5 - drugs used in general anaesthesia

A general anaesthetic (or anesthetic, see spelling differences) drug is an anaesthetic drug that brings about a reversible loss of consciousness. These drugs are generally administered by an anesthesia provider in order to induce or maintain general anaesthesia to facilitate surgery.

Drugs given to induce or maintain general anaesthesia are either given as:

• Gases or vapors (inhalational anaesthetics)
• Injections (intravenous anaesthetics)

Most commonly these two forms are combined, with an injection given to induce anaesthesia and a gas used to maintain it, although it is possible to deliver anaesthesia solely by inhalation or injection.

Inhalational anaesthetic substances are either volatile liquids or gases and are usually delivered using an anaesthesia machine. An anaesthesia machine allows composing a mixture of oxygen, anaesthetics and ambient air, delivering it to the patient and monitoring patient and machine parameters. Liquid anaesthetics are vaporized in the machine.

Many compounds have been used for inhalation anaesthesia, but only a few are still in widespread use. Desflurane, isoflurane and sevoflurane are the most widely used volatile anaesthetics today. They are often combined with nitrous oxide. Older, less popular, volatile anesthetics, include halothane, enflurane, and methoxyflurane. Researchers are also actively exploring the use of xenon as an anaesthetic.

Injection anaesthetics are used for induction and maintenance of a state of unconsciousness. Anaesthetists prefer to use intravenous injections as they are faster, generally less painful and more reliable than intramuscular or subcutaneous injections. Among the most widely used drugs are:

• Propofol
• Etomidate
• Barbiturates such as methohexital and thiopentone/thiopental
• Benzodiazepines such as midazolam and diazepam (commonly known as Valium)
• Ketamine is used in the UK as "field anaesthesia", for instance at a road traffic incident, and is more frequently used in the operative setting in the US.

The volatile anaesthetics are a class of general anaesthetic drugs. They share the property of being liquid at room temperature, but evaporating easily for administration by inhalation (some experts make a distinction between volatile and gas anesthetics on this basis, but both are treated in this article, since they probably do not differ in mechanism of action). All of these agents share the property of being quite hydrophobic (i.e., as liquids, they are not freely miscible with in water, and as gases they dissolve in oils better than in water

3 - general anaesthesia

In modern medical practice, general anaesthesia (AmE: anesthesia) is a state of total unconsciousness resulting from general anaesthetic drugs. A variety of drugs are given to the patient that have different effects with the overall aim of ensuring unconsciousness, amnesia, analgesia and paralysis. The anaesthetist (AmE: "anesthesiologist," if a medical doctor, "nurse anesthetist" if an advanced clinical practitioner who does not hold a medical degree; CRNA=certified registered nurse anesthetist) selects the optimal technique for any given patient and procedure.

Overview

General anaesthesia is a complex procedure involving:

• Preanaesthetic assessment
• Administration of general anaesthetic drugs
• Cardiorespiratory monitoring
• Analgesia
• Airway management
• Fluid management
• Postoperative pain relief

Preanaesthetic evaluation

Prior to surgery, the anaesthetist interviews the patient to determine the best combination and drugs and dosages and the degree of monitoring required to ensure a safe and effective procedure.

Pertinent information is the patient's age, weight, medical history, current medications, previous anaesthetics, and fasting time. Usually, the patients are required to fill out this information on a separate form during the pre-operative evaluation. Depending on the existing medical conditions reported, the anaesthetist will review this information with the patient either during his pre-operative evaluation or on the day of his or her surgery.

Truthful and accurate answering of the questions is important so the anaesthetist can select the proper anaesthetics. For instance, a heavy drinker or drug user who does not disclose their chemical uses could be undermedicated, which could then lead to anesthesia awareness or dangerously high blood pressure. Commonly used medications such as Viagra can interact with anaesthesia drugs; failure to disclose such usage can endanger the patient.

An important aspect of this assessment is that of the patient's airway, involving inspection of the mouth opening and visualisation of the soft tissues of the pharynx. The condition of teeth and location of dental crowns and caps are checked, neck flexibility and head extension observed. If an endotracheal tube is indicated and airway management is deemed difficult, then alternative placement methods such as fiberoptic intubation may be used.

Stages of anaesthesia

The progression of stages described here was devised for anaesthesia using diethyl ether and is largely replaced by the 3 stage classification.

Stage 1

Stage 1 anaesthesia, also known as the "induction," is the period between the initial administration of the induction medications and loss of consciousness. During this stage the patient progresses from analgesia without amnesia to analgesia with amnesia. Patients can carry on a conversation at the time.

Stage 2

Stage 2 anesthesia, also known as the "excitement stage," is the period following loss of consciousness and marked by excited and delirious activity. During this stage, respirations and heart rate may become irregular. In addition, there may be uncontrolled movements, vomiting, breath holding, and pupillary dilation. Since the combination of spastic movements, vomiting, and irregular respirations may lead to airway compromise, rapidly acting drugs are used to minimize time in this stage and reach stage 3 as fast as possible.

Stage 3

Stage Three: Surgical Anesthesia. During this stage, the skeletal muscles relax, and the patient's breathing becomes regular. The gag reflex and corneal reflex are lost. Eye movements slow, then stop, and surgery can begin.

Stage 4

Stage 4 anaesthesia, also known as "overdose," is the stage where too much medication has been given and the patient has severe brain stem or medullary depression. This results in a cessation of respiration and potential cardiovascular collapse. This stage is lethal without cardiovascular and respiratory support.

Postoperative Analgesia

The anaesthesia concludes with a management plan for postoperative pain relief. This may be in the form of regional analgesia, oral, transdermal or parenteral medication. Minor surgical procedures are amenable to oral pain relief medications such as paracetamol and NSAIDS such as ibuprofen. Moderate levels of pain require the addition of mild opiates such as codeine.

Major surgical procedures may require a combination of modalities to confer adequate pain relief. Parenteral methods include Patient Controlled Analgesia System (PCAS) involving morphine, a strong opiate. Here, the patient presses a button to activate a pump containing morphine. This administers a preset dose of the drug. As the pump is programmed not to exceed a safe amount of the drug, the patient cannot self administer a toxic dose.

Mortality rates

Overall, the mortality rate for general anaesthesia is about five deaths per million anaesthetic administrations.^[1] Death during anaesthesia is most commonly related to surgical factors or pre-existing medical conditions. These include major haemorrhage, sepsis, and organ failure (eg. heart, lungs, kidneys, liver). Common causes of death directly related to anaesthesia include:

• aspiration of stomach contents
• suffocation (due to inadequate airway management)
• allergic reactions to anaesthesia (specifically and not limited to anti-nausea agents) and other deadly genetic predispositions
• human error
• equipment failure

In the US, up until about 1980 anesthesia was a significant risk, with at least one death per 10,000 times administered. After becoming something of a public scandal, a careful effort was made to understand the causes and improve the results. It is generally believed that anesthesia is now at least ten times safer than it was then.However, there is some controversy about this. In the US, the data is not made public (in fact, the data is not even collected), so the truth is uncertain.The rate for dental anesthesia is reported to be one out of 350,000.

3 - drugs used in local anaesthesia

Local Anaesthetics

The World Federation of Societies of Anaesthesiologists have this excellent article on "The Pharmacology of Local Anaesthetic Agents" as part of "Update in Anaesthesia", a journal for anaesthetists in developing countries. They also have this page on local anaesthetic toxicity. See also Wikipedia, Anaesthetist.com, FRCA site and E-Medicine.

Allan Palmer has set up a slide show on Local Anaesthetics. It includes some very clear images but can be slow to download.

See also a related chapter on Local and Regional Anaesthetic Techniques.

Bupivacaine

Bupivacaine has been widely used as a long-lasting amide local anaesthetic. Adrenaline improves duration of block by say 30-50% (the effect is less obvious than for lignocaine). The most feared toxicity is prolonged cardiac arrest which may occur before convulsions commence. CPR should be maintained for at least an hour. Adrenaline +/- vasopressin are important during CPR to maintain blood pressure. Adrenaline may worsen the arrythmias Insuling/Glucose/K, clonidine and lipid have been suggested as adjunctive therapy. See Weinberg 2002.

Overview from Wikipedia. More detail from drugs.com.

The levo (S) enantiomer of bupivacaine is less cardiotoxic but provides similar analgesia than the racemic mixture. The additional margin of safety may be 25% to 40% with risk of cardiotoxicity bupivacaine > L-bupivacaine > ropivacaine. See Royse 2005.

Lignocaine

The original amide local anaesthetic. Information from Astra-Zeneca, Wikipedia, History Holmdahl 1998.

Mepivacaine

Information from Astra Wikipedia.

Ropivacaine

Only the s-racemate was marketed; it should result in less chance of cardiac arrest than bupivacaine following overdose or IV administration but otherwise be clinically similar. See also this paper by Morrison 2000. A detailed meta-analysis s of its use in labour suggests that any clinical differences are minor. This paper from Washington University provides a concise summary.

Pharmacology: Wikipedia, RxList: physical properties and kinetics. Ropivacaine in obstetric anaesthesia by Stephen Gatt. Also experience with ropivacaine for labour analgesia by Genevieve Goulding, all from Manbit, from about 1995. Brief summary from Astra.

EMLA

Eutectic mixture of local anaesthetics. Topical application provides good superficial skin anaesthesia. Information from the Astra-Zeneca site

2 - local anaesthesia

Local anesthesia is any technique to render part of the body insensitive to pain without affecting consciousness. It allows patients to undergo surgical and dental procedures with reduced pain and distress. In many situations, such as cesarean section, it is safer and therefore superior to general anesthesia. It is also used for relief of non-surgical pain and to enable diagnosis of the cause of some chronic pain conditions. Anaesthetists sometimes combine both general and local anesthesia techniques.

The following terms are often used interchangeably:

• Local anesthesia, in a strict sense, is anesthesia of a small part of the body such as a tooth or an area of skin.
• Regional anesthesia is aimed at anesthetizing a larger part of the body such as a leg or arm.
• Conduction anesthesia is a comprehensive term which encompasses a great variety of local and regional anesthetic techniques.

Techniques

To achieve conduction anesthesia a local anesthetic is injected or applied to a body surface. The local anesthetic then diffuses into nerves where it inhibits the propagation of signals for pain, muscle contraction, regulation of blood circulation and other body functions. Relatively high drug doses or concentrations inhibit all qualities of sensation (pain, touch, temperature etc.) as well as muscle control. Lower doses or concentrations may selectively inhibit pain sensation with minimal effect on muscle power. Some techniques of pain therapy, such as walking epidurals for labor pain use this effect, termed differential block.

incomplete entry: Known to block voltage gated sodium channels.

Anesthesia persists as long as there is a sufficient concentration of local anesthetic at the affected nerves. Sometimes a vasoconstrictor drug is added to decrease local blood flow, thereby slowing the transport of the local anesthetic away from the site of injection. Depending on the drug and technique, the anesthetic effect may persist from less than an hour to several hours. Placement of a catheter for continuous infusion or repeated injection allows conduction anesthesia to last for days or weeks. This is typically done for purposes of pain therapy.

Local anesthetics can block almost every nerve between the peripheral nerve endings and the central nervous system. The most peripheral technique is topical anesthesia to the skin or other body surface. Small and large peripheral nerves can be anesthetized individually (peripheral nerve block) or in anatomic nerve bundles (plexus anesthesia). Spinal anesthesia and epidural anesthesia are applied near the spinal cord where the peripheral nervous system merges into the central nervous system.

Clinical techniques include:

• Surface anesthesia - application of local anesthetic spray, solution or cream to the skin or a mucous membrane. The effect is short lasting and is limited to the area of contact.
• Infiltration anesthesia - injection of local anesthetic into the tissue to be anesthetized. Surface and infiltration anesthesia are collectively topical anesthesia.
• Field block - subcutaneous injection of a local anesthetic in an area bordering on the field to be anesthetized.
• Peripheral nerve block - injection of local anesthetic in the vicinity of a peripheral nerve to anesthetize that nerve's area of innervation.
• Plexus anesthesia - injection of local anesthetic in the vicinity of a nerve plexus, often inside a tissue compartment that limits the diffusion of the drug away from the intended site of action. The anesthetic effect extends to the innervation areas of several or all nerves stemming from the plexus.
• Epidural anesthesia - a local anesthetic is injected into the epidural space where it acts primarily on the spinal nerve roots. Depending on the site of injection and the volume injected, the anesthetized area varies from limited areas of the abdomen or chest to large regions of the body.
• Spinal anesthesia - a local anesthetic is injected into the cerebrospinal fluid, usually at the lumbar spine (in the lower back), where it acts on spinal nerve roots and part of the spinal cord. The resulting anesthesia usually extends from the legs to the abdomen or chest.
• Intravenous regional anesthesia (Bier's block) - blood circulation of a limb is interrupted using a tourniquet (a device similar to a blood pressure cuff), then a large volume of local anesthetic is injected into a peripheral vein. The drug fills the limb's venous system and diffuses into tissues where peripheral nerves and nerve endings are anesthetized. The anesthetic effect is limited to the area that is excluded from blood circulation and resolves quickly once circulation is restored.
• Local anesthesia of body cavities (e.g. intrapleural anesthesia, intraarticular anesthesia)

Uses in surgery and dentistry

Virtually every part of the body can be anesthetized using conduction anesthesia. However, only a limited number of techniques are in common clinical use. Sometimes conduction anesthesia is combined with general anesthesia or sedation for the patient's comfort and ease of surgery. Typical operations performed under conduction anesthesia include:

• Dentistry (surface anesthesia, infiltration anesthesia, nerve blocks)
• Eye surgery (surface anesthesia with topical anesthetics, retrobulbar block)
• ENT operations, head and neck surgery (infiltration anesthesia, field blocks, peripheral nerve blocks, plexus anesthesia)
• Shoulder and arm surgery (plexus anesthesia, intravenous regional anesthesia)
• Heart and lung surgery (epidural anesthesia combined with general anesthesia)
• Abdominal surgery (epidural/spinal anesthesia, often combined with general anesthesia)
• Gynecological, obstetrical and urological operations (spinal/epidural anesthesia)
• Bone and joint surgery of the pelvis, hip and leg (spinal/epidural anesthesia, peripheral nerve blocks, intravenous regional anesthesia)
• Surgery of skin and peripheral blood vessels (topical anesthesia, field blocks, peripheral nerve blocks, spinal/epidural anesthesia)
• Lip stitching - a local anesthesia can also be injected into the lip when having stitches there, as the needle goes in it is extremely painful and must be injected in to several different places in the lip for it to work. Then the pain is over until the stitches are in. You can actually feel the stitch-needle go in to your lip tissue.

Uses in acute pain

Acute pain may occur due to trauma, surgery, infection, disruption of blood circulation or many other conditions in which there is tissue injury. In a medical setting it is usually desirable to alleviate pain when its warning function is no longer needed. Besides improving patient comfort, pain therapy can also reduce harmful physiological consequences of untreated pain.

Acute pain can often be managed using analgesics. However, conduction anesthesia may be preferable because of superior pain control and fewer side effects. For purposes of pain therapy, local anesthetic drugs are often given by repeated injection or continuous infusion through a catheter. Low doses of local anesthetic drugs can be sufficient so that muscle weakness does not occur and patients may be mobilized.

Some typical uses of conduction anesthesia for acute pain are:

• Labor pain (epidural anesthesia)
• Postoperative pain (peripheral nerve blocks, epidural anesthesia)
• Trauma (peripheral nerve blocks, intravenous regional anesthesia, epidural anesthesia)

Uses in chronic pain

Chronic pain of more than minor intensity is a complex and often serious condition that requires diagnosis and treatment by an expert in pain medicine. Local anesthetics can be applied repeatedly or continuously for prolonged periods to relieve chronic pain, usually in combination with medication such as opioids, NSAIDs, and anticonvulsants.

Miscellaneous uses

Topical anesthesia, in the form of lidocaine/prilocaine (EMLA) is most commonly used to enable relatively painless venipuncture (blood collection) and placement of intravenous cannulae. It may also be suitable for other kinds of punctures such as ascites drainage and amniocentesis.

Surface anesthesia also facilitates some endoscopic procedures such as bronchoscopy (visualization of the lower airways) or cystoscopy (visualization of the inner surface of the bladder).

History

The leaves of the coca plant were traditionally used as a stimulant in Peru. It is believed that the local anesthetic effect of coca was also known and used for medical purposes. Cocaine was isolated in 1860 and first used as a local anesthetic in 1884. The search for a less toxic and less addictive substitute led to the development of the aminoester local anesthetic procaine in 1904. Since then, several synthetic local anesthetic drugs have been developed and put into clinical use, notably lidocaine in 1943, bupivacaine in 1957 and prilocaine in 1959.

Shortly after the first use of cocaine for topical anesthesia, blocks on peripheral nerves were described. Brachial plexus anesthesia by percutaneous injection through axillary and supraclavicular approaches was developed in the early 20th century. The search for the most effective and least traumatic approach for plexus anesthesia and peripheral nerve blocks continues to this day. In recent decades, continuous regional anesthesia using catheters and automatic pumps has evolved as a method of pain therapy.

Intravenous regional anesthesia was first described by August Bier in 1908. This technique is still in use and is remarkably safe when drugs of low systemic toxicity such as prilocaine are used.

Spinal anesthesia was first used in 1885 but not introduced into clinical practice until 1899, when August Bier subjected himself to a clinical experiment in which he observed the anesthetic effect, but also the typical side effect of postpunctural headache. Within few years, spinal anesthesia became widely used for surgical anesthesia and was accepted as a safe and effective technique. Although atraumatic (non-cutting-tip) cannulas and modern drugs are used today, the technique has otherwise changed very little over many decades.

Epidural anesthesia by a caudal approach had been known in the early 20th century, but a well-defined technique using lumbar injection was not developed until the 1930s. With the advent of thin flexible catheters, continuous infusion and repeated injections have become possible, making epidural anesthesia a highly successful technique to this day. Beside its many uses for surgery, epidural anesthesia is particularly popular in obstetrics for the treatment of labor pain.

Adverse Effects

Adverse effects depend on the local anesthetic agent, method, and site of administration and is discussed in depth in the local anesthetic sub-article.

Overall the effects can be:

1. localized prolonged anesthesia or paresthesia due to infection, hematoma, excessive fluid pressure in a confined cavity, and severing of nerves & support tissue during injection,
2. systemic reactions such as depressed CNS syndrome, allergic reactions, and cyanosis due to local anesthetic toxicity.
3. lack of anesthetic effect due to infectious puss such as an abscess.