Desflurane was developed in the 1990s and has the lowest blood-gas solubility of all inhalational anesthetic agents, allowing for the fastest induction and recovery. It is prepared through a multistep chemical process and requires a specialized vaporizer due to its low boiling point. Desflurane causes dose-dependent cardiovascular and respiratory depression as well as muscle relaxation. While it has rapid onset and offset, it is also highly irritating to the airway and its use requires careful monitoring due to potential for sympathetic stimulation.
2. HISTORY AND PREPARATION
● Desflurane was produced by Dr.Ross Terell along with
isoflurane, sevoflurane and enflurane.
● Desflurane was approved for clinical use in the USA in
1992.
● Desflurane is prepared by reacting hexafluoropropene
epoxide with methanol to form methyl 2-
methoxytetrafluoropropionate which is hydrolyzed to the
corresponding acid.
3. How is it prepared?
● The acid is decarboxylated to form 1,2,2,2-
tetrafluoroethyl methyl ether which is then chlorinated to
form 1,2,2,2-tetrafluoroethyl dichloromethyl ether.
● Fluorine-chlorine exchange of the ether by conventional
fluorination produces desflurane.
4. Physical properties
● Desflurane has a pungent odour, which makes it irritating and
unpleasant to inhale and produces appreciable incidence of
salivation, breath-holding, coughing, or laryngospasm when given to
an awake patient.
● It has a boiling point of 22.8 °C, which is just above room
temperature, and its SVP of 88.3 kPa (664 mmHg) at 20°C. This
means that it cannot be administered using a standard vaporizer.
5. ● To facilitate accurate delivery of desflurane, a new vaporizer
has been developed ,in which the anesthetic agent is
converted to a gas ,by heating it to a constant temperature
and maintaining it at a constant pressure [about 200kPa
/1500 mmHg].
● It is then mixed in a controlled fashion with the carrier gas.
● Unlike other vaporizers, this is a heated and pressurized
vaporizer that needs an external power source.
7. ● Desflurane has a blood-gas solubility coefficient of 0.42,the
lowest of all the inhalational agents available with the
exception of xenon, which means equilibration and recovery
should occur quickly.
● It has a lower solubility in rubber and plastic than halothane,
isoflurane, or sevoflurane.
● The MAC of desflurane varies from 4.58% to 7.25%
depending on the stimulus used, and as with the other
agents the MAC decreases with increasing age.The MAC is
reduced by nitrous oxide.
8. Pharmacokinetics
● Desflurane has the lowest blood-gas solubility of all the
volatile anesthetic agents, and thus results in fastest
induction and recovery.
● The elimination of desflurane is also faster. It is almost
exclusively through the lungs, with metabolism by the liver
estimated to be less than 0.02%
● The distribution of desflurane follows a five-compartment
model which, may be as follows - the lungs, the vessel-rich
group of organs, muscle, fat around the vessel-rich organs,
and, finally peripheral fat.
9. ● Desflurane undergoes minimal metabolism which is seen by
increased serum and urinary trifluoroacetate , but the levels
were only about 1/10th of the levels seen after exposure to
isoflurane.
● Desflurane is degraded by desiccated CO2 absorbent,
mainly Ba(OH)2 lime, into clinically significant levels of
carbon monoxide.
● Presence of carboxyhemoglobin may be detected by arterial
blood gas analysis
● Disposing dried out absorbent or use of Ca(OH)2 can
minimise the risk of CO poisoning.
10. Pharmacodynamics
● CVS Effects-
-Desflurane causes a dose-dependent tachycardia in
that is associated with a depression in myocardial
contractility and a decrease in the SVR resulting from
peripheral vasodilation. These changes occur at
concentrations ranging from 0.83-1.66 MAC.
-Desflurane is a direct coronary vasodilator and produces an
overall reduction in cardiac work.
11. - A rapid increase in the concentration of desflurane to greater
than 1 MAC will cause an increase in heart rate and blood
pressure .
- This transient cardiovascular stimulation
is greater with desflurane than with isoflurane, and it is
reduced by nitrous oxide. It can be significantly attenuated
by small doses of opioids, clonidine, or esmolol.
12. ● CNS Effects-
-Desflurane causes dose-dependent cerebral vasodilation,thus
increasing CBF, cerebral blood volume and intracranial
pressure at normotension and normocapnia.
-There is marked reduction in cerebral metabolic rate of O2
that causes cerebral vasoconstriction and moderate any
increase in CBF.
-Cerebral oxygen consumption is decreased during desflurane
anaesthesia.
13. -Thus, during periods of desflurane-induced hypotension, CBF is
adequate to maintain aerobic metabolism despite a low
cerebral perfusion pressure.
- Desflurane produces a dose-dependent burst suppression of
the EEG at concentrations greater than 1.24 MAC, and at a
MAC of greater than 1.66 the EEG becomes isoelectric.
-The more rapid recovery associated with desflurane anesthesia
may offer a small advantage in patients undergoing prolonged
neurosurgical procedures.
14. ● Respiratory Effects-
- Desflurane is a potent respiratory depressant.
- Desflurane causes a decrease in tidal volume and an
increase in respiratory rate with an overall reduction in
minute alveolar ventilation.
- Desflurane is unsuitable for an inhalation induction because it
is extremely irritating to the airway. Despite this fact, the
incidence of bronchospasm in asthmatics is not increased
during the induction of anesthesia with desflurane.
15. ● Neuromuscular Effects-
-Desflurane is associated with dose-dependent decrease in
the response to train of four and tetanic peripheral nerve
stimulation.
-It can provide sufficient relaxation to allow tracheal
intubation. This effect is independent of the duration of
anaesthesia.
-It also potentiates the action of nondepolarizing muscle
relaxants to the same degree as isoflurane.
16. Clinical uses
● Desflurane has the lowest blood-gas solubility of the halogenated
anesthetic agents, and therefore provides the most rapid induction
and recovery.
● Desflurane is 1/4th as potent as other volatile agents, but 17 times
more potent than nitrous oxide.
● It undergoes minimal metabolism, and thus the risk of toxicity
from metabolites is expected to be very low, although it is
metabolized to TFA, which has been implicated in hepatotoxicity.
17. Disadvantages
● Desflurane is quite irritating to the airway and therefore it is
not suitable for an inhalation induction.
● Rapid changes in the inspired concentration are associated
with sympathetic stimulation, resulting in hypertension and
tachycardia, and there are also some concerns about its use
in patients with ischemic heart disease.
● It offers no advantage over sevoflurane except for a lower
blood-gas solubility coefficient, a property that may have no
significant clinical impact.