Inhalation agents

·         Pharmacokinetics.

·         Nitrous oxide.

·         Halothane.

·         Other halogenated agents.

Pharmacokinetics

1.    Low blood solubility: rapid rise in arterial tension – faster induction of anaesthesia.

2.    High anaesthetic concentration in air: increase both maximum tension in alveoli and rate of increase in arterial tension; useful for anaesthetics of moderate blood solubility, e.g. enflurane or halothane.

3.       Increased pulmonary ventilation: increase arterial tension.

4.    Low pulmonary blood flow: increase rate of rise in arterial tension.

5.       Duration of exposure:

a.       Affect time of recovery.

b.    Long duration of exposure causes accumulation of anaesthetic in tissues with low blood perfusion.

6.       Diffusion hypoxia:

a.       When anaesthetic is discontinued, there is a flow of the gaseous agent from the blood into the alveoli.

b.       Causes a decrease in oxygen tension in the alveoli.

c.    In the case of nitrous oxide, this can account for as much as 10% of the expired volume .

d.       Oxygen should therefore be given to such patients during the last few minutes of anaesthesia and the early postanaesthetic period.

e.       Occurs with all gaseous anaesthetics, but is most prominent with gases that are insoluble in blood.

7.       Minimum alveolar anaesthetic concentration (MAC):

a.    The concentration at 1 atmosphere pressure which causes immobility in 50% of patients when exposed to a noxious stimulus such as surgical incision.

b.    MAC of different anaesthetics provides a comparison of their relative potency.

c.       Nitrous oxide is the least potent with a MAC value of greater than 100% while that for halothane is 0.75%.

d.    The dose administered can be stated in multiples of MAC.

e.    MAC is decreased in elderly patients and in the presence of adjuvant drugs such as opioid analgesics or sedative-hypnotics.

Nitrous oxide

1.       Neither flammable nor explosive, it is a non-irritating and odorless gas which produces light anaesthesia without depressing the respiratory of vasomotor center.

2.       Advantages:

a.       Reduces the requirements for other more effective and toxic anaesthetic agents.

b.    Has a strong analgesic action.

c.       Induction is rapid and not unpleasant.

d.       Recovery time rarely exceeds 4min even after prolonged administration.

3.       Disadvantages:

a.       Expensive to buy and to transport.

b.    Must be used in conjunction with more effective anaesthetics and muscle relaxants to produce a state of full surgical anaesthesia.

4.       Uses:

a.       Maintain surgical anaesthesia in combination with other agents, e.g. halothane, isoflurane, thiopentone or ketamine and muscle relaxants.

b.    In 50% concentration with oxygen (Entonox), it provides analgesia for obstetric practice, for emergency management of injuries, during postoperative physiotherapy and for refractory pain in terminal illness.

5.       Dosage: for maintenance of anaesthesia, nitrous oxide must always be mixed with at least 30% oxygen.

6.       Contraindications:

a.       Intestinal obstruction.

b.       Occlusion of middle ear.

c.       Arterial air embolism.

d.       Severe chronic obstructive airway disease.

e.       Emphysema.

7.       Adverse effects:

a.       Incidence of nausea and vomiting increases with the duration of anaesthesia.

b.       Slight teratogenic risk.

c.    May cause bone marrow depression after prolonged use.

Halothane and other halogenated agents

1.    A colorless, volatile liquid with a sweet smell.

2.    In anaesthetic dosage, it depresses both cerebral function and sympathetic autonomic activity.

3.       Advantages:

a.    Has high therapeutic efficacy.

b.    Non-irritant and non-flammable.

c.       Induction is smooth and rapid.

d.       Surgical anaesthesia can be produced in 2 – 5 min.

e.    Does not augment salivary or bronchial secretions.

f.       Recovery time is rapid and the incidence of postoperative nausea and vomiting is low.

g.       Diffusion hypoxia is insignificant.

4.       Disadvantages:

a.    Little margin exists between the dose needed to produce respiratory and vasomotor depression.

b.       Usually combined with nitrous oxide.

c.       Sensitizes the heart to the dysrhythmic effects of catecholamines and hypercapnia.

d.    20% is metabolized and it induces hepatic enzymes.

5.       Contraindications:

a.       History of unexplained jaundice.

b.       Family history of malignant hyperthermia.

c.       Raised cerebrospinal fluid pressure.

6.       Adverse effects:

a.       Causes a dose-dependent decrease in blood pressure.

b.       Bradycardia.

c.       Cardiac arrhythmias: AV dissociation, nodal rhythm and ventricular extrasystoles.

d.       Hepatic damage occurs in a small proportion of exposed patients.

e.       Typically fever develops 2 or 3 days after anaesthesia accompanied by anorexia, nausea and vomiting.

f.     In more severe cases this is followed by transient jaundice or very rarely, fatal hepatic necrosis.

7.    Drug interactions:

a.       Halothane potentiates the response to antihypertensives.

b.       Premedication with atropine reduces the risk of hypotension and bradycardia.

8.       Enflurane:

a.    More likely to cause respiratory depression.

b.       Prolonged use results in sufficient release of free inorganic fluoride to cause polyuric renal failure.

9.       Isoflurane:

a.    Has the most favorable risk-benefit profile of the inhalational agents in current use.

b.       Rapid induction.

c.    Tend to cause bronchial irritation.

d.       Minimally metabolized.

e.    Has least effect in increasing cerebral blood flow.

f.       Causes least depression of the myocardium.

Oxygen in anaesthesia

1.       Oxygen should be added routinely to inhalational agents to protect against hypoxia.

2.    The concentration of oxygen in inspired anaesthetic gases should never be less than 21%.