Wednesday, 9 January 2013

Feeling sleepy? The science of anaesthesia

Jonathan Smith

The discovery of the first inhalational anaesthetics in 1846 changed how surgery was carried out. Instead of needing to complete a procedure in the fastest time possible amidst the protests of a fully aware patient, a surgeon was able to attempt much more ambitious techniques while the patient was held in a painless state of unconsciousness. Today, anaesthetic drugs can be administered intravenously (e.g. Thiopental) or by inhalation (e.g. Isoflurane). There are many levels of anaesthesia ranging from full consciousness through sedation down to the loss of consciousness, loss of reflexes and analgesia. Additionally, cardiac and respiratory muscle contraction are weakened at surgical doses and for this reason, there is often a narrow margin between surgical anaesthesia and respiratory death. Anaesthetists have the fiddly task of monitoring and adjusting the level of anaesthesia throughout surgery.

Anaesthesia of a patient occurs in three main phases: induction, maintenance and recovery. A common procedure in major surgery is to induce unconsciousness rapidly with an intravenous agent, maintain unconsciousness using inhalational anaesthetics and withdraw them in the recovery stage. Additional application of painkilling drugs such as opioids and neuromuscular blockers (relaxants) is often made. The speed of recovery needs to be maximised so that the chance of respiratory failure is kept low.

How do these drugs actually work? Inhalational and intravenous agents are all soluble in lipids to varying degrees and this is an important factor determining their characteristics. This solubility means that they easily cross lipid-based cell membranes and alter cellular function. It is thought that anaesthetics accumulate in cell membranes and influence the excitability of the cells. This can be through the increase of inhibitory transmission or the decrease of excitatory transmission or both. By doing this, anaesthetics are able to depress the nervous system and induce a loss of function.

This lipid solubility also affects other aspects of anaesthesia. Inhalational anaesthetics must cross from the lungs into the bloodstream and often take longer to exert their effect than injected anaesthetics. In addition to higher potency, high lipid solubility in these agents means that the onset and recovery from anaesthesia is slower. If a patient has higher amounts of fatty tissue such as in obesity, the extra fat sponges up large amounts of the drug and as a result, obese patients are much harder to anaesthetise.

Though anaesthesia always carries risks, these are often short-term. One long-term risk that has been hypothesised is the effect of anaesthetics on child development. Epidemiological studies and preclinical studies on rodents have suggested that the depressant effect of anaesthesia may have a permanent impact in the maturation of infant nervous systems that are very sensitive to environmental factors. In reality, however, this risk is not proven since the anaesthesia in these studies is difficult to separate from diseases that the child had at the time and translation of rodent studies to human is also difficult e.g. differences in development rates.

In summary, general anaesthetics are an essential part of surgery due to inducing a loss of consciousness that makes procedures much easier for all parties. Their non-specific mechanism of action also means that there are many risks, especially in the respiratory system.