Desflurane agent

Desflurane is less potent than the other fluorinated anesthetics having MAC values of 5.7 to 8.9% in animals (76,85), and 6% to 7.25% in surgical patients. The respiratory effects are similar to isoflurane. Heart rate is somewhat increased and blood pressure decreased with increasing concentrations. Cardiac output remains fairly stable. Desflurane does not sensitize the myocardium to epinephrine relative to isoflurane (86). EEG effects are similar to isoflurane and muscle relaxation is satisfactory (87). Desflurane is not metabolized to any significant extent (88,89) as levels of fluoride ion in the semm and urine are not increased even after prolonged exposure. Desflurane appears to offer advantages over sevoflurane and other inhaled anesthetics because of its limited solubiHty in blood and other tissues. It is the least metabolized of current agents. 

After drawing and labelling the axis draw a series of build-up negative exponential curves with different gradients as shown. The order of the curves is according to the blood gas partition coefficients. The more insoluble the agent, the steeper the curve and the faster the rate of onset. The exceptions to this are the N20 and desflurane curves, which are the opposite way round. This is because of the concentration effect when N20 is administered at... 

Desflurane stimulates the sympathetic nervous system and causes abrupt transient tachycardia during induction or as the concentration of the agent is raised to meet the patient s changing needs. 

It is a noninflammable, non-irritant agent and chemically related to ether. Induction with this agent is smooth and rapid. The respiratory, hemodynamic and other changes caused by desflurane are similar to those of isoflurane. This agent is undergoing clinical trial. 

An increase in alveolar ventilation will cause an increase in the alveolar concentration of inhaled agent when semi-closed or open breathing circuits are employed. The effect is most noticeable with a highly soluble anaesthetic, such as diethyl ether. With modern, relatively insoluble agents, such as isoflurane and desflurane, the effects of changes in alveolar ventilation are less pronounced. 

The stability of modern volatile agents is the result of the heavy fluorination of the ether molecule. The effect is most pronounced for CF3 and CF2 moieties. In the case of desflurane, of the eight available binding sites for halogens, six are occupied by fluorine atoms. Similarly, sevoflurane has seven fluorine atoms out of a possible ten. The lack of hydrogen atoms reduces both flammability and potency. 

Sevoflurane, in common with all volatile agents, reduces cardiac output and systemic blood pressure. It does so mainly through a reduction in peripheral vascular resistance. Although it is a systemic vasodilator it does not appear to produce significant dilatation of small coronary vessels and there is no possibility of coronary steal as hypothesised for isoflurane. A small increase in heart rate may be observed. This is less pronounced than with isoflurane and desflurane and is almost certainly the result of reflex activity secondary to the reduction in peripheral vascular resistance. Sevoflurane is associated with a stable heart rhythm and does not predispose the heart to sensitisation by catecholamines. In children, halothane causes a greater decrease in heart rate, myocardial contractility and cardiac output than sevoflurane at all concentrations. For these reasons sevoflurane is advocated for use in outpatient dental anaesthesia, especially in children. 

Desflurane is a fluorinated methyl ethyl ether identical to isoflurane except for the substitution of a chlorine by a fluorine atom (Figure 3.2). It is the least soluble of all the volatile anaesthetics with a similar blood/gas solubility to nitrous oxide (0.42). It is non-flammable under all clinical conditions. The vapour pressure of desflurane approaches 1 atm at 23°C making controlled administration impossible with a conventional vaporiser. A desflurane vaporiser is an electronically controlled pressurised device that delivers an accurately metered dose of vaporised desflurane into a stream of fresh gases passing through it. The MAC of desflurane (6.5% in adults) is the highest of any modern fluorinated agent but in common with these the value decreases in the elderly and in other circumstances (see below). 

Desflurane does not have a marked bronchodilator effect and in cigarette smokers it is associated with significant bronchoconstriction. In clinical practice, both humidification of inspired gases and opioids are thought to reduce airway irritability but even at moderate concentrations (2 MAC), desflurane is more likely to cause coughing than sevoflurane. In common with other volatile agents, desflurane causes dose-related respiratory depression. Tidal volume is reduced and respiratory rate increases, initially. As inspired concentrations of desflurane increase, the trend is to hypoventilation and hypercardia and apnoea is to be expected at concentrations of 1.5 MAC or greater. 

The chemical structures of the currently available inhaled anesthetics are shown in Figure 25-2. The most commonly used inhaled anesthetics are isoflurane, desflurane, and sevoflurane. These compounds are volatile liquids that are aerosolized in specialized vaporizer delivery systems. Nitrous oxide, a gas at ambient temperature and pressure, continues to be an important adjuvant to the volatile agents. However, concerns about environmental pollution and its ability to increase the incidence of postoperative nausea and vomiting (PONV) have resulted in a significant decrease in its use. 

Desflurane 0.42 1.3 6-7 < 0.05% Low volatility poor induction agent (pungent) rapid recovery... 

The newer volatile anesthetics, desflurane and sevoflurane, have physicochemical characteristics (ie, low blood gas partition coefficients) that are favorable to a more rapid onset and shorter duration of anesthetic actions compared with isoflurane and halothane. However, both of these newer agents also have certain limitations. The low volatility of desflurane necessitates the use of a specialized heated vaporizer, and the pungency of the drug leads to a high incidence of coughing and sympathomimetic side effects that make it less than ideally suited for induction of anesthesia. 

Sevoflurane comes close to having the characteristics of an ideal inhaled anesthetic however, a more insoluble compound that lacks the pungency of desflurane and has greater chemical stability than sevoflurane could be a useful alternative to the currently available inhaled agents. One of the possible new inhaled anesthetics that could be developed for clinical use in the future is xenon. However, the high cost of this novel drug may preclude its use in routine clinical practice. 

Of the inhaled anesthetics, nitrous oxide is the least likely to increase cerebral blood flow. At low concentrations, all of the halogenated agents have similar effects on cerebral blood flow. However, at higher concentrations, the increase in cerebral blood flow is less with the less soluble agents such as desflurane and sevoflurane. If the patient is hyperventilated before the volatile agent is started, the increase in intracranial pressure can be minimized. 

Halothane, isoflurane, and enflurane have similar depressant effects on the EEG up to doses of 1-1.5 MAC. At higher doses, the cerebral irritant effects of enflurane may lead to development of a spike-and-wave pattern and mild generalized muscle twitching (ie, myoclonic activity). However, this seizure-like activity has not been found to have any adverse clinical consequences. Seizure-like EEG activity has also been described after sevoflurane, but not desflurane. Although nitrous oxide has a much lower anesthetic potency than the volatile agents, it does possess both analgesic and amnesic properties when used alone or in combination with other agents as part of a balanced anesthesia technique. 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

Inhaled anesthetics currently in use include halo-genated volatile liquids such as desflurane, enflurane, halothane, isoflurane, methoxyflurane, and sevoflurane (Table 11-1). These volatile liquids are all chemically similar, but newer agents such as desflurane and sevoflurane are often used preferentially because they permit a more rapid onset, a faster recovery, and better control during anesthesia compared to older agents such as halothane.915 These volatile liquids likewise represent the primary form of inhaled anesthetics. The only gaseous anesthetic currently in widespread use is nitrous oxide, which is usually reserved for relatively short-term procedures (e.g., tooth extractions). Earlier inhaled anesthetics, such as ether, chloroform, and cyclopropane, are not currently used because they are explosive in nature or produce toxic effects that do not occur with the more modern anesthetic agents. 

Inhaled anesthetics that are relatively insoluble in blood (low blood gas partition coefficient) and brain are eliminated at faster rates than more soluble anesthetics. The washout of nitrous oxide, desflurane, and sevoflurane occurs at a rapid rate, which leads to a more rapid recovery from their anesthetic effects compared to halothane and isoflurane. Halothane is approximately twice as soluble in brain tissue and five times more soluble in blood than nitrous oxide and desflurane its elimination therefore takes place more slowly, and recovery from halothane anesthesia is predictably less rapid. The duration of exposure to the anesthetic can also have a marked effect on the time of recovery, especially in the case of more soluble anesthetics. Accumulation of anesthetics in tissues, including muscle, skin, and fat, increases with continuous inhalation (especially in obese patients), and blood tension may decline slowly during recovery as the anesthetic is gradually eliminated from these tissues. Thus, if exposure to the anesthetic is short, recovery may be rapid even with the more soluble agents. However, after prolonged anesthesia, recovery may be delayed even with anesthetics of moderate solubility such as isoflurane. 

Desflurane has the lowest blood/gas partition coefficient of any inhaled anaesthetic agent and thus gives particularly rapid onset and offset of effect. As it undergoes negligible metabolism (0.03%), any release of free inorganic fluoride is minimised this characteristic favours its use for prolonged anaesthesia. Desflurane is extremely volatile and caimot be administered with conventional vaporisers. It has a very pimgent odour and causes airway irritation to an extent that limits its rate of induction of anaesthesia. 

This patient had multiple risk factors for anesthesia-induced hepatitis, including obesity, middle age, female sex, a history of drug allergies, and multiple exposures to fluorinated anesthetic agents. Desflurane has a very low rate of hepatic oxidative metabolism (0.02 versus 20% for halothane), and is considered to be one of the safest volatile agents as far as hepatotoxicity is concerned. Nevertheless, this case shows that it can cause severe hepatotoxicity. 

In old people, the MAC of desflurane, with or without nitrous oxide, was less than that in patients aged 18-65 years. Doses of desflurane must therefore be reduced in older people, as with aU other inhalation agents (16). 

Peripheral neuropathy has been reported in two healthy men anesthetized with 1.25 MAC sevoflurane at 21/minute fresh gas flow for 8 hours. Their average concentrations of compound A were 45 and 28 ppm. Both had had previous minor injuries in the regions in which the neuropathies were reported. The authors suggested that compound A, or other factors associated with sevoflurane anesthesia, may predispose patients to peripheral neuropathy. Both men were volunteers for earlier published studies comparing the nephrotoxic properties of sevoflurane and desflurane, sponsored by Baxter PPD, New Jersey, the manufacturer of desflurane, a rival inhalational anesthetic agent these reports need to be regarded with caution. 

The effects of sevoflurane, isoflurane, and desflurane on macroscopic renal structure have been studied in 24 patients undergoing nephrectomy (35). All anesthetics were administered using a fresh gas flow of 11/minute and a sodium hydroxide absorber and had an average duration of 3 hours. No injury to nephrons was observed by pathologists blinded to which anesthetic agent had been used. Postoperative creatinine concentrations and urine volumes did not differ significantly between the groups. 

Modem inhalation anesthetics are fluoiinated to reduce flammabihty. Initially, these inhaled agents were believed to be biochemically inert. Over the past 30 years, however, research findings have demonstrated that not only are inhaled anesthetics metabolized in vivo [27], but their metabolites are also responsible for both acute and chronic toxicities [28,29]. Therefore, the use of some anesthetics has been discontinued, including methoxyflurane because of its nephrotoxicity and other anesthetics are more selectively used, e.g. halothane due to a rare incidence of liver toxicity. Studies have also provided the impetus to develop new agents - isoflurane and desflurane - with properties that lower their toxic potential. The result has been improved safety, but there is room for further improvement as our insight into toxicological mechanisms expands. 

Halothane and sevoflurane are commonly used for inhaled induction of anesthesia in children because they do not have a noxious smell. These drugs and isoflurane or desflurane are then used to maintain anesthesia, according to the preference of the anesthesiologist. Enflurane is rarely used today because it irritates the airway [115]. Therefore, of the inhaled agents currently used in pediatric patients, only sevoflurane has nephrotoxic potential. 

Desflurane has the lowest bloodigas partition coefficient of all of the modern inhalation anesthetic agents. Rapid onset of anesthesia and short recovery times are associated with its use in horses (Tendillo et al 1997). Mask induction with desflurane in unsedated horses (vaporizer setting 18%, 101/min oxygen flow rate) resulted in... 

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