Sevoflurane Nitrous oxide

Agents that have low solubility in blood, i.e., a low blood/gas partition coefficient (nitrous oxide, sevoflurane), provide a rapid induction of anaesthesia because the blood reservoir is small and agent is available to pass into the brain sooner. 

Fentanyl, ketamine, midazolam, propofol, thiopental Enflurane, desflurane, halothane, isoflurane, nitrous oxide, sevoflurane... 

Vereecke HE, Proost JH, Heyse B, Eleveld DJ, Katoh T, Luginbuhl M, et al. Interaction between nitrous oxide, sevoflurane, and opioids a response surface approach. Anesthesiology 2013 118 894—902. 

Sevoflurane. Sevoflurane, l,l,l,3,3,3-hexafluoro-2-propyl fluromethyl ether [28523-86-6] is nonpungent, suggesting use in induction of anesthesia. The blood/gas partition coefficient is less than other marketed products (Table 1) yet similar to nitrous oxide, suggesting fast onset and recovery. In animal studies, recovery was faster for sevoflurane than for isoflurane, enflurane, or halothane (76). Sevoflurane is stable to light, oxygen, and metals (28). However, the agent does degrade in soda lime (77). 

Two methods of anaesthesia are currently in use, the application of inhaled gaseous or volatile anaesthetics such as halothane, sevoflurane and isoflurane to maintain a level of anaesthesia. Older compounds in this category include nitrous oxide and chloroform. 

General anaesthetics are administered for many surgical procedures where the patient is likely to undergo a severely painful procedure, and complete unconsciousness and immobility is required for the surgety to be performed. The most commonly used volatile anaesthetics are halothane, isoflurane and sevoflurane. Nitrous oxide is also commonly used, particularly during... 

The distribution of anesthetic throughout the entire body may be viewed as an equilibration process (Fig. 7.1.13), with tissues characterized by high blood flows reaching equilibration faster than muscle and fatJ4 Nevertheless, an anesthetic that is excessively soluble in blood will not partition substantially into brain and other tissues. The anesthetic properties of nitrous oxide and diethyl ether have been known since the 1840s. Zeneca Pharmaceuticals introduced the first modem inhalation anesthetic fluothane in 1957. Methoxyfluorane followed in 1960, enflurane 1973, isoflurane 1981, desflurane by Anaquest (Liberty Comer, NJ) in 1992, and sevoflurane by Abbott Laboratories in 1995J6 ... 

Halothane Isoflurane Enflurane Sevoflurane Desflurane Nitrous oxide... 

Children (1 year of age and older) - The table below summarizes the recommended doses in pediatric patients, predominantly American Society of Anesthesiologists (ASA) physical status I, II, or III. In pediatric patients, remifentanil was administered with nitrous oxide or nitrous oxide in combination with halothane, sevoflurane, or isoflurane. 

Inhalation anesthetics still in use include nitrous oxide and the halogenated hydrocarbon inhalation anesthetics such as halothane, isoflurane, methoxyflurane and sevoflurane. 

Sevoflurane has a dose-dependent effect on cerebral blood flow and intracranial pressure cerebral autoregulation is preserved (this is not the case with isoflurane). During hypocarbia, in the absence of nitrous oxide, 1 MAC does not increase intracranial pressure (ICP). It reduces the cerebral metabolic rate for oxygen (CMR02) by approximately 50% at concentrations approaching 2 MAC. This is similar to the reduction observed during isoflurane anaesthesia. 

For inhalational induction of anaesthesia in children, 6% sevoflurane in 50% nitrous oxide and oxygen is probably optimal. However, some anaesthetists consider it to be inferior to halothane for the management of the irritable or constricted airway and for anaesthesia for bronchoscopy. Sevoflurane is preferred for dental procedures as there is a lower risk of cardiac arrhythmias than with halothane, especially in children. In children with congenital heart disease, whereas the cardiac index is reduced by halothane it is preserved with sevoflurane. In adults, 8% sevoflurane is well tolerated and, provides rapid induction of anaesthesia without adversely affecting haemodynamic stability. 

These are shown in Table 3.3. Xenon (MAC 70%) has a potency of about twice that of nitrous oxide (MAC 104%). Thus, it can be given in anaesthetic concentrations in o> gen with less risk of hypoxia. It is highly insoluble in all body tissues with a blood/gas partition coefficient of 0.14 (nitrous oxide, 0.47 sevoflurane, 0.65 desflurane, 0.42). 

Rapidity of recovery has been one of the most consistent and compelling features of anaesthesia with xenon. After 2 hours of xenon anaesthesia recovery is two to three times as fast as recovery from equi-MAC mixtures of N20/sevoflurane and N20/isoflurane. Marked emetic effects after both nitrous oxide and xenon were reported in a volunteer study, but this was conducted under highly artificial conditions. 

An anxious 5-year-old child with chronic otitis media and a history of poorly controlled asthma presents for placement of ventilating ear tubes. General anesthesia is required for this short elective ambulatory surgery procedure. What preanesthetic medication should be administered Which of the three commonly used anesthetic techniques would you choose to use in this situation (1) inhalational anesthesia with sevoflurane for induction and maintenance in combination with nitrous oxide, (2) intravenous anesthesia with propofol for induction and maintenance of anesthesia in combination with remifentanil, or (3) balanced anesthesia using propofol for induction of anesthesia followed by a combination of sevoflurane and nitrous oxide for maintenance of anesthesia ... 

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. 

Inhaled anesthetics that are relatively insoluble in blood (ie, possess low blood gas partition coefficients) and brain are eliminated at faster rates than the more soluble anesthetics. The washout of nitrous oxide, desflurane, and sevoflurane occurs at a rapid rate, leading to a more rapid recovery from their anesthetic effects compared with 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- and isoflurane-based anesthesia is predictably less rapid. 

The metabolism of enflurane and sevoflurane results in the formation of fluoride ion. However, in contrast to the rarely used volatile anesthetic methoxyflurane, renal fluoride levels do not reach toxic levels under normal circumstances. In addition, sevoflurane is degraded by contact with the carbon dioxide absorbent in anesthesia machines, yielding a vinyl ether called "compound A," which can cause renal damage if high concentrations are absorbed. (See Do We Really Need Another Inhaled Anesthetic ) Seventy percent of the absorbed methoxyflurane is metabolized by the liver, and the released fluoride ions can produce nephrotoxicity. In terms of the extent of hepatic metabolism, the rank order for the inhaled anesthetics is methoxyflurane > halothane > enflurane > sevoflurane > isoflurane > desflurane > nitrous oxide (Table 25-2). Nitrous oxide is not metabolized by human tissues. However, bacteria in the gastrointestinal tract may be able to break down the nitrous oxide molecule. 

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 (volatile) anesthetics potentiate the neuromuscular blockade produced by nondepolarizing muscle relaxants in a dose-dependent fashion. Of the general anesthetics that have been studied, inhaled anesthetics augment the effects of muscle relaxants in the following order isoflurane (most) sevoflurane, desflurane, enflurane, and halothane and nitrous oxide (least) (Figure 27-9). The most important factors involved in this interaction are the following (1) nervous system depression at sites proximal to the neuromuscular junction (ie, central nervous system) (2) increased muscle blood flow (ie, due to peripheral vasodilation produced by volatile anesthetics), which allows a larger fraction of the injected muscle relaxant to reach the neuromuscular junction and (3) decreased sensitivity of the postjunctional membrane to depolarization. 

Nishiyama T, Yamashita K, Yokoyama T. Stress hormone changes in general anesthesia of long duration isoflura-ne—nitrous oxide vs sevoflurane—nitrous oxide anesthesia. J Clin Anesth 2005 17(8) 586-91. 

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. 

An increase in pulmonary blood flow (increased cardiac output) slows the rate of rise in arterial tension, particularly for those anesthetics with moderate to high blood solubility. This is because increased pulmonary blood flow exposes a larger volume of blood to the anesthetic thus, blood "capacity" increases and the anesthetic tension rises slowly. A decrease in pulmonary blood flow has the opposite effect and increases the rate of rise of arterial tension of inhaled anesthetics. In a patient with circulatory shock, the combined effects of decreased cardiac output (resulting in decreased pulmonary flow) and increased ventilation will accelerate the induction of anesthesia with halothane and isoflurane. This is not likely to occur with nitrous oxide, desflurane, or sevoflurane because of their low blood solubility. 

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. 

An interaction of sevoflurane with cyamemazine was suggested as a possible explanation, without precluding a role of nitrous oxide. 

Most commonly with nitrous oxide and oxygen, or oxygen and air, plus a volatile agent, e.g., isoflurane or sevoflurane. Additional doses of a neuromuscular blocker or opioid are given as required. 

A study of single vital-capacity breath inhalational induction using either isoflurane or sevoflurane combined with 67% nitrous oxide in 67 adults showed that isoflurane was unsuitable for this technique (16). There was an 87% incidence of induction complications with isoflurane, including involuntary movements, cough, laryngospasm, and failure of induction. 

In 75 patients of ASA grades 1 or 2, recovery from anesthesia after maintenance with isoflurane + nitrous oxide was significantly slower than with sevoflurane + nitrous oxide (17). 

---