This document discusses properties of inhalational anesthetic agents. It notes that halothane has a pleasant odor and allows for rapid induction of anesthesia. However, it can cause arrhythmias and liver toxicity with repeated use. While it provides muscle relaxation and bronchodilation, disadvantages include poor analgesia and risk of post-operative shivering.

1. Inhalational anaesthetic agents

2. Key concepts
• 1. The greater the uptake of anesthetic agent, the greater the
difference between inspired and alveolar concentration, and the slower
the rate of induction.
• 2. Three factors affect anesthetic uptake: solubility in the blood,
alveolar blood flow and the difference in partial pressure between
alveolar gas and venous blood.
• 3. Low output states predispose patients to over dosage with soluble
agents, as the rate of rise in alveolar concentrations will be markedly
increased.
• 4. Many of the factors that speed induction also speed recovery:
elimination of rebreathing, high fresh gas flows, low anesthetic circuit
volume, low absorption by the anesthetic circuit, decreased solubility, high
cerebral blood flow, and increased ventilation.
• 5. The unitary hypothesis proposes that all inhalational agents share a
common mechanism of action at the molecular level. This is supported by
the observation that the anesthetic potency of inhalation agents
correlates directly with their lipid solubility.

3. Con…
• 6. The minimum alveolar concentration (MAC) is the alveolar concentration of
an inhalational anesthetic that prevents movement in 50% of patients in response
to a standardized stimulus (e.g. surgical incision).
• 7. Prolonged exposure to anesthetic concentrations of nitrous oxide can result
in bone marrow depression (megaloblastic anemia) and even neurological
deficiencies (peripheral neuropathies).
• 8. Halothane hepatitis is extremely rare (1 per 35000 cases). Patients exposed
to multiple halothane anesthetics at short intervals, middle aged obese women,
and persons with a familial predisposition to halothane toxicity or a personal
history of toxicity are considered to be at increased risk. Isoflurane undergo much
less metabolism than halothane, resulting in fewer of the metabolite protein
adducts that lead to immunologically mediated hepatic injury.
• 9. Isoflurane dilates coronary arteries, but is not nearly as potent a dilator as
nitroglycerin or adenosine. Dilation of normal coronary arteries could theoretically
divert blood away from fixed stenotic lesions.
• 10. Non pungency and rapid increase in alveolar anesthetic concentration make
sevoflurane an excellent choice for smooth and rapid inhalation inductions in
pediatric and adult patients.

4. Properties of the ideal inhalational
anaesthetic agent
• (1) Pleasant odor, non-irritant to the respiratory tract
and allow pleasant and rapid induction of anaesthesia.
• (2) Low blood/ gas solubility, which permits rapid
induction of and rapid recovery from anaesthesia.
• (3) Chemically stable in storage, not interact with the
material of anaesthetic circuits or with soda lime.
• (4) Neither flammable nor explosive.
• (5) Produce unconsciousness, analgesia and some
degree of muscle relaxation.
• (6) Potent enough to allow the use of high inspired
oxygen concentration.

5. Con…
• (7) Not metabolized in the body, non- toxic
and not provoke allergic reactions.
• (8) Minimal depression of CVS and RS and
should not interact with other drugs used
commonly during anaesthesia e.g. presser
agents or catecholamines.
• (9) It should be completely inert and
eliminated completely and rapidly in an
unchanged form via the lungs.

6. Minimum alveolar anaesthetic
concentration (MAC)
• The minimum alveolar concentration (MAC) is
the alveolar concentration of an inhalational
anesthetic that prevents movement in 50% of
patients in response to a standardized
stimulus (e.g. surgical incision).

7. MAC values vary under the following
circumstances
• (1) ↓in pre medicated patients.
• (2) ↓in presence of N2O.
• (3) Change in some diseases, e.g. ↑ in thyrotoxicosis and ↓ in
myxoedema.
• (4) ↑ in pyrexia.
• (5) ↑ in sympathoadrenal stimulation induced, for example, by
hypercapnia.
• (6) ↓ with advancing age. MAC is higher in infants and neonates
than in adults and ↓ with advancing years.
• (7) Drugs which affect release of CNS neurotransmitters affect MAC.
MAC ↑ in the presence of ephedrine and ↓ by methyldopa,
pancuronium and clonidine.
• (8) As atmospheric pressure ↑, MAC ↓, and vice versa

8. Halothane
• Colorless liquid with a relatively pleasant
smell.
• A relatively low blood/gas solubility
coefficient, thus induction of anaesthesia is
relatively rapid.
• Approximately 20% metabolized in the liver.

9. RS:
Non irritant and pleasant to breathe during
induction. There is rapid loss of pharyngeal
and laryngeal reflexes and inhibition of salivary
and bronchial secretions increase in ventilatory
rate and reduction in tidal volume.
PaCO2 increases as the depth of halothane
anaesthesia increases.
Halothane antagonizes bronchospasm and
reduces airway resistance in patients with
bronchoconstriction.

10. CVS:
Halothane is a potent depressant of
myocardial contractility. Thus, there is a
reduction in arterial pressure. Reduction in
heart rate which is treated by atropine and this
will improve the blood pressure.
Arrhythmias are very common during
halothane anaesthesia and fare more frequent
than with isoflurane.

11. Arrhythmias are produced by:
(1) Increased myocardial excitability
augmented by the presence of hypercapnia,
hypoxaemia or increased circulating
catecholamine.
(2) Bradycardia caused by central vagal
stimulation.
During local infiltration with adrenaline or
adrenaline containing local anaesthetic
solutions, multifocal ventricular extra systoles
and sinus tachycardia have been observed and
cardiac arrest has been reported.

12. Thus, caution should be exercised when these
solutions are used. The following
recommendations have been made:
(1) Avoid hypoxaemia and hypercapnia.
(2) Avoid concentration of adrenaline greater
than 1 in 100 000.
(3) avoid a dosage in adults exceeding 10 ml of
1in 100 000 adrenaline in10 min or 30 ml per
h.
So that doses of epinephrine above 1.5 mcg/kg
should be avoided.

13. Cerebral:
By dilating cerebral vessels, halothane lowers
cerebral vascular resistance and increases CBF.
Autoregulation, the maintenance of constant
CBF during changes in arterial blood pressure,
is blunted. Concomitant rises in intracranial
pressure can be prevented by establishing
hyperventilation prior to administration of
halothane. Cerebral activity is decreased,
leading to EEG slowing and modest reductions
in metabolic oxygen requirements.

14. Renal:
Halothane reduces renal blood flow,
glomerular filtration rate, and urinary output.
Part of this decrease can be explained by a fall
in arterial blood pressure and cardiac output.
Because the reduction in renal blood flow is
greater than the reduction in glomerular
filtration rate, the filtration fraction is
increased. Preoperative hydration limits these
changes.

15. Hepatic:
Halothane causes hepatic blood flow to
decrease in proportion to the depression of
cardiac output. Hepatic artery vasospasm has
been reported during halothane anesthesia.
The metabolism and clearance of some drugs
(e.g. fentanyl, phenytoin, and verapamil) seem
to be impaired by halothane.

16. Pregnant uterus:
Halothane relaxes pregnant uterine muscle
and cause post-partum haemorrhage. A
concentration of less than 0.5% is not
associated with increased blood loss during
anaesthesia for CS, but causes increased blood
loss during therapeutic abortion.

17. Skeletal muscle:
Halothane causes skeletal muscle
relaxation and potentiates non depolarizing
relaxants. Post-operatively, shivering is
common; this increases oxygen requirements
and results in hypoxaemia unless oxygen is
administered.

18. Contraindications:
It is prudent to withhold halothane from
patients with unexplained liver dysfunction
following previous anesthetic exposure.
Halothane, like all inhalational anesthetics,
should be used with care in patients with
intracranial mass lesions because of the
possibility of intracranial hypertension
secondary to increased cerebral blood volume
and blood flow.
Hypovolemic patients and some patients with
severe reductions in left ventricular function
may not tolerate halothanes negative inotropic
effects. Sensitization of the heart to
catecholamines limits the usefulness of
halothane when exogenous epinephrine is
administered or in patients with
pheochromocytoma.

19. Drug interactions:
The myocardial depression seen with
halothane is exacerbated by ẞ adrenergic
blocking agents and calcium channel blocking
agents. Tricyclic antidepressants and
monoamine oxidase inhibitors have been
associated with fluctuations in blood pressure
and arrhythmias, although neither represents
an absolute contraindication. The combination
of halothane and aminophylline has resulted in
serious ventricular arrhythmias.

20. In Summary
• halothane is very useful inhalational anaesthetic
agent.
• Its main advantages are:
• (1) Rapid, smooth induction.
• (2) Minimal stimulation of salivary and bronchial
secretions, prior administration of atropine is
unnecessary.
• (3) Bronchodilatation.
• (4) Muscle relaxation.
• (5) Relatively rapid recovery.

21. Con…
• The disadvantages are:
• (1) Poor analgesia.
• (2) Arrhythmias.
• (3) Post-operative shivering.
• (4) Possibility of liver toxicity, especially with
repeated administration.