What is the clinical pharmacology of sevoflurane?
Sevoflurane - Clinical Pharmacology. Sevoflurane is an inhalational anesthetic agent for use in induction and maintenance of general anesthesia. Minimum alveolar concentration (MAC) of Sevoflurane in oxygen for a 40 year old adult is 2.1%. The MAC of Sevoflurane decreases with age (See DOSAGE AND ADMINISTRATION for details).
What is the average concentration of sevoflurane to achieve Mac?
-MAC decreases with increasing age; the average concentration of sevoflurane to achieve MAC in an 80 year old is approximately 50% of that required in a 20 year old. -Know the concentration delivered from a vaporizer during anesthesia; use a vaporizer calibrated specifically for sevoflurane.
What is the Mac of desflurane in oxygen?
For example, in order to maintain a total MAC of 1.2 in an 80‐yr‐old patient using desflurane and nitrous oxide 67% in oxygen, it is clear from Fig. 3 that an increase in the FIO2 from 33 to 100%, associated with eliminating nitrous oxide, requires a compensatory three‐fold increase in the end‐expired concentration of desflurane, from 2 to 6.25%.
What is the Mac of isoflurane for dogs?
As a guide the minimum alveolar concentration (MAC) for isoflurane is approximately 1.3% in the dog and 1.6% in the cat.
What is isoflurane MAC?
Isoflurane. 1.17. Halothane. 0.75. The minimum alveolar concentration (MAC) value is the concentration of an inhalation anesthetic agent in the lung alveoli required to prevent movement in response to a surgical stimulus in 50% of patients.
What is the MAC value of sevoflurane in the cat?
2.58 +/- 0.30%The minimal alveolar concentration (MAC) for sevoflurane in the cats was found to be 2.58 +/- 0.30% (mean +/- SD). The ratios of MAC values between sevoflurane and halothane, enflurane and isoflurane in cats were very similar to those ratios found in humans and dogs.
At what age is the MAC for sevoflurane the highest?
AcknowledgementAgentAge95% CL(± % MAC40)Enflurane2.0817Sevoflurane2.296Desflurane8.310Xenon92164 more rows•Aug 1, 2003
What is the MAC value of sevoflurane in the dog?
approximately 2.4%As a guide the minimum alveolar concentration (MAC) for isoflurane is approximately 1.3% in the dog and 1.6% in the cat. This is considerably lower than the MAC of sevoflurane at approximately 2.4% in both species.
What is the difference between ISO and SEVO?
Isoflurane has more incidence of airway hyper reactivity though milder level, when compared to sevoflurane. Incidence of nausea and vomiting and requirement of postoperative analgesia are comparable in both the groups. Isoflurane is less costly in comparison to sevoflurane.
Is isoflurane more potent than sevoflurane?
Agents with nonoverlapping 95% confidence intervals are significantly different from each other ( i.e. , sevoflurane is more potent than isoflurane), as shown in table 2 .
What does a MAC of 1 mean?
The hypothesis correlates lipid solubility of an anaesthetic agent with potency (1/MAC) and suggests that onset of anaesthesia occurs when sufficient molecules of the anaesthetic agent have dissolved in the cell's lipid membranes, resulting in anaesthesia.
How do you calculate MAC anesthesia?
4:327:46MAC calculation - YouTubeYouTubeStart of suggested clipEnd of suggested clipAnd then we have to take our flow of nitrous oxide. Divide that by our total flow to give us ourMoreAnd then we have to take our flow of nitrous oxide. Divide that by our total flow to give us our percentage of nitrous oxide delivered. And in this case it's simply 2 litres of nitrous oxide.
What is a MAC hour?
Anesthetic gas exposures are quantified in MAC-hours, defined as an exposure at 1 times the minimum alveolar concentration that prevents movement with a noxious stimulus in 50% of subjects (MAC) for 1 hour (2).
What is minimum alveolar concentration in anesthesia?
The minimum alveolar concentration (MAC) is the minimum concentration of an inhaled anesthetic at 1 atm of pressure that prevents skeletal muscle movement in response to a surgical incision in 50% of patients. The MAC of a volatile anesthetic changes with the patient's age (see Table 13-1).
What is the MAC value of nitrous oxide?
Nitrous oxide has low potency (MAC = 104), but its impressive record of safety allows use of sub-MAC concentrations that are ideal in allaying apprehension and anxiety regarding injections of local anesthetics and treatment in general.
How do you calculate oxygen flow through anesthesia?
To calculate this, you take the tidal volume (TV) and multiply it by six. Bag size= (TV) 6 Tidal volume is the volume of air inhaled and exhaled with each breath, 10 -20 ml/kg The number that you get will be in milliliters, so just convert it to liters, and that is the size bag that your patient needs.
Usual Adult Dose for Anesthesia
Surgical levels of anesthesia can usually be achieved with inspired concentrations of 0.5 to 3% sevoflurane with or without the concomitant use of nitrous oxide. Average MAC (minimum alveolar concentration) with sevoflurane in oxygen: -25 year old: 2.6% -40 year old: 2.1% -60 year old: 1.7% Average MAC with sevoflurane in 65% N2O/35% O2: -25 year old: 1.4% -40 year old: 1.1% -60 year old: 0.9% Comments: -Know the concentration delivered from a vaporizer during anesthesia; use a vaporizer calibrated specifically for sevoflurane. -Individualize and titrate dose to the desired effect according to the patient's age and clinical status. -Premedicate according to patient needs, at the discretion of the anesthesiologist. -Suitable for mask induction as it has a nonpungent odor and does not cause respiratory irritability. Use: Induction and maintenance of general anesthesia for inpatient and outpatient surgery.
Usual Geriatric Dose for Anesthesia
Surgical levels of anesthesia can usually be achieved with inspired concentrations of 0.5 to 3% sevoflurane with or without the concomitant use of nitrous oxide. Average MAC (minimum alveolar concentration) with sevoflurane in oxygen: -80 year old: 1.4% Average MAC with sevoflurane in 65% N2O/35% O2: -80 year old: 0.7% Comments: -MAC decreases with increasing age; the average concentration of sevoflurane to achieve MAC in an 80 year old is approximately 50% of that required in a 20 year old. -Know the concentration delivered from a vaporizer during anesthesia; use a vaporizer calibrated specifically for sevoflurane. -Individualize and titrate dose to the desired effect according to the patient's age and clinical status. -Premedicate according to patient needs, at the discretion of the anesthesiologist. -Suitable for mask induction as it has a nonpungent odor and does not cause respiratory irritability. Use: Induction and maintenance of general anesthesia for inpatient and outpatient surgery.
Usual Pediatric Dose for Anesthesia
Surgical levels of anesthesia can usually be achieved with inspired concentrations of 0.5 to 3% sevoflurane with or without the concomitant use of nitrous oxide. Average MAC (minimum alveolar concentration) with sevoflurane in oxygen: -0 to 1 month: 3.3% -1 to less than 6 months: 3% -6 months to less than 3 years: 2.8% -3 to 12 years: 2.5% Average MAC with sevoflurane in 60% N2O/40% O2: -6 months to less than 3 years: 2% Comments: -The concentration required for maintenance of general anesthesia is age dependent. -When used in combination with nitrous oxide, reduce the MAC equivalent dose. -MAC in premature infants has not been determined. -Know the concentration delivered from a vaporizer during anesthesia; use a vaporizer calibrated specifically for sevoflurane. -Individualize and titrate dose to the desired effect according to the patient's age and clinical status. -Premedicate according to patient needs, at the discretion of the anesthesiologist. -Suitable for mask induction as it has a nonpungent odor and does not cause respiratory irritability. Use: Induction and maintenance of general anesthesia for inpatient and outpatient surgery.
Other Comments
Administration advice: -Administer only by persons trained in the administration of general anesthesia. -Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment, and circulatory resuscitation must be immediately available. -Since level of anesthesia may be altered rapidly, only vaporizers producing predictable concentrations of sevoflurane should be used. General: -Replace CO2 absorbent for suspicion of desiccation. Occupational Caution: -There is no specific work exposure limit established for sevoflurane. -The National Institute for Occupational Safety and Health recommends an 8 hour time-weighted average limit of 2 ppm for halogenated anesthetic agents in general (0.5 ppm when coupled with exposure to N2O).
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
What is the MAC of sevoflurane?
Sevoflurane is an inhalational anesthetic agent for use in induction and maintenance of general anesthesia. Minimum alveolar concentration (MAC) of Sevoflurane in oxygen for a 40-year-old adult is 2.1%. The MAC of Sevoflurane decreases with age (see DOSAGE AND ADMINISTRATION for details). Pharmacokinetics.
What is the solubility of sevoflurane?
Because of the low solubility of Sevoflurane in blood (blood/gas partition coefficient @ 37°C = 0.63- 0.69), a minimal amount of Sevoflurane is required to be dissolved in the blood before the alveolar partial pressure is in equilibrium with the arterial partial pressure.
What is the second pathway for degradation of sevoflurane?
The second pathway for degradation of Sevoflurane occurs primarily in the presence of desiccated CO 2 absorbents and leads to the dissociation of Sevoflurane into hexafluoroisopropanol (HFIP) and formaldehyde.
How long can you work with sevoflurane?
There is no specific work exposure limit established for Sevoflurane. However, the National Institute for Occupational Safety and Health has recommended an 8 hour time-weighted average limit of 2 ppm for halogenated anesthetic agents in general (0.5 ppm when coupled with exposure to N 2 O) (see ADVERSE REACTIONS ).
Can sevoflurane cause hyperthermia?
Sevoflurane can cause malignant hyperthermia. It should not be used in patients with known sensitivity to Sevoflurane or to other halogenated agents nor in patients with known or suspected susceptibility to malignant hyperthermia.
Does sevoflurane increase heart rate?
Sevoflurane is a dose-related cardiac depressant. Sevoflurane does not produce increases in heart rate at doses less than 2 MAC.#N#A study investigating the epinephrine induced arrhythmogenic effect of Sevoflurane versus isoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg with both Sevoflurane and isoflurane. Consequently, the interaction of Sevoflurane with epinephrine appears to be equal to that seen with isoflurane.#N#Clinical Trials#N#Sevoflurane was administered to a total of 3185 patients. The types of patients are summarized as follows:#N#Table 5. Patients Receiving Sevoflurane in Clinical Trials
Is sevoflurane inducible by barbiturates?
The metabolism of Sevoflurane is not inducible by barbiturates. As shown in Figure 5, inorganic fluoride concentrations peak within 2 hours of the end of Sevoflurane anesthesia and return to baseline concentrations within 48 hours post-anesthesia in the majority of cases (67%).
Abstract
Background. The motivation for this study was the current difficulty in estimating the total age‐related MAC for a patient in a clinical setting.
Methods
When a volatile anaesthetic is administered at an end‐expired concentration ( Fe ′) in oxygen, this can be described as a multiple (or submultiple) k of MAC:
Results
Iso‐MAC charts for the inhalational agents isoflurane, sevoflurane and desflurane are shown in Figs 1 – 3. Dots on the curves are to help alignment with age. The ordinates (left and right) are scaled as end‐expired agent concentration (%) and the abscissa is scaled as years of age.
Discussion
The iso‐MAC charts have been designed to make it easy for the depth of anaesthesia to be determined in MAC units when using volatile agents, not only in oxygen 100% but also in conjunction with two commonly used concentrations of nitrous oxide, and for a wide range of ages.
Appendix
If the end‐expired concentration of any one agent i is expressed as a multiple (or submultiple) ki of the relevant value of MAC, then
Acknowledgement
The authors would like to thank colleagues who tested the iso‐MAC charts in clinical practice.
Author notes
1Department of Anaesthesia, City Hospital, Nottingham, UK. 2Department of Anaesthetics and Intensive Care Medicine, University of Wales College of Medicine, Cardiff CF14 4XN, UK
When was sevoflurane first used?
It was introduced into clinical practice initially in Japan in 1990 by Maruishi Pharmaceutical Co., Ltd. Osaka, Japan. The rights for sevoflurane worldwide were held by AbbVie. It is now available as a generic drug . Sevoflurane is an inhaled anaesthetic that is often used to put children asleep for surgery.
Who discovered sevoflurane?
Sevoflurane was discovered by Ross Terrell and independently by Bernard M Regan. A detailed report of its development and properties appeared in 1975 in a paper authored by Richard Wallin, Bernard Regan, Martha Napoli and Ivan Stern.
What is the name of the ether used for inhalational anesthesia?
Sevoflurane. Sevoflurane is a sweet-smelling, nonflammable, highly fluorinated methyl isopropyl ether used as an inhalational anaesthetic for induction and maintenance of general anesthesia. After desflurane, it is the volatile anesthetic with the fastest onset .
Is sevoflurane as soluble as isoflurane?
While sevoflurane is only half as soluble as isoflurane in blood, the tissue blood partition coefficients of isoflurane and sevoflurane are quite similar.
Is sevoflurane a volatile anesthetic?
After desflurane, it is the volatile anesthetic with the fastest onset . While its offset may be faster than agents other than desflurane in a few circumstances, its offset is more often similar to that of the much older agent isoflurane. While sevoflurane is only half as soluble as isoflurane in blood, the tissue blood partition coefficients of isoflurane and sevoflurane are quite similar. For example, in the muscle group: isoflurane 2.62 vs. sevoflurane 2.57. In the fat group: isoflurane 52 vs. sevoflurane 50. As a result, the longer the case, the more similar will be the emergence times for sevoflurane and isoflurane.
Is sevoflurane an allosteric modulator?
The exact mechanism of the action of general anaesthetics has not been delineated. Sevoflurane acts as a positive allosteric modulator of the GABA A receptor in electrophysiology studies of neurons and recombinant receptors. However, it also acts as an NMDA receptor antagonist, potentiates glycine receptor currents, and inhibits nAChR and 5-HT 3 receptor currents.
Is sevoflurane a halothane?
Together with desflurane, sevoflurane is replacing isoflu rane and halothane in modern anesthesia practice. It is often administered in a mixture of nitrous oxide and oxygen. Sevoflurane has an excellent safety record, but is under review for potential hepatotoxicity, and may accelerate Alzheimer's.
What is ultane used for?
ULTANE® (sevoflurane) is indicated for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery. ULTANE should be administered only by persons trained in the administration of general anesthesia. Facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment, ...
Is ultane used for glycosuria?
ULTANE may be associated with glycosuria and proteinuria when used for long procedures at low flow rates. KOH containing CO 2 absorbents are not recommended for use with ULTANE. An exothermic reaction occurs when ULTANE is exposed to CO 2 absorbents. This reaction is increased when the absorbent becomes desiccated.
Is succinylcholine a concomitant drug?
Concomitant use of succinylcholine has been associated with most, but not all, of these cases. Early, aggressive intervention to treat both hyperkalemia and resistant arrhythmias, and subsequent evaluation for latent neuromuscular disease, is recommended.
Can hydrocarbon anesthetics cause hepatic dysfunction?
It has been reported that previous exposure to halogenated hydrocarbon anesthetics may increase the potential for hepatic injury.
Is ultane safe to use?
IMPORTANT SAFETY INFORMATION 1. ULTANE can cause malignant hyperthermia. Postmarketing reports of malignant hyperthermia, some of which have been fatal, have occurred. ULTANE should not be used in patients with known sensitivity to sevoflurane or to other halogenated agents, or in patients with known or suspected susceptibility to malignant ...
Can ultane cause seizures?
Seizures have been reported in association with ULTANE use, the majority of which have occurred in children and young adults, most of whom had no predisposing risk factors. Clinical judgment should be exercised when using ULTANE in patients who may be at risk for seizures.
Does ultane cause respiratory depression?
Due to ULTANE’s insolubility in blood, hemodynamic changes may occur more rapidly than with other volatile anesthetics. Excessive decreases in blood pressure or respiratory depression may be related to depth of anesthesia and may be corrected by decreasing the inspired concentration of ULTANE.
How many times MAC is sevoflurane?
When you consider that surgical anaesthesia is normally achieved at 1.5 times MAC it becomes clear that a considerably higher vaporiser setting will be required when using sevoflurane compared to if the same patient were anaesthetised using isoflurane.
Why is sevoflurane used in surgery?
This means that proportionally more sevoflurane will be used to ensure the patient remains at an adequate depth for surgery. In real terms if using the same fresh gas flow rate more sevoflurane will be used, making it a less economical option. The blood-gas solubility of sevoflurane is lower than that of isoflurane.
Is isoflurane a licensed drug?
Whilst the development and licensing of sevoflurane for the veterinary market obviously may have some benefits in the anaesthesia of critical patients, due to the more rapid change in anaesthetic depth, isoflurane is still the licensed drug for many species and should be considered under the VMD regulations and under the prescribing cascade. As sevoflurane becomes more affordable and potentially may be licensed for a greater variety of species it could be a valuable addition to veterinary anaesthesia. Currently in dogs it provides the option of masked induction of anaesthesia, providing rapid onset of anaesthesia.
Is sevoflurane a lower solubility than isoflurane?
The blood-gas solubility of sevoflurane is lower than that of isoflurane. This difference is not as great as the difference between isoflurane and halothane. However, the lower the blood-gas solubility, the more rapidly the agent achieves an effect in the brain and in turn the quicker the drug is released from the brain.
Does isoflurane cause depression?
Both isoflurane and sevoflurane cause similar side effects including dose-dependent depression of the central nervous system, respiratory depression, depression of body temperature regulating centers, hypotension, vasodilation, myocardial depression and muscle relaxation. Both agents can cause a reduction in cerebral metabolic rate whilst also ...
Is isoflurane a halogenated ether?
Sevoflurane and isoflurane are both from the halogenated ether group of inhalational anaesthetic agents and both agents are indicated for the induction and maintenance of general anaesthesia. Isoflurane is currently licensed in the UK for use in dogs, cats, horses, ornamental birds, reptiles and small mammals including rabbits, ...
Is sevoflurane good for dogs?
However, the author accepts that for critical canine cases sevoflurane may be advantageous providing the anaesthetist is experienced in its use.
Description
Safety
- Sevoflurane is nonflammable and nonexplosive as defined by the requirements of International Electrotechnical Commission 601-2-13. Sevoflurane has a nonpungent odor and does not cause respiratory irritability. Sevoflurane is suitable for mask induction in adults. In 196 patients, mask induction was smooth and rapid, with complications occurring wit...
Properties
- Sevoflurane is a clear, colorless, liquid containing no additives. Sevoflurane is not corrosive to stainless steel, brass, aluminum, nickel-plated brass, chrome-plated brass or copper beryllium. Sevoflurane is nonpungent. It is miscible with ethanol, ether, chloroform, and benzene, and it is slightly soluble in water. Sevoflurane is stable when stored under normal room lighting condition…
Formation
- Sevoflurane alkaline degradation occurs by two pathways. The first results from the loss of hydrogen fluoride with the formation of pentafluoroisopropenyl fluoromethyl ether, (PIFE, C4H2F6O), also known as Compound A, and trace amounts of pentafluoromethoxy isopropyl fluoromethyl ether, (PMFE, C5H6F6O), also known as Compound B. The second pathway for deg…
Mechanism
- In the first pathway, the defluorination pathway, the production of degradants in the anesthesia circuit results from the extraction of the acidic proton in the presence of a strong base (KOH and/or NaOH) forming an alkene (Compound A) from Sevoflurane similar to formation of 2-bromo-2-chloro-1, 1-difluoro ethylene (BCDFE) from halothane. Laboratory simulations have sho…
Toxicity
- Compound A has been shown to be nephrotoxic in rats after exposures that have varied in duration from one to three hours. No histopathologic change was seen at a concentration of up to 270 ppm for one hour. Sporadic single cell necrosis of proximal tubule cells has been reported at a concentration of 114 ppm after a 3-hour exposure to Compound A in rats. The LC50 reported a…
Synthesis
- Because of the low solubility of Sevoflurane in blood (blood/gas partition coefficient @ 37°C = 0.63 to 0.69), a minimal amount of Sevoflurane is required to be dissolved in the blood before the alveolar partial pressure is in equilibrium with the arterial partial pressure. Therefore there is a rapid rate of increase in the alveolar (end-tidal) concentration (FA) toward the inspired concentr…
Performance
- In a study in which seven healthy male volunteers were administered 70% N2O/30%O2 for 30 minutes followed by 1.0% Sevoflurane and 0.6% isoflurane for another 30 minutes the FA/FI ratio was greater for Sevoflurane than isoflurane at all time points. The time for the concentration in the alveoli to reach 50% of the inspired concentration was 4 to 8 minutes for isoflurane and appr…
Pharmacology
- The effects of Sevoflurane on the displacement of drugs from serum and tissue proteins have not been investigated. Other fluorinated volatile anesthetics have been shown to displace drugs from serum and tissue proteins in vitro. The clinical significance of this is unknown. Clinical studies have shown no untoward effects when Sevoflurane is administered to patients taking drugs tha…
Side effects
- It has been reported that following administration of methoxyflurane, serum inorganic fluoride concentrations >50 µM were correlated with the development of vasopressin-resistant, polyuric, renal failure. In clinical trials with Sevoflurane, there were no reports of toxicity associated with elevated fluoride ion levels.
Chemistry
- Fluoride concentrations have been measured after single, extended, and repeat exposure to Sevoflurane in normal surgical and special patient populations, and pharmacokinetic parameters were determined.
Prognosis
- Compared with healthy individuals, the fluoride ion half-life was prolonged in patients with renal impairment, but not in the elderly. A study in 8 patients with hepatic impairment suggests a slight prolongation of the half-life. The mean half-life in patients with renal impairment averaged approximately 33 hours (range 21 to 61 hours) as compared to a mean of approximately 21 hou…
Research
- Sevoflurane was studied in 14 healthy volunteers (18 to 35 years old) comparing Sevoflurane-O2 (Sevo/O2) to Sevoflurane-N2O/O2 (Sevo/N2O/O2) during 7 hours of anesthesia. During controlled ventilation, hemodynamic parameters measured are shown in Figures 7-10:
Interactions
- A study investigating the epinephrine induced arrhythmogenic effect of Sevoflurane versus isoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg with both Sevoflurane and isoflurane. …
Administration
- Sevoflurane was administered to total of 3185 patients. The types of patients are summarized as follows:
Medical uses
- Sevoflurane (n=91) was compared to halothane (n=89) in a single-center study for elective repair or palliation of congenital heart disease. The patients ranged in age from 9 days to 11.8 years with an ASA physical status of II, III, and IV (18%, 68%, and 13% respectively). No significant differences were demonstrated between treatment groups with respect to the primary outcome …