This page shows what was measured, who it was measured in, and what that does not settle.
What Sevoflurane does in the body
A gas that puts a person to sleep for surgery and keeps them asleep, breathed in rather than injected
Sevoflurane is breathed in, crosses from the lung into the blood and then into the brain. It barely dissolves in blood at all, which sounds like a disadvantage and is the opposite: because the blood cannot soak much of it up, the amount in the lungs and the amount in the brain come into balance within a few minutes, in both directions. So the anaesthetist can raise or lower the depth quickly and can read the concentration off the patient's own exhaled breath. Once there, it does not act on one receptor. It nudges several kinds of ion channel at once, mostly in the direction of making neurons harder to excite.
What happened in people
A blood-gas partition coefficient of 0.63 to 0.69 at 37 degrees C, and a minimum alveolar concentration of 2.1% in oxygen for a 40-year-old adult
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
On the WHO Model List of Essential Medicines, and the standard agent for inhalational induction in children worldwide because it does not irritate the airway
Where it acts
Lipid-facing pockets and subunit interfaces of ion channels throughout the cortex, thalamus, brainstem and spinal cord
Kind of result
A step measured inside a person
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 38LVP0K73A · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 160 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Full-scale intelligence quotient on WPPSI-III at five years of age, equivalence margin 5 points
✓ The study showed what it set out to show
Who was studied
GAS — general anaesthesia versus awake-regional anaesthesia in infancy (NCT00756600)
How many people
722
Study design
International assessor-masked randomised controlled equivalence trial
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Mean FSIQ 99.08 (SD 18.35) awake-regional versus 98.97 (SD 19.66) general anaesthesia; difference in means 0.23 (95% CI -2.59 to 3.06) — equivalence demonstrated
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The trial tested a median 54 minutes of anaesthesia, once, in a predominantly male population, and there were 74 protocol violations in the awake-regional arm against two in the general anaesthesia arm. It cannot speak to repeated or prolonged exposure.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Volatile liquid for inhalation, delivered as vapour from an agent-specific calibrated vaporiser into a circle breathing system, with a carbon dioxide absorber and scavenging
Interval reported. 95% CI -2
Written into the record, not signed off as a reviewed claim.
2.8% volatile versus 3.0% intravenous; relative risk 0.94, 95% CI 0.69 to 1.29, P=0.71
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Stopped for futility at the second interim analysis; no secondary outcome or prespecified adverse event differed, including myocardial infarction.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Volatile liquid for inhalation, delivered as vapour from an agent-specific calibrated vaporiser into a circle breathing system, with a carbon dioxide absorber and scavenging
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
One-year all-cause mortality in older patients at increased risk after major surgery
✗ The study did not show it
Who was studied
BALANCED — anaesthetic depth and complications after major surgery
How many people
6644
Study design
International randomised controlled trial at 73 centres in 7 countries
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
6.5% at bispectral index target 50 versus 7.2% at target 35; hazard ratio 0.88, 95% CI 0.73 to 1.07, absolute risk reduction 0.8% (95% CI -0.5 to 2.0)
Repeated elsewhere
Unreplicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Separation was achieved — median bispectral index 47.2 versus 38.8 and 30% less volatile agent in the light group — so this is a negative result rather than a failed intervention.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Volatile liquid for inhalation, delivered as vapour from an agent-specific calibrated vaporiser into a circle breathing system, with a carbon dioxide absorber and scavenging
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Urinary albumin, glucose, alpha-glutathione-S-transferase and pi-glutathione-S-transferase after 8 hours at 1.25 MAC
✓ The study showed what it set out to show
Who was studied
Eger volunteer comparison of sevoflurane and desflurane renal injury markers
How many people
19
Study design
Controlled volunteer study
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Sevoflurane produced transient glomerular, proximal tubular and distal tubular injury markers at a mean inspired Compound A of 41 +/- 3 ppm; desflurane produced none. Serum creatinine and blood urea nitrogen were unchanged by either agent.
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Between-subject variation was extreme: 24-hour albumin excretion on day 3 ranged from normal to 4.4 g. Sevoflurane also produced small rises in serum alanine aminotransferase, suggesting mild transient hepatic injury.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Volatile liquid for inhalation, delivered as vapour from an agent-specific calibrated vaporiser into a circle breathing system, with a carbon dioxide absorber and scavenging
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Postoperative change in serum creatinine and blood urea nitrogen
✓ The study showed what it set out to show
Who was studied
Mazze pooled analysis of renal function across 22 sevoflurane trials
How many people
3436
Study design
Retrospective pooled analysis of 22 clinical trials
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Similar incidences of raised serum creatinine and blood urea nitrogen between 1,941 sevoflurane and 1,495 control patients; no trend by fresh gas flow rate, nephrotoxic antibiotic co-treatment or absorbent type, for exposures under 4 MAC-hours
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The two outcome measures are the two the volunteer study explicitly reported as having failed to reveal the injury it detected with sensitive markers. This is a valid result about clinically apparent nephrotoxicity and not a refutation of the biomarker finding.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Volatile liquid for inhalation, delivered as vapour from an agent-specific calibrated vaporiser into a circle breathing system, with a carbon dioxide absorber and scavenging
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Sevoflurane
What a person takes: Volatile liquid for inhalation, delivered as vapour from an agent-specific calibrated vaporiser into a circle breathing system, with a carbon dioxide absorber and scavenging.
The measurement behind this step
The delivery system is a machine, not a formulation, and the machine changes the drug. Fresh gas flow, absorbent chemistry and absorbent hydration determine how much Compound A the patient inhales, so the same vaporiser setting delivers different exposures on different circuits. The agent is stabilised with water because it degrades on contact with Lewis acids. Uniquely among the agents in routine use it is non-pungent, which is why a child can be anaesthetised through a mask without a cannula, and that property is a physical fact about the molecule rather than a clinical claim.
Getting in
Vaporised into the breathing circuit at a set percentage
A calibrated vaporiser turns the liquid into a precise percentage of the gas being breathed. Unlike an injected drug, the dose can be turned down as easily as it was turned up.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The label requires vaporisers producing predictable concentrations, because the depth of anaesthesia can change rapidly. Saturated vapour pressure and the agent-specific vaporiser design are what make a percentage dial meaningful; sevoflurane's non-pungency, unusual in this class, is what allows a mask induction without airway irritation.
It barely dissolves in blood, which is why it is fast
Blood can only soak up a small amount of it. That means the concentration in the lungs and the concentration reaching the brain come into balance within minutes, in both directions.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The blood-gas partition coefficient at 37 degrees C is 0.63 to 0.69, among the lowest of the agents in routine use. Low solubility means a small amount dissolved is needed before alveolar partial pressure equals arterial partial pressure, so wash-in and wash-out are both rapid and the end-tidal concentration is a usable proxy for the brain concentration.
There is no single lock this key fits. It nudges several kinds of ion channel at once, all in the direction of quietening neurons.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Volatile anaesthetics potentiate GABA-A and glycine receptors, activate two-pore-domain potassium channels of the TASK and TREK families, inhibit NMDA receptors and depress presynaptic sodium channels and transmitter release. The decisive evidence that this is genuinely multi-target is genetic: beta3(N265M) knock-in mice lose the anaesthetic action of propofol and etomidate entirely and are only slightly less sensitive to enflurane and halothane.
As the concentration rises, the parts of the brain that normally talk to each other stop doing so in a coordinated way, and consciousness ends.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The practical potency measure is minimum alveolar concentration: 2.1% in oxygen for a 40-year-old adult, falling with age, and defined as the concentration preventing movement to surgical incision in half of subjects. Immobility at MAC is largely a spinal cord effect, while unconsciousness occurs at lower concentrations, so the single number conflates two separable endpoints.
Some of it is degraded in the machine, not in the patient
The carbon dioxide absorber in the anaesthetic machine contains a strong base, and it attacks the molecule to produce a breakdown product that is toxic to rat kidneys. The lower the fresh gas flow, the more of it forms.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Strong base extracts the acidic proton from the fluoromethyl group, eliminating hydrogen fluoride to give pentafluoroisopropenyl fluoromethyl ether, Compound A, with trace Compound B. Formation rises with absorbent temperature, sevoflurane concentration, desiccation of the absorbent — especially potassium hydroxide-containing types — and falling fresh gas flow. The label restricts exposure at flows of 1 to under 2 L/min and does not recommend flows below 1 L/min.
Only a small fraction is metabolised. The rest leaves through the lungs the way it came in, and then leaves the building through the theatre's scavenging system into the atmosphere.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Roughly 3 to 5% undergoes hepatic defluorination by CYP2E1, producing inorganic fluoride and hexafluoroisopropanol, which is glucuronidated; the rest is exhaled. Because elimination is by ventilation rather than metabolism, emergence tracks the same low solubility that made induction fast. The exhaled remainder is vented, which is why a measured 100-year global warming potential of 210 is a property of the treatment and not a footnote to it.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Most children having an operation, and a very large fraction of adults. It is on the WHO Model List of Essential Medicines.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On pediatric, the label states: “Induction and maintenance of general anesthesia with sevoflurane have been established in controlled clinical studies in pediatric patients aged 1 to 18 years (see CLINICAL STUDIES , ADVERSE REACTIONS ).”
US prescribing information · 22700993-851a-48aa-941e-1d2b6b04081f · read 2026-08-30
On older people, the label states: “The average concentration of sevoflurane to achieve MAC in an 80 year old is approximately 50% of that required in a 20 year old.”
US prescribing information · 22700993-851a-48aa-941e-1d2b6b04081f · read 2026-08-30
On people who are pregnant, the label states: “Risk Summary There are no adequate and well-controlled studies in pregnant women.”
US prescribing information · 22700993-851a-48aa-941e-1d2b6b04081f · read 2026-08-30
On people who are breastfeeding, the label states: “It is not known whether sevoflurane or its metabolites are present in human milk.”
US prescribing information · 22700993-851a-48aa-941e-1d2b6b04081f · read 2026-08-30
Where the result stopped carrying
Volatile cardioprotection, tested in 5,400 bypass patients and stopped for futility
The depth-of-anaesthesia mortality hypothesis, tested in 6,644 patients with a real 9-point bispectral index separation and no survival difference
The original assumption that Compound A was a rodent-only concern — sensitive urinary markers found real, if transient, human injury
Equally, the assumption that Compound A causes clinically important nephrotoxicity in ordinary practice, which 3,436 patients did not support
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (11)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Prescription only
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Volatile liquid for inhalation, delivered as vapour from an agent-specific calibrated vaporiser into a circle breathing system, with a carbon dioxide absorber and scavenging
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S1.
No source is stored against this line.
What is in the pack
The delivery system is a machine, not a formulation, and the machine changes the drug. Fresh gas flow, absorbent chemistry and absorbent hydration determine how much Compound A the patient inhales, so the same vaporiser setting delivers different exposures on different circuits. The agent is stabilised with water because it degrades on contact with Lewis acids.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: Uniquely among the agents in routine use it is non-pungent, which is why a child can be anaesthetised through a mask without a cannula, and that property is a physical fact about the molecule rather than a clinical claim.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Contraindicated in known or suspected genetic susceptibility to malignant hyperthermia, which every volatile agent triggers. The label warns of Compound A-associated renal injury and restricts fresh gas flow accordingly, and carries the class Pediatric Neurotoxicity warning describing animal evidence of neuronal apoptosis with exposures over three hours in the developing brain, with the clinical significance stated as unclear. Emergence agitation in young children is common and self-limiting. Reaction with desiccated carbon dioxide absorbents, particularly potassium hydroxide-containing types, has caused extreme absorber heating and fire. Depth changes rapidly, which is the drug's main advantage and the reason the label restricts administration to trained personnel with vaporisers of predictable output. No dosing guidance appears on this page.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Volatile liquid for inhalation, delivered as vapour from an agent-specific calibrated vaporiser into a circle breathing system, with a carbon dioxide absorber and scavenging
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Fresh gas flow, absorbent chemistry and absorbent hydration determine how much Compound A the patient inhales, so the same vaporiser setting delivers different exposures on different circuits. The agent is stabilised with water because it degrades on contact with Lewis acids.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold. The rest of the recorded wording: Uniquely among the agents in routine use it is non-pungent, which is why a child can be anaesthetised through a mask without a cannula, and that property is a physical fact about the molecule rather than a clinical claim.
No source is stored against this line.
What is recorded as being sold
21 products list this as an active ingredient in the United States drug directory. 21 of them contain it and nothing else.
FDA National Drug Code directory · 0781-6160 · read 2026-08-29
They are sold as liquid, taken respiratory (inhalation).
FDA National Drug Code directory · 0781-6160 · read 2026-08-29
The regulator's established pharmacologic class for it is general anesthesia [pe] and general anesthetic [epc].
FDA National Drug Code directory · 0781-6160 · read 2026-08-29
13 published labels name it as an active ingredient. 13 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · fedfd1db-7e32-44b2-89e9-7bb00ee6810d · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · fedfd1db-7e32-44b2-89e9-7bb00ee6810d · read 2026-08-29
SEVOFLURANE is respiratory (inhalation) at HOW SUPPLIED Sevoflurane, USP, Volatile Liquid for Inhalation, is available as: NDC 10019-653-64 - Aluminum bottle with plastic screw-on cap containing 250 mL sevoflurane, USP., recorded as fda label in effect 2025-04-30 in the United States.
US prescribing information · 22700993-851a-48aa-941e-1d2b6b04081f · read 2026-08-30
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Sevoflurane studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That neuronal apoptosis in developing animal brains predicts cognitive harm in children — the label states the clinical significance is not clear, and the one randomised human test found equivalence
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That normal creatinine and urea across 3,436 patients rules out Compound A renal injury, when the volunteer study reported those exact measures as insensitive to it
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That laboratory anaesthetic preconditioning of myocardium translates into fewer deaths after bypass surgery
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the observed association between deep anaesthesia and later death is causal rather than a marker of how sick the patient was
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a gas induction avoiding a needle in a frightened child is a trivial advantage; it is not measured in any trial here, and it is the main reason this agent exists in paediatric practice
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Sevoflurane are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
GAS: an hour of sevoflurane in infancy left IQ at five years unchanged
In plain words
The strongest fear about this drug is that it damages a developing brain. Seven hundred and twenty-two babies were randomly assigned to a sevoflurane anaesthetic or to an awake spinal for the same hernia operation, and their intelligence was measured at five. The difference was a quarter of a point.
What was measured
Full-scale intelligence quotient at five years, per protocol, against a predefined equivalence margin of 5 points
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The GAS trial recruited infants under 60 weeks postmenstrual age, born after 26 weeks gestation, undergoing inguinal herniorrhaphy, with no previous general anaesthesia and no risk factors for neurological injury, at 28 hospitals in seven countries. They were randomised 1:1 to awake-regional anaesthesia or sevoflurane-based general anaesthesia; assessors were masked. The primary outcome was full-scale IQ on the Wechsler Preschool and Primary Scale of Intelligence, third edition, at five years, with a predefined clinical equivalence margin of 5 points. Of 4,023 infants screened, 722 were randomised, 363 to awake-regional and 359 to general anaesthesia. Median duration of general anaesthesia was 54 minutes (IQR 41 to 70). Mean full-scale IQ was 99.08 (SD 18.35) with awake-regional and 98.97 (SD 19.66) with general anaesthesia, a difference in means of 0.23 (95% CI -2.59 to 3.06) — strong evidence of equivalence, with the confidence interval well inside the margin. The intention-to-treat analysis agreed. The trial is explicit about its scope: it tested slightly under an hour of anaesthesia, once, in a predominantly male population.
Written into the record, not signed off as a reviewed claim
The paediatric neurotoxicity warning on the label rests on animal studies
In plain words
The label warns that anaesthetics used for more than three hours in a very young child may cause lasting cognitive harm. In the label's own words, that comes from published animal studies, and the clinical significance is not clear.
What was measured
That anaesthetic-induced neuronal apoptosis in developing animal brains predicts cognitive harm in young children — an extrapolation the label explicitly declines to confirm
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The approved United States label states that published animal studies demonstrate that anaesthetic and sedation drugs which block NMDA receptors or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than three hours, and that the clinical significance of these findings is not clear. It places the window of vulnerability from the third trimester through the first several months of life, possibly extending to about three years of age in humans. It notes that some published studies in children suggest similar deficits after repeated or prolonged exposure, that those studies have substantial limitations, and that it is not clear whether the observed effects are due to the drugs or to the surgery and underlying illness. This audit is not a claim that the warning is wrong. It is a statement of what supports it: an animal model, plus observational human studies the label itself describes as substantially limited, against one randomised human trial of a single short exposure that found equivalence. The warning is an inference from apoptosis in rodent brains to intelligence in human children, and the label says so.
Source
FDA-approved US prescribing information for sevoflurane, WARNINGS — Pediatric Neurotoxicity (DailyMed SPL 22700993-851a-48aa-941e-1d2b6b04081f)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Compound A: real biomarker injury in volunteers, then reassurance measured the wrong thing
In plain words
Sevoflurane breaks down in the anaesthetic machine into a compound that damages rat kidneys. In volunteers, careful urine tests found genuine kidney injury markers — and the routine blood tests missed it entirely. The large study that reassured everyone used those routine blood tests.
What was measured
That normal postoperative serum creatinine and blood urea nitrogen across 3,436 patients rules out the renal injury Compound A produces — using the two markers the volunteer study reported as insensitive to it
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Sevoflurane reacts with the strong base in carbon dioxide absorbents to form pentafluoroisopropenyl fluoromethyl ether, known as Compound A, and the amount formed rises as fresh gas flow falls. Eger and colleagues gave fluid-restricted volunteers eight hours of 1.25 MAC sevoflurane (n=10) or desflurane (n=9) at 2 L/min in a standard circle absorber. Mean inspired Compound A was 41 +/- 3 ppm. Desflurane produced no renal injury. Sevoflurane produced transient injury at three sites: glomerular, shown by post-anaesthetic albuminuria; proximal tubular, shown by glucosuria and raised urinary alpha-glutathione-S-transferase; and distal tubular, shown by raised urinary pi-glutathione-S-transferase. The magnitude varied enormously between subjects — on day 3, 24-hour albumin excretion ranged from normal in one volunteer to 4.4 g in another. Critically, neither agent changed serum creatinine or blood urea nitrogen, and neither changed urinary concentrating ability in response to vasopressin: in the authors' words, these measures failed to reveal the injury produced. Three years later Mazze and colleagues pooled 22 trials with 3,436 adult surgical patients — 1,941 sevoflurane, 1,495 control — and found similar incidences of raised serum creatinine and blood urea nitrogen, with no trend by fresh gas flow rate or absorbent type. That is a real and useful result about clinically apparent nephrotoxicity, and it uses precisely the two measurements the volunteer study had shown to be insensitive to the injury in question. The label still restricts fresh gas flow.
Written into the record, not signed off as a reviewed claim
MYRIAD: volatile cardioprotection did not exist at the scale of a mortality trial
In plain words
Laboratory work had shown for decades that these gases protect heart muscle from injury during interrupted blood supply. Five thousand four hundred bypass patients were randomised to gas or intravenous anaesthesia, and after a year the death rates were 2.8% and 3.0%.
What was measured
Death from any cause at one year after elective coronary artery bypass grafting
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Landoni and colleagues randomised 5,400 patients at 36 centres in 13 countries scheduled for elective coronary artery bypass grafting to an intraoperative regimen including desflurane, isoflurane or sevoflurane, or to total intravenous anaesthesia. On-pump bypass was used in 64%, mean bypass duration 79 minutes. Death from any cause at one year, the primary outcome, was 2.8% versus 3.0% (relative risk 0.94, 95% CI 0.69 to 1.29, P=0.71), with data for 99.1% of patients; 30-day mortality was 1.4% versus 1.3%. No secondary outcome and no prespecified adverse event differed, including myocardial infarction. The data and safety monitoring board stopped the trial for futility at the second interim analysis. Anaesthetic preconditioning is a well-replicated laboratory phenomenon, and this is what happened when it was asked to move a clinical endpoint in the population where it should have been easiest to see.
Written into the record, not signed off as a reviewed claim
BALANCED: running the gas deeper or lighter did not change one-year survival
In plain words
Observational studies had linked deeper anaesthesia to dying sooner afterwards. Six and a half thousand older patients were randomised to a light or a deep target on a brain monitor. One-year death was 6.5% and 7.2%.
What was measured
One-year all-cause mortality in older patients at increased risk after major surgery
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Short and colleagues recruited patients aged 60 and over with significant comorbidity, having surgery expected to last more than two hours, at 73 centres in seven countries, and randomised 6,644 to light general anaesthesia at a bispectral index target of 50 or deep general anaesthesia at a target of 35. The separation achieved was real: median bispectral index 47.2 against 38.8, mean arterial pressure 3.5 mmHg higher in the light group, and volatile anaesthetic use 0.26 minimum alveolar concentration — about 30% — lower in the light group. One-year all-cause mortality, the primary outcome, was 6.5% (212 patients) against 7.2% (238), hazard ratio 0.88, 95% CI 0.73 to 1.07, absolute risk reduction 0.8% (95% CI -0.5 to 2.0). Grade 3 and grade 4 adverse events were the same in both arms. The trial defines a broad range of anaesthetic depth over which no mortality difference is detectable, and it is included here because the observational association it tested was widely believed and is a textbook example of confounding by patient frailty.
Written into the record, not signed off as a reviewed claim
A 100-year global warming potential of 210, measured from its infrared spectrum
In plain words
Almost all of the gas a patient breathes in is breathed straight back out and vented to the atmosphere unchanged. Its heat-trapping power was measured directly: 210 times that of carbon dioxide over a century.
What was measured
Radiative efficiency in W m^-2 ppb^-1 and 100-year global warming potential derived from measured infrared spectra
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Sulbaek Andersen and colleagues measured the infrared spectra of isoflurane, desflurane and sevoflurane and calculated their contribution to radiative forcing, accounting for the wavelength dependence of the effect. Radiative efficiencies were 0.453, 0.469 and 0.351 W m^-2 ppb^-1 and 100-year global warming potentials were 510, 1,620 and 210 respectively. On that basis the average climate impact per anaesthetic procedure at the University of Michigan was equivalent to about 22 kg of carbon dioxide, and global emissions of inhalation anaesthetics were estimated to have a climate impact comparable to one coal-fired power plant or a million passenger cars. This is on the page because it is a directly measured property of the molecule that differs eightfold between agents that are otherwise interchangeable, and it is a real basis for choosing between them that has nothing to do with the patient in front of you.
Written into the record, not signed off as a reviewed claim
Malignant hyperthermia is a labelled trigger, and it is inherited
In plain words
In people with a particular inherited muscle variant, this gas can set off a runaway rise in body temperature and muscle breakdown. It is on the label as a contraindication and it is genetic.
What was measured
Labelled contraindication with named susceptibility genes RYR1 and CACNA1S
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The approved label contraindicates sevoflurane in patients with known or suspected genetic susceptibility to malignant hyperthermia, and its warnings describe the hypermetabolic state with muscle rigidity, hyperkalaemia and resistant arrhythmias, advising early and aggressive treatment of hyperkalaemia and subsequent evaluation for latent neuromuscular disease. Susceptibility is associated with variants in the ryanodine receptor gene RYR1 and in CACNA1S, and the label notes that variant pathogenicity should be assessed on clinical experience, functional studies and prevalence data. This audit is filed as measured rather than inferred because the trigger relationship is a labelled, mechanistically characterised, genetically defined phenomenon and not a statistical association.
Source
FDA-approved US prescribing information for sevoflurane, CONTRAINDICATIONS and WARNINGS — Malignant Hyperthermia (DailyMed SPL 22700993-851a-48aa-941e-1d2b6b04081f)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
How many documents were read
13 documents were read for this substance.
RNAWiki source record
13 of them state the same halfLife, and they agree.
RNAWiki source record
13 of them state the same tMax, and they agree.
RNAWiki source record
Where else this substance is registered
FDA substance identifier (UNII)
38LVP0K73A
RxNorm concept
200243
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Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
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Suppression classes recorded: S1.
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What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
6 approved applications cover products containing this substance. The earliest was NDA020478, approved 19950607 to ABBVIE.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
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Felt, measured, or meaningful — found nothing in the sources checked.
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The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
A fluorinated ether so insoluble in blood — a blood-gas partition coefficient of 0.63 to 0.69 — that alveolar and arterial concentrations equilibrate within minutes, giving anaesthesia you can titrate off the exhaled breath; the largest randomised test of the fear attached to it found that just under an hour of it in infancy left full-scale IQ at age five at 98.97 against 99.08 for awake-regional anaesthesia, a difference of 0.23 points.
Recorded evidence blocks (10)
Q2
On the Sevoflurane label: indicated for what?
"Sevoflurane is indicated for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery. Sevoflurane should be administered only by persons trained in the administration of general anesthesia.": indications and usage on Sevoflurane's label. DailyMed label · 0ca6da3a-6a18-400d-8c49-08a5534b025f · 2026-03-23
Q3
439 registered trials of Sevoflurane — at which phases?
Registered studies posting no result
393 of 439
439 registered studies of Sevoflurane: 179 na, 139 phase4, 47 na or unstated, 35 phase3, 28 phase2, 15 phase1, 5 early phase1. CLINICALTRIALS_SNAPSHOT · 2026-09-01
withdrawn; "We are not going to complete this study with healthy volunteers at this time."
NCT02604459
terminated; "Limited availability of subjects meeting inclusion criteria resulting in early termination (lack of funding) before meeting target enrollment."
NCT02664922
terminated; "Poor study design and too many study groups."
NCT02671084
terminated; "interim analysis suggests futility"
NCT02683837
withdrawn; "Principal investigator left the institution"
NCT02946437
withdrawn; "Patients failed to be enrolled because of tight exclusion criteria."
NCT03005860
withdrawn; "Funding could not be arranged, so the study was prematurely terminated"
NCT03408340
terminated; "The study activities were suspended due to COVID-19, and the interim analysis did not yield positive results once resumed."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Sevoflurane used Sevoflurane at 1.5 and 2.5% end tidal — over how long?
studies of Sevoflurane used the recorded amount. ClinicalTrials.gov · 2026-09-01
6 recorded entries; human; also "Sevoflurane at 1.5 and 2.5% end tidal", "1% Sevoflurane", "subanesthetic sevoflurane in 60% oxygen"
15-23 hours; The half-life is in the range of 15-23 hours.
tmaxpharmacokinetics
2 hours; As shown in Figure 6, peak concentrations occur within 2 hours of the end of anesthesia and are less than 25 µM (475 ng/mL) for the majority of the population after 10 hours.
metabolismpharmacokinetics
Metabolism Sevoflurane is metabolized by cytochrome P450 2E1, to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO 2 .
recorded 2026-03-23 · last checked 2026-09-04
Q7
Which running trial of Sevoflurane could settle inflammatory markers?
NCT07271459 measures IL-6 level 24 hours postoperatively compared to baseline value, reading out 2026-10.
6 open trials; n 40; "Effect of Total Intravenous Anesthesia vs Inhalational Anesthesia on the Level of Inflammatory Markers"
Show the evidence
Trial
NCT07271459
"Effect of Total Intravenous Anesthesia vs Inhalational Anesthesia on the Level of Inflammatory Markers"; n 40; "IL-6 level 24 hours postoperatively compared to baseline value"; 2026-10
NCT05663242
"The Effects of Using Different Anesthetics on the Prognosis of Primary Lung Tumors and Its Mechanism of Action"; n 300; "Overall survival"; 2026-11-30
NCT05331911
"Impact of Propofol-Based Total Intravenous Anesthesia Versus Anesthesia With Sevoflurane on Long-term Outcomes With Patients Undergoing Elective Excision of Primary Liver Tumors"; n 500; "Overall survival"; 2027-03-31
NCT03643367
"Sevoflurane Sedation in Patients With Septic Shock"; n 153; "Concentration of interleukin-6 over time"; 2027-11
NCT04513808
"Total Intravenous Anesthesia and Recurrence Free Survival"; n 1614; "Recurrence-free survival"; 2027-12
NCT04259398
"Anesthesia and Cancer Study: Colon Cancer"; n 797; "five year survival"; 2028-05-03
Q8
Which 223 trials of Sevoflurane posted no result?
Posted no result
223 of 223 completed trials
Registrations
NCT00988520, NCT00984633, NCT02785653, NCT00477737, NCT00534586 and NCT00569816, and 217 more
Completion dates
oldest 2003-09; newest 2024-08-14
Show the evidence
Trial
NCT00988520
2003-09
NCT00984633
2003-12
NCT02785653
2006-11
NCT00477737
2006-12
NCT00534586
2007-05
NCT00569816
2007-05
14 further recorded trials
NCT00521612
2007-11
NCT00516711
2007-12
NCT00575354
2007-12
NCT00586118
2007-12
NCT00484575
2008-12
NCT00733564
2009-03
NCT01196754
2009-05
NCT00815269
2009-12
NCT00924222
2009-12
NCT01084200
2010-01
NCT01219569
2010-01
NCT01124383
2010-02
NCT01096797
2010-03
NCT00337051
2010-06
Q9
At the median, Sevoflurane's trials enrolled 76 people — anything larger?
Median enrolment
76
Largest enrolment
27034
Registered trials counted
437
Q10
What do 1303 spontaneous reports say about Sevoflurane — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Sevoflurane appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1303 reaction mentions were counted: hypotension 222; anaesthetic complication 164; bradycardia 145; unwanted awareness during anaesthesia 130. FAERS via Open Targets · CHEMBL1200694 · 2026-06-24
Show the evidence
hypotension
222
anaesthetic complication
164
bradycardia
145
unwanted awareness during anaesthesia
130
anaesthetic complication neurological
126
cardiac arrest
125
4 more recorded rows
hyperthermia malignant
119
tachycardia
103
oxygen saturation decreased
87
low birth weight baby
82
recorded 2026-06-24 · last checked 2026-09-04
Q11
Which 10 reactions does Sevoflurane's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
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This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.