Write a MD Anaesthesiology exam notes on difference between Sevoflurane and isolflurane in points form
Reading File
Finding Sources
Finding Sources
Reading File
Reading File
Reading File
Reading File
Finding Sources
Reading File
Reading File
I now have comprehensive data from Morgan & Mikhail (7e) and Barash Clinical Anesthesia (9e). I have enough to write thorough MD Anaesthesiology exam notes. Let me compile the full notes now.
Sevoflurane vs Isoflurane - MD Anaesthesiology Exam Notes
Comparison at a Glance
| Property | Sevoflurane | Isoflurane |
|---|---|---|
| Chemical class | Fluorinated methyl isopropyl ether (fully fluorinated) | Fluorinated methyl ethyl ether (halogenated - contains chlorine) |
| Odor | Sweet, non-pungent | Pungent, ethereal |
| Blood:gas partition coefficient (λ b/g) | 0.65 | 1.4 |
| MAC (in O2, 40 yr) | 2.0% | 1.15% |
| MAC (with 60% N2O) | ~0.6% | ~0.5% |
| Oil:gas partition coefficient | 47-54 | 91 |
| Vapor pressure at 20°C | ~160 mmHg | ~240 mmHg |
| Vaporizer type | Conventional variable-bypass vaporizer | Conventional variable-bypass vaporizer |
| Flammability | Non-flammable | Non-flammable |
| Potency (MAC) | Less potent (MAC 2%) | More potent (MAC 1.15%); "gold standard" |
1. Physical and Chemical Properties
Sevoflurane
- Completely fluorinated (no chlorine atom) - sweet smell, zero pungency
- Lower blood:gas solubility (0.65) - faster induction and emergence
- Lower oil:gas solubility - lower potency (MAC ~2%)
- Can be used in a conventional variable-bypass vaporizer (vapor pressure ~160 mmHg)
- Less chemically stable - degrades with desiccated CO2 absorbents (KOH/NaOH) to produce Compound A (nephrotoxic in rats; debated in humans)
- Susceptible to reaction with soda lime but considered safe at flow rates ≥2 L/min
- Does NOT produce trifluoroacetate on metabolism
Isoflurane
- Has one chlorine atom on the alpha-ethyl component (unlike desflurane which replaces it with F)
- Blood:gas solubility 1.4 - slower induction and emergence than sevoflurane
- Higher potency (MAC 1.15%) - "gold standard" volatile anesthetic since the 1970s
- Pungent odor - irritates upper airway; cannot be used for inhalational induction
- Very high physical stability - no significant degradation on storage for up to 5 years or on UV exposure
- Metabolized to trifluoroacetic acid (TFA)
- Conventional variable-bypass vaporizer
2. Pharmacokinetics
| Parameter | Sevoflurane | Isoflurane |
|---|---|---|
| Induction speed | Rapid (low b:g solubility 0.65) | Slower (b:g 1.4) |
| Emergence | Rapid; independent of anesthetic duration | Slower; prolonged with longer cases |
| Recovery to orientation | Not affected by duration of anesthesia | Delayed with longer surgical duration |
| Inhalation induction | Yes - preferred for pediatric & adult mask induction | No - pungency precludes mask induction |
| Metabolism | 3-5% (significant compared to isoflurane) | <0.2% (minimal) |
| Metabolites | Inorganic fluoride ions + Compound A (via soda lime) | Trifluoroacetic acid + minor fluoride |
| Elimination t1/2 (120 min washout) | 2-2.5x faster than isoflurane | Reference (slowest among newer agents) |
- Sevoflurane is 10-20 times more vulnerable to metabolism than isoflurane (Barash 9e)
- Despite higher fluoride ion levels with sevoflurane, renal concentrating defects have NOT been associated (unlike methoxyflurane)
- Isoflurane: fluoride levels may rise but nephrotoxicity is extremely unlikely
3. Cardiovascular Effects
| Effect | Sevoflurane | Isoflurane |
|---|---|---|
| Myocardial contractility | Mild depression | Minimal depression in vivo |
| Heart rate | Little or no increase | Increases (partial preservation of baroreflexes) |
| Cardiac output | Not as well maintained (no HR compensation) | Maintained (HR increase compensates) |
| SVR / BP | Declines slightly less than isoflurane | Decreases SVR more, lowers BP |
| Coronary vasodilation | Half as potent as isoflurane | Potent coronary vasodilator |
| Coronary steal | Not a concern | Theoretical concern (largely abandoned clinically) |
| QT interval | May prolong QT interval (clinical significance uncertain; persists up to 60 min post-emergence in infants) | No significant QT prolongation |
| Epinephrine arrhythmia threshold | Less sensitization | Less sensitization (safe up to 4.5 mcg/kg epi) |
| Ischemic preconditioning | Yes - produces preconditioning | Yes - produces preconditioning |
- Both are safe in patients with CAD, but isoflurane historically raised concerns about "steal" syndrome via dilation of normal coronary arteries diverting flow from fixed stenoses - concern largely abandoned
- Sevoflurane does NOT increase heart rate - so if cardiac output falls, there is no compensatory tachycardia
4. Respiratory Effects
| Effect | Sevoflurane | Isoflurane |
|---|---|---|
| Respiratory depression | Yes - dose dependent | Yes - dose dependent; tachypnea less pronounced |
| Effect on minute ventilation | Depresses | More pronounced fall in MV |
| Bronchodilation | Good bronchodilator (potent) | Good bronchodilator (less potent than halothane) |
| Airway irritation | None - non-pungent, no coughing or laryngospasm | Pungent - can cause coughing, breath-holding, laryngospasm on induction |
| Suitable for mask induction | Yes (4-8% in 50% N2O/O2 - induction in <1 min) | No |
| Hypoxic ventilatory response | Blunted (like all volatiles) | Blunted even at 0.1 MAC |
- Sevoflurane is preferred for inhalation induction in children AND adults due to non-pungency and sweet smell
- Both provide bronchodilation - sevoflurane comparable to isoflurane; useful in asthma
5. Neurological / CNS Effects
| Effect | Sevoflurane | Isoflurane |
|---|---|---|
| CBF at normocarbia | Slight increase (some studies show decrease) | Increases at >1 MAC |
| ICP | Slight increase | Increases at >1 MAC (less than halothane) |
| CMR (O2 consumption) | ↓↓↓ (same as isoflurane) | ↓↓↓ (greatest max depression - up to 50%) |
| EEG at 2 MAC | No electrical silence reported | Electrically silent EEG at 2 MAC |
| Seizure activity | Not reported | Not reported (may be protective) |
| Autoregulation of CBF | Impaired at >1.5 MAC (less pronounced than isoflurane) | Impaired - more pronounced impairment |
| Hyperventilation pretreatment | Not required before induction | Not required before induction (unlike halothane) |
| Use in neurosurgery | Acceptable; avoid high concentrations (>1.5 MAC) | Acceptable with controlled ventilation |
- Isoflurane produces the greatest maximal CMR depression (up to 50% reduction) - useful for cerebral protection
- CSF production: Isoflurane (±), Sevoflurane (unknown); CSF absorption: Isoflurane (↑), Sevoflurane (unknown) per Morgan & Mikhail Table 26-1
6. Neuromuscular Effects
| Effect | Sevoflurane | Isoflurane |
|---|---|---|
| Muscle relaxation | Adequate for intubation after inhalation induction | Relaxes skeletal muscle |
| Potentiation of NMBDs | Yes | Yes (same extent as desflurane) |
| Malignant hyperthermia | Trigger agent | Trigger agent |
- Both potentiate non-depolarizing NMBDs
- Both are absolute contraindications in malignant hyperthermia susceptible patients
7. Renal Effects
| Effect | Sevoflurane | Isoflurane |
|---|---|---|
| Renal blood flow | Slightly decreases | Decreases RBF, GFR, and urinary output |
| Nephrotoxicity | Controversial - Compound A (from soda lime degradation) causes renal tubular necrosis in rats; no confirmed nephrotoxicity in humans | Extremely unlikely; fluoride levels may rise but nephrotoxicity essentially absent |
| Fluoride levels | Elevated (due to higher metabolism) | Minimally elevated |
| Low-flow anesthesia | Use caution with very low flows (<1 L/min) - increased Compound A accumulation | Safe at all fresh gas flows |
| Clinical recommendation | Minimum fresh gas flow 2 L/min (FDA recommendation) | No restriction on flow |
- Key exam point: Sevoflurane is metabolized to inorganic fluoride + Compound A via soda lime/baralyme. Despite elevated fluoride and Compound A, no confirmed human nephrotoxicity has been demonstrated in clinical trials comparing low-flow sevoflurane vs isoflurane (Bito & Ikeda, 1999)
8. Hepatic Effects
| Effect | Sevoflurane | Isoflurane |
|---|---|---|
| Portal vein flow | Decreases | May be reduced |
| Hepatic artery flow | Increases (compensatory) | Preserved |
| Total hepatic blood flow | Maintained | May be reduced overall |
| Liver function tests | Usually unaffected | Usually unaffected |
| Hepatotoxicity | Not metabolized to TFA - immune-mediated hepatitis essentially absent | Metabolized to TFA - very rare risk of hepatitis (much less than halothane) |
| Risk of halothane hepatitis cross-reactivity | None (no TFA production) | Very low risk |
- Sevoflurane's advantage: does NOT produce trifluoroacetate - therefore no risk of immune-mediated hepatitis
- Isoflurane produces TFA but at very low levels - hepatitis is rare; still safer than halothane
9. Biotransformation and Toxicity Summary
| Feature | Sevoflurane | Isoflurane |
|---|---|---|
| Extent of metabolism | 3-5% | <0.2% |
| Primary metabolite | Inorganic fluoride, hexafluoroisopropanol (HFIP) | Trifluoroacetic acid (TFA) |
| Compound A | Yes - from reaction with desiccated CO2 absorbent | No |
| Carbon monoxide production | Minimal | Minimal (desiccated absorbent can produce CO) |
| Greenhouse gas potential | Lower than isoflurane | Significant atmospheric impact |
| Degradation by sunlight | Stable | Very stable (no deterioration for 5 years) |
10. Vaporizer / Equipment
| Feature | Sevoflurane | Isoflurane |
|---|---|---|
| Vaporizer | Conventional variable-bypass (Tec 7 / Penlon) | Conventional variable-bypass (Tec 3/5/7) |
| Misfilling risk | If misfilled with isoflurane: delivers ~3% isoflurane when set to 2% sevoflurane (>double the MAC multiple) | - |
| Special heating required | No | No |
| Fresh gas flow restriction | ≥2 L/min recommended (FDA) | None |
11. Clinical Use - Key Differences
| Indication | Sevoflurane | Isoflurane |
|---|---|---|
| Inhalation induction | First choice | Contraindicated (pungent) |
| Pediatric anesthesia | Preferred agent | Not suitable for induction |
| Rapid emergence needed | Better | Slower emergence |
| Long surgery (>4-6h) | Recovery duration independent of anesthetic length | Emergence delayed with prolonged cases |
| Asthma / bronchospasm | Preferred | Good alternative |
| Neurological surgery | Acceptable (avoid >1.5 MAC) | Acceptable; best CMR depression |
| Outpatient/day surgery | Preferred (faster emergence) | Less preferred |
| Cost | More expensive | Less expensive (established agent) |
| Malignant hyperthermia | Contraindicated | Contraindicated |
| Hypovolemia | Contraindicated | Contraindicated |
12. Key Exam Points / Mnemonics
-
"SEVO = SAFE induction" - Sweet smell, Every patient (pediatric + adult), Variable bypass vaporizer OK, Outcome (faster emergence)
-
Compound A = formed from sevoflurane + desiccated soda lime (KOH/NaOH); rat nephrotoxicity; no proven human nephrotoxicity; use FGF ≥2 L/min
-
Coronary steal = classically associated with isoflurane (not sevoflurane) - though largely a theoretical/historical concern
-
QT prolongation = sevoflurane (not isoflurane) - especially in infants
-
CMR depression - Both ↓↓↓ equally; Isoflurane produces maximum depression at 2 MAC (isoelectric EEG)
-
Metabolism - Sevoflurane 3-5% >> Isoflurane <0.2% - "sevoflurane is 10-20x more metabolized"
-
Blood:gas coefficient - Sevoflurane 0.65 vs Isoflurane 1.4 - lower = faster
-
No TFA production = sevoflurane; therefore no immune-mediated hepatitis
-
Isoflurane = gold standard historically; most potent of the two (MAC 1.15% vs 2.0%)
-
Recovery from long cases - Sevoflurane recovery independent of case duration; isoflurane recovery time increases with case length (Barash Fig 18-7)
13. Contraindications (Shared)
- Malignant hyperthermia susceptibility
- Severe hypovolemia
- Known sensitivity/allergy to halogenated agents
- Raised intracranial pressure (relative - use with caution; control PaCO2)
Sources: Morgan and Mikhail's Clinical Anesthesiology 7e (pp. 306-314); Barash, Cullen & Stoelting's Clinical Anesthesia 9e (pp. 1402-1404); Miller's Anesthesia 10e
This is a shared conversation. Sign in to Orris to start your own chat.