General anaesthetic

General anesthetics are a diverse group of chemical compounds used in medical practice. They are designed to induce a loss of consciousness in humans or a loss of the righting reflex in animals. In a clinical setting, these drugs can also induce a coma. This state prevents a patient from being aware of painful stimuli during surgery. It is important to distinguish these from sedatives or analgesics, which serve different purposes. While analgesics focus on pain, general anesthetics aim to achieve a complete state of unresponsiveness. This state typically involves several reversible effects: immobility, analgesia, amnesia, unconsciousness, and reduced autonomic responsiveness to noxious stimuli.

To achieve these effects, doctors use different methods of administration. Inhalational anesthetics are delivered as gases or volatile liquids. These are typically managed using an anesthesia machine. This machine creates a mixture of oxygen, ambient air, and the anesthetic agent. The machine also monitors the patient and the equipment. Most liquid anesthetics are vaporized within the machine before being inhaled. Common volatile anesthetics used today include sevoflurane, isoflurane, and desflurane. These are often combined with nitrous oxide. Other older options include halothane, enflurane, and methoxyflurane. Researchers are also studying xenon for potential use.

Another method is through injection, which can be intravenous, intramuscular, or subcutaneous. Anesthetists generally prefer intravenous injections because they are faster and more reliable. They are also typically less painful for the patient. Common injectable drugs include propofol and etomidate. Doctors also use barbiturates, such as methohexital and thiopentone. Benzodiazepines, like midazolam, are often used as sedatives in combination with other drugs. In the United Kingdom, ketamine is used for "field anesthesia" during emergencies like road traffic incidents. This allows operations to occur at the scene. In the United States, ketamine is more frequently used in standard operative settings.

How these drugs actually work is a complex subject of ongoing research. It is believed that they act by targeting specific pathways in the central nervous system (CNS). One primary method is the activation of inhibitory receptors. This means the drugs turn on parts of the brain that slow down activity. Another method is the inactivation of excitatory receptors. By blocking these, the drugs prevent the brain from sending certain signals. Doctors often use a combinatorial drug approach. This means they use different drugs together to control both the state of unconsciousness and any physiological side effects.

Scientists have identified several specific biological targets for these drugs. GABAA receptor agonists are a major group. These drugs, such as propofol and benzodiazepines, act on chloride channels to hyperpolarize neurons. This action helps induce sedation or unconsciousness. Another target is the NMDA receptor. Ketamine acts as an NMDA receptor antagonist. This helps with analgesia and can alter arousal. When used alone, ketamine can cause a dissociative state involving hallucinations. Additionally, some anesthetics affect two-pore potassium channels, known as K2Ps. These channels help regulate the resting membrane potential in neurons. Activating these channels reduces neuronal excitability. Research shows that specific channels, like TREK-1 and TASK, play roles in inducing anesthesia.

Other drugs are used to support the main anesthetic state. Opioid receptor agonists, such as fentanyl or morphine, are used for their analgesic effects. While they can cause sedation, they do not cause a loss of consciousness on their own. Therefore, they are used alongside other anesthetics. Dexmedetomidine is an alpha2 adrenergic receptor agonist that produces sedation similar to non-REM sleep. Patients can be easily aroused from this state. In the past, dopamine receptor antagonists were used to create neuroleptic anesthesia. This included states of catalepsy and unresponsiveness. However, these are no longer used because patients often remained aware of the medical procedures despite being unable to move.

As a patient receives anesthesia, they pass through distinct stages known as Guedel's signs. The first stage is analgesia, where the patient may feel confusion or amnesia. The second stage is excitement, characterized by delirium, confusion, and irregular breathing. Patients may experience nausea, vomiting, or even panic during this stage. The third stage is surgical anesthesia. This is when normal breathing resumes, though it may eventually cease. Doctors monitor the depth of this stage by checking pupil size and eye movement. The final stage is medullary depression. In this stage, respiration stops and circulatory failure can occur. Without medical support for breathing and circulation, death is common at this stage.

General anesthetics also cause various physiological side effects that require careful management. They can lead to a reduction in blood pressure by dilating vasculature or reducing cardiac contractility. This drop can sometimes trigger a reflex increase in heart rate. Patients are also at risk for hypothermia. This happens because vasodilation increases heat loss through the skin. Furthermore, anesthetics affect the respiratory system by reducing tidal volume and the respiratory rate. They also dampen protective reflexes like coughing or gagging. This increases the risk of airway obstruction or asphyxiation. Because of these risks, healthcare providers must use devices like endotracheal tubes to ensure safety.