For nearly a century, general anesthetics have been frequently used in medical procedures to completely eliminate pain and suffering of surgical patients. The process itself involves the administering of general anesthetic drugs to induce conditions such as amnesia, muscle paralysis, sedation, and analgesia. As opposed to the other departments of anesthesia previously discussed (local and regional anesthesia), general anesthesia places the patient in a complete state of unconsciousness, thus rendering all areas of the body unable to feel painful stimuli. After undergoing general anesthesia, the patient is in a state that is characterized by the following: unable to respond/feel to pain, unable to remember recent events due to the inducement of amnesia, unable to breathe or move as a result of lingering muscle paralysis, and susceptible to cardiovascular changes caused by the side effects of in taking general anesthetics.
How it is taken
The two most common methods of receiving general anesthetics in the medical community are as an inhalant via an endotracheal tube (provides anesthetic and oxygen) or taken intravenously through an IV line. In some cases, the two mechanisms are actually used simultaneously in an operation, where the intravenous injection begins the procedure by inducing initial unconsciousness while exposure to anesthetic inhalants prolong and sustain the effects. After the surgery is completed, the gasses and IV line are terminated. The patients are then taken to a PACU (post-anesthesia care unit) to recover from lingering effects of general anesthesia for a period of time, dependent on the magnitude of the operation or tolerance of the individual to anesthesia. Such symptoms that appear post general anesthesia include vomiting, nausea, sore throat, and incisional pain. In regards to the recent era, general anesthesia has had a relatively low rate of mortality (1:100,000) due to advances in technology and in the medical world.
Mechanism of Action
It is not fully understood regarding the mechanism of action of a general anesthetic compound when inserted into the body. However, decades of use and research have led to several theories. One popular theory (aside from interaction with glutamate-activated NMDA ion channels) is the interaction of a general anesthetic with the GABA receptors in the brain. At a molecular level, anesthetics are able to induce their effects because they tamper with the functions and behavior of neurons. Neurons are the source of our daily consciousness, complex thoughts, and general mental capabilities so by altering neuron functionality, specifically the ion channels within the neurons, anesthetics are able to induce a temporary loss of feeling.
As seen in previous blog posts, anesthetics change the electrical activity (or electrical excitability) in ion channels through the control of ion flow (excitatory or inhibitory ions) across the neuron cell membrane. For general anesthetics, effects are procured primarily through either the enhancement of inhibitory signals or the blockade of excitatory signals in GABA receptors (ion channel). These receptors are part of a Cys-loop superfamily, characterized by a disulfide bond between two cysteine residues, of ligand-gated ion channels and are composed of a combination of trans-membrane polypeptide subunits.
Due to the fact that they are integral to the functionality of the central nervous system, their function primarily involves with memory, awareness, and consciousness. Subsequently, the fact that the interaction of general anesthetics with these GABA receptors, by reducing excitatory and increasing inhibitory ion flow, induces unconsciousness and temporary amnesia is of no surprise and definitely a plausible theory. GABA receptors are very sensitive to the presence of general anesthetics. The molecules of these anesthetics tend to bind at sites within the receptor thus modulating the actions of the GABA receptor. Specifically, in the presence of general anesthetics, the ability of the GABA receptor to open its ion channel is increased thus increasing the inhibitory activity of the receptor.
Though general anesthesia induces complete unconsciousness and lack of response to painful stimuli, it may not be the best course of action because it affects the entire body and each patient has their own unique medical condition. Choosing to undergo either local or regional anesthesia may ultimately be a better option, ensuring safety of the patient. The advantages and disadvantages of general anesthesia are the following:
- It is a reversible process that can be administered very quickly
- If a patient has some sensitivity/allergic response to local anesthetics, general anesthesia can be used.
- Very low probability of patient being able to recall moments of the procedure and sustain consciousness during the process.
- Easily adaptable
- Complex process that demands intricate care by the medical professional and costs relatively high for the patient.
- Chance of causing malignant hypothermia; a rare muscular condition in which exposure to some general anesthetics lead to dangerous temperature rise, hyperkalemia, hypercarbia, and metabolic acidosis.
Desflurane (also known suprane) is a common general anesthetic that is a nonflammable liquid at temperature below 22.8°C but is administered as an inhalant using a vaporizer. A fluorinated methyl ethyl ether, desflurane has a chemical formula of C3H2F6O and has a relatively low solubility in blood therefore making it ideal for general anesthesia. An interesting yet unfortunate drawback of desflurane is its tendency to react with carbon dioxide absorbents to produce carbon monoxide, which may result in an increase level of carboxyhemoglobin in patients thus limiting the capacity of regular hemoglobin to bind and deliver oxygen to areas of the body.
The anesthetic drug is indeed a recent discovery and has been widely used/purchased in the commercial medical market. Subsequently, multiple routes for synthesizing desflurane have been discovered and patented. One process is the preparation of desflurane from the treatment of isoflurane with hydrogen fluoride in the presence of antimony pentachloride: CF3CHClOCHF2+HF+SbCl5 → CF3CHFOCHF2+HCl. In most cases, to conduct the reaction, the hydrogen fluoride is added to a mixture of isoflurane and antimony pentachloride. It is recommended that HF in its liquid state be utilized and added to the mixture at a rate of 0.25 to 0.5 molar equivalents per hour. Since the reaction is endothermic, precautions must also be taken so that the temperature is maintained at about 9 to 18° C. The entire process is then conducted in a reaction vessel that is inert to the reagents. Materials recommended for the composition of the reaction vessel are the following: polytetrafluoroethylene, carbon steel, copper, and nickel. These are just several steps to ensure that the amount of desflurane produced is optimized. Another process that synthesizes desflurane in a relatively inexpensive and environmentally safe manner is reacting hexafluoropropene epoxide with methanol to form methyl 2-methoxytetrafluoropropionate which is then hydrolyzed to develop an acid. The acid is then decarboxylated to create an ether, which is then chlorinated to form CF3CFHOCHCl2. The last step requires the reaction of the previous product with a fluorinating agent to ultimately produce desflurane. In the chlorination process, the reduction is executed by illuminating the reaction with UV light in the presence of a lower alkanol. One reason why this route of synthesis is favorable is due to the advantages of using hexafluoropropene as a starting substrate. It is chemically stable, abundant, relatively inexpensive, and environmentally friendly.
Whether it is local, regional, or general, the discovery and implementation of anesthesia in the medical community has significantly changed how surgical operations are performed and the efficiency at which they are executed. Anesthetics are truly mind-boggling and remarkable products of chemistry, wielding the powerful ability to make the body unable to experience pain. The fact that a mere molecule is able to alter the way we think, move, and feel by interacting with receptors in our brains is extraordinary, a fact that seems supernatural. Over the course of our blog posts, we hope that you were able to learn something new about anesthesia and partake in our fascination with the subject. The era of anesthesia has just begun; a boundless future awaits us.