Sevoflurane

At-a-glance

Non-pungent, sweet-smelling volatile agent; suitable for inhalational induction (especially paediatrics).
Low blood:gas solubility → rapid onset/offset; good for day-case anaesthesia.
MAC ~2% (adult); decreases with age and with opioids/benzodiazepines.
Cardiovascular: dose-dependent ↓SVR and ↓BP; relatively stable heart rate; less arrhythmogenic than halothane.
Respiratory: dose-dependent respiratory depression; bronchodilation.
CNS: ↓CMRO2, ↑CBF (dose-dependent), can ↑ICP unless controlled ventilation; provides amnesia but limited analgesia.
Metabolism ~3–5% (higher than isoflurane/desflurane) → inorganic fluoride + hexafluoroisopropanol (HFIP).
CO2 absorbent interaction: degradation to Compound A (nephrotoxic in rats) with strong base absorbents and low flows; modern practice mitigates risk.
Triggers malignant hyperthermia; can cause postoperative nausea/vomiting; emergence agitation in children.

How to use clinically

Induction: incremental inspired concentration (e.g., 1–8%) in oxygen/air ± nitrous oxide; maintain airway patency and monitor for apnoea.
- Non-pungency makes it well tolerated vs desflurane/isoflurane.
Maintenance: typical end-tidal ~1–2 MAC depending on adjuncts; titrate to haemodynamics and depth monitoring if used.
Low-flow anaesthesia: ensure appropriate absorbent (avoid desiccated strong-base absorbents), monitor inspired CO, consider fresh gas flow policies locally.
Neurosurgery: maintain normocapnia or mild hypocapnia to limit ICP rise; avoid high concentrations if intracranial compliance is poor.

Physical & chemical properties

Halogenated methyl isopropyl ether; non-flammable; pleasant odour.
Vapour pressure ~160 mmHg at 20°C (agent-specific vaporiser required).
Blood:gas partition coefficient ~0.65 → rapid induction and recovery.
Oil:gas partition coefficient ~50 (lower potency than isoflurane; higher MAC).

Potency (MAC) and modifiers

MAC (adult, 40 years) approximately 2.0%.
MAC decreases with: increasing age, hypothermia, pregnancy, opioids, benzodiazepines, alpha-2 agonists.
MAC increases with: hyperthermia, chronic alcohol use (classically), some stimulants.
Nitrous oxide reduces sevoflurane requirement (MAC-sparing).

Pharmacokinetics (uptake, distribution, elimination)

Low blood solubility → faster rise of alveolar concentration (FA/FI) and faster washout.
Uptake influenced by: alveolar ventilation (↑VA speeds), cardiac output (↑CO slows), alveolar–venous partial pressure gradient, and solubility.
Elimination mainly via lungs; metabolism ~3–5% via CYP2E1 → fluoride + HFIP (rapidly conjugated).

Pharmacodynamics — cardiovascular

Dose-dependent vasodilation → ↓SVR and ↓MAP; myocardial depression is modest at clinical concentrations.
Heart rate: often maintained or mild increase; less tachycardia than desflurane (especially during rapid increases).
Coronary effects: maintains coronary perfusion reasonably; does not have the same concern as historical 'coronary steal' discussions with older agents.
Arrhythmias: less sensitisation to catecholamines than halothane; still caution with high exogenous catecholamines.

Pharmacodynamics — respiratory

Dose-dependent respiratory depression: ↓tidal volume, ↑respiratory rate; overall ↓minute ventilation and ↑PaCO2.
Blunts ventilatory responses to CO2 and hypoxia.
Bronchodilator; suitable in reactive airway disease; minimal airway irritation compared with desflurane/isoflurane.

Pharmacodynamics — CNS and neuromuscular

CNS: ↓CMRO2; dose-dependent cerebral vasodilation → ↑CBF and potential ↑ICP (mitigated by controlled ventilation).
EEG: increasing dose leads to burst suppression at high concentrations.
Potentiates non-depolarising neuromuscular blockers (reduced dose requirement).

Other organ effects

Hepatic: generally preserves hepatic blood flow better than older agents; rare immune-mediated hepatitis is far less common than with halothane.
Renal: reduces renal blood flow and GFR via haemodynamic effects; inorganic fluoride rises but clinically significant fluoride nephrotoxicity is uncommon at standard exposures.
Uterus: relaxes uterine smooth muscle at higher concentrations (may increase bleeding risk in obstetrics).

Adverse effects and cautions

Malignant hyperthermia trigger (like other potent volatile agents).
PONV: volatile agents are emetogenic; consider prophylaxis based on risk.
Emergence agitation/delirium: more common in children; mitigate with analgesia, calm environment, alpha-2 agonists where appropriate.
Compound A formation with CO2 absorbents (especially strong bases) and low flows; theoretical renal risk—avoid desiccated absorbent and follow machine/department low-flow guidance.
Carbon monoxide can be produced with desiccated absorbent (classically Baralyme/strong base); risk is higher with some agents but good absorbent management is key.

Interactions

Additive CNS depression with opioids, benzodiazepines, propofol; reduces MAC.
Potentiates hypotension with other vasodilators/negative inotropes; consider vasopressors and depth reduction.
Neuromuscular blockers: potentiation of non-depolarising block; monitor with nerve stimulator.

Practical points for the anaesthetic machine

Requires a sevoflurane-specific vaporiser (agent-specific, temperature-compensated, calibrated).
Low-flow practice: ensure CO2 absorbent not desiccated; follow local minimum fresh gas flow recommendations.
End-tidal monitoring is preferred for titration (reflects alveolar/brain partial pressure more closely than inspired).

Describe sevoflurane and compare it with isoflurane/desflurane in terms of onset and offset.

Focus on solubility and how it affects FA/FI and washout.

Sevoflurane has a low blood:gas partition coefficient (~0.65) → rapid rise in alveolar partial pressure and rapid recovery.
Isoflurane is more soluble (slower onset/offset); desflurane is even less soluble than sevoflurane (fastest), but is pungent and irritant.
Clinical implications: sevoflurane is a good compromise—fast and suitable for inhalational induction; desflurane better for very rapid wake-up but less tolerated for induction.

What is MAC for sevoflurane and what factors alter MAC?

Examiners want a number and a structured list of modifiers.

MAC is approximately 2.0% in a typical adult (varies with age).
MAC decreases with: increasing age, hypothermia, pregnancy, opioids, benzodiazepines, alpha-2 agonists.
MAC increases with: hyperthermia and chronic alcohol use (classically).

Explain why sevoflurane is commonly used for inhalational induction. What are the disadvantages?

Often asked in paediatric viva stations.

Advantages: non-pungent, minimal airway irritation, bronchodilation, low blood solubility → smooth and rapid induction.
Disadvantages: dose-dependent respiratory depression/apnoea; hypotension at higher concentrations; emergence agitation in children; PONV.

Discuss the cardiovascular effects of sevoflurane.

Aim: mechanism + clinical pattern + comparison points.

Dose-dependent vasodilation → ↓SVR and ↓MAP; modest myocardial depression at clinical doses.
Heart rate is often stable or mildly increased; less sympathetic surge than desflurane during rapid increases.
Less catecholamine sensitisation than halothane; arrhythmias can still occur with high catecholamine states.

Describe the respiratory effects of sevoflurane and how this influences your management during induction.

Tie physiology to practical steps.

Dose-dependent respiratory depression: ↓tidal volume, blunted CO2/hypoxic drive → rising PaCO2 if spontaneous ventilation.
Management: maintain airway patency (jaw thrust/airway adjunct), monitor capnography, be prepared to assist ventilation, avoid excessive concentration escalation in vulnerable patients.
Bronchodilation and minimal irritation support use in reactive airway disease.

What are the effects of sevoflurane on cerebral physiology and how would you use it in neurosurgery?

Common FRCA theme: CBF/CMRO2/ICP and CO2 control.

↓CMRO2; dose-dependent cerebral vasodilation → ↑CBF and potential ↑ICP, especially at higher MAC.
Controlled ventilation to maintain normocapnia or mild hypocapnia reduces CBF and helps control ICP.
Avoid excessive concentrations in patients with poor intracranial compliance; consider TIVA if tight brain conditions required.

Outline the metabolism of sevoflurane and the clinical relevance of fluoride ions.

They want the percentage, pathway, and why it matters.

Metabolism ~3–5% via CYP2E1 producing inorganic fluoride and HFIP (then conjugated).
Fluoride levels rise more than with isoflurane/desflurane, but clinically significant fluoride nephrotoxicity is uncommon with modern exposures.
Renal effects are more commonly haemodynamic (↓RBF/↓GFR) than direct toxicity.

What is Compound A? How is it formed and why does it matter?

Classic FRCA machine/volatile interaction question.

Compound A is a degradation product of sevoflurane formed in the presence of CO2 absorbents (particularly strong base absorbents) and promoted by low fresh gas flows and higher temperatures.
It is nephrotoxic in animal studies (rats); human clinical significance is much less clear, but prudent practice is to avoid desiccated absorbent and follow low-flow guidance.
Practical steps: regular absorbent changes, avoid prolonged very low flows in high-risk contexts per local policy, monitor inspired/expired gases.

A child becomes agitated on emergence after sevoflurane. What is this phenomenon and how would you reduce it?

Often examined as a paediatric recovery issue.

Emergence agitation/delirium: transient agitation, inconsolability, disorientation; more common after sevoflurane and desflurane in children.
Reduce risk: good analgesia, calm environment, consider alpha-2 agonists (e.g., clonidine/dexmedetomidine) and avoid rapid, untreated pain on wake-up.
Exclude other causes: hypoxia, hypercarbia, full bladder, hypoglycaemia, local anaesthetic failure.

How does sevoflurane affect neuromuscular blockade and what are the practical implications?

Link pharmacodynamics to monitoring and dosing.

Potentiates non-depolarising neuromuscular blockers (increased depth and duration of block).
Practical implications: use lower doses or longer intervals, monitor with quantitative/qualitative nerve stimulation, and ensure adequate reversal and recovery (TOF ratio target per local standard).

What are the key safety issues when using sevoflurane with circle systems and CO2 absorbents?

Expect mention of absorbent condition, byproducts, and monitoring.

Ensure CO2 absorbent is not desiccated (reduces risk of degradation products and carbon monoxide formation).
Be aware of Compound A formation with low flows; follow departmental low-flow policies and use modern absorbents where available.
Use end-tidal agent monitoring; maintain appropriate fresh gas flows; regular machine checks and absorbent replacement schedules.

List contraindications or situations where you would avoid sevoflurane (or use with caution).

Aim for MH, ICP concerns, and specific machine/low-flow considerations.

Avoid in known/suspected malignant hyperthermia susceptibility (use non-triggering technique).
Use caution in raised ICP/poor intracranial compliance (avoid high MAC; control PaCO2).
Use caution with prolonged very low-flow techniques depending on local policy and absorbent type/condition (Compound A considerations).