Overview
Historically there have been several accounts of the use of various forms of anesthesia from cannabis and other herbs to carotid compression. The earliest account of modern anesthesia was in the 1840s when ether was used to excise a neck tumor. The first public demonstration of the use of ether was in 1846.
Inhaled Anaesthetic agents
| Gases | Nitric Oxide, Oxygen |
|---|---|
| Halogenated hydrocarbons (Volatile) | Halothane, Diethyl ether |
| Halogenated ethers (Volatile) | Sevoflurane, Isoflurane, Enflurane, Desflurane, Methoxyflurane |
- Ideal properties of an inhalational iagent
- Minimal toxicity: especially to the CVS, RS, Renal, Hepatic and CNS.
- No unwanted side effects e.g. seizures, nausea and vomiting
- Safe for personnel: waste gas vapours should have minimal toxicity
- User friendly: pleasant and non-irritating
- Rapid and gentle induction/recovery
- Depth of anaesthesia easily controlled and quickly altered when necessary
- Not dependent on the liver and kidney for metabolism or excretion
- Good muscle relaxation
- Adequate analgesia
- Low cost
- Adequate potency to achieve surgical anaesthesia
- Handling is easy and safe: non-flammable, non-explosive, chemically stable
- Does not require specialized or expensive equipment
- Does not react with anaesthetic machine equipment: rubber, metal, carbon dioxide absorber
Pharmacokinetics
The pharmacokinetics of inhaled anesthetics can be divided into uptake, distribution into the CNS, metabolism, and elimination. The goal of inhaled anaesthetics is to produce partial pressure of gas in the alveolus that equilibrates with that in the CNS to cause anesthesia. At equilibrium Pcns = Parterial blood = Palveoli.
Definition of terms
| Term | Definition |
|---|---|
| FI (Inspired Concentration) | Determined by gas flow, volume of breathing, and absorption by machine/circuit |
| FA (Alveolar Concentration) | Determined by uptake, alveolar ventilation, and concentration/second gas effect |
| FA/FI ratio | The rate of rise in FA/FI ratio is a marker of anesthetic uptake by blood. It rises most rapid with least soluble anaesthetics(Nitrous oxide, Desflurane, Sevoflurane) and more slowly with more soluble anaesthetics (Halothane) |
| PA (Alveolar Partial pressure) | Determined by input (delivery) minus uptake (loss) |
| Uptake | Affected by solubility in blood, alveolar blood flow (cardiac output), and alveolar-venous partial pressure difference |
| Alveolar blood flow | In the absence of shunts, blood flow to the alveolus = cardiac output |
| Blood: gas partition coefficient | The ratio of the concentration of gas in the blood to the concentration of gas in the alveoli when the partial pressure in both compartments is equal. For example. Blood: gas partition coefficient of Nitrous is 0.46. 1ml of blood contains 0.46 as much Nitrous as does 1ml of alveolar gas. |
Gas properties
| Blood:Gas Partition Coefficient | Vapor pressure (mmHg) at 20 C | MAC | |
|---|---|---|---|
| Nitrous oxide | 0.46 | 38,770 | 104% |
| Desflurane | 0.45 | 669 | 6% |
| Sevoflurane | 0.65 | 160 | 1.85% |
| Isoflurane | 1.46 | 240 | 1.15% |
| Halothane | 2.54 | 244 | 0.76% |
| Enflurane | 1.9 | 172 | 1.63% |
Atmosphere longevity
| Gas | Atmosphere longevity |
|---|---|
| Nitrous | 114 years |
| Desflurane | 10 years |
| Sevoflurane | 3.6 years |
| Isoflurane | 1.2 years |
- What is the effect of altitude on inhaled anaesthetic agents?
- Higher altitudes with lower atmospheric pressure (< 760mmHg) causes the same amount of inhaled agents to have a lower partial pressure in the alveolus and thus a REDUCED anaesthetic effect.
- What is the effect of gas solubility on CNS uptake?
- For highly soluble gases, more gas is required to saturate blood before uptake by the CNS
- What is the effect of Cardiac Output on CNS uptake?
- High cardiac output requires more gas for uptake by the CNS. High CO = Large Tank = Need to fill the tank before the agent is taken up by the CNS
- Low cardiac output predisposes the patients to overdose of inhalational agents (Fa/Fi will be faster)
- Poorly soluble gases are less affected by cardiac output (since so little is taken up into the blood)
- What factors lead to faster induction of inhaled anesthetics? These factors cause decreased uptake and increased FA/FI ratio
- Low blood solubility (low blood: gas partition coefficient)
- Low cardiac output (affects soluble gases more)
- Low alveolar-venous partial pressure difference(meaning less uptake by blood)
- Which gases have the fastest rise in FA/FI ratio
- Gases with the lowest solubility e.g. Desflurane. Less uptake means a faster rise in FA/FI ratio
- What is the effect of a right-to-left shunt on induction?
- Right-to-left shunt causes slower induction since shunted blood (with no gas) mixes with blood from ventilated alveoli (with gas) diluting the partial pressure of the gas
- There will also be a more significant delay in onset of poorly soluble agents
- IV anaesthetics will have a faster onset (if bypassing lungs, will reach the CNS quicker) Right to left shunts = intracardiac or transpulmonary e.g. mainstem intubation
- What is the effect of a left-to-right shunt on induction?
- Minimal effect on the speed of induction for IV or volatile anaesthetics
Inhaled anaesthetics FA/FI rise graph (nitrous has a higher rise since it is given in higher concentrations, even though desflurane is slightly less soluble)
Pharmacodynamics
Inhaled anaesthetics have no clear mechanism of action. They bind to amphiphilic cavities in proteins but it is unclear how this causes anaesthesia. It is likely that they enhance inhibitory channels and decrease the activity of excitatory channels. The potency of anaesthetics is linked to its lipid solubility.
Nitrous Oxide
Nitrous is commonly administered as an anaesthetic adjuvant. It has deleterious effects to the environment since it is a greenhouse gas that takes >100 years to be degraded. Its low solubility in blood facilitates rapid uptake and elimination. It however has low potency (MAC 104%, can never reach 1 MAC). It does not produce muscle relaxation. It has analgesic properties since it is an NMDA antagonist.
Nitrous is stored in a blue container. It is always given with Oxygen. A concentration of 50% Oxygen and 50% Nitrous can be used for labour pains. When using nitrous, air should be periodically let out of the ETT to avoid tracheal injury.
- Adverse effects
- Post-operative Nausea and Vomiting (can be controlled with antiemetics)
- Can diffuse into air-filled cavities and cause expansion of these structures (enters cavities faster than it can leave)
- Myocardial depression in Coronary Artery Disease or Severe Hypotension
- Pulmonary hypertension if used for a prolonged period.
- Bone Marrow depression and Peripheral neuropathy in prolonged exposure
- Contraindications
- Abnormal air pockets (Pneumothorax, Small Bowel Obstruction, Laparoscopy, Middle Ear obstruction). It is poorly soluble and will rapidly expand into any air spaces
Halothane
Halothane is the most potent volatile (MAC 0.75). It produces poor analgesia and muscle relaxation. It is highly lipid soluble. It can be used in asthmatic patients (potent bronchodilator properties)
- Adverse effects
- Hepatic necrosis
- Sensitizes the myocardium to Adrenaline → Arrhythmia
- Decreased myocardial contractility → Shock
- Vasodilatation → Shock
- Contraindications
- Hypotension
- Labour (can lead to uterine atony)
Isoflurane
Isoflurane is a popular agent for maintenance and is specifically recommended for raised ICP and Neuroanaesthesia (since it has minimal effect on cerebral blood flow). It is highly pungent and the least expensive volatile anaesthetic. It is the second most potent agent (MAC 1.15%). It causes vasodilatation. At 2 MAC it produces electrically silent EEG.
- Adverse effects
- Coronary steal (vasodilation of normal coronary arteries causes blood to be diverted from stenotic vessels)
- Vasodilatation causes low BP, Increased CBF and Increased ICP (but lower effect than halothane)
- Contraindications
- Shock
- Susceptible to Malignant Hyperthermia
Sevoflurane
Sevoflurane is preferred for induction since it has rapid uptake, rapid elimination and smells sweet. It has the smallest impact on the atmosphere but is more expensive. It is half as potent as Isoflurane (MAC 1.8%). It also causes potent bronchodilation. It also has very little cardiovascular effect.
- Adverse effect
- Malignant hypertehrmia
- Precautions
- Can form Carbon Monoxide in desiccated CO2 absorbent which can lead to fires
- Broken down into Compound A when exposed to CO2 absorbent (Barium hydroxide/Baralyme or soda lime) which is nephrotoxic in rats (some recommend keeping fresh gas flow to >2 L/min to prevent rebreathing compound A)
Desflurane
Desflurane has only one Fluorine molecule as the halogen. It has the greatest CO2 impact on the environment. It has the lowest blood: gas solubility coefficient (lower than N20) and hence quick uptake and quick elimination. It is preferred for maintenance since it is pungent. It uses a different heated vaporizer system that delivers anaesthetic at a fixed percent concentration and NOT at a fixed partial pressure (like sevoflurane and isoflurane vaporizers). Desflurane is being discontinued as an anaesthetic in multiple hospitals across the world.
- Adverse effects
- Malignant hyperthermia
- Causes breath holding, bronchospasm, laryngospasm, coughing, and salivation when administered to awake patients via face mask (it is very pungent)
- Can form CO in desiccated CO2 absorbent (more than other volatiles)
- Can cause increased sympathetic response (tachycardia, hypertension) when inspired concentration is increased rapidly
