Ep.44 –Introduction to Volatile Anaesthetic Agents For The FRCA Primary

GasGasGas – The FRCA Primary Anaesthetics Exam Podcast

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Key Clinical Concept: The interplay between blood-gas solubility (determining onset/offset speed) and oil-gas solubility (determining potency) fundamentally shapes how we use volatile agents in practice. An agent that is poorly blood-soluble will onset rapidly but requires careful monitoring during induction, whilst a highly potent agent requires less volume but carries greater risk if delivered inconsistently.

Table 1: Physical Properties of Common Volatile Agents

Property	Sevoflurane	Desflurane	Isoflurane
Boiling Point (°C)	59	23	48.5
Saturated Vapour Pressure at 20°C (kPa)	21	89	32
Critical Temperature (°C)	Below room temp	Below room temp	Below room temp
Molecular Weight (g/mol)	200	168	184.5
Appearance	Clear, colourless liquid	Clear, colourless liquid	Clear, colourless liquid
Odour	Sweet, non-pungent	Pungent	Pungent, ethereal
Vaporiser Type	Variable bypass	Electrically heated	Variable bypass

Table 2: Partition Coefficients and MAC Values

Agent	Blood-Gas Coefficient	Oil-Gas Coefficient	MAC (%)	Clinical Implication
Desflurane	0.45	26	6.0	Fastest onset/offset, least potent, requires highest concentration
Sevoflurane	0.65	47-54	2.0	Moderate onset/offset, moderate potency, pleasant induction agent
Isoflurane	1.4	91	1.2	Slowest onset/offset, most potent, requires lowest concentration

Clinical Correlation: Lower blood-gas coefficient = faster equilibration = quicker onset and offset. Higher oil-gas coefficient = greater potency = lower MAC requirement.

Table 3: Factors Affecting MAC Requirements

Clinical State	Effect on MAC	Mechanism/Notes
Hyperthermia	↑	Increased metabolic rate, enhanced neuronal excitability
Hypernatraemia	↑	Altered neuronal threshold
Chronic alcohol use	↑	Enzyme induction, CNS tolerance
Acute amphetamine use	↑	CNS stimulation
Hypothermia	↓	Reduced metabolic rate, decreased neuronal activity
Hyponatraemia	↓	Altered neuronal excitability
Pregnancy	↓	Progesterone effects, increased sensitivity
Elderly patients	↓	Reduced neuronal reserve, altered pharmacodynamics
Acute opioid/sedative use	↓	Synergistic CNS depression
Hypothyroidism	↓	Reduced metabolic state
Hypotension/shock	↓	Reduced cerebral perfusion, altered distribution

Classification & Basic Properties

Chemical Class: Halogenated ether derivatives (modern agents)

Fundamental States of Matter Concepts:

Vapour vs Gas – Critical Temperature

The distinction between vapour and gas centres on critical temperature – the threshold above which a substance behaves as a true gas. Any substance below its critical temperature that exists in gaseous form is technically a vapour; above this temperature, it becomes a gas.

• Gas behaviour: Above critical temperature, no amount of pressure will liquefy the substance (e.g., oxygen, nitrogen in clinical practice)
• Vapour behaviour: Below critical temperature, the substance can be liquefied by applying sufficient pressure
• Clinical relevance: All volatile anaesthetic agents used clinically are vapours at room temperature, as their critical temperatures exceed ambient conditions.

Appearance and Storage:

• All modern volatile agents are clear, colourless liquids at room temperature
• Stored in colour-coded bottles (Sevoflurane: yellow; Desflurane: blue; Isoflurane: purple)
• Chemically stable in amber-coloured bottles at room temperature
• No special storage requirements beyond standard pharmaceutical practice

Pharmacodynamics

Mechanism of Action 

Historical Perspective – Meyer-Overton Hypothesis (Discredited):

Early theories correlated lipid solubility with anaesthetic potency, hypothesising that fat-soluble agents disrupted neuronal lipid bilayers. This theory collapsed when potent, less lipid soluble anaesthetics were discovered, proving the mechanism cannot be purely physical disruptive process.

Current Understanding – Protein Receptor Modulation:

Volatile agents produce unconsciousness through direct interaction with specific protein targets:

Primary Target – GABA-A Receptors:

• Allosteric modulation enhances inhibitory neurotransmission
• Prolongs chloride channel opening
• Produces dose-dependent CNS depression
• Likely mediates hypnotic and amnestic effects

Secondary Targets:

• NMDA receptors: Antagonism may contribute to unconsciousness and amnesia
• Two-pore potassium channels: Activation hyperpolarises neurones, reducing excitability
• Neuronal nicotinic receptors: Complex modulation of excitatory transmission

The Unanswered Question:

Despite knowing these molecular targets, the fundamental mechanism by which receptor modulation produces unconsciousness, amnesia, and loss of awareness remains incompletely understood. Volatile agents were discovered empirically (“have a whiff of this – oh, you’re unconscious”) rather than designed rationally, and we continue using them because they work, even whilst the complete mechanistic picture eludes us.

Patient Communication Strategy:

When patients ask how anaesthetics work, an honest approach acknowledges that whilst we understand receptor targets (GABA-A modulation), the translation from receptor binding to complete unconsciousness involves complex neuronal network effects that aren’t fully characterised. This honesty, whilst potentially unsettling, maintains trust if you can admit to what is not known your likely to know what is known….

Specific Applications:

• Maintenance of anaesthesia in spontaneously breathing or mechanically ventilated patients
• Inhalational induction (sevoflurane preferred due to pleasant odour)
• Bronchodilation in acute asthma (historical use, now uncommon)
• Controlled hypotension (dose-dependent vasodilation)

Dosing and Preparations

Vaporiser Settings:

Volatile agents are not “dosed” in traditional mg/kg terms but rather delivered as inspired fractions (volume %), with effect measured as end-tidal concentration correlated to an age adjusted MAC values.

Standard Maintenance Concentrations:

• Sevoflurane: 1.5-3% inspired (targeting ~2% end-tidal for 1 MAC)
• Isoflurane: 1-2% inspired (targeting ~1.2% end-tidal for 1 MAC)
• Desflurane: 5-8% inspired (targeting ~6% end-tidal for 1 MAC)

Induction Concentrations:

• Sevoflurane gas induction: 8% inspired with 100% oxygen, reduced once consciousness lost
• Other agents generally unsuitable for inhalational induction due to pungency

Practical Example (70kg adult):

For maintenance anaesthesia at 1 MAC:

• Set sevoflurane vaporiser to 2%
• With minute ventilation of 5 L/min, delivers approximately 100mL/min of sevoflurane vapour
• End-tidal monitoring confirms ~2% concentration achieved after 5-10 minutes (wash-in period)
• No specific “dose” calculation required – effect-site concentration monitoring guides delivery

Overpressurisation Technique:

During rapid-sequence or emergency induction, temporarily set vaporiser to maximum (e.g., 8% sevoflurane) to accelerate wash-in, then reduce to maintenance levels once adequate depth achieved. This compensates for the unavoidable delay between starting volatile delivery and achieving therapeutic brain concentration. But will increase odds of CVS instability

Side Effects by Organ System 

Cardiovascular System:

• Dose-dependent hypotension (peripheral vasodilation + mild myocardial depression)
• Bradycardia at higher concentrations (reduced sympathetic tone)
• Reduced systemic vascular resistance (almost all agents)
• Preserved or slightly reduced cardiac output (varies by agent)

Respiratory System:

• Dose-dependent respiratory depression (reduced tidal volume and rate)
• Bronchodilation (useful in reactive airways, historical asthma treatment)
• Reduced hypoxic pulmonary vasoconstriction (potential V/Q mismatch)
• Airway irritation (isoflurane and desflurane – not sevoflurane)
• Historical self-regulation: reduced respiratory rate → less volatile uptake → lighter anaesthesia (unreliable safety mechanism)

Central Nervous System:

• Hypnosis and amnesia (therapeutic effects)
• Dose-dependent EEG suppression (burst suppression at high concentrations)
• Cerebral vasodilation (increased intracranial pressure – concern in neuroanaesthesia)
• Reduced cerebral metabolic oxygen consumption (CMRO₂)
• Impaired autoregulation at higher concentrations
• Anticonvulsant properties (generally, though enflurane historically could provoke seizures)

Neuromuscular System:

• Muscle relaxation (potentiates non-depolarising neuromuscular blockers)
• Reduced movement to surgical stimulus (spinal cord depression)
• Synergy with:
  • Non-depolarising muscle relaxants
  • Magnesium (enhances blockade)
  • Aminoglycosides (e.g., gentamicin – prolongs neuromuscular blockade)

Uterine Effects:

• Dose-dependent uterine relaxation
• Risk of uterine atony in obstetric general anaesthesia
• Increased risk of postpartum haemorrhage
• Lower MAC requirement in pregnancy but higher incidence of awareness regardless

Saturated Vapour Pressure (SVP)

Conceptual Understanding (Timestamp: 03:16-07:16)

Saturated vapour pressure represents the equilibrium state between liquid and vapour phases of a substance within a closed system. Understanding SVP requires imagining a closed container partially filled with volatile agent:

The Tupperware Box Thought Experiment:

When liquid sevoflurane sits in a sealed container:

1. Initial state: Energetic molecules at the liquid surface possess sufficient kinetic energy to escape into the vapour phase
2. Cooling effect: As high-energy molecules escape, the remaining liquid loses heat energy and cools slightly
3. Vapour accumulation: Escaped molecules bounce around the gas space as vapour
4. Reverse phase transition: Some vapour molecules collide with the liquid surface and return to liquid state
5. Equilibrium: Eventually, the rate of liquid→vapour equals vapour→liquid, establishing saturated vapour pressure

Key Determinants of SVP:

• Agent-specific: Each volatile has a characteristic SVP (sevoflurane: 21 kPa at 20°C)
• Temperature-dependent: Higher temperatures increase molecular kinetic energy, raising SVP
• Time-dependent: Equilibrium takes time to establish

Clinical Significance:

At 20°C, sevoflurane’s SVP of 21 kPa represents approximately 21% concentration in equilibrated gas space – far exceeding the 8% maximum deliverable via standard vaporisers. This demonstrates why controlled vaporisation is essential; breathing saturated sevoflurane vapour would deliver a massive overdose.

Memory Aid: Sevoflurane’s SVP at 20°C (21 kPa) equals atmospheric oxygen partial pressure (21 kPa).

Boiling Point and Clinical Implications

Definition and Agent Comparison

Boiling point is the temperature at which vapour pressure equals atmospheric pressure, allowing bulk liquid-to-vapour conversion.

Sevoflurane (BP: 59°C):

• Remains liquid at all clinical temperatures
• Standard variable-bypass vaporiser functions reliably
• Spillage creates localised vapour without rapid dispersion
• Temperature-compensated vaporisation ensures consistent delivery

Desflurane (BP: 23°C):

• Boils at or near room temperature
• Creates extraordinarily high vapour concentrations when spilled (hazardous)
• Standard vaporisers cannot reliably deliver consistent concentrations
• Requires electrically-heated pressurised vaporiser:
  • Maintains desflurane at 39°C (well above boiling point)
  • Creates predictable, saturated vapour at approximately 2 atmospheres pressure
  • Injects calibrated vapour boluses into fresh gas flow
  • Requires electrical power (environmental concern)

Practical Consideration: A desflurane spill in a warm environment creates a dense, invisible cloud of highly concentrated vapour – potentially hazardous to staff before atmospheric dilution occurs.

Blood-Gas Partition Coefficient and Onset/Offset 

Definition:

The blood-gas partition coefficient represents the ratio of volatile agent dissolved in blood versus alveolar gas at equilibrium. This single number profoundly influences clinical onset and offset speed.

The Counterintuitive Principle:

Lower blood-gas coefficient = Faster onset/offset

This seems paradoxical: if an agent is poorly blood-soluble, how does it reach the brain faster?

The Explanation:

When inspired volatile fills the alveolus, poorly blood-soluble agent “reluctantly” enters blood because concentration gradient forces dictate it must. Once in blood, it equally “reluctantly” remains there, preferentially leaving for more attractive tissue (brain, fat) at first opportunity.

The Process:

1. Alveolar filling: Inspired volatile rapidly achieves high alveolar concentration
2. Reluctant blood entry: Poor blood solubility means blood quickly saturates with agent
3. Rapid brain delivery: First-pass blood delivers agent to highly perfused brain
4. Quick tissue uptake: Agent preferentially leaves blood for brain tissue
5. Fast equilibration: Poor blood solubility means inspired, alveolar, blood, and brain concentrations equilibrate rapidly

Offset Mechanism:

Upon discontinuing volatile delivery:

1. Alveolar concentration drops to zero
2. Concentration gradient reverses (high brain → low alveolar)
3. Agent diffuses from brain → blood → alveoli → exhalation
4. Low blood solubility means rapid clearance from circulation

Clinical Values:

• Desflurane (0.45): Fastest onset/offset – excellent for ambulatory surgery
• Sevoflurane (0.65): Moderate speed – balanced profile for general use
• Isoflurane (1.4): Slowest onset/offset – less suitable for rapid induction

Oil-Gas Partition Coefficient and Potency

Definition:

The oil-gas partition coefficient quantifies agent solubility in lipid (oil) relative to gas phase, directly correlating with anaesthetic potency.

The Principle:

Higher oil-gas coefficient = Greater potency = Lower MAC

This relationship makes biological sense: the brain is 60% lipid; agents more lipid-soluble concentrate more effectively in neuronal membranes and reach therapeutic receptor concentrations at lower inspired fractions.

Clinical Values:

• Isoflurane (91): Most lipid-soluble → Most potent → MAC 1.2%
• Sevoflurane (47-54): Moderate lipid solubility → Moderate potency → MAC 2.0%
• Desflurane (26): Least lipid-soluble → Least potent → MAC 6.0%

Working Backwards from MAC:

If you know an agent requires 6% end-tidal concentration for 1 MAC (desflurane), you can deduce it must have relatively low oil-gas solubility – you need “more of it” because it’s less potent. Conversely, isoflurane at MAC 1.2% must be highly oil-soluble and therefore more potent.

Exam Strategy:

In MCQs presenting MAC values, remember: higher MAC = less potent = lower oil-gas coefficient = faster onset (if blood-gas also provided). The inverse relationships create predictable patterns you can exploit under time pressure.

Wash-In Curves 

Wash-in describes the time-course of Fi/FA (inspired fraction/alveolar fraction) approaching 1.0, indicating near-equilibrium between delivered and effect-site concentrations.

Curve Characteristics:

• Exponential shape: Steep initial rise, then plateau approaching equilibrium
• Agent-specific speed:
  • Desflurane: FA/Fi approaches fastest
  • Sevoflurane: Moderate
  • Isoflurane: Slower
  • Halothane (rathe hecking slow)

Factors Accelerating Wash-In:

• Increased inspired concentration (overpressurisation)
• Increased alveolar ventilation (hyperventilation)
• Reduced cardiac output (less agent removed from alveoli per unit time)
• Reduced functional residual capacity (less dilutional volume)

Factors Slowing Wash-In:

• High cardiac output (rapid agent removal from alveoli to tissues)
• High blood-gas solubility (more agent dissolved in blood before saturating)
• Large tissue mass (obese patients have greater fat reservoir)

Metabolism:

Sevoflurane:

• 3-5% hepatic metabolism via CYP2E1
• Produces inorganic fluoride (generally below nephrotoxic threshold)
• Compound A formation in CO₂ absorbent (low-flow concern, minimal clinical significance)

Isoflurane:

• <0.2% metabolised (clinically insignificant)
• Minimal metabolite production

Desflurane:

• <0.02% metabolised (essentially non-metabolised)
• Negligible metabolite formation

Elimination:

• Primary route: Pulmonary exhalation (>95% for modern agents)
• Minor route: Hepatic metabolism (<5%)
• Elimination half-life:
  • Context-dependent (relates to duration of administration)
  • Longer administrations → greater tissue saturation → slower offset
  • Desflurane: Fastest elimination
  • Sevoflurane: Moderate
  • Isoflurane: Slowest

Minimum Alveolar Concentration (MAC)

Definition

One MAC is defined as: The end-tidal volatile agent concentration at which 50% of subjects do not move in response to a standard surgical stimulus (skin incision, historically Pfannenstiel incision).

Critical Caveats:

• No other anaesthetic agents present (pure volatile anaesthesia)
• No opioids or analgesics administered
• Standard surgical stimulus: Skin incision (not deeper tissue manipulation)
• Population median: 50% moved, 50% did not move (ED₅₀)
• Does not predict awareness (see MAC-Awake below)

Standard MAC Values (Age 40, Sea Level):

• Sevoflurane: 2.0% (some references: 1.8%)
• Isoflurane: 1.2%
• Desflurane: 6.0%

MAC Variants:

MAC-Awake:

• Concentration at which 50% of patients respond to verbal command
• Approximately 0.3-0.4 MAC
• Relevant to emergence and recovery

MAC-Aware: (this is 50:50 remember!) so you would be daft to rock your anaesthetic at 0.6 Mac and think your odds of awareness are low, even with a load of opiates etc on board.

• Concentration preventing awareness/recall
• Approximately 0.6 MAC
• Below MAC, awareness risk increases substantially

MAC-BAR (Block Adrenergic Response):

• Concentration preventing sympathetic response to surgical stimulus
• Approximately 1.3-1.5 MAC
• Relevant when autonomic stability required (neuroanesthesia, hypertensive patients)

Additivity:

MAC is additive across agents and synergistic with other CNS depressants:

• 0.5 MAC sevoflurane + 0.5 MAC nitrous oxide = 1.0 MAC total
• MAC reduced by ~30% with typical opioid doses
• Further additive reduction with benzodiazepines, alpha-2 agonists, etc
• Predicting what all these additions mean is challenging and patient factor dependent…. so always gift yourself a wide safety margin

Emergency Induction and Awareness Risk

Standard elective anaesthesia includes a “built-in” safety margin:

1. Induction in anaesthetic room
2. Nerve blocks or positioning performed
3. Transfer to theatre
4. WHO safety checks
5. Final positioning adjustments
6. Surgical preparation and draping

This 10-20 minute delay allows adequate wash-in time for volatile agents to achieve therapeutic brain concentration before surgical stimulus begins. The initial propofol bolus helps to covers this period.

High-Risk Emergency Scenarios:

Category 1 Caesarean Section (Crash Section):

• Decision-to-delivery is expectedly quite rapid
• No handy delay to ease wash in
• Surgical stimulus begins very quickly post-intubation
• Risk factors:
  • Short available wash-in time
  • Potentially high cardiac output (stress response)
  • Reduced MAC requirement partially protective
  • Higher awareness rates documented (despite parturients having lower Mac requirements, and quite a bit less FRC to concentrate into)

Management Strategy:

• Maintain adequate propofol depth until volatile establishes
• Co-induct with 1mg Alfentanil and tell the paeds team!
• Overpressurise with volatile (8% sevoflurane initially but don’t forget to turn it down)
• Consider additional propofol boluses pre incision
• Accept higher volatile concentrations in initial phase (risk uterine atony vs awareness)

Volatile vs Propofol TIVA – Immobility 

Observation:

Patients maintained on propofol TIVA exhibit more movement to surgical stimulus compared to volatile-maintained anaesthesia, despite apparently adequate depth.

Mechanism:

Volatile agents produce spinal cord depression more effectively than propofol, directly suppressing motor responses to noxious stimuli independent of cerebral effects. This explains why MAC specifically measures immobility rather than unconsciousness.

Clinical Implications:

Propofol TCI + Fentanyl Boluses:

• Movement seems to be more common despite adequate hypnosis
• Spinal reflexes less suppressed
• May require deeper sedation or additional muscle relaxation

Propofol TCI + Remifentanil Infusion:

• Less movement observed
• Remifentanil’s profound analgesia compensates for reduced spinal suppression
• More stable conditions

Volatile + Opioid:

• Spinal depression from volatile
• Analgesia from opioid
• Generally less movement

Synergy with Neuromuscular Blockade:

Volatile agents potentiate non-depolarising muscle relaxants, creating synergistic neuromuscular blockade. This interaction is clinically significant:

• Reduced muscle relaxant requirements (15-25% less)
• Prolonged block duration
• Enhanced by magnesium, aminoglycosides
• Monitor neuromuscular function carefully when combining these agents

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FRCA Primary Viva-Style Questions

Question 1: Saturated Vapour Pressure

Examiner: “Can you explain what saturated vapour pressure means, and why is it clinically relevant?”

Model Answer:

“Saturated vapour pressure represents the pressure exerted by a vapour when it is in equilibrium with its liquid phase at a specific temperature within a closed system.

To understand this, I would describe a closed container partially filled with a volatile agent such as sevoflurane. Molecules at the liquid surface with sufficient kinetic energy escape into the vapour phase. As energetic molecules leave, the remaining liquid cools slightly. Simultaneously, some vapour molecules collide with the liquid surface and return to the liquid state. Eventually, the rate of liquid-to-vapour transition equals the vapour-to-liquid transition, establishing equilibrium. At this point, the partial pressure exerted by the vapour is the saturated vapour pressure.

Several factors influence saturated vapour pressure. Firstly, it is agent-specific – sevoflurane has a saturated vapour pressure of 21 kilopascals at 20 degrees Celsius, whilst desflurane has a much higher saturated vapour pressure of 89 kilopascals at the same temperature. Secondly, it is temperature-dependent – increasing temperature raises molecular kinetic energy, increasing the number of molecules escaping the liquid phase, thereby raising the saturated vapour pressure. Thirdly, ambient pressure has a inverse effect – higher environmental pressure suppresses vapour formation.

The clinical relevance relates to vaporiser design and safe volatile delivery. At 20 degrees, sevoflurane’s saturated vapour pressure of 21 kilopascals represents approximately 21% concentration in the gas phase – far exceeding safe clinical concentrations. The maximum sevoflurane vaporiser setting is typically 8%, itself an excessive concentration for maintenance. Without controlled vaporisation, a patient breathing saturated sevoflurane vapour would receive a massive overdose causing profound cardiovascular collapse. This is why temperature-compensated, variable-bypass vaporisers are essential to deliver precise, safe concentrations regardless of ambient temperature fluctuations.

Additionally, understanding saturated vapour pressure explains why desflurane requires an electrically heated pressurised vaporiser. Its low boiling point of 23 degrees means it generates extremely high vapour pressures at room temperature, making standard vaporiser designs unreliable for consistent delivery.”

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Question 2: Blood-Gas Partition Coefficient

Examiner: “What is the blood-gas partition coefficient, and how does it affect the clinical use of volatile agents? Why does a lower coefficient result in faster onset?”

Model Answer:

“The blood-gas partition coefficient is a ratio describing the relative solubility of a volatile agent in blood compared to gas at equilibrium. Specifically, it represents the amount of agent dissolved in blood divided by the amount in the gas phase when the partial pressures are equal.

The critical principle is that a lower blood-gas coefficient results in faster onset and offset of the volatile agent. For example, desflurane has a blood-gas coefficient of 0.45, sevoflurane 0.65, and isoflurane 1.4. Therefore, desflurane equilibrates most rapidly, whilst isoflurane equilibrates most slowly.

When a poorly blood-soluble agent like desflurane fills the alveoli, a high alveolar partial pressure develops rapidly because minimal agent dissolves into blood. The blood passing through the pulmonary capillaries quickly becomes saturated with the small amount of agent it can hold. This saturated blood then delivers agent to highly perfused tissues like the brain. Because the agent is poorly blood-soluble, it preferentially leaves the blood for more favourable tissue compartments, rapidly establishing a therapeutic brain concentration.

In contrast, a highly blood-soluble agent like isoflurane dissolves readily into blood, acting as a large reservoir. More agent must be delivered to saturate this blood reservoir before alveolar partial pressure rises significantly. This delays equilibration between inspired, alveolar, blood, and brain concentrations. The blood essentially “soaks up” the agent, slowing its delivery to the brain.

Offset follows the same principle in reverse. When volatile delivery ceases, alveolar concentration drops to zero. A poorly blood-soluble agent readily leaves the blood into the alveoli along the concentration gradient because it has minimal affinity for remaining in blood. A highly blood-soluble agent releases more slowly from the blood reservoir, prolonging offset time.

Clinically, this explains why desflurane and sevoflurane are preferred for ambulatory surgery requiring rapid recovery. It also explains the importance of overpressurisation during induction with slower agents – temporarily setting the vaporiser to maximum to accelerate wash-in and compensate for the delay in achieving therapeutic brain concentration, particularly relevant in emergency scenarios where the usual programmed delay between induction and surgical stimulus is absent.”

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Question 3: Characteristics of an Ideal Volatile Anaesthetic Agent

Examiner: “Describe the characteristics of an ideal volatile anaesthetic agent. How would you structure your answer?”

Model Answer:

“I would structure my answer by considering desirable physical properties and pharmacological properties separately, then address practical considerations.

Desirable Physical Properties:

From a physical chemistry perspective, an ideal agent would have a boiling point well above room temperature, ensuring it remains liquid during storage and transport whilst vaporising predictably in clinical vaporisers. Its saturated vapour pressure should be sufficiently high to allow simple vaporiser designs but not so high as to create hazardous concentrations if spilled. The critical temperature should be well above ambient conditions, confirming vapour behaviour.

The agent should be chemically stable – non-flammable, non-explosive, and stable in light and at room temperature, eliminating special storage requirements. It should not react with metals, plastics, or carbon dioxide absorbents, preventing degradation or equipment damage. It should resist absorption into breathing circuit components, ensuring delivered concentration matches vaporiser settings.

Environmentally, an ideal agent would break down rapidly in the atmosphere, possessing minimal global warming potential and zero ozone-depleting properties.

Desirable Pharmacological Properties:

Breaking this down by organ system:

Cardiovascular: The agent should maintain haemodynamic stability, preserving blood pressure, heart rate, and cardiac output across a wide concentration range. It should not sensitise the myocardium to catecholamines or prolong cardiac conduction intervals.

Respiratory: It should have a pleasant, non-pungent odour, facilitating inhalational induction, particularly in paediatric patients. It should be non-irritant to airways whilst providing bronchodilation. Respiratory depression should be minimal, though some is acceptable given controlled ventilation during anaesthesia.

Central Nervous System: The agent should provide reliable hypnosis and amnesia. It should not increase intracranial pressure or reduce cerebral perfusion pressure. Ideally, it would possess anticonvulsant rather than proconvulsant properties. Analgesic properties would be advantageous, though not essential given co-administration of opioids.

Metabolic: Minimal hepatic metabolism would reduce toxic metabolite risk. The agent should not interfere with steroidogenesis, gluconeogenesis, or other metabolic pathways. It should not trigger malignant hyperthermia.

Neuromuscular: Useful muscle relaxant properties would reduce non-depolarising muscle relaxant requirements, though this should not cause awareness due to paralysis without adequate hypnosis.

Pharmacokinetic Properties:

An ideal agent would have a low blood-gas partition coefficient, ensuring rapid onset and offset for quick induction and prompt recovery. Simultaneously, a high oil-gas partition coefficient would provide potency, requiring lower inspired concentrations to achieve therapeutic effect.

Practical Considerations:

Finally, cost-effectiveness is essential. An expensive agent limits accessibility and sustainability in healthcare systems. The agent should be straightforward to manufacture, transport, and administer, requiring no specialised equipment beyond standard vaporisers.

No current volatile agent meets all these criteria. Sevoflurane approaches the ideal for many characteristics – pleasant for induction, moderate speed of onset/offset, reasonable potency, and cardiovascular stability. However, it has environmental concerns due to persistence and global warming potential. Desflurane offers excellent pharmacokinetic properties but requires electrical vaporisation, has a harsh odour precluding inhalational induction, and has the worst environmental profile. Balancing these characteristics guides agent selection for individual clinical scenarios.”

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Supporting Materials Referenced in Episode

1. Peck TE, Hill SA, Williams M.Pharmacology for Anaesthesia and Intensive Care, 4th Edition. Cambridge University Press, 2014.
2. Pharmacology of anaesthetic agents II: inhalation anaesthetic agents
3. E-Learning for Health (e-LfH) – Anaesthesia
   • Graphical representations of wash-in curves (Fi/FA over time)
   • MAC vs time graphs
4. Miller’s Anesthesia, 9th Edition
   • Page 488 onwards: Detailed mechanism of action discussion
   • Comprehensive volatile agent pharmacology
   • Advanced reading for mechanism questions
5. Association of Anaesthetists: Environmental Sustainability
   • Guidelines on reducing volatile agent environmental impact
   • Recommendations for low-flow anaesthesia
   • Available at: https://anaesthetists.org/Home/Resources-publications/Environment/Guide-to-green-anaesthesia

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Previous Gas, Gas, Gas Episodes Referenced:

• Compartmentalized Volatiles (detailed wash-in/wash-out modeling)
• MAC Deep Dive (MAC-Awake, MAC-BAR, awareness thresholds)

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Transcript

Episode 44: Introduction to Volatile Anaesthetic AgentsIntroduction and Episode Overview

00:00-00:32Hello and welcome to Gas, Gas, Gas – the best podcast for the FRCA primary exam. Our goal is to fill your brain with highly useful information. You might be in the gym right now, commuting, or ironing your scrubs. Regardless, revision is eventually going to end, but for now expect facts, concepts, model answers, and the odd tangent. Make sure to check out GasGasGas.uk for show notes with loads more detail. Like and subscribe, and buckle up – get ready for your mind to be bent into a new shape. Let’s get on with the show.Hello everyone, this is James at Gas, Gas, Gas. Today we’re talking about volatile anaesthetic agents. We’re going to introduce these and cover the important physicochemical concepts that govern how they behave in a patient. We’ll think about how they behave physically in the environment around us or in a Tupperware box, and also touch on the pharmacodynamics of volatiles.Key topics covered:

• Critical temperatureSaturated vapour pressure (SVP)Boiling pointBlood-gas partition coefficientsOil-gas partition coefficientsDefinition of MAC and its relationship to oil-gas partition coefficientsHow blood-gas partition coefficient influences onset time

Before we begin, I need to apologise for the kerfuffle with the opioids quiz. The sound engineer has been sacked for the third time – there was an issue with post-recording mastering that made the background music really loud and somehow misaligned itself. Tremendous headache. I hope you can accept my foibles, and we’re going to get on and chat about critical temperature.

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Critical Temperature Explained

00:52-03:16What is critical temperature?Critical temperature is the crossover point where a vapour takes on the true behaviour of a gas. It’s hard for my brain to think about this from the perspective of a vapour, so I press forward and think about why it’s a gas, then consider the contrary to be why it’s a vapour.If you’ve got a gas and it is above its critical temperature – like oxygen, hydrogen, etc. – anything above its critical temperature (which is particular to it as a molecule or atom), you can apply as much pressure as you like and it will not shift phase down to a liquid.If you were to take sevoflurane vapour (that stuff zooming around your anaesthetic circuit) and apply pressure to it, it would begin to shift back into a liquid phase. Above its critical temperature, no pressure will get you there.Key principle: Anything below its critical temperature that is floating around is a vapour, whereas anything above is a gas.When you’re doing a gas anaesthetic, you have the opportunity to be deeply pedantic and say: “No, in fact I am doing a vapour anaesthetic, but I am co-administering air, which is a gas.” You could also argue that you’re administering nitrogen if you’re using an oxygen-air mix, as well as the other molecules in sparser concentrations floating around in our atmosphere, and there’ll be some carbon dioxide in there too.

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Saturated Vapour Pressure and the Tupperware Box Analogy

03:16-07:16We need to conceptualise a mental model before we press further. We need to talk about saturated vapour pressure. Again, this is something that made my head hurt. There is crossover with this concept and humidity, but we’re not hitting humidity today.The Tupperware box thought experiment:You’ve fished out your bottle of sevoflurane from the cupboard, somehow managed to unscrew the top, and you have your Tupperware lunch box that’s airtight. It’s empty – no ham sandwich – and you tip a bit of sevoflurane into your Tupperware box and close it up. What happens in this box?Some of that sevoflurane liquid will shift into a vapour phase. As this liquid shifts into a vapour phase, the remaining liquid gets slightly cooler. Why is this happening?All your molecules of sevoflurane in that bottle have slightly differing amounts of energy in them. Some are a bit more energetic and some are more feckless and lacking energy. We have to imagine this energy as heat energy – vibrating jazzy molecules. Some more jazzy, some less jazzy.The jazzy ones are more likely to escape off the surface of your sevoflurane liquid and become a vapour, bouncing around gleefully in the gas space inside your Tupperware box.Reaching equilibrium:Given enough time, and noting that this is a somewhat fixed space, an equilibrium state will develop whereby quite a few molecules have pinged off the top of the sevoflurane liquid and are bouncing around in the gas. But some of those molecules are also hitting the vapour-liquid interface and returning to a liquid state.There’s an equilibrium that will eventually be reached between the amount of sevoflurane escaping and the amount returning between these two states. When that equilibrium is reached at a particular temperature, you can say that you have reached the saturated vapour pressure of that particular system.Agent-specific properties:Sevoflurane behaves differently to isoflurane and desflurane. They all have slightly different saturated vapour pressures. SVP is the equilibrium state between vapour and liquid in a system.If you were to take a big lungful of this sevoflurane in your Tupperware box, you’d end up with quite a large dose. Why? Because the saturated vapour pressure of sevoflurane is 21 kilopascals at 20 degrees.If we’ve heated our Tupperware to 20 degrees and then taken a lungful of that vapour once it’s equilibrated, we will be getting a stonkingly large dose of sevoflurane – not good for us at all. It’ll end up being 21% more or less sevoflurane. We know that the sevoflurane vaporiser will only actually let us get up to 8%.Clinical relevance:Presumably we can imagine that over 8% is certainly an overdose. If you were to try and do a whole appendicectomy on 8%, you’d end up in a very vasodilated, poorly patient situation. It would not end well – far in excess of what you need. This is why we need vaporisers, because we can then control the fraction of sevoflurane we’re administering to a patient.Key principles of SVP:

• Agent-specificTemperature-specificEnvironmental pressure-specific (somewhat)This pressure is important because if you raise the pressure of that system, noting that we are below the critical temperature of this molecule, you’ll end up with less becoming a vapour because there’s more pressure

Memory aid: To remember the SVP of sevoflurane, you can remember that it’s the same as the partial pressure of atmospheric oxygen: 21.Further study: It’s worth reading about the triple point of water, and also about the difference between absolute and relative humidity. That will help you appreciate how water vapour behaves, and by extension how these other volatile anaesthetic vapours behave.Summary: Saturated vapour pressure is an equilibrium point that’s molecule-specific, temperature-specific, pressure-specific, takes time to achieve, and is where the rate of liquid to vapour and vapour to liquid is even.

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Vaporiser Function and Temperature Effects

07:17-08:12If you were to take off this vapour from this chamber through a tube, you would end up with more agent shifting from liquid state to vapour state. But we should note that we’ve pulled off the warmest molecules at this point in time.Your system has now dropped in temperature slightly, so you will end up with a lower fraction of the molecule equalising to that new vapour state until the system warms through again.Clinical implication: If you’re pulling off rapid amounts of gas from your chamber, the chamber cools, the amount of volatile you are extracting goes down, and then you have an unclear concentration that you’re delivering to your theoretical patient. This is why vaporisers are important.There are contraptions in there that try and facilitate constant temperature, as well as mechanisms that modulate the amount of volatile pulled from the chamber in order to compensate for temperature changes.We’ll talk about vaporisers in another episode, far into the future, I’m sure.

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Boiling Points: Sevoflurane vs Desflurane

08:12-10:02You need to learn about boiling points of volatile anaesthetic agents. All the volatile anaesthetic agents have different properties and different boiling points. Why are we really interested in boiling point?Comparing sevoflurane and desflurane:The easiest way to illustrate this is to compare our bottle of yellow sevoflurane with our bottle of blue desflurane.

• Sevoflurane boils at 59 degrees. I can totally agree that most NHS hospitals probably don’t get to 59 degrees. Although I’m sure in that heatwave when the air conditioning fails and you’ve rolled up your scrubs into shorts (much to the horror of everyone in the room), it’s not quite 59 degrees. The sevoflurane is not boiling.Desflurane boils at 23 degrees. If you’re in a moderately warm room, or perhaps on a lovely beach in Greece somewhere, and you spill some desflurane on the floor, it will rapidly shift into a vapour. It’ll evaporate. That puddle will disappear. Unfortunately, that puddle will disappear into a small cloud of very concentrated desflurane before it gets blown away.

Clinical implications for desflurane:If this were to occur inside our Tupperware box, we would end up with a very large amount of desflurane vapour. This leads to a moderately tricky situation whereby we may inconsistently deliver differing concentrations of desflurane if we were to use a standard bit of vaporising apparatus.That’s why you’ve got to plug in your desflurane vaporiser. It’s bad for the environment because desflurane hangs around for ages, and it’s bad for the environment because it takes electricity to actually use the damn stuff.If you don’t use electricity and you don’t intentionally warm desflurane above its boiling point of 23 degrees, you won’t know how much desflurane you’re giving to your patient. Desflurane vaporisers work in a different manner to inject a certain amount of very concentrated desflurane vapour into the system in order to avoid this problem.

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Blood-Gas Solubility and Onset Time

10:02-12:07We’ve spoken about the physical properties of volatile anaesthetic agents. This is a physical property of it getting in and around a human.What is blood-gas solubility?The first fact to note: the lower your blood-gas coefficient, the faster your drug onsets and offsets.The less soluble (the lower the number), the less able the volatile anaesthetic agent is going to be to sit inside blood.The counterintuitive part:You’re probably thinking (and this is exactly where my brain went as well): “Well, how the hell does it go quicker then if it doesn’t even want to be in the blood? That doesn’t make any sense.”This is because it really bears down on the pressure gradients or the concentration gradients you’re exerting on the human with the sevoflurane.If you fill their alveolus with sevoflurane, it only has one place to go, so it’ll sort of – “Ugh, I don’t want to, but I’m going to have to” – get into the blood. Now that blood has been ejected around the body via the left ventricle and it’s in the brain. The sevoflurane is like: “Oh well, I hate blood, but brain – that looks slightly more attractive.” So it hops out of the blood into tissues.Obviously, the more perfused the tissue is, the more sevoflurane is initially delivered to it.Clinical values:

• Sevoflurane: blood-gas partition coefficient of 0.65Desflurane: 0.45Isoflurane: 1.4

In an exam you would say that desflurane theoretically has a faster onset time and offset time, which is proven in practice. You could note that isoflurane, with its blood-gas partition coefficient of 1.4, takes longer to onset and offset.Offset mechanism:Offset occurs in much the opposite direction. When you reduce that alveolar volatile anaesthetic agent fraction, you shift the concentration gradients from lots in the lung to some in the brain, to some in the brain and not very much in the lung, and it will start creeping back out.Further study: It would certainly be worth listening to that compartmentalised volatiles episode early on in this podcast that goes into this in slightly maniacal detail if you want to really get to grips with this.

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Oil-Gas Solubility and Potency

12:07-13:41Oil-gas solubility dictates the potency of the agent. It’s nothing to do with onset – it’s all about potency of agent. This does conveniently and expectedly marry up relatively well to the MAC values of these agents (more numbers you’ve got to remember, folks).By that virtue you can work backwards and forwards a bit with MAC values to try and figure out your question about which is more soluble or less soluble, which has the higher or lower MAC between these drugs – the joyful SBAs that you get to excitedly do.MAC values:

• Isoflurane: MAC 1.2Sevoflurane: MAC 2.0 (some places say 1.8)Desflurane: requires an end-tidal fraction of around 6%

Working backwards from MAC:Desflurane – 6% end-tidal. You’ve got to get a patient’s brain to 6% desflurane for them to have a MAC of one. So you’d expect that it is quite oil-gas insoluble – i.e., it is less potent, so you need more of it.These are the inverse of one another:

• Low oil-gas solubility → generally higher MACHigh oil-gas solubility → generally lower MAC target for the drug

Oil-gas solubility values:

• Desflurane: 26Sevoflurane: 47-54Isoflurane: 91

If you check out one of the references in the show notes, it takes you to a BJA article talking about all these things, and you can see their lovely tables that they prepared to get to grips with this in even more detail.

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Wash-In Rates and Clinical Implications

13:41-15:51Now we know about potency of volatile anaesthetic agents and the onset/offset time of volatile anaesthetic agents. But it’s probably worth just mentioning this thing called wash-in rate. There’s lots you can do to alter wash-in rate. Again, we’ve spoken about this in a previous episode.The problem with slow onset agents:The important thing to consider is that a drug that is quite soluble in the blood and therefore takes a long time to work – you may end up fighting to achieve a high enough concentration before your propofol wears off.This is much less of an issue with drugs of today. But if you were to induce someone with propofol and then try and get them deep on ether, you’d be waiting a really long time and you most certainly would end up with awareness in the middle, because it’s just so time-consuming to get them deep enough with ether or chloroform. That’s why we have more modern agents.Wash-in curves:There are excellent graphs (I think they’re on e-Learning for Health) that try and describe these wash-in rates. This can either just be MAC on the y-axis and time on the x-axis, or sometimes describing the time it takes for the fraction of inspired volatile agent to marry up somewhat more closely with the alveolar fraction, which is surrogated by the end-tidal volatile agent fraction or percentage that you see on your anaesthetic machine.The fraction inspired over fraction alveolar graphs are in Peck and Hill, I think. Again, a book that you should definitely open earlier rather than later in your primary FRCA studying. I still regret waiting until the week before the exams to open this book and realise that actually everything was there. So just open it, even though it’s intimidating. Open it now.Understanding the curve shape:These wash-in curves probably follow exponential functions (exponential or logarithmic) as opposed to linear processes, because remember you’re reaching a state of equilibration, and the closer you get to equilibrium the slower you go to get there. You can end up with a steep bit of a curve and then a shallow bit of a curve that takes you a while to reach equilibrium. Although I suppose technically you never really, truly ever get to the end. Who knows?

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Awareness Risk and Emergency Scenarios

15:51-17:56Just to perhaps labour the point about awareness: We’ve induced an anaesthetic in the anaesthetic room. We’ve done a few bits and pieces and we’ve now transferred into theatre. In the anaesthetic room we might have done a nerve block whilst the patient’s asleep (maybe we did it awake, but probably asleep). We’ve transferred them into theatre, and now we’re doing WHO safety checks. We’ve messed around positioning them more.The protective delay:There’s been quite a lot of time between delivering that volatile anaesthetic agent and the surgeon actually picking up the diathermy or the scalpel. This sort of programmed delay is actually very convenient for ensuring that you achieve an adequate depth of anaesthesia before surgical stimulus.High-risk scenarios:However, we do find ourselves in situations where that time is very much shortened. For example:

• You’re anaesthetising someone in theatre because they’re periolicYou’re doing an emergency obstetric general anaesthetic for abruption, foetal bradycardia, awfulness

In which case your time to wash in volatile agent is significantly shorter.Managing the risk:You may get away with being covered by that initial propofol dose whilst the surgeon is getting started. They start whilst actually it’s the propofol that’s keeping them asleep and not the volatile. But if they’ve got an exceedingly high cardiac output and they’re equilibrating that propofol away from their brain quite quickly, you might end up with awareness.You should certainly be aware that you should overpressurise them with volatile in that situation and/or give extra doses of propofol to maintain depth of anaesthesia.The threshold consideration:Be aware that that little jolly transfer from the anaesthetic room (where there’s very little stimulus, the propofol’s soaked in, and not much is going on) – the threshold for awareness is still present, but they’re less stimulated, less likely to be aware than if someone is trying to jump into their abdomen to rescue a poorly baby from a situation.Obstetric considerations:The one saving grace in obstetric situations: for some inexplicable reason, they do seem to require less volatile anaesthetic agent to achieve one MAC. But we know that obstetric anaesthesia has a higher rate of accidental awareness under general anaesthesia, so clearly it happens. Just be super thoughtful about that if you end up in that situation, although thankfully it’s rare to require a GA for a section.

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Factors Affecting MAC

17:56-20:22That takes us nicely to thinking about things that influence MAC. This always comes up in exams, so it’s certainly worth digging out a table that compares clinical states that require more volatile anaesthetic agent or less volatile anaesthetic agent.Clinical examples:You could imagine that if someone has had a load of heroin suddenly, they’ll probably need less sevoflurane to be anaesthetised than someone who has been a heroin user for yonks but hasn’t had any in 24 hours – they’re probably going to be rattling.This also bears true for:

• Hypothyroidism vs hyperthyroidism (I’m sure you can work out which way around those are)Low sodium vs high sodium: low sodium = need less volatile; high sodium = need a bit moreEqual for hypo- and hyperpyrexial or hyperthermic states and a number of other states

You’ll find these when you dig out that table. But you can generally work it out as to states that make your central nervous system more jazzed up or less jazzed up.MAC Definition (the one you should know by now):Hopefully if I were to pause for a second, you could actually tell me what MAC is. I’m sure you should know it by now. If not, you didn’t listen to that previous podcast episode yet. So you’re going to say it now. Go on.One MAC is: the volatile agent fraction end-tidal in a patient that means they will not move when they receive a standard surgical stimulus (skin incision) 50% of the time – i.e., 50% of the subjects wriggled, 50% did not wriggle.Caveats:

• No other opiates on boardNo other analgesic agentsNo other anaesthetic agentsThis is pure sevoflurane-maintained depth of anaesthesiaThe standard incision is a Pfannenstiel incision (used for caesarean sections classically)

MAC and awareness:They’ve used this as a surrogate for “will the patient wriggle or not.” It doesn’t tie directly to awareness, because actually the incidence of 50% awareness versus 50% not awareness is at a lower MAC. But a MAC of one is generally a safe place to be where you are unlikely to end up with awareness, because you’ve got a nice margin of error before getting down to MAC fractions where you’re more likely to be aware.Further study: Check out the episode on MAC earlier in the podcast series to really get a better feel for what the cutoffs for awareness are, but also the cutoffs where you will see a completely obtunded sympathetic response to surgery, amongst other things. You’ve got MAC-Awake, MAC-Aware, MAC-BAR – it’s all there.

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Immobility vs Propofol TIVA

20:22-21:13You might have spotted: wriggliness is much more prevalent when you’re doing a TIVA anaesthetic with propofol than it is with a volatile anaesthetic. That’s because volatiles dampen down your spinal cord quite a bit more than propofol does, and also have a fairly significant effect on causing neuromuscular blockade/relaxation – quite synergistic with your neuromuscular blocking drugs as well as your magnesium and gentamicin that make you floppier.You’ll probably see that wriggliness a lot more if you’re being a bit weird and doing a propofol TCI and giving fentanyl boluses. This is because remifentanil is a very potent analgesic and very much does make people quite still, whereas if you’ve gone a bit weird and you’re using large amounts of fentanyl and then propofol TCI, you do see wriggliness more.

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Mechanism of Action

21:13-23:47We’ve just talked about wriggly patients, but that’s not very clinical. If you start telling an examiner that patients are more or less wriggly, you’re not using scientific terminology and you’re not doing yourself a favour. We need to think about the pharmacodynamics of volatile anaesthetics in a bit more detail.How do they work?There are two schools of thought. One of them is now in the bin.Historical theory – Meyer-Overton hypothesis (now discredited):This tried to correlate the fat solubility of an agent with its potency, basing it on the concept that if there’s more fat solubility then it’s going to soak into more lipid bilayers of neurones and block their function and cause loads of mischief.This kind of fell flat on its face once we started getting some quite fat-insoluble anaesthetic agents that caused anaesthesia. Kind of stuffs that in the bag, doesn’t it?Current theory – Protein-based mechanism:We started thinking about the protein-based concept of mechanism of action. Proteins being:

• GABA-A receptors (my beloved friends)NMDA receptorsTwo-pore potassium channels (another presumed target)

Exam answer:If asked in an exam how volatile anaesthetics work, you could probably open with: “They allosterically modulate GABA-A receptors and may also have NMDA and potassium channel activity, altering synaptic transmission of neurones within the central nervous system.”Because we know that these agents bind to these things and we know that those things do stuff.The bigger question:How does an anaesthetic agent actually render you without consciousness? That is a question for the neuroscientists. If you want lots of detail on this, check out Miller’s Anaesthesia. I think page 488 (depending on your edition) and beyond will elaborate in a delight of detail on volatile anaesthetic agent mechanisms. But no one really, really knows.Patient communication:I’ve had a patient who was a pharmacist ask me, “How do anaesthetic agents work?” I had to look at them in the face and say: “Well, yes, it acts on receptors in your brain – a GABA receptor – which alters how those neurones work. But actually how it renders you unable to form memories and asleep is something that is not well understood.”They looked a little bit aghast. I think perhaps they’d decided that they wished they hadn’t asked the question. Because, you know, they were sort of discovered in a bit of a black-box-ish manner. “Here, have a whiff of this. Oh look, you’re unconscious. Well, that’s a useful thing. Maybe we could make use of you being unconscious so we can chop your leg off without it being quite so excruciating.”Even in this day and age, we are in a situation where we know it works, we’re not quite sure exactly how it works, but we know it works. Fascinating, really.Communication strategy:I would argue that telling a patient that we don’t know how something works is not exactly an effective communication strategy. Equally, it is not a lie.

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Side Effects by Organ System

23:55-25:27We talked about mechanism, and now we should probably outline some of the side effects of volatile anaesthetic agents. Each agent actually does have a particular subset of side effects that are relevant to it. I’m just going to cover the broad stuff here.Remember, we should always break these down by organ system.Cardiovascular effects:

• Broadly speaking, volatile anaesthetic agents drop your blood pressureIn higher doses, they can also cause bradycardia

Respiratory effects:

• Dose-dependent reduction in respiratory rateThis can be somewhat utilised (and historically was) – if a patient got too deep breathing their chloroform or ether, they’d breathe less and wake up a bit because they’d metabolise a bit moreThat might help in a marginal realm of that spectrum of sleepiness, but if you’re giving 8% sevoflurane constantly, the patient might stop breathing, but then they’re full of 8% sevoflurane and none of it’s coming out again. Not a perfect way to administer an anaesthetic.Most of them cause bronchodilation, which is useful

CNS effects:

• Obviously, they hypnotise youCan cause a degree of neuromuscular blockade and smooth muscle relaxationMuch like you get bronchodilation, you can get uterine atony, which is something of concern in your GA section where you end up with a higher incidence of obstetric haemorrhage

Malignant hyperthermia: All volatile anaesthetic agents can also trigger malignant hyperthermia, which is an emergency. It is very rare, and it’s something we will cover at the end of this volatile anaesthetic agents chapter with an episode on MH.

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Characteristics of an Ideal Volatile Agent

25:27-27:45All of these things might come up in the exam, but one of the favoured questions (or historically favoured questions) is: “What are the characteristics of an ideal agent?” You could apply that to a hypnotic agent, a pain-relieving agent, etc. But what about the characteristics of an ideal volatile anaesthetic agent?You probably should break this down into useful pharmacological properties and useful physical properties.Pharmacological Properties (think about patient experience and side effect profile):Break the side effect profile down by organ system:Cardiovascular:

• Cardiovascularly stable

Respiratory:

• Pleasant for the patient to smellNon-irritantWould not cause respiratory depressionConveniently bronchodilating

Metabolic:

• Stable from a metabolic perspectiveNot mess with any gluconeogenesis or steroidogenesisNot metabolised into toxic metabolites

Analgesic:

• Very useful if it had analgesic properties (some useful NMDA receptor modulation)

CNS:

• Would not want it to increase intracranial pressureWould not want it to reduce your seizure threshold

Physical Properties:Safety:

• Non-toxic to patient and staffNon-flammable and certainly not able to explode

Storage and stability:

• Stable in light (so you didn’t have to squirrel it away in a corner in the dark)Stable at room temperatureBoiling point that means it had a predictable saturated vapour pressure

Vaporisation:

• Ideally, that saturated vapour pressure would be quite high, so it would vaporise simplistically and easily in your vaporising device

Environmental:

• Rapidly break down in the environmentMinimal to no global warming potentialNo propensity to soak into your tubing, be that plastic or rubber (i.e., halothane)

Kinetic Properties:Onset/offset:

• Low blood-gas partition coefficient, so it had a rapid onset and offset

Potency:

• High oil-gas partition coefficient, so it was more potent, requiring less agent to achieve depth of anaesthesia, meaning you could use less of it

Cost:

• Last but not least, you would want it to be cheap because you don’t want to be spending loads of money

Exam approach:That’s an excellent way to approach that sort of question. Break it down into physical properties and patient-relevant properties with side effects. Never forget about how you administer it and how expensive it is.

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Summary and Future Episodes

27:45-29:35What we covered:

• Blood-gas partition coefficientOil-gas partition coefficientWhy boiling point is importantWhat saturated vapour pressure is (and I’ve flagged you off to go read about humidity, which will help cement that)Touched on reasons why you might need more or less volatile anaesthetic agentThought about wash-in curves and the concept that it takes a while to achieve depth of anaesthesia with volatile because you’ve got to breathe it in – it’s not just injected into someone’s veinsClosed up with the ideal approach to an ideal anaesthetic agent question

Future episodes in this series:

• Episodes specific to each volatile anaesthetic agent: isoflurane, sevoflurane, desflurane, halothaneCombined nitrous and oxygen episode (there is a Vivacast on this, but I’ll tie it all together properly)Episode on the history of volatile anaesthetic agents (ether, chloroform, halothane, and maybe their first use – that’ll be a bit of a laugh)Definitely a quiz at the end of thisEpisodes on malignant hyperthermia (thinking about its mechanisms of treatment)Maybe just for fun at the end, we’ll do xenon, because that is also a general anaesthetic-inducing noble gas, which is quite mad really

Closing thoughts:Thank you very much for listening. If you really enjoyed this episode, feel free to fire up a donation – it’ll help keep the show running and cover the costs of the website and hosting. It would be much appreciated.Thanks for listening, guys. I hope you found it useful. But if you found it awful, do let me know. Please like and subscribe, register with whichever podcast platform you find yourself using, and leave a comment if you think I need to sort something away.

I just want to make sure that you guys know thatevery day you are getting better at this. There is a bucket of content to try and consume, and it is like drinking from a fire hose. Take it day by day, don’t overcook yourself, don’t freak out, and keep studying.