The modern marvel of medicine

University of Oxford| Fri Apr 14 06:03:58 EDT 2017
The modern marvel of medicine

The art and science of general anaesthesia remains a relative mystery to the general public. In an age where instant access to information is the norm through smartphones and tablets, the critically important role of these lynchpin clinicians in so many facets of hospital medicine goes unpublished and unnoticed. It is usually the surgeon or emergency physician, so often popularised through television or film media, who fulfils the public’s desire for medical heroes. Yet, astonishing techniques are being quietly used every day to facilitate safe surgery, for example the administration of drugs to render temporary unconsciousness, cessation, or removal of pain, and the ‘numbing’ of body parts with regional anaesthetic nerve blocks to allow awake surgery.

The term ‘anaesthesia’ was first used by Wendell Holmes (1809─94) and is derived from the Greek ἀναισθησία (anaisthēsía), from ἀν– (an-, “not,” or “without”) with αἴσθησις (aísthēsis, “sensation”). The first use of herbal substances to treat pain and facilitate surgery can be traced back many thousands of years ago to the Mesopotamia era. Remarkably, the most popular ancient remedies of alcohol, cannabis, and the opium poppy remain useful pharmacological adjuncts in modern medicine. Nitrous oxide (or “laughing gas”) was discovered in the 18th century by Joseph Priestley (1733─1804); however, it was Humphrey Davy (1778─1829) who first hypothesised that, when inhaled, it may be useful as a painkiller during surgery.

Following experimentation with diethyl ether by William T G Morton (1819─68) and William Edward Clarke (1819─98), the first inhaled general anaesthesia for surgery was administered by Clarke for dental extraction in 1842. Crawford W Long (1815─78) utilised the properties of inhaled ether for more extensive surgery, such as amputations. Concurrently, Horace Wells (1815─48) had started to use inhaled nitrous oxide regularly for his dental patients. By the mid-19th century, ether became established as the first mainstream general anaesthetic drug. The second half of the 19th century witnessed the introduction of chloroform for general anaesthetic purposes, first demonstrated in 1842 by James Young Simpson (1811─70) whilst self-experimenting with friends.

The ability to render a part of the body insensate to allow surgical procedures without general anaesthesia is a truly phenomenal concept. It is documented that the Incas in Ancient Peru first used the leaves of the coca plant for its local anaesthetic properties. Following extraction from the plant, cocaine was used by Karl Koller (1857─1944) to topically anaesthetise his eye in 1884. However, considerable side effects and addiction encouraged the synthesis of alternative local anaesthetics, for example the development of procaine towards the beginning of the 20th century.

Often described as the forefather of regional anaesthesia, August Bier (1861─1949) was the first to describe and perform spinal blocks and intravenous regional anaesthesia – self-demonstration of the former leaving him with the first post-dural puncture headache. Faster-acting local anaesthetic agents with fewer side effects, coupled with more modern techniques such as the use of ultrasound to locate nerve bundles, have improved the safety profile of modern regional anaesthesia. There now even exists an ‘antidote’ to local anaesthetic overdose in the form of lipid emulsion therapy.

In 1934, the first intravenous anaesthetic agent, sodium thiopental, was synthesized. This heralded a major breakthrough in the induction of general anaesthesia. Although superseded by other intravenous agents such as propofol, etomidate, and ketamine, it still has medical uses today in obstetric anaesthesia and neurointensive care. Of interest, it is also the predominant ingredient used in euthanasia and in the execution of prisoners by lethal injection. A lesser-known fact is its use in smaller doses as ‘truth serum’ during interrogation scenes, popularised by films, television, and fiction novels. The supposed mechanism of action is by reduction of higher brain function coupled with the theory that lying is a more complex neurological action than telling the truth. In reality, there is little scientific evidence that can substantiate the reliability of this technique.

As the 20th century progressed, so did the advancement and discovery of newer anaesthetic drugs. These included opioids to treat pain, for example fentanyl, and muscle relaxants such as atracurium, to aid endotracheal intubation and abdominal surgery. Most notably, the introduction of inhalational volatile agents (such as halothane and sevoflurane) to maintain general anaesthesia provided superior conditions for surgery and prevented accidental awareness, so often associated with exclusive use of nitrous oxide.

So, where does the future lie in the specialty of anaesthesia? Equipment and monitoring will become more sophisticated with the ultimate aim to minimise harm to patients. It is likely that robotics will be integrated within the patient’s surgical pathway to reduce human error and optimise efficiency of care. Newer drugs will be synthesized with fewer adverse effects and complications. Indeed, xenon, a noble gas already used in headlamps and lasers, has been found to possess many of the properties of an ideal inhalational anaesthetic agent, albeit prohibitively expensive in cost at the time of writing. The most elusive code to crack has been the answer to a very simple question: ‘how do general anaesthetics work?’ Initial hypotheses like the Meyer-Overton correlation, were thought to be too simplistic and more recent work points towards the involvement of more specific central nervous system protein receptors, such as GABA and NMDA. Once more is discovered about the mechanism of general anaesthesia at a cellular level, new anaesthetic drugs could be synthesized with safer therapeutic profiles and, perhaps, even targeted to individual patients according to need.

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