|Year : 2012 | Volume
| Issue : 6 | Page : 524-528
The future of anaesthesiology
Department of Anesthesiology, IMS, BHU, Varanasi, Uttar Pradesh, India
|Date of Web Publication||14-Dec-2012|
Department of Anesthesiology, IMS, BHU, Varanasi, Uttar Pradesh
There was an era when bark of mandrake plant, boiled in wine was used to administer anesthesia. Ether, after reigning the kingdom of anaesthesiology for more than a century, came to be superseded by newer and newer agents. Anaesthesiology has witnessed tremendous developments since infancy. The introduction of advanced airway adjuncts, labour analgesia, patient controlled analgesia, fibreoptics, Bispectral Index monitors, workstations, simulators and robotic surgeries are only to name a further few. Anaesthesia for robotic surgery received much impetus and is still a dream to come true in many countries. But then, the rapid spin in technology and fast sophistication of medical field has even surpassed this. The next event to venture is entry of robots into human body made possible by a culmination of intricate medicine and fine technology that is Nanotechnology. This article briefly introduces the field of nanotechnology in relation to its potential benefits to the field of anaesthesiology. As with any new tecnique or application, nanotechnology as applied to anaesthesiology has tremendous potential for research and exploration. This article therefore orients the reader's mind towards the immense potential and benefits that can be tapped by carrying out further studies and experimentations.The literature was searched using databases, peer reviewed journals and books for over a period of one year (till December 2011). The search was carried out using keywords as nanotechnology, robotics, anesthesiology etc. Initially a master database was formed including human as well as animal studies. Later on the broad topic area was narrowed down to developments in nanotechnology as applied to anesthesiology. Further filtering of search results were done based on selection of researches and developments relating to local, regional and general anesthesia as well as critical care and pain and palliative care.
Keywords: Anaesthesiology, future, nanotechnology, robotics
|How to cite this article:|
Agarwal A. The future of anaesthesiology. Indian J Anaesth 2012;56:524-8
| Introduction|| |
In the last 150 years, anaesthesiology has developed into a major speciality, and its rate of advance has surpassed most other branches of medicine. There has been increased understanding of physiology, drug delivery and monitoring. It has made even the most difficult surgical and diagnostic procedures possible to undertake, which were considered impossible earlier. There was an era when bark of mandrake plant was used to administer anaesthesia, and for analgesia, ice, topical pressure, or even hypnosis was used. In 1846, the first public demonstration of ether was held and it paved the way for a new branch of medicine that came to evolve into a speciality and even superspeciality. Ether, after reigning the kingdom of anaesthesiology for more than a century, came to be superseded by newer and newer agents. Even nitrous oxide is all set to be replaced by xenon in developed countries. These were only a few milestones to mention. Anaesthesiology is one specialty of medicine that has witnessed tremendous developments since infancy. They are advanced airway adjuncts, labour analgesia, patient-controlled analgesia, fibreoptics, Bispectral Index (BIS) monitors, workstations, simulators and robotic surgeries, to name a few. Anaesthesia for robotic surgery received much impetus and is still a dream to come true in many countries. But then, the rapid spin in technology and fast sophistication of medical field has even surpassed this. The next event to venture is entry of robots into human body. Yes, microrobots would be injected into the human body where they will perform their highly specific task, and this will be made possible by a culmination of intricate medicine and fine technology, that is nanotechnology. This article highlights the present and future advances possible in anaesthesiology and its branches, with utilisation of nanotechnology. The literature was searched using databases, peer-reviewed journals, and books for over a period of 1 year (till December 2011). The search was carried out using the keywords nanotechnology, robotics, anaesthesiology, etc. Initially, a master database was formed including human as well as animal studies. Later on, the broad topic area was narrowed down to developments in nanotechnology as applied to anaesthesiology. Further filtering of search results was done on selection of researches and developments relating to local, regional and general anaesthesia, as well as critical care and pain & palliative care.
The advances can be seen in all spheres of medicine and much more is expected in the future. Drug delivery, diagnostics and surgery, by making use of technology, may witness major changes. Targeted drug delivery will reduce or eliminate the side effects while maximising desired pharmacological actions. Understanding of human genome will facilitate diagnosis and correction of congenital disorders even in utero, while on the other hand, it may even attempt to reverse the changes associated with ageing. Immunomodulation is another aspect which will possibly change the understanding of diseases and management, aided by miniaturisation of gadgets and high-performance computing, possibly delivered at remote areas. The major advances will largely be driven by technology.
The concept of nanotechnology was first propounded by Nobel Laureate Richard Feynman in 1959.  Later, Prof. Norio Taniguchi and Dr. K. Eric Dressler in 1970s and 1980s, respectively, had important contributions in the initial propagation of the concept. ,, It involves structures of one to several hundred nanometres in size. With nanotechnology, a specific set of materials and improved products can be designed by some changes in the microphysical structure. The biological and medical research communities have exploited the unique properties of nanomaterials for various applications. Functionalities can be added to nanomaterials by interfacing them with biological molecules.  The size of nanomaterials is similar to that of most biological structures, therefore useful for both in vivo and in vitro applications.
A detailed description of medical nanorobots was first published by Robert A Freitas. Once injected, the nanorobots would freely float inside the body, detecting and attaching to very specific receptors, for example, gamma-aminobutyric acid (GABA), opioid and neuromuscular junction receptors.  Thus, they would perform a highly focussed task. In the brain, by attaching to GABA receptors they produce loss of consciousness and amnesia, at the neuromuscular junction they provide full muscle relaxation giving good intubating conditions and activation of opioid receptors causes profound analgesia.
The desirable characteristics of a nanorobot are an optimal size of 0.5-3 μm to enable passage through capillaries, nonagglutinability with blood cells and recognisability of very specific receptors only.
| Advantages of Nanorobots|| |
The only disadvantage associated with nanorobots is the initial high cost and complicated fabrication, but with time, these drawbacks would definitely be overcome.
- As the nanorobots are nonbiological entities and do not generate any harmful activities, there shall be no side effects
- They are useful in both general as well as regional anaesthesia
- Being highly specific and target oriented, they reduce the anaesthesia-associated mortality and morbidity
- Since they reach specific receptors, lesser drug dosage is required, limiting the side effects
- As they bind the terminal receptors, there shall be no peaks and troughs in effect.
| Advances Possible in Present Technology|| |
Nanotechnology has been a boon in the medical field by delivering drugs to specific cells using nanoparticles. The principle exploited is that overall drug consumption and side effects can be lowered significantly by depositing the active agent only in the morbid region and in no higher dosage than needed. This highly selective approach reduces the side effects and cost, at the same time targeting its goal efficiently.
Another principle which makes use of nanotechnology is the use of block co-polymers, which form micelles for drug encapsulation.  They are able to hold small drug molecules, transporting them to the desired location. Also, improved emulsion delivery systems based on nanotechnology, which would directly transport the molecule to end receptors, can be had. Nanotechnology is also opening up new opportunities in implantable drug delivery systems. These implantables are advantageous over injectables because they do not follow first-order kinetics as injectables.  Drugs displaying first-order kinetics have a rapid rise in their concentration and an exponential drop. , This rapid rise can cause difficulties with toxicity and side effects, and drug efficacy can diminish as the drug concentration falls below the targeted range.
| Possible Advances of Nanotechnology in Anaesthesiology|| |
Presently, an anaesthetist, while providing general anaesthesia (GA), induces the patient and maintains a certain level of anaesthesia by repeatedly assessing certain clinical parameters such as blood pressure and heart rate, or sometimes when sophisticated monitoring is not available, by lacrimation, colour of blood, etc. In today's world of rapid automation of almost every other thing, one can dream of automation of the above procedure. With nanotechnology, this dream can be realised in the future. Neuroelectronic interfacing, if successful, will allow nanodevices enabled electronic chips to be joined and linked to the human nervous system. , This would permit control and detection of nerve impulses to be interpreted by an external computer.
A system has been unveiled for regulating anaesthesia via computer. This system would be beneficial in providing computer-controlled GA, similar to the manual titration of anaesthetics in response to BIS, as the anaesthetist does presently. A team of researchers from the Canary Islands has developed a technique for automatically controlling anaesthesia.  The system detects hypnotic state of patient continuously and supplies the most appropriate dose of anaesthetic. It senses patient's encephalogram (EEG) and BIS, measures the hypnotic state and relates this to the patient's level of consciousness. The data are processed by a computer software program which controls the pump that delivers the anaesthetic.
Diseases or injuries might decay or impair the nervous system, resulting in dysfunctional systems and paraplegia. The anaesthetic agents or techniques in such cases might be unpredictable. If computers could control the nervous system through neuroelectronic interface, problems that impair the system could be controlled so that effects of coexisting diseases and injuries impairing anaesthesia could be overcome.
Propofol, a commonly used drug, has some associated drawbacks such as pain on injection, allergic reactions and serving as a culture medium for microbes. These sometimes limit the use of propofol. With nanotechnology, a slight modification in propofol structure is possible.  This results in the development of propofol prodrugs, devoid of drawbacks. Introduction of some of these has already been made possible and further improvements can be expected in the near future.
Bupivacaine overdose: Sometimes anaesthesiologists encounter complications due to local anaesthetic overdose such as high spinal. At present, there is little to do in such cases as there are no antidotes and one has to wait for the drug to metabolise. With nanotechnology, an antidote to bupivacaine overdose is possible. There is a formation of pi-pi complexes between bupivacaine and a pi-electron-rich injectable nanoparticle.  This complex would be devoid of the clinical effects of bupivacaine and would thus render toxic bupivacaine harmless. So, it could be possible in the future to counteract high spinal as soon as it is realised.
Rapid local transdermal anaesthetic has always been desirable. In this context, lidocaine-loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε- caprolactone) (PCL-PEG-PCL) nanoparticles were prepared, and a novel transdermal lidocaine formulation, lidocaine-loaded PCL-PEG-PCL nanoparticles in hydrogel (Nano-Lidogel), was demonstrated.  The size of these lidocaine-loaded PCL-PEG-PCL nanoparticles was 200 nm. This has been shown to be superior in terms of onset of anaesthesia and efficacy. Although the experimental demonstration was in rats, with further research, a preparation for human use can be expected.
| Future Advances in Superspecialities of Anaesthesiology|| |
Pain and palliative care is another upcoming superspeciality of anaesthesiology. Commonly narcotics are used for managing chronic pain. But these have systemic effects and also have significant addiction potential. To overcome this, sustained release anaesthetics have been tried in the past, but unsuccessfully as the anaesthetics and their preservatives caused local toxicity. The solution to this is reflected in the use of saxitoxin, a potent anaesthetic, bundled with liposomes.  This slow- release formulation can produce a nerve block lasting from days to weeks and even months, at the same time being nontoxic to the nerves or the surrounding tissue. This formulation possible with nanotechnology can potentially revolutionise the treatment of chronic and even acute pain.
Critical care: Most of the Intensive Care Units (ICUs) the world over are under the domain of anaesthesiologists and critical care is emerging as a superspeciality in anaesthesiology. Be it infection control, ventilator dependence, antibiotic resistance or any other issue, nanotechnology provides the hope to find a solution to the problems. Few future concepts are vasculoids, respirocytes and clottocytes. 
Nanoatropine: Organophosphorus poisoning is commonly encountered in ICUs and atropine is one of the primary therapeutic drugs. In such cases, the faster the onset of treatment, the better is the outcome. Presently, IV atropine has to be given besides other management. But facilities and apparatus for IV cannulation and drug delivery are usually not available in field conditions where the poisoning is most common. Also sometimes, the first responders in field conditions are not confident with IV drug delivery. Nanotechnology has enabled formulation of inhaled atropine in the form of dry powder which can be inhaled quickly by the time other therapeutic options are arranged. ,
This inhaled drug would be easy to administer as there would be absolutely no requirement of equipment or expertise. It could be possible to supply this drug along with organophosphorus compounds with a note mentioning that it can be given through nose in case of accidental poisoning.
Vasculoids: A vasculoid is a single, complex, multisegmented nanotechnological medical robotic system capable of all transport functions of the blood, including circulation of respiratory gases, glucose, hormones, cytokines, waste products and cellular components. , This nanorobotic system could substitute the human vascular system.  The vasculoid system conforms to the shape of existing blood vessels and serves as a complete replacement for natural blood.
Respirocytes: These nanostructures transport oxygen in human body similar to erythrocytes.  Originally proposed by Robert Frietas in 1996, , they are less than a micron in diameter, possibly made of diamond, a biocompatible material. They also transport carbon dioxide. The proposed structure consists of three chambers. One would store oxygen, the other carbon dioxide, and the third would act as a buoyancy chamber, making the structure floatable in blood. The structure would also have rotors to control the intake and exit of carbon dioxide and oxygen, and for a controlled entry of glucose inside the structure to combine with oxygen and produce energy for the activity of respirocyte.  Until now, a popular dictum in science was that no machine is more efficient than the human body, but this invention would even change this as it is capable of releasing cent percent of its oxygen store, whereas a natural erythrocyte is estimated to be capable of releasing only about one-fourth of the stored gas. Even a modification of these respirocytes is on a design proposal that can quickly remove certain poisonous substances from the body in poisoning patients, a condition sometimes quite common in ICUs the world over, for example, CO poisoning, nitrobenzene poisoning, etc. Respirocytes would also speed up weaning from ventilators. At present, prolonged ventilator stay is a demon for the intensivist as it makes the patient prone to Ventilator Associated Pneumonia (VAP). VAP decreases the oxygen diffusion, thus making a patient further dependent on the ventilator. Once respirocytes are practically successful, they can bypass this ventilator dependency and would prove to be a pillar of strength to the intensivist.
Clottocytes or artificial platelets would halt bleeding 100-1000 times faster than natural haemostasis.  Besides being faster than natural platelets, the number required for the desired activity will also be less.  Specially programmed motile clottocytes would even be able to detect internal bleeding and spontaneously seal the site, thus giving the hope that some emergency surgeries might be avoided. Also, this might help in bringing down the ICU mortality as at present, sometimes, despite intense ICU treatment, patient yields to uncontrolled bleeding.
Microbivores would mimic white cells and perform phagocytosis of specific bacteria, viruses or fungi.  The microbivore would be able to bind and target the pathogen with enzymes that would reduce the microorganism into basic amino acids, fats and sugars that would be harmless to the human body.  Today, physicians are facing the rapidly emerging problem of antibiotic resistance. Many bacteria are resistant even to the highest class of antibiotics and pan-drug resistance is becoming common on microbiology charts, especially in ICU patients. To further the gravity of problem, no newer antibiotic would be available and is even not in pipeline for the next few years. The microbivores could thus be the future answer to rapidly evolving antibiotic resistance, especially in the ICUs.
Thus, it seems that nanotechnology is bound to touch each sphere of life. Change is the sign of life, and a lot can be expected in foreseeable future. These are some of the areas where technology will impact the practice of anaesthesiology. Nanotechnology may be considered at the core. The present day anaesthesiologist will experience paradigm shift in the practice of speciality and should be prepared for the same.
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