ANESTHESIA
Introduction:
Anaesthesia is a state of temporary loss of consciousness induced for medical purposes. It may include muscle relaxation (paralysis), loss of memory (amnesia) unconsciousness and some analgesic effects like relief from pain.
Anaesthesia is used to provide a painless performance of medical procedures that would not be bearable to an unanesthetized patient. There are three categories of anaesthesia
1.general anaesthesia that suppresses CNS activity and causes unconsciousness
2.sedation that also suppresses CNS but to a lesser degree without resulting in unconsciousness.
3.local and regional anaesthesia that blocks the transmission of nerve impulses to specific body parts.
The medical procedures that require anaesthesia have three factors such as the health of the patient, complexity of the procedure and anaesthesia technique. Among them, the health of the patient has a great impact. If anaesthesia is given preoperatively, it may have major risks like death, heart attack and pulmonary embolism. If it is given postoperatively, it may have minor risks like nausea, vomiting and hospital readmission.
Therapeutic effects of general anaesthetics:
General anaesthetics have been in clinical use for more than 170 years, but their mechanism of action is still unknown. Ongoing research has focused on molecular, cellular and network effects to identify the mechanism of general anaesthetics.
Anaesthetics affect neurons at various cellular locations, but the primary focus has been on the synapse. A presynaptic action may alter the release of neurotransmitter, whereas the postsynaptic effect may change the frequency of impulses exiting the synapse. The cumulative effect of these actions may produce strengthened inhibition or diminished excitation within key areas of CNS. Excitatory transmission is impaired more strongly by anaesthetics than inhibitory effects are potentiated, demonstrated by the studies on isolated spinal cord tissue.
The principal molecular targets of anaesthetic action that have been studied are neuronal ion channels that mediate impulse conduction in the CNS. The chloride channels and potassium channels remain the primary inhibitory ion channels considered as a legitimate candidates of anaesthetic action. Excitatory ion channel targets include those activated by acetylcholine, by glutamate, kainate or by serotonin.
Recently, researches using powerful new investigational tools such as extended array electroencephalograms and functional magnetic resonance imaging have focused on neural networks within the brain that are altered by general anaesthetics.
Drugs used in general anaesthetics:
Propofol is the most frequently administered drug as anaesthesia. It has effects on CNS, cardiovascular system, respiratory system and others. It has IV administration with a dose of 1–2.5mg/kg. Children require a higher dose of 2.5–3.5mg/kg.
Fospropofol is a water-soluble prodrug of propofol rapidly metabolised by alkaline phosphatase and converted into propofol, phosphate and formaldehyde. It also has an IV route of administration with a dose of 6.5mg/kg. The dose should be reduced by 25% in patients older than 65 years.
Barbiturates hypnotics have been largely replaced by propofol but as a general anaesthetics, it provides a combination of enhancement of inhibitory transmission by the activating GABA receptor complex and also causes the inhibition of excitatory neurotransmission. Barbiturates include thiopental having dose 3–5mg/kg IV and methohexital having dose 1–1.5mg/kg IV for the induction of anaesthesia which occurs in less than 30seconds.
Other drugs are benzodiazepines, etomidate, ketamine, dexmedetomidine, etc. inhaled anaesthetics include nitrous oxide, desflurane, sevoflurane, isoflurane, enflurane, and halothane.
Sedation:
Many diagnostic and minor therapeutic surgical procedures can be performed without general anaesthesia technique. Though local anaesthesia augmented with midazolam or propofol and opioid analgesics may be a more suitable and safer approach than general anaesthesia for superficial surgical procedures.
The technique typically involves premedication with intravenous midazolam to produce anxiolysis, amnesia, and mild sedation, followed by a titrated, variable-rate propofol infusion. A potent opioid analgesic or ketamine may be added to blunt pain associated with the injection of local anaesthesia and the procedure itself.
Therapeutic effects of local and regional anaesthetics:
Clinicians can determine systemic absorption of injected local anaesthesia from the injected area by several factors like dosage, site of injection, drug-tissue binding, local tissue blood flow, use of vasoconstrictor and the drug’s physicochemical properties itself.
If a local anaesthetic is applied to a highly vascular area such as the tracheal mucosa or the tissue surrounding the intercostal nerves, it results in rapid absorption and higher blood levels as compared to the local anaesthetic injected into a poorly perfused tissue such as subcutaneous fat.
The primary mechanism of action of local anaesthetics is a blockade of voltage-gated sodium channels present in the membrane of nerve axons like the membranes of cardiac muscle and neuronal cell bodies.
Drugs used as local anaesthetics:
Subclass: amides
Lidocaine block sodium channels. It slows down and then blocks the action potential propagation. It has many routes of administration like topical, intravenous, infiltration, spinal, and epidural with a duration of 1–2h and 2–4h with epinephrine.
Bupivacaine also blocks Na channels causing the same effects as lidocaine. It possesses the same administration except for topical and IV with a duration of 3–6h. Both are parenteral drugs.
Other drugs that come in the subclass amides have anaesthetic effects are prilocaine, mepivacaine, articaine, ropivacaine and levobupivacaine.
Subclass: esters
Chloroprocaine has the same effects as above with very short procedures and is not administered topically and intravenously. It is parenteral with a duration of 30–60min and 60–90min with epinephrine.
Cocaine has the same effects along with sympathomimetic effects too. Its procedures require high surface activity and vasoconstriction. It is topical or parenteral with a duration of 1–2h.
Other ester subclass drugs are procaine, tetracaine and benzocaine.
Opioid analgesics in anaesthesia:
Opioids are analgesic agents and are distinct from general anaesthetics and hypnotics. Even when high doses of opioid analgesic are administered, recall cannot be prevented reliably unless hypotonic agents such as benzodiazepines are also used. Opioid analgesics are routinely used to achieve postoperative analgesia and intraoperatively as part of a balanced anaesthesia regimen.
In addition to their use as a part of a balanced anaesthesia regimen, opioids in large doses have been used in combination with large doses of benzodiazepines to achieve a general anaesthetic state, particularly in patients with a limited circulatory reserve who undergo cardiac surgery. When administered in large doses, potent opioids such as fentanyl can induce chest wall rigidity, thereby acutely impairing mechanical ventilation.
