly integrated into the practice of anesthesia. In 1960, Janssen's team synthesized fentanyl, the first of the piperidinone

N-Phenethyl-4-piperidinone

N-Phenethyl-4-piperidinone is a derivative of 4-piperidinone with the molecular formula C13H17NO. 4-Piperidone is used as an intermediate in the manufacture of chemicals and pharmaceutical drugs such as fentanyl....

-derived opioids. Fentanyl was followed by sufentanil

Sufentanil

Sufentanil is a powerful synthetic opioid analgesic drug, approximately 5 to 10 times more potent than its analog, fentanyl. Sufentanil is marketed for use by specialist centres under different trade names, such as Sufenta and Sufentil...

 (1974), alfentanil

Alfentanil

Alfentanil is a potent but short-acting synthetic opioid analgesic drug, used for anaesthesia in surgery. It is an analogue of fentanyl with around 1/4 the potency of fentanyl and around 1/3 of the duration of action, but with an onset of effects 4x faster than fentanyl...

 (1976), carfentanil

Carfentanil

Carfentanil or carfentanyl is an analogue of the popular synthetic opioid analgesic fentanyl, and is one of the most potent opioids known . Carfentanil was first synthesized in 1974 by a team of chemists at Janssen Pharmaceutica which included Paul Janssen...

 (1976), and lofentanil

Lofentanil

Lofentanil is one of the most potent opioid analgesics known and is an analogue of fentanyl, which was developed in 1960. It is most similar to the highly potent opioid carfentanil , only slightly more potent. Lofentanil can be described as 3-methylcarfentanil, or 3-methyl-4-carbomethoxyfentanyl...

 (1980). Janssen and his team also developed etomidate

Etomidate

Etomidate is a short acting intravenous anaesthetic agent used for the induction of general anaesthesia and for sedation for short procedures such as reduction of dislocated joints, tracheal intubation and cardioversion...

 (1964), a potent intravenous anesthetic induction agent.

The concept of using a fiberoptic endoscope for tracheal intubation was introduced by Peter Murphy, an English anesthetist, in 1967. By the mid-1980s, the flexible fiberoptic bronchoscope had become an indispensable instrument within the pulmonology

Pulmonology

In medicine, pulmonology is the specialty that deals with diseases of the respiratory tract and respiratory disease. It is called chest medicine and respiratory medicine in some countries and areas...

 and anesthesia communities.

21st century

The "digital revolution"

Information Age

The Information Age, also commonly known as the Computer Age or Digital Age, is an idea that the current age will be characterized by the ability of individuals to transfer information freely, and to have instant access to knowledge that would have been difficult or impossible to find previously...

 of the 21st century has brought newer technology to the art and science of tracheal intubation. Several manufacturers have developed video laryngoscopes which employ digital technology such as the CMOS

CMOS

Complementary metal–oxide–semiconductor is a technology for constructing integrated circuits. CMOS technology is used in microprocessors, microcontrollers, static RAM, and other digital logic circuits...

 active pixel sensor

Active pixel sensor

An active-pixel sensor is an image sensor consisting of an integrated circuit containing an array of pixel sensors, each pixel containing a photodetector and an active amplifier. There are many types of active pixel sensors including the CMOS APS used most commonly in cell phone cameras, web...

 (CMOS APS) to generate a view of the glottis so that the trachea may be intubated. The Glidescope video laryngoscope is one example of such a device.

Xenon

Xenon

Xenon is a chemical element with the symbol Xe and atomic number 54. The element name is pronounced or . A colorless, heavy, odorless noble gas, xenon occurs in the Earth's atmosphere in trace amounts...

 has been used as a general anesthetic. Although it is expensive, anesthesia machines that can deliver xenon are about to appear on the European market, because advances in recovery and recycling of xenon have made it economically viable.

See also

• A.C.E. mixture
  A.C.E. mixture
  A.C.E. mixture is an old anaesthetic agent for general anaesthesia, which was first suggested by Dr. George Harley and first used in England around 1860, and in 1864 it was recommended for use by the Royal Medical and Surgical Society’s Chloroform Committee...
  
  
• American Society of Anesthesiologists
  American Society of Anesthesiologists
  The American Society of Anesthesiologists is an association of physicians, primarily anesthesiologists, that share a common goal of raising the standard of the medical specialty of anesthesiology and the improvement of patient care by fostering and encouraging education through research and...
  
  
• Arthur Ernest Guedel
  Arthur Ernest Guedel
  Arthur Ernest Guedel was an American anesthesiologist. He was known for his studies on the uptake and distribution of inhalational anesthetics, as well for defining the various stages of general anesthesia.-References:...
  
  
• ASA physical status classification system
• Blood transfusion
  Blood transfusion
  Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
  
  
• Boyle's machine
  Boyle's machine
  In medicine, Boyle's machine is the name given to the continuous-flow apparatus used by anesthesiologists to administer general anesthesia to patients in operation theaters....
  
  
• Curare
  Curare
  Curare is a common name for various arrow poisons originating from South America. The three main types of curare are:* tubocurare...
  
  
• Fidel Pagés
  Fidel Pagés
  Fidel Pagés Miravé was a Spanish military surgeon, known for developing the technique of epidural anesthesia....
  
  
• Henry Edmund Gaskin Boyle
  Henry Edmund Gaskin Boyle
  Henry Edmund Gaskin Boyle OBE was a pioneering anaesthetist best remembered for the development of early anaesthetic machines.-Early life:...
  
  
• History of anatomy
  History of anatomy
  The development of anatomy as a science extends from the earliest examinations of sacrificial victims to the sophisticated analyses of the body performed by modern scientists. It has been characterized, over time, by a continually developing understanding of the functions of organs and structures...
  
  
• History of medicine
  History of medicine
  All human societies have medical beliefs that provide explanations for birth, death, and disease. Throughout history, illness has been attributed to witchcraft, demons, astral influence, or the will of the gods...
  
  
• History of neuroscience
• History of surgery
  History of surgery
  Surgery is the branch of medicine that deals with the physical manipulation of a bodily structure to diagnose, prevent, or cure an ailment. Ambroise Paré, a 16th century French surgeon, stated that there were to perform surgery: "To eliminate that which is superfluous, restore that which has been...
  
  
• History of tracheal intubation
  History of tracheal intubation
  Tracheal intubation , an invasive medical procedure, is the placement of a flexible plastic catheter into the trachea. For millennia, tracheotomy was considered the most reliable method of tracheal intubation...
  
  
• Local anesthesia
  Local anesthesia
  Local anesthesia is any technique to induce the absence of sensation in part of the body, generally for the aim of inducing local analgesia, that is, local insensitivity to pain, although other local senses may be affected as well. It allows patients to undergo surgical and dental procedures with...
  
  
• Takamine Tokumei
  Takamine Tokumei
  Takamine Tokumei was an Okinawan interpreter . His another name was Gishitetsu. He was ordered to learn hairlip surgery and successfully performed surgery for the grandson of King Sho Tei, Sho Eki under general anesthesia....
  
  
• Walter Channing
  Walter Channing (physician)
  Walter Channing was an American physician and professor of medicine.Born in Newport, Rhode Island, Channing entered Harvard in 1804, but left in 1807 on account of the “rebellion” of that year, and afterward received his degree out of course...
  
  

Additional reading

• Arashiro Toshiaki, Ryukyu-Okinawa Rekishi Jinbutsuden, Okinawajijishuppan, 2006 p66 ISBN 978-4-903042-04-6
• Reevaluation of surgical achievements by Tokumei Takamine]. Matsuki A. Masui. 2000 Nov;49(11):1285-9. Japanese.
• The secret anesthetic used in the repair of a hare-lip performed by Tokumei Takamine in Ryukyu. Matsuki A. Nippon Ishigaku Zasshi. 1985 Oct;31(4):463-89. Japanese.

External links

• Chloroform: The molecular lifesaver An article at University of Bristol providing interesting facts about chloroform.
• Australian & New Zealand College of Anaesthetists Monitoring Standard
• Royal College of Anaesthetists Patient Information page
• Turning the Pages: a virtual reconstruction of Hanaoka's Surgical Casebook, c. 1825. From the U.S. National Library of Medicine Die Geschichte der Anästhesie.