Sevoflurane


Article Author:
Trevor Edgington


Article Editor:
Christopher Maani


Editors In Chief:
Sebastiano Cassaro
Joseph Lee
Tanya Egodage


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Avais Raja
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Abdul Waheed
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Radia Jamil
Patrick Le
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Hassam Zulfiqar
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James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
6/1/2019 3:08:49 PM

Indications

Sevoflurane is a halogenated inhalational anesthetic that is FDA approved for induction and maintenance of general anesthesia in adults and pediatric patients for inpatient and outpatient surgery. Sevoflurane is a volatile anesthetic that provides hypnosis, amnesia, analgesia, akinesia, and autonomic blockade during surgical and procedural interventions. Clinical Uses

  • Inhalational induction of general anesthesia in neonatal and pediatric patients secondary to inadequate pre-induction intravenous access
  • Inhalational induction of general anesthesia in adult patients whose clinical condition necessitates spontaneous respirations during induction
  • May be used for complete maintenance of general anesthesia or concurrently with intravenous anesthetics to maintain general anesthesia in adult and pediatric patients

Mechanism of Action

Similar to other halogenated inhalational anesthetics, the precise mechanism of action of sevoflurane to induce and maintain general anesthesia is unknown. There have been multiple attempts to identify a unitary hypothesis. However, no single proposed mechanism of action has fully explained their clinical effects. A current working hypothesis is that inhaled anesthetics enhance inhibitory postsynaptic channel activity (gamma-aminobutyric acid (GABA), and glycine), and inhibit excitatory synaptic channel activity (N-methyl-D-aspartate (NMDA), nicotinic acetylcholine, serotonin, and glutamate) in the central nervous system.[1]

Administration

Route of Administration

Sevoflurane is an inhaled halogenated anesthetic that is delivered via a sevoflurane specific calibrated vaporizer attached to an anesthesia machine. Sevoflurane is delivered via the lungs as a volume percent of inspired gas. Pharmacodynamics/Kinetics

For sevoflurane to exert its effect, the agent must be passed from the inspired gas into the blood of the pulmonary capillaries, then circulated into the central nervous system. The onset of action of sevoflurane is determined by the inspired concentration of the agent, partition coefficients, the patient’s minute ventilation, and the patient’s pulmonary blood flow. These 4 factors are responsible for the speed of equilibration between the concentration gradient of sevoflurane between the alveoli, pulmonary blood flow, and the central nervous system, and therefore responsible for the speed of anesthetic induction. Dosing

Adults MAC Values for Surgical Levels of Anesthesia

  • Age 25 years: Sevoflurane in oxygen: 2.6%
  • Age 40 years: Sevoflurane in oxygen: 2.1%
  • Age 60 years: Sevoflurane in oxygen: 1.7%
  • Age 80 years: Sevoflurane in oxygen: 1.4%

Pediatric MAC Values for Surgical Levels of Anesthesia

  • Newborn to 1-month-old full-term neonates: Sevoflurane in oxygen: 3.3%
  • One to  younger than 6 months: Sevoflurane in oxygen: 3%
  • Six months to younger than 1 year: Sevoflurane in oxygen: 2.8%
  • One to younger than 3 years: Sevoflurane in oxygen: 2.8%

Metabolism

Sevoflurane undergoes minimal hepatic metabolism or renal excretion. Clearance

Clearance of sevoflurane and termination of its anesthetic effects depend on the same factors that influence the agent’s uptake. Factors Affecting Inhalational Sevoflurane Uptake and Clearance

  1. The concentration of inhaled anesthetic
  2. Partition coefficients (Blood: Gas, Brain: Blood, Tissue: Blood, Oil: Gas)
  3. Patient’s minute ventilation
  4. Patient’s pulmonary blood flow

Adverse Effects

Cardiovascular

Sevoflurane induces a dose-dependent reduction in blood pressure and cardiac output primarily through reduction of systemic vascular resistance.

Respiratory

Like all of the volatile anesthetic agents, sevoflurane is an airway irritant and may precipitate coughing, apnea, and laryngospasm. These reactions are less likely to be seen with sevoflurane as compared to desflurane and isoflurane due to the sweet smell, and low pungency of sevoflurane. Respiratory side effects are more commonly seen in patients with pre-existing lung pathology such as asthma, chronic obstructive pulmonary disease, and or cystic fibrosis. Sevoflurane, and all other inhaled anesthetics, also result in bronchodilation, blunting of the hypoxia/hypercapnia ventilatory response, and reverse hypoxic pulmonary vasoconstriction.

Central Nervous System

Sevoflurane causes a dose-dependent vasodilation of cerebral vasculature, thereby increasing cerebral blood flow and intracranial pressure. Sevoflurane reduces the cerebral metabolic rate. 

Pregnancy and Neurodevelopmental deficits: While several observational studies have found an increased risk of neurodevelopmental deficits in children exposed to anesthesia, at this time there is no compelling evidence to attribute this effect to the anesthesia directly. At this time, no specific anesthetic agent should be avoided during pregnancy, nor should any necessary surgery be delayed due to concerns regarding neurotoxicity.

Adverse Reactions

Less than 10%

  • Dose-dependent cardiovascular collapse: Hypotension (4% to 11%)
  • Central nervous system: Emergence delirium and agitation (7% to 15%)
  • Gastrointestinal: Nausea (25%); vomiting (18%)

One to 10%

  • Cardiovascular: Tachycardia, bradycardia, hypertension
  • Respiratory: Laryngospasm (2-8%), breath holding, apnea 

Less than 1%

Anaphylaxis, anaphylactoid reaction, cardiac arrhythmias, QT prolongation, increased intracranial pressure, hepatotoxicity, electrolyte disturbances, malignant hyperthermia

Drug Interactions

Sevoflurane undergoes minimal hepatic metabolism, the small percentage that is, acts as a substrate for multiple CYP enzymes (CYP2A6, CYP2B6, CYP3A4, CYP2E1). This creates the potential for many clinically relevant drug interactions secondary to the large percentage of drugs metabolized by this hepatic enzymes.

Contraindications

Sevoflurane is contraindicated in patients with known hypersensitivity to sevoflurane or any other halogenated anesthetics. The agent is also contraindicated in any patient with known or suspected susceptibility to malignant hyperthermia.

Monitoring

During the administration of sevoflurane for general anesthesia, there should be continuous monitoring following the recommendations of the American Society of Anesthesiologists (ASA). Standard ASA monitors include continuous pulse oximetry, electrocardiography, a noninvasive blood pressure device, temperature monitor, measurement of end-tidal carbon dioxide, inspired oxygen concentration, the use of low oxygen concentration and ventilator disconnect alarms, and the continuous presence of a qualified anesthesia provider. The ASA also encourages the quantitative monitoring of the volume of expired anesthetic gas.

Toxicity

Sevoflurane poses potential risk of hepatotoxicity, nephrotoxicity, and neurotoxicity. Hepatotoxicity

There have been several proposed mechanisms for post-operative hepatic dysfunction, to include viral hepatitis, impaired hepatic perfusion, and intrahepatic cholestasis. However, newer evidence suggests an immune-mediated mechanism. Sevoflurane, like other volatile anesthetics, is partially oxidized in the liver by a specific enzyme of CYP (2E1) to a metabolite, fluoroacetic acid. This specific metabolite has been found to modify liver microsomal proteins that subsequently act as triggering antigens for an immune-mediated antibody response. Although this response this rare due to the low percentage of sevoflurane metabolized in this fashion, the theoretical risk does exist. Nephrotoxicity

The potential nephrotoxic effect of sevoflurane can be attributed to 2 factors. The first factor is the metabolite discussed above, fluoroacetic acid, which has been shown to be nephrotoxic, as well has hepatotoxic. The second is the creation of Compound A. Compound A is another fluorinated byproduct created from an exothermic reaction between sevoflurane and the carbon dioxide absorbents utilized in anesthetic delivering systems; which has been reported to cause mild and reversible renal injury in animal studies.[2] The theoretical risk of Compound A-induced nephrotoxicity in humans may be dose and exposure time dependent. Neurotoxicity

Currently, there are no anesthetic agents, including sevoflurane, that should be avoided during pregnancy, in neonates, nor the pediatric population due to concerns regarding neurotoxicity. At this time there are several animal studies suggesting sevoflurane to induce neurotoxicity via microRNA manipulation.[3][4] However, there is yet to be compelling evidence to attribute neurotoxicity development in humans secondary to sevoflurane use directly.

Enhancing Healthcare Team Outcomes

Sevoflurane is usually administered by the anesthesiologist or anesthesia nurse. At all times, a dedicated staff member should continuously monitor the vital sigsn while the patient is under anesthesia.


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Sevoflurane - Questions

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Which is not a feature of sevoflurane?



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Which of the following anesthetics is the preferred method to induce anesthesia on a pediatric patient who is 3 years old?



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Which receptors are responsible for the proposed mechanism of action of sevoflurane?



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A 5-year-old child is undergoing general anesthesia for an emergent appendectomy. He is going to be maintained on sevoflurane. Which of the following monitors is not required per the American Society of Anesthesiologists (ASA) guidelines?



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Which of the following patients would have a slowed onset of anesthetic action if undergoing inhalational induction with sevoflurane?



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Sevoflurane - References

References

Sevoflurane‑induced neurotoxicity is driven by OXR1 post‑transcriptional downregulation involving hsa‑miR‑302e., Yang L,Shen Q,Xia Y,Lei X,Peng J,, Molecular medicine reports, 2018 Sep 3     [PubMed]
Sevoflurane anesthesia represses neurogenesis of hippocampus neural stem cells via regulating microRNA-183-mediated NR4A2 in newborn rats., Shao CZ,Xia KP,, Journal of cellular physiology, 2018 Sep 7     [PubMed]
Campagna JA,Miller KW,Forman SA, Mechanisms of actions of inhaled anesthetics. The New England journal of medicine. 2003 May 22     [PubMed]
Gentz BA,Malan TP Jr, Renal toxicity with sevoflurane: a storm in a teacup? Drugs. 2001     [PubMed]

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