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PHARMACOKINETICS OF INHALATIONAL ANAESTHETICS

Inhalational anaesthetics are gases or vapours that diffuse rapidly across pulmonary alveoli and tissue barriers. The depth of anaesthesia depends on the potency of the agent (MAC is an index of potency) and its partial pressure (PP) in the brain, while induction and recovery depend on the rate of change of partial pressure in the brain. 

Partial pressure of anaesthetic in the inspired gas This is proportional to its concentration in the inspired gas mixture. Higher the inspired tension more anaesthetic will be transferred to the blood. Thus, induction can be hastened by administering the general anesthesia at high concentration in the beginning.

Pulmonary ventilation: It governs delivery of the general anesthesia to the alveoli. Hyperventilation will bring in more anaesthetic per minute and respiratory depression will have the opposite effect. Influence of minute volume on the rate of induction is greatest in the case of agents which have high blood solubility because their partial pressure in blood takes a long time to approach the partial pressure in alveoli. However, it does not affect the terminal depth of anaesthesia attained at any given concentration of a general anesthesia.

The general anesthesia diffuse freely across alveoli, but if alveolar ventilation and perfusion are mismatched (as occurs in emphysema and other lung diseases) the attainment of equilibrium between alveoli and blood is delayed: well perfused alveoli may not be well ventilated blood draining these alveoli carries less anaesthetic and dilutes the blood coming from well ventilated alveoli. Induction and recovery both are slowed.

Solubility of anaesthetic in blood is the most important property determining induction and recovery. Large amount of an anaesthetic that is highly soluble in blood (ether) must dissolve before its partial pressure is raised. The rise as well as fall of partial pressure in blood and consequently induction as well as recovery are slow. Drugs with low blood solubility, eg. Nitrous oxide, sevoflurane, desflurane induce quickly. Blood: gas partition coefficient given by the ratio of the concentration of the anaesthetic in blood to that in the gas phase at equilibrium is the index of solubility of the general anesthesia in blood.

Relative solubility of the anaesthetic in blood and a tissue determines its concentration in that tissue at equilibrium. Most of the general anesthesia are equally soluble in lean tissues as in blood, but more soluble in fatty tissue. Anaesthetics with higher lipid solubility (halothane) continue to enter adipose tissue for hours and also leave it slowly. The concentration of these agents is much higher in white matter than in grey matter.

Brain is a highly perfused organ; as such general anesthesia are quickly delivered. to it. This can be hastened by CO, inhalation. which causes cerebral vasodilatation induction and recovery are accelerated. Carbon dioxide stimulates respiration and this also speeds up the transport. Elimination When inhalation of the anaesthetic is discontinued, gradients are reversed and the channel of absorption (pulmonary epithelium) becomes the channel of elimination. All inhaled anaesthetics are eliminated mainly through lungs. The same factors which govern induction also govern recovery.

Anaesthetics, in general, continue to enter and persist for long periods in adipose tissue because of their high lipid solubility and low blood flow to fatty tissues. Muscles occupy an intermediate position between brain and adipose tissue. Most general anesthesias are eliminated unchanged. Metabolism is significant only for halothane which is >20% metabolized in liver. Others are practically not metabolized. Recovery may be delayed after prolonged anaesthesia, especially in case of more lipid soluble anaesthetics (halothane, isoflurane), because large quantities of the anaesthetic have entered the muscle and fat, from which it is released slowly into blood.

Different techniques are used according to facility available, agent used, condition of the patient, type and duration of operation. Open drop method: Liquid anaesthetic is poured over a mask with gauze and its vapour is inhaled with air. A lot of anaesthetic vapour escapes in the surroundings and the concentration of anaesthetic breathed by the patient cannot be determined. It is wasteful can be used only for a cheap anaesthetic. However, it is simple and requires no special apparatus. Use now is limited to peripheral areas. Ether is the only agent administered by this method, especially in children.

Anaesthetic machines is made of gas cylinders, specialized graduated vaporizers, flow meters, unidirectional valves, corrugated rubber tubing and reservoir bag. The gases are delivered to the patient through a tightly fitting face mask or endotracheal tube. Administration of the anaesthetic can be more precisely controlled and in many situations its concentration estimated. Respiration can be controlled and assisted by the anaesthetist.

Open system: The exhaled gases are allowed to escape through a valve and fresh anaesthetic mixture is drawn in each time. No rebreathing is allowed flow rates are high-more drug is consumed. However, predetermined O, and anaesthetic concentration can be accurately delivered.

Closed system: The patient rebreaths the exhaled gas mixture after it has circulated through sodalime which absorbs CO,. Only as much O, and anaesthetic as have been taken up by the patient are added to the circuit. Flow rates are low. This is especially useful for expensive and explosive agents (little anaesthetic escapes in the surrounding air). Halothane, isoflurane, desflurane can be used through closed system. However, control of inhaled anaesthetic concentration is imprecise. Semiclosed system Partial rebreathing is allowed through a partially closed valve. Conditions are intermediate with moderate flow rates.

Published : Oct 20 2023