DESFLURANE

Dr.J.N.Sahitya1st Year PGDept of AnaesthesiologyChairperson- Dr.Satyanarayana

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.

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.

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.

● 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.

desflurane vaporiser

● 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.

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.

● 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.

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.

- 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.

● 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.

-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.

● 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.

● 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.

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.

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.

Properties Halothane Isoflurane Sevoflurane Desflurane

Boiling Point 50.2 ℃ 48.5 ℃ 58.5 ℃ 22.8 ℃

MAC 0.75 1.15 2.1 6 - 7.25

Saturated Vapor Pressure

243 239 160 678

Blood - Gas Solubility Coefficient

2.5 1.4 0.69 0.42

Oil - Gas Solubility Coefficient

60 45 48 27

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